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A recent CLOUD (Cosmics Leaving OUtdoor Droplets) chamber study showed that sulfuric acid and dimethylamine produce new aerosols very efficiently and yield particle formation rates that are compatible with boundary layer observations. These previously published new particle formation (NPF) rates are reanalyzed in the present study with an advanced method. The results show that the NPF rates at 1.7 nm are more than a factor of 10 faster than previously published due to earlier approximations in correcting particle measurements made at a larger detection threshold. The revised NPF rates agree almost perfectly with calculated rates from a kinetic aerosol model at different sizes (1.7 and 4.3 nm mobility diameter). In addition, modeled and measured size distributions show good agreement over a wide range of sizes (up to ca. 30 nm). Furthermore, the aerosol model is modified such that evaporation rates for some clusters can be taken into account; these evaporation rates were previously published from a flow tube study. Using this model, the findings from the present study and the flow tube experiment can be brought into good agreement for the high base-to-acid ratios (∼ 100) relevant for this study. This confirms that nucleation proceeds at rates that are compatible with collision-controlled (a.k.a. kinetically controlled) NPF for the conditions during the CLOUD7 experiment (278 K, 38 % relative humidity, sulfuric acid concentration between 1 × 106 and 3 × 107 cm−3, and dimethylamine mixing ratio of ∼ 40 pptv, i.e., 1 × 109 cm−3).
Mannitol is the major compatible solute, next to glutamate, synthesized by the opportunistic human pathogen Acinetobacter baumannii under low water activities. The key enzyme for mannitol biosynthesis, MtlD, was identified. MtlD is highly similar to the bifunctional mannitol‐1‐phosphate dehydrogenase/phosphatase from Acinetobacter baylyi. After deletion of the mtlD gene from A. baumannii ATCC 19606T cells no longer accumulated mannitol and growth was completely impaired at high salt. Addition of glycine betaine restored growth, demonstrating that mannitol is an important compatible solute in the human pathogen. MtlD was heterologously produced and purified. Enzyme activity was strictly salt dependent. Highest stimulation was reached at 600 mmol/L NaCl. Addition of different sodium as well as potassium salts restored activity, with highest stimulations up to 41 U/mg protein by sodium glutamate. In contrast, an increase in osmolarity by addition of sugars did not restore activity. Regulation of mannitol synthesis was also assayed at the transcriptional level. Reporter gene assays revealed that expression of mtlD is strongly dependent on high osmolarity, not discriminating between different salts or sugars. The presence of glycine betaine or its precursor choline repressed promoter activation. These data indicate a dual regulation of mannitol production in A. baumannii, at the transcriptional and the enzymatic level, depending on high osmolarity.
Spatial modelling of malaria cases associated with environmental factors in South Sumatra, Indonesia
(2018)
Background: Malaria, a parasitic infection, is a life-threatening disease in South Sumatra Province, Indonesia. This study aimed to investigate the spatial association between malaria occurrence and environmental risk factors.
Methods: The number of confirmed malaria cases was analysed for the year 2013 from the routine reporting of the Provincial Health Office of South Sumatra. The cases were spread over 436 out of 1613 villages. Six potential ecological predictors of malaria cases were analysed in the different regions using ordinary least square (OLS) and geographically weighted regression (GWR). The global pattern and spatial variability of associations between malaria cases and the selected potential ecological predictors was explored.
Results: The importance of different environmental and geographic parameters for malaria was shown at global and village-level in South Sumatra, Indonesia. The independent variables altitude, distance from forest, and rainfall in global OLS were significantly associated with malaria cases. However, as shown by GWR model and in line with recent reviews, the relationship between malaria and environmental factors in South Sumatra strongly varied spatially in different regions.
Conclusions: A more in-depth understanding of local ecological factors influencing malaria disease as shown in present study may not only be useful for developing sustainable regional malaria control programmes, but can also benefit malaria elimination efforts at village level.
The emerging relapsing fever spirochete Borrelia (B.) miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD). More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a plasmin(ogen) receptor that enables B. miyamotoi to interact with the serine protease plasmin(ogen). Recombinant CbiA was able to bind plasminogen in a dose-dependent fashion. Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was inhibited by the lysine analog tranexamic acid as well as increasing ionic strength. Of relevance, plasminogen bound to CbiA can be converted by urokinase-type plasminogen activator (uPa) to active plasmin which cleaved both, the chromogenic substrate S-2251 and its physiologic substrate fibrinogen. Concerning the involvement of specific amino acids in the interaction with plasminogen, lysine residues located at the C-terminus are frequently involved in the binding as reported for various other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine residues located within the C-terminal domain were substituted with alanine to generate single, double, triple, and quadruple point mutants. However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the C-terminus might be involved in the interaction.
The quasi-two-dimensional organic charge-transfer salt κ -(BEDT-TTF) 2 Cu 2 (CN) 3 is one of the prime candidates for a quantum spin-liquid due the strong spin frustration of its anisotropic triangular lattice in combination with its proximity to the Mott transition. Despite intensive investigations of the material’s low-temperature properties, several important questions remain to be answered. Particularly puzzling are the 6 K anomaly and the enigmatic effects observed in magnetic fields. Here we report on low-temperature measurements of lattice effects which were shown to be particularly strongly pronounced in this material (R. S. Manna et al., Phys. Rev. Lett. 2010, 104, 016403)). A special focus of our study lies on sample-to-sample variations of these effects and their implications on the interpretation of experimental data. By investigating overall nine single crystals from two different batches, we can state that there are considerable differences in the size of the second-order phase transition anomaly around 6 K, varying within a factor of 3. In addition, we find field-induced anomalies giving rise to pronounced features in the sample length for two out of these nine crystals for temperatures T< 9 K. We tentatively assign the latter effects to B-induced magnetic clusters suspected to nucleate around crystal imperfections. These B-induced effects are absent for the crystals where the 6 K anomaly is most strongly pronounced. The large lattice effects observed at 6 K are consistent with proposed pairing instabilities of fermionic excitations breaking the lattice symmetry. The strong sample-to-sample variation in the size of the phase transition anomaly suggests that the conversion of the fermions to bosons at the instability is only partial and to some extent influenced by not yet identified sample-specific parameters.
Compact objects - black holes and neutron stars - are fascinating objects, not only for the astrophysicists, but for a wide range of researchers, including astronomers, theoretical physicists, particle and nuclear physicists, condensed matter physicists and arguably for the layman as well.
First theorized in the first part of the twentieth century, for a long time these objects have been considered just exotic ideas or mathematical curiosities. Pulsar were however detected in the late 1960s and readily identified as rotating, radiating neutron stars, while the first candidate black hole, Cygnus X-1, was observed in 1972. Since then the interest in these objects has steadily grown.
The reasons behind this interest are easily understood considering that compact object dwell at the intersection of many different areas of physics, and are ideal laboratories to explore the interplay between these areas.
Black holes, which are purely gravitational objects, are perfectly suited to study the nature of gravity, its manifestations such as gravitational waves, and the differences between various theories of gravity in the regime where they are expected to be most relevant, i.e. the strong field regime. However, just like any massive astrophysical object, black holes are interested by accretion phenomena, which are thought to be the power source of some very bright astrophysical emitters of electromagnetic signals, such as active galactic nuclei or X-ray binaries.
At the same time, black holes exist in a variety of different mass scales, from stellar mass to supermassive black holes billions of times heavier. The latter play a very important and yet not fully understood role in the formation and evolution of galaxies, as well as in shaping the large scale structure of the universe, making them relevant to cosmology as well.
Neutron stars share with black holes the characteristic of being gravitationally dominated systems; but because they are composed of baryon matter, they display a much richer behaviour. It has been realized early on that the matter in neutron star cores reaches extreme densities, exceeding the one in atomic nuclei. This means that neutron stars could provide invaluable information on the behaviour of matter in such extreme conditions (which are impossible to achieve in laboratory experiments), such as details of the nucleonic interaction, the properties of hyperons or of quark-gluon plasmas.
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Diploid transgenic organisms are either hemi- or homozygous. Genetic assays are, therefore, required to identify the genotype. Our AGameOfClones vector concept uses two clearly distinguishable transformation markers embedded in interweaved, but incompatible Lox site pairs. Cre-mediated recombination leads to hemizygous individuals that carry only one marker. In the following generation, heterozygous descendants are identified by the presence of both markers and produce homozygous progeny that are selected by the lack of one marker. We prove our concept in Tribolium castaneum by systematically creating multiple functional homozygous transgenic lines suitable for long-term fluorescence live imaging. Our approach saves resources and simplifies transgenic organism handling. Since the concept relies on the universal Cre-Lox system, it is expected to work in all diploid model organisms, for example, insects, zebrafish, rodents and plants. With appropriate adaptions, it can be used in knock-out assays to preselect homozygous individuals and thus minimize the number of wasted animals.
The mission of the Compressed Baryonic Matter (CBM) experiment is to investigate the phase diagram of strongly interacting matter in the region of high net-baryon densities and moderate temperatures. According to various transport models, matter densities of more than 5 times saturation density can be reached in collisions between gold nuclei at beam energies between 5 and 11 GeV per nucleon, which will be available at FAIR. The core detector of the CBM experiment is the Silicon Tracking System (STS), which is used to measure the tracks of up to 700 particles per collision with high efficiency (>95%) and good momentum resolution (<1.5%). The technological and experimental challenge is to realize a detector system with very low material budget, in order to reduce multiple scattering of the particles, and a free-streaming data readout chain, in order to achieve reaction rates up to 10 MHz together with an online event reconstruction and selection.
The STS comprises 8 tracking stations positioned between 30 cm and 100 cm downstream the target inside a magnetic field, covering polar emission angles up to 25 degrees. A station consists of vertical structures with increasing number (between 8 and 16, depending on station number), each structure carrying between 2 and 10 double-sided microstrip silicon sensors, which are connected through low-mass microcables to the readout electronics placed at the detector periphery outside the active detector area.
The work presented in this thesis focuses on the detector performance simulation and local hit pattern reconstruction in the STS. For efficient detector design and reconstruction performance, a reliable detector response model is of utmost importance. Within this work, a realistic detector response model was designed and implemented in the CBM software framework. The model includes non-uniform energy loss of an incident particle within a sensor, electric field of a planar p-n junction, Lorentz shift of the charge carriers, their diffusion, and the influence of parasitic capacitances. The developed model has been verified with experimental data from detector tests in a relativistic proton beam. Cluster size distributions at different beam incident angles are sensitive to charge sharing effects and were chosen as an observable for the verification. Taking into account parasitic capacitances further improves the agreement with measured data.
Using the developed detector response model, the cluster position finding algorithm was improved. For two-strip clusters, a new, unbiased algorithm has been developed, which gives smaller residuals than the Centre-Of-Gravity algorithm. For larger clusters, the head-tail algorithm is used as the default one. For an estimate of the track parameters, the Kalman Filter based track fit requires not only hit positions but their uncertainties as an input. A new analytic method to estimate the hit position errors has been designed in this work. It requires as input neither measured spatial resolution nor information about an incident particle track. The method includes all the sources of uncertainties independently, namely: the cluster position finding algorithm itself, the non-uniform energy loss of incident particles, the electronics noise, and the discretisation of charge in the readout chip.
The verification with simulations shows improvements in hit and track pull distributions as well as x²-distributions in comparison to the previous simple approach. The analytic method improves the track parameters reconstruction by 5-10%.
Several STS module prototypes have been tested in a relativistic proton beam. A signal to-noise ratio was obtained at the level of 10-15 for modules made of 30 cm long microcable and of either one or two 6.2 x 6.2 cm² CiS sensors.
First simulations have shown that this signal-to-noise ratio is sufficient to reach the required efficiency and momentum resolution. The high-radiation environment of CBM operation will deteriorate the sensor performance. Radiation hardness of sensors has been studied in the beam with sensors irradiated to 2 x 10[hoch 14] 1MeV [neq/cm²], twice the lifetime dose expected for CBM operation. Charge collection efficiency drops by 17-25%, and simultaneously noise levels increase 1.5-1.75 times. The simulations show that if all sensors in the STS setup are exposed to such a fluence uniformly, the track reconstruction efficiency drops from 95.5% to 93.2% and the momentum resolution degrades from 1.6% to 1.7%.
Rationale: Classic histology is the gold standard for vascular network imaging and analysis. The method however is laborious and prone to artefacts. Here, the suitability of ultramicroscopy (UM) and micro-computed tomography (CT) was studied to establish potential alternatives to histology.
Methods: The vasculature of murine organs (kidney, heart and atherosclerotic carotid arteries) was visualized using conventional 2D microscopy, 3D light sheet ultramicroscopy (UM) and micro-CT. Moreover, spheroid-based human endothelial cell vessel formation in mice was quantified. Fluorescently labeled Isolectin GS-IB4 A647 was used for in vivo labeling of vasculature for UM analysis, and analyses were performed ex vivo after sample preparation. For CT imaging, animals were perfused postmortem with radiopaque contrast agent.
Results: Using UM imaging, 3D vascular network information could be obtained in samples of animals receiving in vivo injection of the fluorescently labeled Isolectin GS-IB4. Resolution was sufficient to measure single endothelial cell integration into capillaries in the spheroid-based matrigel plug assay. Because of the selective staining of the endothelium, imaging of larger vessels yielded less favorable results. Using micro-CT or even nano-CT, imaging of capillaries was impossible due to insufficient X-ray absorption and thus insufficient signal-to-noise ratio. Identification of lumen in murine arteries using micro-CT was in contrast superior to UM.
Conclusion: UM and micro-CT are two complementary techniques. Whereas UM is ideal for imaging and especially quantifying capillary networks and arterioles, larger vascular structures are easier and faster to quantify and visualize using micro-CT. 3D information of both techniques is superior to 2D histology. UM and micro-CT together may open a new field of clinical pathology diagnosis.
Three fungi associated with living leaves of plants are new records for Panama: Annellophora phoenicis causing leaf spots of Cocos nucifera (Arecaceae), Cercospora corniculatae (C. apii s. lat.) on living leaves of Oxalis barrelieri (Oxalidaceae) with and without discoloration, and Sclerotium coffeicola on zonate leaf spots of Annona montana (Annonaceae) and Dioscorea alata (Dioscoreaceae). Some records of A. phoenicis and S. coffeicola relevant for known geographical distribution and available by literature are critically revised.
Background: The Asian tiger mosquito Aedes albopictus is an extremely invasive, globally distributed and medically important vector of various human and veterinary pathogens. In Germany, where this species was recently introduced, its establishment may become modulated by interspecific competition from autochthonous mosquito species, especially Culex pipiens (s.l.). While competitive superiority of Ae. albopictus to Cx. pipiens (s.l.) has been described elsewhere, it has not been assessed in the epidemiological conditions of Germany. The present study aimed to determine if such superiority exists under the physicochemical and microclimatic conditions typical for container habitats in Germany.
Methods: In a replacement series experiment, the larval and pupal responses of Ae. albopictus and Cx. pipiens (s.l.) (mortality, development time, growth) to interspecific interaction (five larval ratios) at (sub-)optimal temperatures (15, 20 and 25 °C) and differing food supply (3 and 6 mg animal-based food larva-1) were investigated using a randomized split-plot design. In addition to physicochemical measurements of the test media, natural physicochemical conditions were determined for comparative analyses in mosquito breeding sites across the Rhine-Main metropolitan region of Germany.
Results: Under the physicochemical and microclimatic conditions similar to the breeding sites of the Rhine-Main region, competitive superiority of Cx. pipiens (s.l.) to Ae. albopictus in terms of larval survival was more frequently observed than balanced coexistence. Food regime and multifactorial interactions, but not temperature alone, were controlling factors for interspecific competition. Larval food regime and the larval ratio of Ae. albopictus influenced the physicochemistry and algal growth at 15 °C, with increased Ae. albopictus mortality linked to a decreasing number of Scenedesmus, Oocystis and Anabaena algae.
Conclusions: Under the present environmental conditions, the spread of Ae. albopictus from isolated foci in Germany may generally be slowed by biotic interactions with the ubiquitous Cx. pipiens (s.l.) (and potentially other container-breeding mosquito species) and by limnic microalgae in microhabitats with high resource levels. Detailed knowledge of the context dependency in temperate mosquito ecology, and interrelations of physicochemistry and phycology may help to achieve a better understanding of the upcoming Ae. albopictus colonization processes in central and northern Europe.
Adipose-derived mesenchymal stem cells (ASCs) have crucial functions, but their roles in obesity are not well defined. We show here that ASCs from obese individuals have defective primary cilia, which are shortened and unable to properly respond to stimuli. Impaired cilia compromise ASC functionalities. Exposure to obesity-related hypoxia and cytokines shortens cilia of lean ASCs. Like obese ASCs, lean ASCs treated with interleukin-6 are deficient in the Hedgehog pathway, and their differentiation capability is associated with increased ciliary disassembly genes like AURKA. Interestingly, inhibition of Aurora A or its downstream target the histone deacetylase 6 rescues the cilium length and function of obese ASCs. This work highlights a mechanism whereby defective cilia render ASCs dysfunctional, resulting in diseased adipose tissue. Impaired cilia in ASCs may be a key event in the pathogenesis of obesity, and its correction might provide an alternative strategy for combating obesity and its associated diseases.
The genus Pseudolatirus Bellardi, 1884, with the Miocene type species Fusus bilineatus Hörnes, 1853, has been used for 13 Miocene to Early Pleistocene fossil species and eight Recent species and has traditionally been placed in the fasciolariid subfamily Peristerniinae Tryon, 1880. Although the fossil species are apparently peristerniines, the Recent species were in their majority suspected to be most closely related to Granulifusus Kuroda & Habe, 1954 in the subfamily Fusininae Wrigley, 1927. Their close affinity was confirmed by the molecular phylogenetic analysis of Couto et al. (2016). In the molecular phylogenetic section we present a more detailed analysis of the relationships of 10 Recent Pseudolatirus-like species, erect two new fusinine genera, Okutanius gen. nov. (type species Fusolatirus kuroseanus Okutani, 1975) and Vermeijius gen. nov. (type species Pseudolatirus pallidus Kuroda & Habe, 1961). Five species are described as new for science, three of them are based on sequenced specimens (Granulifusus annae sp. nov., G. norfolkensis sp. nov., Okutanius ellenae gen. et sp. nov.) and two (G. tatianae sp. nov., G. guidoi sp. nov.) are attributed to Granulifusus on the basis of conchological similarities to sequenced species. New data on radular morphology is presented for examined species.
The taxonomy of the American Onthophagus Latreille, 1802 included in the “hirculus” group is revised, and a study of their morphology allows for the delineation of five species-complexes. Herein, we provide a diagnosis of the “hirculus” group, an illustrated key to the complexes, along with a descriptive overview of their taxonomy and geographic distribution. Onthophagus hirculus Mannerheim, 1829 is considered to be a junior synonym of O. hircus Billberg, 1815, which is here demonstrated to be a valid species name. Thus, the “hirculus” group is here renamed the “hircus” group. Furthermore, a general scheme of the genital organs of American Onthophagus is provided, including names of different anatomical parts and a brief discussion on the need for nomenclatural stability for the genitalia of scarab beetles.
Two obligate cave-dwelling species of cyclopoid copepods (Copepoda, Cyclopoida) were discovered inside caves in central Thailand. Siamcyclops cavernicolus gen. et sp. nov. was recognised as as a member of a new genus. It resembles Bryocyclops jankowskajae Monchenko, 1972 from Uzbekistan (part of the former USSR). It differs from it by (1) lack of pointed triangular prominences on the intercoxal sclerite of the fourth swimming leg, (2) mandibular palp with three setae, (3) spine and setal formulae of swimming legs 3.3.3.2 and 5.5.5.5, respectively, and (4) specific shape of spermatophore. Metacyclops thailandicus sp. nov. resembles M. cushae Reid, 1991 from Louisiana (USA). It differs from it by (1) distal segment of the endopod of the fourth swimming leg with one apical spine, (2) the fifth swimming legs with one broad segment, (3) the spine formula of the distal segment of the exopod of the swimming legs 3.4.3.3, and (4) well developed anal operculum reaching articulation with caudal rami. Detailed descriptions of the habitats of the new species and up-to-date keys to the genera and subgenera of the Bryocyclops and Microcyclops groups are provided, along with an updated list of obligate groundwater species of Copepoda in Southeast Asia.
This paper presents an improved diagnosis and definition of the genus Stenaelurillus Simon, 1886, with new taxonomic and faunistic data for 23 species. The genera Microheros Wesołowska & Cumming, 1999 and Mashonarus Wesołowska & Cumming, 2002 are synonymized with Stenaelurillus. Six new species are described: Stenaelurillus bandama sp. nov. (♂♀, from Côte d’Ivoire), S. belihuloya sp. nov. (♂, from Sri Lanka), S. jocquei sp. nov. (♂♀, from Cameroon), S. pseudoguttatus sp. nov. (♂, from Namibia), S. senegalensis sp. nov. (♂♀, from Senegal), and Stenaelurillus siyamae sp. nov. (♀, from Sudan). Lectotypes are designated for two species: S. albopunctatus Caporiacco, 1949 (♂) from Kenya and S. werneri Simon, 1906 (♀) from South Sudan. Six new combinations are proposed: Aelurillus ambiguus (Denis, 1966), comb. nov. (ex Stenaelurillus); Evarcha werneri (Simon, 1906), comb. nov. (ex Stenaelurillus); Phlegra davidi (Caleb, Mungkung & Mathai, 2015), comb. nov. (ex Mashonarus); Stenaelurillus brandbergensis (Wesołowska, 2006), comb. nov. (ex Mashonarus); Stenaelurillus guttatus (Wesołowska & Cumming, 2002), comb. nov. (ex Mashonarus); and S. termitophagus (Wesołowska & Cumming, 1999), comb. nov. (ex Microheros). Two species names are synonymized: Evarcha elegans Wesołowska & Russell-Smith, 2000 with E. werneri comb. nov.; and Aelurillus sahariensis Berland & Millot, 1941 with Stenaelurillus nigricaudus Simon
We describe five new species of fungi of the order Laboulbeniales Lindau growing on millipedes and belonging to the genera Diplopodomyces W.Rossi & Balazuc and Troglomyces S.Colla. Three new species of Diplopodomyces, viz. Diplopodomyces coronatus Santam., Enghoff & Reboleira sp. nov. living on Serboiulus spelaeophilus Gulicka, 1967 from Bulgarian caves, Diplopodomyces liguliphorus Santam., Enghoff & Reboleira sp. nov. on an unidentified species of Spirobolida from Sri Lanka, and Diplopodomyces ramosus Santam., Enghoff & Reboleira sp. nov. on Pachyiulus spp. from Turkey, Macedonia and Serbia; and two new species of Troglomyces, viz. Troglomyces dioicus Santam., Enghoff & Reboleira sp. nov. on Nepalmatoiulus sp. from Myanmar, and Troglomyces tetralabiatus Santam., Enghoff & Reboleira sp. nov. on Caucaseuma Strasser, 1970 and Heterocaucaseuma Antić & Makarov, 2016 from caves in Western Caucasus. Troglomyces dioicus sp. nov. is the first dioecious species described in the genus Troglomyces. Keys for all hitherto known species of Diplopodomyces and Troglomyces are presented, as is a discussion of the status of both genera. Additional records for Diplopodomyces lusitanipodos Santam., Enghoff & Reboleira and Troglomyces manfrediae S.Colla are also included.
An unexpected new subgenus and species of Campodeidae (Diplura), Plusiocampa (Pentachaetocampa) inopinata subgen. et sp. nov., a troglobitic species found in Schallsinger Höhle in an isolated karstic region in southwestern Germany is described. The new taxon shows two unique characters for the genus Plusiocampa: five dorsal femoral macrosetae and the presence of g1-glandular setae in females. Two other Plusiocampa species have been studied and taxonomic remarks made for them; both are also cave dwelling species from Germany: Plusiocampa dobati Condé in Dobat, 1975 studied from eight caves in the Swabian Alb, and one unnamed species of Plusiocampa (Plusiocampa) from four caves in the Franconian Alb. The biogeographical and taxonomic affinities among Plusiocampa species of Central Europe are discussed. The distribution of Plusiocampa species in Central Europe runs alongside the frontier of the Pleistocene glaciations, with non-troglomorphic Plusiocampa species adjacent to the glacial limits and troglomorphic Plusiocampa species below. Worthy of note is the presence only in the northeast of the Central Alps of two relict Plusiocampinae species, the already known Hystrichocampa pelletieri Condé, 1948 and the new species P. (P.) inopinata subgen. et sp. nov.
The Charipinae Dalla Torre & Kieffer, 1910 present in the Palaearctic region are revised; 2410 specimens have been identified, belonging to 75 species: 52 to Alloxysta, one to Apocharips, six to Dilyta and 16 to Phaenoglyphis. For 33 species, new country-level distribution records are provided. Two new species are here described: Alloxysta palearctica Ferrer-Suay & Pujade-Villar sp. nov. and Alloxysta pascuali Ferrer-Suay sp. nov. A diagnosis for these species is included and their diagnostic features are shown in different figures. A key to identify all the species of Charipinae in the Palaearctic region is also given.
Chlorine and bromine atoms lead to catalytic depletion of ozone in the stratosphere. Therefore the use and production of ozone-depleting substances (ODSs) containing chlorine and bromine is regulated by the Montreal Protocol to protect the ozone layer. Equivalent effective stratospheric chlorine (EESC) has been adopted as an appropriate metric to describe the combined effects of chlorine and bromine released from halocarbons on stratospheric ozone. Here we revisit the concept of calculating EESC. We derive a refined formulation of EESC based on an advanced concept of ODS propagation into the stratosphere and reactive halogen release. A new transit time distribution is introduced in which the age spectrum for an inert tracer is weighted with the release function for inorganic halogen from the source gases. This distribution is termed the release time distribution. We show that a much better agreement with inorganic halogen loading from the chemistry transport model TOMCAT is achieved compared with using the current formulation. The refined formulation shows EESC levels in the year 1980 for the mid-latitude lower stratosphere, which are significantly lower than previously calculated. The year 1980 is commonly used as a benchmark to which EESC must return in order to reach significant progress towards halogen and ozone recovery. Assuming that – under otherwise unchanged conditions – the EESC value must return to the same level in order for ozone to fully recover, we show that it will take more than 10 years longer than estimated in this region of the stratosphere with the current method for calculation of EESC. We also present a range of sensitivity studies to investigate the effect of changes and uncertainties in the fractional release factors and in the assumptions on the shape of the release time distributions. We further discuss the value of EESC as a proxy for future evolution of inorganic halogen loading under changing atmospheric dynamics using simulations from the EMAC model. We show that while the expected changes in stratospheric transport lead to significant differences between EESC and modelled inorganic halogen loading at constant mean age, EESC is a reasonable proxy for modelled inorganic halogen on a constant pressure level.
Background: The risk for major depression and obesity is increased in adolescents and adults with attention-deficit / hyperactivity disorder (ADHD) and adolescent ADHD predicts adult depression and obesity. Non-pharmacological interventions to treat and prevent these co-morbidities are urgently needed. Bright light therapy (BLT) improves day–night rhythm and is an emerging therapy for major depression. Exercise intervention (EI) reduces obesity and improves depressive symptoms. To date, no randomized controlled trial (RCT) has been performed to establish feasibility and efficacy of these interventions targeting the prevention of co-morbid depression and obesity in ADHD. We hypothesize that the two manualized interventions in combination with mobile health-based monitoring and reinforcement will result in less depressive symptoms and obesity compared to treatment as usual in adolescents and young adults with ADHD.
Methods: This trial is a prospective, pilot phase-IIa, parallel-group RCT with three arms (two add-on treatment groups [BLT, EI] and one treatment as usual [TAU] control group). The primary outcome variable is change in the Inventory of Depressive Symptomatology total score (observer-blinded assessment) between baseline and ten weeks of intervention. This variable is analyzed with a mixed model for repeated measures approach investigating the treatment effect with respect to all three groups. A total of 330 participants with ADHD, aged 14 – < 30 years, will be screened at the four study centers. To establish effect sizes, the sample size was planned at the liberal significance level of α = 0.10 (two-sided) and the power of 1-β = 80% in order to find medium effects. Secondary outcomes measures including change in obesity, ADHD symptoms, general psychopathology, health-related quality of life, neurocognitive function, chronotype, and physical fitness are explored after the end of the intervention and at the 12-week follow-up.
Discussion: This is the first pilot RCT on the use of BLT and EI in combination with mobile health-based monitoring and reinforcement targeting the prevention of co-morbid depression and obesity in adolescents and young adults with ADHD. If at least medium effects can be established with regard to the prevention of depressive symptoms and obesity, a larger scale confirmatory phase-III trial may be warranted.
Trial registration: German Clinical Trials Register, DRKS00011666. Registered on 9 February 2017. ClinicalTrials.gov, NCT03371810. Registered on 13 December 2017.
Convection-permitting models (CPMs) have proven their usefulness in representing precipitation on a sub-daily scale. However, investigations on sub-hourly scales are still lacking, even though these are the scales for which showers exhibit the most variability. A Lagrangian approach is implemented here to evaluate the representation of showers in a CPM, using the limited-area climate model COSMO-CLM. This approach consists of tracking 5‑min precipitation fields to retrieve different features of showers (e.g., temporal pattern, horizontal speed, lifetime). In total, 312 cases are simulated at a resolution of 0.01 ° over Central Germany, and among these cases, 78 are evaluated against a radar dataset. The model is able to represent most observed features for different types of convective cells. In addition, the CPM reproduced well the observed relationship between the precipitation characteristics and temperature indicating that the COSMO-CLM model is sophisticated enough to represent the climatological features of showers.
Myomas, also known as fibroids, are a specific characteristic of the human species. No other primates develop fibroids. At a cellular level, myomas are benign hyperplastic lesions of uterine smooth muscle cells. There are interesting theoretical concepts that link the development of myomas in humans with the highly specific process of childbirth from an upright position and the resulting need for greatly increased “expulsive” forces during labor. Myomas might be the price our species pays for our bipedal and highly intelligent existence. Myomas affect, with some variability, all ethnic groups and approximately 50% of all women during their lifetime. While some remain asymptomatic, myomas can cause significant and sometimes life-threatening uterine bleeding, pain, infertility, and, in extreme cases, ureteral obstruction and death. Traditionally, over 50% of all hysterectomies were performed for fibroids, leading to a significant healthcare burden. In this article, we review the developments of the past 20 years with regard to multiple new treatment strategies that have evolved during this time.
We present a study of the influence of disorder on the Mott metal-insulator transition for the organic charge-transfer salt κ -(BEDT-TTF) 2 Cu[N(CN) 2 ]Cl. To this end, disorder was introduced into the system in a controlled way by exposing the single crystals to X-ray irradiation. The crystals were then fine-tuned across the Mott transition by the application of continuously controllable He-gas pressure at low temperatures. Measurements of the thermal expansion and resistance show that the first-order character of the Mott transition prevails for low irradiation doses achieved by irradiation times up to 100 h. For these crystals with a moderate degree of disorder, we find a first-order transition line which ends in a second-order critical endpoint, akin to the pristine crystals. Compared to the latter, however, we observe a significant reduction of both, the critical pressure pc and the critical temperature Tc . This result is consistent with the theoretically-predicted formation of a soft Coulomb gap in the presence of strong correlations and small disorder. Furthermore, we demonstrate, similar to the observation for the pristine sample, that the Mott transition after 50 h of irradiation is accompanied by sizable lattice effects, the critical behavior of which can be well described by mean-field theory. Our results demonstrate that the character of the Mott transition remains essentially unchanged at a low disorder level. However, after an irradiation time of 150 h, no clear signatures of a discontinuous metal-insulator transition could be revealed anymore. These results suggest that, above a certain disorder level, the metal-insulator transition becomes a smeared first-order transition with some residual hysteresis.
The continuous conversion of natural wildlife habitats into agricultural areas, as well as the fragmentation of the last wildlife refuges, is increasing the interface between people and wildlife. When wildlife negatively impacts on people and vice versa, we speak about human-wildlife conflicts (HWCs). This definition includes losses on both sides and takes into consideration the rooting of most of these conflicts between different groups of interest, such as advocates for nature conservation and economic groups. The centres of highest biodiversity are located in developing countries, which are also characterized by poverty. In African and Asian countries, people living in the vicinity of national parks and other conservation areas mostly receive only little support through the government or conservation organisations. Especially for those people who are dependent on agriculture, damage to fields and harvests can have catastrophic consequences. If the species causing damage is protected by national or even international law, the farmer is not allowed to use lethal methods, but has to approach the authority in charge. If this agency, however, cannot offer appropriate support, resentment, anger or even hate develops, and the support for wildlife conservation activities declines. For this reason, HWCs were declared as one of the most important conservation topics today, being particularly relevant for large and threatened species such as the African and Asian elephant, hippopotamus and the greater one-horned rhino, as well as for large predators. Up to today, no general assessment scheme has been recommended for damage caused by protected wildlife species.
In my study, HWCs in Asia and Africa are compared, focussing on all herbivorous species identified which damaged crops. For the French NGO Awely, des animaux et des hommes, I developed a detailed assessment scheme suitable for all terrestrial ecosystems, and any type of HWCs and any species (Chapter 2). This HWC assessment scheme was used in four different study areas located in two African countries (South Luangwa/Zambia (SL), Tarangire/Tanzania (TA)) and two Asian countries (Bardia/Nepal (BA) and Manas/India (MA)). This scheme ran for six consecutive years (2009 to 2014) for Zambia, Nepal and India and two years (2010 to 2011) for Tanzania. To carry out the assessments, I trained local HWC officers (Awely Red Caps) to assess HWCs by field observations (measurement of damage, identification of species through signs of presence, landscape attributes etc.) and interviews with aggrieved parties (socio economic data). Results of this assessment are presented in Chapters 2-4.
To determine whether elephants prefer or avoid specific crop species, two field experiments were carried out, one in SL and one in BA (Chapter 5 and 6). For this, two test plots were set up and damage by elephants (and other herbivores) were quantified.
Within this doctoral thesis, 3306 damage events of 7408 aggrieved parties were analysed. In three out of the four study areas (SL, BA, MA), elephants caused the highest number of damage events compared to all other wildlife species, however, in TA, most fields were damaged by zebra. Furthermore, the greater one-horned rhino, hippopotamus, wild boar, bushpig, deer and antelope, as well as primates, caused damage to fields and harvests. Damage to houses and other property were nearly exclusively caused by elephants.
With this doctoral thesis I was able to show that season, crop availability, type and the phenological stage of the crop played an important role for crop damaging behavior of herbivores (Chapter 2). Elephants especially damaged rice, maize and wheat and preferred all crop types in a mature stage of growth. In contrast, rhinos preferred wheat to rice and similar to antelope and deer, they preferred crops at earlier stages of growth, before ripening. Crop damage by wildlife species varied strongly in size; most damages fell below 40% of the total harvest per farmer, but in several cases (3 to 8% depending on the study area), harvests were completely destroyed. Interestingly, during times of low nutritional availability in the natural habitat (dry season), crop damages in all four study areas were significantly less than during other seasons.
In all four study areas, crop protection strategies, such as active guarding in the fields, chasing wildlife with noise or fire torches or erecting barriers, were used. In some cases protection strategies were combined. Analysis of data revealed that traditional protection strategies did not reduce the costs of damage (Chapter 3). In some cases, costs of damage, on protected fields were even higher than for unprotected fields. Only in MA did strategic and cohesive guarding significantly reduce crop damage by wildlife species.
Besides damage in the fields, elephants also caused damage to properties in the villages. In search for stored staple crops, they damaged houses, grain stores and kitchens. Such damage was analysed in three study areas (SL, BA, MA) (Chapter 4). Although property damage occurred less frequently compared to crop damage in the fields, the mean cost of this damage was found to be double in BA/MA and four times higher in SL, compared to the costs of crop damage in the fields. It is further remarkable that property damage significantly increased towards the dry season, when the harvest was brought into the villages.
The findings of this study underpin the assumption that wildlife herbivores, especially elephants, are lured to fields and crops because the highly nutritional food (crop) being readily available. Traditional crop protection is cost and labour intensive and does not reduce the costs of damage. For this reason, crop types, which are thought to be not consumed by elephants were systematically tested on their attractiveness in field experiments in SL and BA (Chapter 5 and 6). In SL, lemon grass, ginger and garlic were proven to be less attractive to African elephants than maize and in BA, basil, turmeric, chamomile, coriander, mint, citronella and lemon grass were found to be less attractive to Asian elephants than rice.
The results of this doctoral thesis are relevant for the management of wildlife conservation as they can lead to new approaches to the mitigation of HWCs in African and Asian countries. Finally, specific needs for more scientific research in this field have been identified.
Most of the elements in the universe are produced via charged-particle fusion reactions during the primordial nucleosynthesis and different stellar burning stages, as well as via neutron-capture reactions. Around 35 heavy, proton-rich isotopes are bypassed by those reaction paths, the p nuclei. A series of photo-disintegration reactions occurring in supernovae, called the γ process, was suggested as a mechanisms to produce the p nuclei. Numerical simulations of the γ process have been unable to reproduce the observed abundances of the light p isotopes. Recent models showed that a series of proton capture reactions could provide the observed abundances. Hence, the cross sections of the crucial capture reactions have to be measured in order to test those assumptions.
Radiative proton captures in addition to the γ-process could reproduce the observed abundance pattern. This thesis presents preparations of a proton capture measurement on the radioactive 91Nb in standard kinematics with a calorimetric 4π setup. The 91Nb(p,γ)92Mo reaction might be the key to explain the production of one of the most abundant p-nuclei, 92Mo. So far, no experimental data for this reaction is available.
We produced a sample of 91Nb, with a half-life of 680 yr, at the Physikalisch Technische Bundesanstalt in Braunschweig, Germany, by irradiating 92Mo with protons in the energy range of 12 – 20MeV. 91Nb was produced via the reaction 92Mo(p,2p)91Nb and via 92Mo(p,pn)91Mo, where 91Mo decays to 91Nb with a half-life of 15.5min. To predict the amount of produced 91Nb the cross section of 92Mo(p, 2p) was measured. It was found to be higher than the value given by theoretical calculations with TALYS. Finally, 91Nb was chemically separated from the molybdenum carried at Paul-Scherrer- Institut, Villigen, Switzerland.
In-beam total absorption cross-section measurement of the reaction 91Nb(p,γ)92Mo with 2 MeV protons at FRANZ is planed with the produced 91Nb. A 4π BaF2 detector consisting of 41 crystals will be used. During this experiment we will measure the sum energy and the multiplicity of each event. The freshly produced 91Nb constitutes only a minor component of the sample material. The sum energy and multiplicity are crucial to distinguish the desired 91Nb(p,γ) from all the other more dominant reactions. The expected multiplicity and the efficiency of the setup were carefully simulated with DICEBOX and GEANT4. It was possible to show that background reactions can be effectively suppressed. The most important background contributions could be identified and result from 92Mo(p,γ), 19F(p,γ), and 19F(p,α).
The Siriella brevicaudata species group from the West Indo-Pacific, defined and designated by Murano & Fukuoka (2008), previously contained five nominal species. In this study we describe five new species in the brevicaudata group: S. bassi sp. nov. from the Bass Strait, southern Australia, S. occulta sp. nov. from the Arabian Gulf, S. muranoi sp. nov. from the coast of Northern Territory, Australia, S. tabaniocula sp. nov. from Ningaloo Reef of Western Australia and Lodestone Reef off Queensland, and S. talbotae sp. nov. from Lizard Island, Queensland, Australia. Furthermore, Siriella hanseni W.M. Tattersall, 1922 from India and S. vincenti W.M. Tattersall, 1927 from South Australia are redescribed based on re-examination of their type material. A re-examination of specimens subsequently attributed to these two species from other geographical regions showed that these were misidentifications, partly representing three of the new species described herein. Siriella gibbosa (Ledoyer, 1970), which was previously synonymized with S. brevicaudata Paulson, 1875 by Bačescu, is revalidated and included within the brevicaudata group. Siriella lacertilis Talbot, 2009, from Lizard Island, is placed within the brevicaudata group. Diagnostic features for all the members of the group and the group itself are updated. As a result of the present study, the brevicaudata group now comprises 12 valid species.
Five species of Batillipes Richters, 1909 were collected from subtidal sediments of the Portuguese coast. Two of them, B. algharbensis sp. nov. and B. lusitanus sp. nov., are new to science. Batillipes algharbensis sp. nov. differs from all the other Batillipes species in having the middle toes 3 on the fourth feet longer than middle toes 4 and by the presence of rounded lateral body projections between legs III and IV. Batillipes lusitanus sp. nov. has the middle toes of the fourth feet equal in length, but it exhibits a dorsal cuticular ornamentation, constituted by large pillars, similar to the cuticle of B. adriaticus Grimaldi de Zio, Morone De Lucia, D’Addabbo Gallo & Grimaldi, 1979 and B. roscoffensis Kristensen, 1978. However, contrary to B. adriaticus, the caudal apparatus of B. lusitanus sp. nov. is a roundish cuticular expansion and B. roscoffensis lacks caudal apparatus. Batillipes adriaticus and B. phreaticus Renaud-Debyser, 1959 are new records for Portugal. Based on the examination of specimens of B. phreaticus collected at the Portuguese coast and their comparison with type material of this species and also of B. littoralis Renaud-Debyser, 1959, the toe arrangement patterns in species of Batillipes are clarified and a new identification key to species of this genus is provided.
The described Afrotropical species of the genus Hexophthalma Karsch, 1879 (under the genus name Sicarius Walckenaer, 1847), of the spider family Sicariidae Keyserling, 1880, were recently reviewed. In the present paper the Afrotropical species of the genus Hexophthalma are revisited. After a thorough examination of all the available specimens from nine major collections, the species H. testacea (Purcell, 1908) is here synonymized with H. hahni (Karsch, 1878), three new species are described – H. binfordae sp. nov., H. goanikontesensis sp. nov. (both from Namibia) and H. leroyi sp. nov. (from South Africa) – and the male of H. dolichocephala (Lawrence, 1928) is described for the first time. The distribution of the species is also revised and a new updated key to the species is compiled.
Homollea Arènes (Rubiaceae, subfamily Ixoroideae, tribe Pavetteae) is a genus of shrubs and small trees endemic to western and northern Madagascar. The genus comprises five species occurring in dry deciduous forest, often in limestone areas. The five species are narrow endemics and their conservation status is either Endangered (4 species) or Critically Endangered (1 species). Homollea is characterized by few-flowered, pseudo-axillary, pedunculate inflorescences, well-developed calyces with the lobes much longer than the tube, laterally flattened seeds with a shallow, elongated to linear hilum and entire endosperm, ovules arising from the upper margin of the placenta, and, pollen grains with supratectal elements in the shape of microgemmae. Until now, three species were known and their descriptions are amended. Two further species, H. furtiva De Block sp. nov. and H. septentrionalis De Block sp. nov., are described as new for science. The five species are dealt with in detail: descriptions, distribution maps, conservation assessments, illustrations, lists of exsiccatae and an identification key are given.
A new monotypic genus of flatid planthoppers (Hemiptera: Fulgoromorpha: Flatidae), Medleria gen. nov., is described for Medleria caudata gen. et sp. nov. (type species) from the island of Socotra (Yemen). Habitus, male and female external and internal genital structures of the new species are illustrated and compared with similar taxa. Medleria caudata gen. et sp. nov. is probably endemic to Socotra where it is known to date from a small area of the Dixam mountain plateau only.
We describe two new species of the annelid genus Trilobodrilus Remane, 1925 (Dinophilidae Verill, 1892) from an intertidal and a subtidal location in San Diego, California. These two species show morphological and molecular divergences between each other and the previously described, geographically distant species. Intertidal T. windansea sp. nov. differs from subtidal T. ellenscrippsae sp. nov. most remarkably in the number and pattern of ciliary tufts and bands on the prostomium and along the body length, besides showing ca. 15% difference in gene fragments of COI and CytB. Trilobodrilus windansea sp. nov., though nesting with T. ellenscrippsae sp. nov. in the molecular phylogenetic analyses, morphologically resembles the Japanese T. itoi Kajihara, Ikoma, Yamasaki & Hiruta, 2015 most closely, but still differs from this species in the higher number of apical ciliary tufts, an additional ciliary row posterior to the second ciliary band, and by lacking a forth ciliary band and segmentally arranged lateral ciliary tufts. Trilobodrilus ellenscrippsae sp. nov. is morphologically most similar to the Japanese T. nipponicus Uchida & Okuda, 1943, but is much shorter, has more apical ciliary tufts, and less regularly arranged lateral ciliary tufts along the body. All species differ significantly in all compared gene fragments, and no obvious correlation was found between habitat and the species morphology or relationships.
The skeleton and the relationships of Libanopycnodus wenzi gen. et sp. nov. and of Sigmapycnodus giganteus gen. et sp. nov., two pycnodontiform fishes from the marine Cenomanian (Late Cretaceous) of Lebanon, are studied in detail. Both species belong to the family Pycnodontidae, as shown by their parietal brush-like process. Some osteological characters (bifid cloacal scale, large well visible dilatator fossa surrounded by the dermosphenotic and the dermopterotic, etc.) indicate that they are members of the subfamily Pycnodontinae. Libanopycnodus gen. nov. has the preopercle much deeper than the exposed region of the hyomandibula-dermohyomandibula and is the most primitive genus of this lineage. Sigmapycnodus gen. nov. is one of the most advanced members of the subfamily. It shares with Oropycnodus Poyato-Ariza & Wenz, 2002 and Pycnodus Agassiz, 1833 an apomorphy not present in the less specialized Pycnodontinae, the arcocentra in hypercomplex contact.
Three new species of Entomobrya Rondani, 1861 from China are described: E. leviseta sp. nov. and E. polychaeta sp. nov. from Shaanxi Province and E. dingi sp. nov. from Yunnan Province. This is the first report of Entomobrya from Shaanxi Province. Entomobrya leviseta sp. nov. is characterised by prelabral smooth chaetae on the labrum; E. polychaeta sp. nov. by three pairs of longitudinal dark blue stripes from Th. II to Abd. III and eight lateral mac on Abd. III; and E. dingi sp. nov. by only a little pigment on the body and 5 central mac on And. II & III. A key to all Chinese species of Entomobrya is given.
The concept of the jumping spider genus Pochytoides Berland & Millot, 1941 is reviewed, based on the examination of described and undescribed species. Pochytoides is elevated from the subgeneric to the generic rank and a short diagnosis and description of the genus are presented. Redescriptions or descriptions of all species are provided together with a key to the species. Two new combinations are proposed: Pochytoides perezi (Berland & Millot, 1941) comb. nov. and P. poissoni (Berland & Millot, 1941) comb. nov. (both from Pochyta). Pochyta remyi Berland & Millot, 1941 originally placed in the subgenus Pochytoides is excluded; new combination Thiratoscirtus remyi (Berland & Millot, 1941) comb. nov. is proposed for it (but its generic status is uncertain). Six new species are described: Pochytoides monticola sp. nov., P. obstipa sp. nov., P. lamottei sp. nov., P. patellaris sp. nov., P. securis sp. nov. and P. spiniger sp. nov. The genus has a West African distribution.
The Palaearctic species of Ismaridae Thomson, 1858 are reviewed. Thirteen species of Ismaridae are recognized from the Palaearctic. Five species are described as new: Ismarus brevis Kim & Lee sp. nov. from the Russian Far East and South Korea; I. distinctus Kim, Notton & Ødegaard sp. nov. from Norway and the United Kingdom; I. excavatus Kim & Lee sp. nov. from China, Japan and South Korea; I. similis Kim, Notton & Lee sp. nov. from the United Kingdom and I. tripotini Kim & Lee sp. nov. from South Korea. Ismarus apicalis Kolyada & Chemyreva, 2016 is newly recorded from China, France, Japan and South Korea; I. dorsiger (Haliday, 1831) from France, Montenegro, Norway, South Korea and Switzerland; I. flavicornis (Thomson, 1858) from Bulgaria and Norway; I. grandis Alekseev, 1978, I. halidayi Förster, 1850 and I. multiporus Kolyada & Chemyreva from Japan and South Korea; I. rugulosus Förster, 1850 from Austria and I. spinalis Kolyada & Chemyreva, 2016 from China, Japan and South Korea. An identification key to all species found in the Palaearctic region is presented.
A new classification of Ophiuroidea, considering family rank and above, is presented. The new family and superfamily taxa in O’Hara et al. (2017) were proposed to ensure a better readability of the new phylogeny but are unavailable under the provisions of the ICZN. Here, the morphological diagnoses to all 33 families and five superfamilies are provided. Ten new families, Ophiosphalmidae fam. nov., Ophiomusaidae fam. nov., Ophiocamacidae fam. nov., Ophiopteridae fam. nov., Clarkcomidae fam. nov., Ophiopezidae fam. nov., Ophiernidae fam. nov., Amphilimnidae fam. nov., Ophiothamnidae fam. nov. and Ophiopholidae fam. nov., are described. The family Ophiobyrsidae Matsumoto, 1915, not yet discovered in the previous publication, is added, based on new molecular data. A new phylogenetic reconstruction is presented. Definitions of difficult-to-apply morphological characters are given.
The genus Camafroneta gen. nov. is established to accomodate Camafroneta oku gen. et sp. nov., a new species of mynoglenine spider from Cameroon, West Africa, with unusual complex male genitalia. Phylogenetic analyses suggest that the new species does not belong to a known genus of mynoglenine spiders. Another three new species of Afroneta Holm, 1968 from East Africa are described: Afroneta flavescens sp. nov., Afroneta serrata sp. nov. and Afroneta sarahae sp. nov. We also describe the missing sex (♂) of Afroneta elgonensis Merrett, 2004.
An update of the current knowledge of Anacharis Dalman, 1823 for the Palaearctic and Indomalayan regions is given. The previously known Palaearctic species Anacharis antennata Belizin, 1951, Anacharis eucharoides (Dalman, 1818), Anacharis immunis Walker, 1835 and Anacharis parapsidalis Belizin, 1951 are redescribed. Three new species are described: Anacharis fergussoni sp. nov. from Europe, Anacharis norvegica sp. nov. from Norway and Anacharis belizini sp. nov. from Thailand, the first recorded Indomalayan species for the genus. Anacharis gracilipes Ionescu, 1969, is synonymized with A. eucharoides, while Anacharis flavidicornis Kieffer, 1910 is transferred to the genus Aegilips Haliday, 1835, resulting in Aegilips flavidicornis (Kieffer, 1910) comb. nov. Diagnostic characters and data about the biology, distribution and affinities with other species of Anacharis are discussed. An identification key for the Palaearctic and Indomalayan species of Anacharis is given.
A new genus and species of owlfly from eastern and southern Africa (Neuroptera: Ascalaphidae)
(2018)
The genus Dorsomitus Tjeder, 1992, is considered a nomen nudum. Dorsomitus gen. nov. is described and validated here. A new combination, Dorsomitus neavei (Kimmins, 1949) gen. et comb. nov. is proposed, Dorsomitus tjederi gen. et sp. nov. is described, and Disparomitus neavei Kimmins, 1949, is designated as type species of the genus Dorsomitus gen. nov.
The recently described family Chummidae, now the sister clade of Macrobuninae, so far only known from two South African species, is extended with seven new species, six from the southern part of South Africa and one from Lesotho: Chumma bicolor sp. nov. (♀), C. foliata sp. nov. (♂♀), C. interfluvialis sp. nov. (♂♀), C. lesotho sp. nov. (♀), C. striata sp. nov. (♂♀), C. subridens sp. nov. (♂♀) and C. tsitsikamma sp. nov. ♂. A key to the species is provided. Although Chumma is part of a clade containing the Macrobuninae, it is argued that the family name Chummidae should remain valid.
The Late Jurassic–Early Cretaceous Slottsmøya Member of the Agardhfjellet Formation in central Spitsbergen has yielded two new species of asteroids and two species of ophiuroids, one of which is described as new. Polarasterias janusensis Rousseau & Gale gen. et sp. nov. is a forcipulatid neoasteroid with elongated arms, small disc and very broad ambulacral grooves with narrow adambulacrals. Savignaster septemtrionalis Rousseau & Gale sp. nov. is a pterasterid with welldeveloped interradial chevrons. The Spitsbergen specimens are the first described articulated material of Savignaster and reveal the overall arrangement of the ambulacral groove ossicles. Ophiogaleus sp. is an ophiacanthid with relatively long jaws and lateral arm plates, with a coarsely reticulate outer surface. Here again, we report the first articulated skeletons of this genus, providing unprecedented insights into the disc morphology. Ophioculina hoybergia Rousseau & Thuy gen. et sp. nov. is an ophiopyrgid with a well-developed arm comb and tentacle pores reduced to within-plate perforations starting at median arm segments. These new finds are important additions to the asterozoan fossil record with regard to their good degree of articulation and the high latitudinal position of the localities. They significantly add to the set of exhaustively known fossil asterozoan taxa which play a key role in the phylogenetic analysis and reconstruction of evolutionary history.
The identity of Barbus capensis, as described by Andrew Smith (1841), is reviewed following a careful examination of the lectotype in the Natural History Museum, London. Evidence shows clearly that it represents a specimen of the Berg-Breede River whitefish or ‘witvis’ and not the species known as the Clanwilliam yellowfish, to which it was attributed until recently. The original illustration of the species is shown to be a composite of these two different species. A replacement name for the Clanwilliam yellowfish is drawn from the earliest described synonym, Labeobarbus seeberi (Gilchrist & Thompson, 1913). Following widespread recognition that the genus Barbus Daudin, 1805 does not occur in sub-Saharan Africa, the generic status of the Berg-Breede River whitefish (witvis) and other tetraploid cyprinines of southern Africa is reviewed, taking genetic and morphological characters into account. Five distinct lineages, each representing a genus, are recognized, including the genera Pseudobarbus Smith, 1841 and Cheilobarbus Smith, 1841, and three new genera described herein: Amatolacypris gen. nov., Sedercypris gen. nov. and Namaquacypris gen. nov.
The nutty world of hazel names - a crtitical taxonomic checklist of the genus Corylus (Betulaceae)
(2018)
Hazelnuts (Corylus L.) are the source of one of the globally most important nut crops. Despite their economic and cultural importance, taxonomic knowledge is poor, even the number of species is equivocal. Weak morphological differentiation, the inconsistent taxonomic treatment of horticultural selections and cultivars, and uncritical regional treatments generated a multitude of names. The situation is further complicated by an ancient history of use (at least 10 400 years), trade (at least 4000 years) and domestication (at least 2000 years). Here, we present an annotated checklist of the taxa in the genus Corylus based on an extensive literature review, electronic database research, and visits to some European herbaria. Full citations are given for all names, typifications are provided for the majority of them. Cultivars are listed if described under the rules of the ICN. We designate lectotypes and neotypes for 28 names, and discuss the identity of enigmatic C. maxima Mill., a taxon not known from the wild.
This paper provides descriptions of Calcigorgia gorgonians collected from the Sea of Okhotsk and shores of the Kurile Islands between 3 Aug. 1984 and 20 Aug. 1987. New species described are the deep-water gorgonians Calcigorgia matua sp. nov. and C. simushiri sp. nov., belonging to the temperate fauna of the North Pacific hemisphere. Specimens belonging to all species of the genus were examined and the distinctive characters for each one are provided and summarized in a table. A modified diagnosis of the genus is proposed. The finding of a previously undescribed species emphasizes the need of further surveys, particularly in shelf and deeper waters, in order to improve our knowledge of this neglected fauna in Far East seas.
Synchroidae Lacordaire, 1859 is a taxonomically and biologically poorly known group. In the present paper, diagnostic characters used to separate genera are analysed and the phylogenetic relationships within this family are preliminarily investigated. Results suggest that the characteristic Synchroa pangu Hsiao, Li, Liu & Pang, 2016 can be removed to establish a new genus, Thescelosynchroa gen. nov. The new combination, T. pangu (Hsiao, Li, Liu & Pang) gen. et comb. nov., is proposed. The definitions of Synchroa Newman, 1838 and Synchroina Fairmaire, 1898 are revised. Moreover, morphological analysis and character comparison also suggest that the familial placement of Mallodrya subaenea Horn, 1888 is questionable. Six species are re-examined and rediagnosed: Synchroa chinensis Nikitsky, 1999, S. elongatula Nikitsky, 1999, S. formosana Hsiao, 2015, S. melanotoides Lewis, 1895, S. punctata Newman, 1838 and Synchroina tenuipennis Fairmaire, 1898. The male of S. chinensis and the female of S. formosana are described for the first time. Synchroa elongatula and Synchroina tenuipennis are newly recorded from Laos and Indonesia, respectively. We also hypothesize that the Eastern Asian-North American disjunction of Synchroa could be connected to a Mid-Late Tertiary migration of plants via the Bering Land Bridge.
New species of Neanura MacGillivray, 1893 and Deutonura Cassagnau, 1979 are described from northern Iran. Both taxa are characterized by unusual features that place them in isolated positions within the genera. Neanura deharvengi sp. nov. differs from congeners by the extreme reduction of head chaetotaxy and fused lateral tubercles on the head. These characteristics of the new species broaden the existing diagnosis of the genus Neanura. An updated diagnosis is provided herein. Deutonura persica sp. nov. is most similar to D. plena (Stach, 1951), known from the Carpathians. The new species can be distinguished by the strong reduction of its head, labial, and labral chaetotaxy as well as the relative length of chaetae De2 and De3 on abdominal segments I–III. The Iranian records of D. decolorata (Gama & Gisin, 1964) are questioned. Brief remarks on the importance of the newly described species for the knowledge of both genera are also provided.
Two new species of the family Selachinematidae Cobb, 1915 from an intertidal sandy flat in the East China Sea are described. Both species are distinct rapacious nematodes, preying on other nematodes. Gammanema magnum sp. nov. is characterized by its leaf-like labial setae, large loop-shaped amphideal fovea in the male and small spiral ones in the female, an anterior buccal cavity reinforced by 12 rhabdia, each rhabdion with about six denticles, and two unequally long spicules. Gammanema magnum sp. nov. is a striking species, exhibiting extreme sexual dimorphism in the amphideal fovea, but lacking a gubernaculum or precloacal supplements, all features by which it can be differentiated from congeneric species. Synonchium caudatubatum sp. nov. is characterized by a posterior buccal cavity, with three mandibles each with a large tooth flanked by three smaller teeth on both sides, a transverse oval-shaped multispiral amphideal fovea, and a bluntly rounded tail with a protuberant caudal duct. Synonchium caudatubatum sp. nov. is unique in the genus in having a protuberant caudal duct in the tail end. Furthermore, it differs from its congeners by its mandibles, which have seven teeth each. Synonchium caudatubatum sp. nov. lacks a gubernaculum and a precloacal supplement, both features present in congeners except S. depressum Gerlach, 1954.
The vividly coloured Neotropical genus Callipia Guenée (1858) (Lepidoptera Linnaeus, 1758, Geometridae (Leach, 1815), Larentiinae (Leach, 1815), Stamnodini Forbes, 1948) is revised and separated into four species groups, according to a provisional phylogeny based on Cytochrome Oxidase I (COI) gene data and morphology. Fourteen new species are described using COI data and morphology: a) in the balteata group: C. fiedleri sp. nov., C. jakobi sp. nov., C. lamasi sp. nov.; b) in the vicinaria group: C. hausmanni sp. nov., C. walterfriedlii sp. nov.; c) in the parrhasiata group: C. augustae sp. nov., C. jonai sp. nov., C. karsholti sp. nov., C. levequei sp. nov., C. milleri sp. nov., C. sihvoneni sp. nov., C. wojtusiaki sp. nov. and d) in the constantinaria group: C. hiltae sp. nov., C. rougeriei sp. nov. One new subspecies is described: C. wojtusiaki septentrionalis subsp. nov. Two species are revived from synonymy: C. intermedia Dognin, 1914 stat. rev. and C. occulta Warren, 1904 stat. rev. The taxon hamaria Sperry, 1951 is transferred from being a junior synonym of C. constantinaria Oberthür, 1881 to being a junior synonym of C. occulta stat. rev. The taxon admirabilis Warren, 1904 is confirmed as being a junior synonym of C. paradisea Thierry-Mieg, 1904. The taxon languescens Warren, 1904 is confirmed as being a junior synonym of C. rosetta, Thierry-Mieg, 1904 and the taxon confluens Warren, 1905 is confirmed as being a junior synonym of C. balteata Warren, 1905. The status of the remaining species is not changed: C. aurata Warren, 1904, C. brenemanae Sperry, 1951, C. parrhasiata Guenée, 1858, C. flagrans Warren, 1904, C. fulvida Warren, 1907 and C. vicinaria Dognin. All here recognised 26 species are illustrated and the available molecular genetic information of 25 species, including Barcode Index Numbers (BINs) for most of the taxa is provided. The almost threefold increase from 10 to 26 valid species shows that species richness of tropical moths is strongly underestimated even in relatively conspicuous taxa. Callipia occurs from medium to high elevations in wet parts of the tropical and subtropical Andes from Colombia to northern Argentina. The early stages and host plants are still unknown.
A new species complex, the eparmata complex, is established within the subgenus Phortica s. str., based on eight known and five new species, all of which are endemic to the Oriental Region: P. bipartita (Toda & Peng, 1992), P. eparmata (Okada, 1977), P. lanuginosa Chen & Toda, 2007, P. latipenis Chen & Gao, 2005, P. pangi Chen & Wen, 2005, P. setitabula Chen & Gao, 2005, P. unipetala Chen & Wen, 2005 and P. zeta Chen & Toda, 2007; P. jadete sp. nov., P. kava sp. nov., P. mengda sp. nov., P. wongding sp. nov. and P. yena sp. nov. A key to all species of this complex is provided. Barcoding sequences (mitochondrial COI gene) were obtained for 22 specimens of five known and the five abovementioned new species. The intra- and inter-specific pairwise K-2P (Kimura’s two-parameter) distances of COI were determined. Phylogenetic analysis was performed using Bayesian inference based on COI sequences, confirming the monophyletic status of the eparmata complex, which is distinct from the species complexes of magna, omega, variegata and another two ungrouped species.
The Astyanax orthodus species-group includes nine species: Astyanax boliviensis sp. nov., A. bopiensis nom. nov., A. embera sp. nov., A. gandhiae sp. nov., A. moorii comb. nov., A. orthodus, A. superbus, A. villwocki and A. yariguies comb. nov. The group is diagnosed by the presence of a series of pinnate-shaped marks (chevrons) located along the lateral midline, which extends from the humeral region to the caudal peduncle. Astyanax bopiensis nom. nov. is proposed as a substitute name for Astyanacinus multidens, which, along with Astyanax yariguies comb. nov., we reassign to Astyanax. We also propose the synonymy of Astyanacinus with Astyanax. The members of the A. orthodus speciesgroup are distributed in northwestern South America, occurring in the Patia River drainage (A. embera sp. nov.) of the Pacific coast of Colombia, the Atrato River Basin (A. orthodus), the Magdalena River Basin (A. yariguies comb. nov.) of Caribbean Colombia, streams of the southern flank of the Andes of the Orinoco Basin in Venezuela (A. superbus), in the upper Amazon River Basin of Colombia, Ecuador and Peru (A. villwocki, A. gandhiae sp. nov.), from the upper Paraguay River (A. moorii comb. nov.), the Madidi and Mamore Rivers, Bolivia (A. boliviensis sp. nov. and A. bopiensis nom. nov.). All species currently included in Astyanacinus are reassigned to the Astyanax orthodus species-group.
The Quedius mutilatus group, a very poorly known presumably monophyletic complex of wingless, possibly hypogean species confined to the Tien-Shan Mountains, is characterized as such for the first time. Newly available material clarified the identity of Q. mutilatus Eppelsheim, 1888 and Q. kalabi Smetana, 1995, each hitherto known from a handful of non-conspecific and vaguely georeferenced specimens only. Additional material is reported for Q. equus Smetana, 2014 and bionomics for all these four species of the group are summarized.
Bees of the genus Lasioglossum (Hymenoptera: Halictidae) from Greater Puerto Rico, West Indies
(2018)
The species of Lasioglossum from Greater Puerto Rico are reviewed. Nine species are recognized, including five new species described herein: asioglossum (Dialictus) genaroi sp. nov., L. (D.) dispersum sp. nov., L. (D.) enatum sp. nov., L. (D.) monense sp. nov. and L. (D.) amona sp. nov. The latter two are known only from Mona Island. Keys and images are provided to assist in identification. Details of nesting biology, floral hosts and distribution are provided where available. Three species, L. (D.) parvum (Cresson, 1865), L. (D.) busckiellum (Cockerell, 1915), and L. (D.) mestrei (Baker, 1906) are removed from the list of species for Puerto Rico. Details on their revised distribution are provided. Three new records for Haiti, L. (D.) gundlachii (Baker, 1906), L. (D.) ferrerii (Baker, 1906) and L. (D.) busckiellum are documented. Notes on other species in the Greater Antilles are provided, including the synonymy of Lasioglossum bruesi (Cockerell, 1912) and L. jamaicae (Ellis, 1914) under L. gemmatum (Smith, 1853).
The genus Raveniola Zonstein, 1987 is found to be represented in Western Asia by 16 species: ♂♀ R. adjarica sp. nov. (Georgia), ♂ R. anadolu sp. nov. (Turkey), ♂ R. arthuri Kunt & Yağmur, 2010 (Turkey), ♂ R. birecikensis sp. nov. (Turkey), ♂♀ R. dunini sp. nov. (Armenia, Azerbaijan, Iran), ♂♀ R. hyrcanica Dunin, 1988 (Azerbaijan), ♂ R. marusiki sp. nov. (Iran), ♂ R. mazandaranica Marusik, Zamani & Mirshamsi, 2014 (Iran), ♂♀ R. micropa (Ausserer, 1871) (Turkey), ♀ R. nana sp. nov. (Turkey), ♂♀ R. niedermeyeri (Brignoli, 1972) (Iran), ♂♀ R. pontica (Spassky, 1937) (Russia, Georgia), ♀ R. sinani sp. nov. (Turkey), ♂♀ R. turcica sp. nov. (Turkey), ♂♀ R. vonwicki Zonstein, 2000 (Iran) and ♂♀ R. zaitzevi (Charitonov, 1948) (Azerbaijan, Georgia) = ♀ Brachythele recki Mcheidze, 1983, syn. nov. Eight species are described as new; others are redescribed from types and/or conspecific material. Males of R. micropa and R. zaitzevi, hitherto unknown, are described for the first time. Data on the variability, relationships, distribution and ecology of all considered species are also provided.
Two new species of marine Platyhelminthes, Microstomum laurae sp. nov. and Microstomum edmondi sp. nov. (Macrostomida: Microstomidae) are described from the west coast of Sweden. Microstomum laurae sp. nov. is distinguished by the following combination of characters: rounded anterior and posterior ends; presence of approximately 20 adhesive papillae on the posterior rim; paired lateral red eyespots located level with the brain; preoral gut extending anterior to brain and and very small sensory pits. Microstomum edmondi sp. nov. is a protandrous hermaphrodite with a single ovary, single testis and male copulatory organ with stylet. It is characterized by a conical pointed anterior end, a blunt posterior end with numerous adhesive papillae along the rim, and large ciliary pits. The stylet is shaped as a narrow funnel with a short, arched tip. In addition, the first records of fully mature specimens of Microstomum rubromaculatum von Graff, 1882 from Fiskebäckskil and a phylogenetic analysis of Microstomum Schmidt, 1848 based on the mitochondrial cytochrome oxidase I (COI) gene are presented.
The frog Pristimantis marmoratus was originally described als Hylodes marmoratus by George A. Boulenger in 1900 based on a single specimen reported to have been collected at the foot of Mount Roraima in Guyana in 1898. We herein discuss the exact location of the type locality of P. marmoratus and provide a redescription of the species based on new material from Kaieteur National Park and from the slopes of Maringma-tepui in Guyana. We also describe the previously unknown vocalization and breeding ecology of the species, and conducted an exploratory molecular analysis of the phylogenetic relationships within the genus Pristimantis represented by the members of the "unistrigatus species group" in the Guiana Shield. Pristimantis marmoratus is a small-sized species mainly distinguished from its known Guiana Shield congeners by the combination of F I < II, SVL ≤ 20.4 in males, presence of vocal slits in males, granular/pustulate dorsal skin with well-developed scapular ridges, basal webbing between fingers, fringes in fingers and toes, crossed iris, diffuse yellow or pale green wash on groin, and absence of flashy colour on axillary/pre-axillary region. The advertisement call consists of a single note repeated at a rate of ca 11 calls/min with a dominant frequency ranging from 2756 to 3101 Hz. Pristimantis marmoratus is primarily arboreal, exclusively active at dusk, and propably restricted to the pristine rainforests of the Pantepui uplands and highlands, east of the Gran Sabana between ca 600 and 1800 m above sea level. Preliminary molecular analyses recovered Pristimantis marmoratus as sister to an unnamed species from the Eastern Guiana Shield. On grounds of the newly established distributional extent we suggest maintaining the IUCN conservation status as Least Concern.
Following a taxonomic revision of Begonia L. (Begoniaceae, Cucurbitales) from Northeast India based on 332 herbarium specimens, 38 species are confirmed to occur in the region, of which ten are endemic. One new species is described, Begonia koelzii R.Camfield sp. nov., in B. sect. Platycentrum (Klotzsch) A.DC. One species is reduced into synonymy; B. barbata Wall. is now a synonym of B. thomsonii A.DC. Three species, B. difformis (Irmsch.) W.C.Leong, C.I Peng & K.F.Chung, B. labordei H.Lév. and B. handelii Irmsch., are reported new for India, and B. lushaiensis C.E.C.Fisch. is reinstated as an accepted species, having previously been synonymised under B. modestiflora Kurz. A key to the species in the region and preliminary conservation assessments are presented.
Chigger mites of the African continent are reviewed using data acquired from the literature and examination of the collections deposited at the Royal Museum for Central Africa (Tervuren, Belgium) and the Natural History Museum (London, UK). All findings for 443 valid chigger species belonging to 61 genera are reported, along with details on their collection locality and host species. Three new synonyms are proposed: Straelensia Vercammen-Grandjean & Kolebinova, 1968 (= Anasuscuta Brown, 2009 syn. nov.); Herpetacarus (Herpetacarus) Vercammen-Grandjean, 1960 (= Herpetacarus (Lukoschuskaaia) Kolebinova & Vercammen-Grandjean, 1980 syn. nov.); Gahrliepia brennani (Jadin & Vercammen-Grandjean, 1952) (= Gahrliepia traubi Audy, Lawrence & Vercammen-Grandjean, 1961 syn. nov.). A new replacement name is proposed: Microtrombicula squirreli Stekolnikov, 2017 nom. nov. pro Eltonella myonacis heliosciuri Vercammen-Grandjean, 1965 (praeocc. Vercammen-Grandjean, 1965). Ninety new combinations are proposed. Keys to subfamilies, genera and subgenera of African trombiculid larvae and diagnoses of these taxa are given.
Damacornu gen. nov. (type species: D. transversum gen. et sp. nov.), Geotypodon papei sp. nov. and Spinotarsus fortehamatus sp. nov. are described, and Helicochetus dimidiatus (Peters, 1855), H. mutaba Kraus, 1960 and Hoffmanides dissutus (Hoffman, 1963) are recorded from the Udzungwa Mts, Tanzania. A complete overview of the 39 odontopygid species now known from the Udzungwa Mts is given, including notes on endemism, biogeographical relationships and altitudinal distribution patterns.
A group of Amazonian harvestmen is recognized and described as Amazochroma gen. nov. This taxon includes Discocyrtus carvalhoi Mello-Leitão, 1941 (type species), the only species of Discocyrtus previously thought to occur in Amazonia, and Amazochroma pedroi gen. et sp. nov., described here from the Brazilian states of Acre and Rondônia. New records are added for Amazochroma carvalhoi gen. et comb. nov, expanding its distribution from the Brazilian state of Mato Grosso northwards also to Pará and Amazonas in Brazil and additionally French Guiana and Suriname. Diagnostic features of Amazochroma gen. nov. include: trichromatic pattern of legs, dry marks on the dorsal scutum and base of legs and diastema in the row of macrosetae C of the penis ventral plate. A morphological maximum parsimony analysis (1022 scorings; 16 taxa; 64 characters) is performed to test whether Amazochroma gen. nov. is a member of Discocyrtus and if the traditional allocation of Discocyrtus in Pachylinae is defendable. A clade is retrieved containing three groups: Amazochroma carvalhoi gen. et comb. nov, here described as a new subfamily of Gonyleptidae - Roeweriinae subfam. nov. Discocyrtanus Roewer, 1929 and Roeweria Mello-Leitão, 1923 are accordingly here transferred from Pachylinae to Roeweriinae subfam. nov.
The species of the subgenus Conocetus Desbrochers des Loges, 1875 are reviewed and Polydrusus (Conocetus) transjordanus sp. nov. is described. Upon examination of the holotype of Polydrusus bardus Gyllenhal, 1834, it was observed that the species hitherto determined sensu auctorum as P. bardus was a misidentification. The specimen in question was therefore unnamed and is thus newly described as Polydrusus (Conocetus) crinipes sp. nov. Polydrusus femoratus (Stierlin, 1888) is a junior synonym of P. angustus (Lucas, 1854). Polydrusus gracilicornis Kiesenwetter, 1864, P. cylindrithorax (Desbrochers des Loges, 1900) and P. quadraticollis (Desbrochers des Loges, 1902) are proposed as junior synonyms of P. bardus. Polydrusus zurcheri (Schilsky, 1912) is proposed as a junior synonym of P. grandiceps (Desbrochers des Loges, 1875). Polydrusus kahri Kirsch, 1865 is transferred from subgenus Conocetus to Denticonocetus subgen. nov., with P. siculus Desbrochers des Loges, 1872 and P. vodozi Desbrochers des Loges, 1903 both recognized as new junior synonyms of P. kahri. The lectotypes of P. gracilicornis, P. zurcheri, P. marcidus Kiesenwetter, 1864, P. gracilis (Stierlin, 1888), P. rhodiacus (Schilsky, 1912) and P. grandiceps are designated. A key, figures, label data and distribution maps are provided for all species, except for P. longus (Stierlin, 1884), for which no specimens were available for examination, and whose placement in the subgenus Conocetus remains uncertain (thus categorized as incertae sedis). Polydrusus angustus is recorded for the first time for Italy, P. rhodiacus for mainland Turkey and P. festae (Solari, 1925) for Greece.
Regulation of the antiapoptotic protein cFLIP by the glucocorticoid Dexamethasone in ALL cells
(2018)
We recently reported that the Smac mimetic BV6 and glucocorticoids, e.g. Dexamethasone (Dexa), synergize to induce cell death in acute lymphoblastic leukemia (ALL) in vitro and in vivo. Here, we discover that this synergism involves Dexa-stimulated downregulation of cellular FLICE-like inhibitory protein (cFLIP) in ALL cells. Dexa rapidly decreases cFLIPL protein levels, which is further enhanced by addition of BV6. While attenuating the activation of non-canonical nuclear factor-kappaB (NF-κB) signaling by BV6, Dexa suppresses cFLIPL protein but not mRNA levels pointing to a transcription-independent downregulation of cFLIPL by Dexa. Analysis of protein degradation pathways indicates that Dexa causes cFLIPL depletion independently of proteasomal, lysosomal or caspase pathways, as inhibitors of the proteasome, lysosomal enzymes or caspases all failed to protect from Dexa-mediated loss of cFLIPL protein. Also, Dexa alone or in combination with BV6 does not affect overall activity of the proteasome. Importantly, overexpression of cFLIPL to an extent that is no longer subject to Dexa-imposed downregulation rescues Dexa/BV6-mediated cell death. Vice versa, knockdown of cFLIP increases BV6-mediated cell death, thus mimicking the effect of Dexa. Altogether, these data demonstrate that Dexa-mediated downregulation of cFLIPL protein promotes Dexa/BV6-mediated cell death, thereby providing novel insights into the synergistic antitumor activity of this combination treatment.
Although effective antibody-based vaccines have been developed against multiple viruses, such approaches have so far failed for the human immunodeficiency virus type 1 (HIV-1). Despite the success of anti-retroviral therapy (ART) that has turned HIV-1 infection into a chronic disease and has reduced the number of new infections worldwide, a vaccine against HIV-1 is still urgently needed. We discuss here the major reasons for the failure of “classical” vaccine approaches, which are mostly due to the biological properties of the virus itself. HIV-1 has developed multiple mechanisms of immune escape, which also account for vaccine failure. So far, no vaccine candidate has been able to induce broadly neutralizing antibodies (bnAbs) against primary patient viruses from different clades. However, such antibodies were identified in a subset of patients during chronic infection and were shown to protect from infection in animal models and to reduce viremia in first clinical trials. Their detailed characterization has guided structure-based reverse vaccinology approaches to design better HIV-1 envelope (Env) immunogens. Furthermore, conserved Env epitopes have been identified, which are promising candidates in view of clinical applications. Together with new vector-based technologies, considerable progress has been achieved in recent years towards the development of an effective antibody-based HIV-1 vaccine.
The mechanisms involved in malignant transformation of mature B and T lymphocytes are still poorly understood. In a previous study, we compared gene expression profiles of the tumor cells of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) to their normal cellular counterparts and found the basic leucine zipper protein ATF-like 3 (BATF3) to be significantly upregulated in the tumor cells of both entities. To assess the oncogenic potential of BATF3 in lymphomagenesis and to dissect the molecular interactions of BATF3 in lymphoma cells, we retrovirally transduced murine mature T and B cells with a BATF3-encoding viral vector and transplanted each population into Rag1-deficient recipients. Intriguingly, BATF3-expressing B lymphocytes readily induced B-cell lymphomas after characteristic latencies, whereas T-cell transplanted animals remained healthy throughout the observation time. Further analyses revealed a germinal center B-cell-like phenotype of most BATF3-initiated lymphomas. In a multiple myeloma cell line, BATF3 inhibited BLIMP1 expression, potentially illuminating an oncogenic action of BATF3 in B-cell lymphomagenesis. In conclusion, BATF3 overexpression induces malignant transformation of mature B cells and might serve as a potential target in B-cell lymphoma treatment.
Titanium is a biocompatible material that is frequently used for making implantable medical devices. Nanoengineering of the surface is the common method for increasing material biocompatibility, and while the nanostructured materials are well-known to represent attractive substrata for eukaryotic cells, very little information has been documented about the interaction between mammalian cells and bactericidal nanostructured surfaces. In this study, we investigated the effect of bactericidal titanium nanostructures on PC12 cell attachment and differentiation—a cell line which has become a widely used in vitro model to study neuronal differentiation. The effects of the nanostructures on the cells were then compared to effects observed when the cells were placed in contact with non-structured titanium. It was found that bactericidal nanostructured surfaces enhanced the attachment of neuron-like cells. In addition, the PC12 cells were able to differentiate on nanostructured surfaces, while the cells on non-structured surfaces were not able to do so. These promising results demonstrate the potential application of bactericidal nanostructured surfaces in biomedical applications such as cochlear and neuronal implants.
A large body of evidence suggests that the 11+ warm-up programme is effective in preventing football-related musculoskeletal injuries. However, despite considerable efforts to promote and disseminate the programme, it is unclear as to whether team head coaches are familiar with the 11+ and how they rate its feasibility. The present study aimed to gather information on awareness and usage among German amateur level football coaches. A questionnaire was administered to 7893 individuals who were in charge of youth and adult non-professional teams. Descriptive and inferential statistics were used to analyse the obtained data. A total of 1223 coaches (16%) returned the questionnaire. There was no risk of a non-response bias (p>.05). At the time of the survey, nearly half of the participants (42.6%) knew the 11+. Among the coaches who were familiar with the programme, three of four reported applying it regularly (at least once per week). Holding a license (φ = .28, p < .0001), high competitive level (Cramer-V = .13, p = .007), and coaching a youth team (φ = .1, p = .001) were associated with usage of 11+. Feasibility and suitability of the 11+ were rated similarly by aware and unaware coaches. Although a substantial share of German amateur level coaches is familiar with the 11+, more than half of the surveyed participants did not know the programme. As the non-usage does not appear to stem from a lack of rated feasibility and suitability, existing communication strategies might need to be revised.
The structural diversity of terpenoids is limited by the isoprene rule which states that all primary terpene synthase products derive from methyl-branched building blocks with five carbon atoms. With this study we discover a broad spectrum of novel terpenoids with eleven carbon atoms as byproducts of bacterial 2-methylisoborneol or 2-methylenebornane synthases. Both enzymes use 2-methyl-GPP as substrate, which is synthesized from GPP by the action of a methyltransferase. We used E. coli strains that heterologously produce different C11-terpene synthases together with the GPP methyltransferase and the mevalonate pathway enzymes. With this de novo approach, 35 different C11-terpenes could be produced. In addition to eleven known compounds, it was possible to detect 24 novel C11-terpenes which have not yet been described as terpene synthase products. Four of them, 3,4-dimethylcumene, 2-methylborneol and the two diastereomers of 2-methylcitronellol could be identified. Furthermore, we showed that an E. coli strain expressing the GPP-methyltransferase can produce the C16-terpene 6-methylfarnesol which indicates the condensation of 2-methyl-GPP and IPP to 6-methyl-FPP by the E. coli FPP-synthase. Our study demonstrates the broad range of unusual terpenes accessible by expression of GPP-methyltransferases and C11-terpene synthases in E. coli and provides an extended mechanism for C11-terpene synthases.
Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.
Methods and results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies.
In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95–1.02) in group A, 0.98 (0.93–1.04) in group B, and 0.95 (0.89–1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07–1.23) in group A, 1.13 (1.05–1.22) in group B, and 1.12 (1.05–1.20) in group C.
Conclusions: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
Empiric antibiotics are often used in combination with mechanical debridement to treat patients suffering from periodontitis and to eliminate disease-associated pathogens. Until now, only a few next generation sequencing 16S rDNA amplicon based publications with rather small sample sizes studied the effect of those interventions on the subgingival microbiome. Therefore, we studied subgingival samples of 89 patients with chronic periodontitis (solely non-smokers) before and two months after therapy. Forty-seven patients received mechanical periodontal therapy only, whereas 42 patients additionally received oral administered amoxicillin plus metronidazole (500 and 400 mg, respectively; 3x/day for 7 days). Samples were sequenced with Illumina MiSeq 300 base pairs paired end technology (V3 and V4 hypervariable regions of the 16S rDNA). Inter-group differences before and after therapy of clinical variables (percentage of sites with pocket depth ≥ 5mm, percentage of sites with bleeding on probing) and microbiome variables (diversity, richness, evenness, and dissimilarity) were calculated, a principal coordinate analysis (PCoA) was conducted, and differential abundance of agglomerated ribosomal sequence variants (aRSVs) classified on genus level was calculated using a negative binomial regression model. We found statistically noticeable decreased richness, and increased dissimilarity in the antibiotic, but not in the placebo group after therapy. The PCoA revealed a clear compositional separation of microbiomes after therapy in the antibiotic group, which could not be seen in the group receiving mechanical therapy only. This difference was even more pronounced on aRSV level. Here, adjunctive antibiotics were able to induce a microbiome shift by statistically noticeably reducing aRSVs belonging to genera containing disease-associated species, e.g., Porphyromonas, Tannerella, Treponema, and Aggregatibacter, and by noticeably increasing genera containing health-associated species. Mechanical therapy alone did not statistically noticeably affect any disease-associated taxa. Despite the difference in microbiome modulation both therapies improved the tested clinical parameters after two months. These results cast doubt on the relevance of the elimination and/or reduction of disease-associated taxa as a main goal of periodontal therapy.
After entorhinal deafferentiation of the hippocampal dentate gyrus a reinnervation of the denervated neurons by axon collaterals can be observed. This process takes place in a matter of weeks. However, the overall functional effect on the hippocampal network is still unclear.
In an effort to investigate this effect of axonal sprouting on the neuronal network of the dentate gyrus we compared the electrophysiological response of the dentate gyrus after electric stimulation in wild-type mice (WT mice) with a normal post-lesion sprouting, with genetically modified mice with an overexpression of the growth-protein CAP23 (cytoskeleton-associated protein 23). CAP23 overexpressing mice (CAP23tg mice) are known to have an enhanced axonal growth and sprouting after lesion.
The mice (both the WT as well as the CAP23tg mice) were deeply anesthetized and a lesion of the perforant path was induced stereotactically with a wire knife. After that the mice were permitted to survive for 4-6 weeks for partial reinnervation of the dentate gyrus before they were again operated and evoked potentials were measured (extracellular recordings of evoked potentials in the dentate gyrus). Non-lesioned litter-mate mice were taken as reference. The sprouting and the correct position of the electrodes was confirmed histologically.
For electrophysiological investigation we assessed laminar profiles and calculated a current-source density (CSD). In lesioned CAP23tg mice compared to lesioned WT mice this CSD-analysis revealed a significant enhancement of the current sink in the area of deafferentiation (outer molecular layer) and a significant excitation in the granule-cell layer.
Our results show that axonal sprouting seems to enhance the excitability of granule-cells. Thus, even if an enhanced axonal sprouting might accelerate the reinnervation of denervated dendrites after lesion, but it also leads to posttraumatic hyperexcitability of the neuronal network. In a therapeutic approach of fascilitating axonal sprouting this hyperexcitability has to be taken into consideration.
Objective: The present study aims to elucidate the state of gender equality in high-quality dermatological research by analysing the representation of female authorships from January 2008 to May 2017.
Design: Retrospective, descriptive study.
Setting: 113 189 male and female authorships from 23 373 research articles published in 23 dermatological Q1 journals were analysed with the aid of the Gendermetrics Platform.
Results: 43.0% of all authorships and 50.2% of the firstauthorships, 43.7% of the coauthorships and 33.1% of the last authorships are held by women. The corresponding female-to-male ORs are 1.41 (95% CI 1.37 to 1.45) for first authorships, 1.07 (95% CI 1.04 to 1.10) for coauthorships and 0.60 (95% CI 0.58 to 0.62) for last authorships. The annual growth rates are 1.74% overall and 1.45% for first authorships, 1.53% for coauthorships and 2.97% for last authorships. Women are slightly under-represented at prestigious authorships compared with men (Prestige Index=−0.11). The under-representation remains stable in highly competitive articles attracting the highest citation rates, namely, articles with many authors and articles that were published in highest-impact journals. Multiauthor articles with male key authors are only slightly more frequently cited than those with female key authors. Women publish slightly fewer papers compared with men (47.2% women hold 43.0% of the authorships). At the level of individual journals, there is a high degree of uniformity in gender-specific authorship odds. By contrast, distinct differences at country level were revealed. The prognosis for the next decades forecasts a consecutive harmonisation of authorship odds between the two genders.
Conclusions: In high-quality dermatological research, the integration of female scholars is advanced as compared with other medical disciplines. A gender gap consists mainly in the form of a career dichotomy, with many female early career researchers and few women in academic leadership positions. However, this gender gap has been narrowed in the last decade and will likely be further reduced in the future.
In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group.
Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed.
No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P < .001, P = .022 and P = .0042, respectively). Recipient preoperative and perioperative characteristics were comparable. Postoperatively in group 1 there was a higher incidence of extracorporeal life support (27.3 vs 9.1%, P = .019). There were no significant differences in chronic lung allograft dysfunction-free survival between group 1 and 2: 92.3 vs 94% at 1 year and 65.9 vs 75.5% at 3 years (P = .99). The estimated cumulative survival rate was also similar between groups: 68.2 vs 83.2% at 1 year and 68.2% versus 72% at 3 years (P = .3758).
Hanging as a donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation.
This study aimed to appraise two quantitative magnetic resonance imaging techniques, T2* imaging and diffusion-weighted imaging (DWI), for the diagnosis of the intervertebral disc degeneration of the cervico-thoracic junction. Influence of specific factors and diagnostic accuracy of both techniques were particularly explored. Sixty-one volunteers with neck and upper back pain were recruited and evaluated with both T2* imaging and DWI. The Pfirrmann grade, T2* relaxation time and apparent diffusion coefficient (ADC) value of each disc between C7 and T3 were recorded. Stratified analyses were performed for different anatomic levels, genders, age ranges and Pfirrmann grades. The diagnostic accuracy of both techniques was investigated using the receiver operating characteristic (ROC) curves. No statistically significant difference of either T2* relaxation time or ADC value was detected between males and females. Both parameters decreased with the increasing age and Pfirrmann grade. The ROC curves showed the higher sensitivity and specificity for T2* imaging than DWI to quantitatively identify the disc degeneration. Particularly, T2* imaging allowed for a quantitative distinguishing the normal, mild and moderate disc degeneration from the severe degeneration, which was unable to accomplish with DWI. In conclusion, we demonstrated that T2* imaging possess a better accuracy than DWI to quantitatively diagnose the intervertebral disc degeneration at the cervico-thoracic junction.
Perception, particularly in the visual domain, is drastically influenced by rhythmic changes in ambient lighting conditions. Anticipation of daylight changes by the circadian system is critical for survival. However, the neural bases of time-of-day-dependent modulation in human perception are not yet understood. We used fMRI to study brain dynamics during resting-state and close-to-threshold visual perception repeatedly at six times of the day. Here we report that resting-state signal variance drops endogenously at times coinciding with dawn and dusk, notably in sensory cortices only. In parallel, perception-related signal variance in visual cortices decreases and correlates negatively with detection performance, identifying an anticipatory mechanism that compensates for the deteriorated visual signal quality at dawn and dusk. Generally, our findings imply that decreases in spontaneous neural activity improve close-to-threshold perception.
Reconstructing the evolution of baleen whales (Mysticeti) has been problematic because morphological and genetic analyses have produced different scenarios. This might be caused by genomic admixture that may have taken place among some rorquals. We present the genomes of six whales, including the blue whale (Balaenoptera musculus), to reconstruct a species tree of baleen whales and to identify phylogenetic conflicts. Evolutionary multilocus analyses of 34,192 genome fragments reveal a fast radiation of rorquals at 10.5 to 7.5 million years ago coinciding with oceanic circulation shifts. The evolutionarily enigmatic gray whale (Eschrichtius robustus) is placed among rorquals, and the blue whale genome shows a high degree of heterozygosity. The nearly equal frequency of conflicting gene trees suggests that speciation of rorqual evolution occurred under gene flow, which is best depicted by evolutionary networks. Especially in marine environments, sympatric speciation might be common; our results raise questions about how genetic divergence can be established.
Diagnostic approaches for invasive aspergillosis—specific considerations in the pediatric population
(2018)
Invasive aspergillosis (IA) is a major cause of morbidity and mortality in children with hematological malignancies and those undergoing hematopoietic stem cell transplantation. Similar to immunocompromised adults, clinical signs, and symptoms of IA are unspecific in the pediatric patient population. As early diagnosis and prompt treatment of IA is associated with better outcome, imaging and non-invasive antigen-based such as galactomannan or ß-D-glucan and molecular biomarkers in peripheral blood may facilitate institution and choice of antifungal compounds and guide duration of therapy. In patients in whom imaging studies suggest IA or another mold infection, invasive diagnostics such as bronchoalveolar lavage and/or bioptic procedures should be considered. Here we review the current data of diagnostic approaches for IA in the pediatric setting and highlight the major differences of performance and clinical utility of the tests between children and adults.
Background: Anger and aggression belong to the core symptoms of borderline personality disorder. Although an early and specific treatment of BPD is highly relevant to prevent chronification, still little is known about anger and aggression and their neural underpinnings in adolescents with BPD.
Method: Twenty female adolescents with BPD (age 15–17 years) and 20 female healthy adolescents (age 15–17 years) took part in this functional magnetic resonance imaging (fMRI) study. A script-driven imagery paradigm was used to induce rejection-based feelings of anger, which was followed by descriptions of self-directed and other-directed aggressive reactions. To investigate the specificity of the neural activation patterns for adolescent patients, results were compared with data from 34 female adults with BPD (age 18–50 years) and 32 female healthy adults (age 18–50 years).
Results: Adolescents with BPD showed increased activations in the left posterior insula and left dorsal striatum as well as in the left inferior frontal cortex and parts of the mentalizing network during the rejection-based anger induction and the imagination of aggressive reactions compared to healthy adolescents. For the other-directed aggression phase, a significant diagnosis by age interaction confirmed that these results were specific for adolescents.
Discussion: The results of this very first fMRI study on anger and aggression in adolescents with BPD suggest an enhanced emotional reactivity to and higher effort in controlling anger and aggression evoked by social rejection at an early developmental stage of the disorder. Since emotion dysregulation is a known mediator for aggression in BPD, the results point to the need of appropriate early interventions for adolescents with BPD.
G-protein coupled receptors (GPCRs) are a predominant class of cell-surface receptors in eukaryotic life. They are responsible for the perception of a broad range of ligands and involved in a multitude of physiological functions. GPCRs are therefore of crucial interest for biological and pharmaceutical research. Molecular analysis and functional characterisation of GPCRs is frequently hampered by challenges in efficient large-scale production, non-destructive purification and long-term stability. Cell-free protein synthesis (CFPS) provides new production platforms for GPCRs by extracting the protein synthesis machinery of the cell in an open system that allows target-oriented modulations of the synthesis process and direct access to the nascent polypeptide chain. CFPS is fast, reliable and highly adaptable. Unfortunately, highly productive cell-free synthesis of GPCRs is often opposed by low product quality. This thesis was aimed to adapt and improve some of the new possibilities for the cell-free production of GPCRs in high yield and quality for structural and pharmaceutical analysis. An E. coli based CFPS system was applied to synthesise various turkey and human Beta-adrenergic receptor (Beta1AR) derivatives as well as human Endothelin receptors type A and B (ETA and ETB) constructs. Both receptor families are important drug targets and pharmacologically addressed in the treatment of several cardiovascular diseases. CF-synthesis was mainly performed in presence of nanodiscs (ND), which are reconstituted high density lipoprotein particles forming discoidal bilayer patches with a diameter varyring from 6 to approx. 15 nm. The supplementation of ND in the CF-synthesis reaction caused the co-translational solubilisation of the freshly synthesised GPCRs. The fraction of the solubilised GPCR that was correctly folded was analysed by the competence to bind its ligand alprenolol or Endothelin-1, respectively. Both the solubilisation efficiency and the ability to fold in a ligand binding competent state was strongly affected by the lipid composition of the supplied ND. Best results were generally achieved with lipids having phosphoglycerol headgroups and unsaturated fatty acid chains with 18 carbon atoms. Furthermore, thermostabilisation by introduction of point mutations had a large positive impact on the folding efficiency of both Beta1AR and ETB receptor. Formation of a conserved disulphide bridge in the extracellular region was additionally found to be crucial for the function of the ETB receptor. Disulphide bridge formation could be enhanced by applying a glutathione-based redox system in the CFPS. Further improvements in the quality of ETB receptor could be made by the enrichment of heat-shock chaperones in the CF-reaction. Depending on the receptor type and DNA-template, roughly 10 – 30 nmol (350 – 1500 µg) of protein could be synthesised in 1 ml of CF-reaction mixture. After the applied optimisation steps, the fractions of correctly folded receptor could be improved by several orders of magnitude and were finally in between 35% for the thermostabilised turkey Beta1AR, 9% for the thermostabilised ETB receptor, 6.5% for the non-stabilised ETB receptor, 1 - 5% for non-stabilised turkey Beta1AR and for human Beta1AR isoforms and 0.1% for ETA receptor. Therefore, between 2 and 120 µg of GPCR could be synthesised in a ligand binding competent form, depending on the receptor and its modifications. Correctly folded turkey Beta1AR and ETB receptors were thermostable at 30°C and could be stored at 4°C for several weeks after purification. Yields of the thermostabilised turkey Beta1AR were sufficient to purify the receptor in a two-step process by ligand-binding chromatography to obtain pure and correctly folded receptor in the lipid bilayer of a ND. Furthermore, a lipid dependent ligand screen could be demonstrated with the turkey Beta1AR and significant alterations in binding affinities to currently in-use pharmaceuticals were found. The established protocols are therefore suitable and highly competetive for a variety of applications such as screening of GPCR ligands, analysis of lipid effects on GPCR function or for the systematical biochemical characterisation of GPCRs. Most promising for future approaches appears to address the suspected bottlenecks of intial insertion of the GPCR-polypeptide chain in the ND bilayer and the thermal stability of the receptors. Nevertheless, the estabilised protocols for the analysed targets in this thesis are already highly competitive to previously published production protocols either in cell-based or cell-free systems with regard to yield of functional protein, speediness and costs. Moreover, the direct accessibility and other general characteristics of cell-free synthesis open a large variety of possible applications and this work can therefore contribute to the molecular characterisation of this important receptor type and to the development of new pharmaceuticals.
The article is designed to introduce and analyze authoritarian constitutionalism as an important phenomenon in its own right, not merely a deficient or deviant version of liberal constitutionalism. Therefore it is not adequate to dismiss it as sham or window-dressing. Instead, its crucial features – participation as complicity, power as property and the cult of immediacy – are related to the basic assumption that authoritarian constitutions are texts with a purpose that warrant careful analysis of the domestic and transnational audience.
This dissertation discusses the mutual influence between leaders and followers on perception, emotion and behavior, using an attachment theory perspective. Some individuals are more likely to be seen as leaders than others. On the one hand this is determined by the characteristics or attributes as well as skills of the person in question. However, on the other hand, followers’ perception and expectations play a big role as well, in particular which expectations of an ideal leader can be fulfilled by followers’ current leader. Although attachment theory and – styles have only recently entered the organizational psychology literature, this dissertation advances that literature by looking at the role of attachment orientations between leaders and followers. In doing so, this dissertation answers several recent research calls on this topic. The three main subsequent chapters discuss the predictive role of attachment orientations with regard to leader preferences, the transference of behavioural expectations from one leader to another, and the perception of leader prototypicality in groups. The first chapter discusses the connection between implicit leader preferences and attachment orientations as predictors. Results show that avoidant attached individuals prefer a more autonomous and independent leadership style, whereas anxious attached individuals prefer a supportive and team-oriented leadership style. In the second chapter I study the transference of behavioural expectations from one leader to another. Results show that avoidant attached individuals are more likely to engage in this transference process. In addition, I discuss and empirically test the influence of culture with regard to leader transference. In the final chapter, I examine the behavioural influence of attachment orientations on how likely someone is perceived to be a leader in groups. Based on 57 project groups, I find that team members actually perceive avoidant attached individuals to be the most leader-like. Put differently, given certain environmental conditions, insecure attachment orientations can be perceived as leaders. These results show that it is even more important that leaders somewhat adapt to their followers’ preferences and not commit to merely one particular leadership style.
Cells within a tissue form highly complex, cellular interactions. This architecture is lost in two-dimensional (2D) cell cultures. To close the gap between 2D cell cultures and in vivo tissues, three-dimensional (3D) cell cultures such as spheroids or embryoid bodies were developed. To fully take advantage of the third dimension, imaging techniques are essential. The emerging field of "image-based systems biology" exploits the information in images and builds a connection between experimental and theoretical investigation of biological processes. Such interdisciplinary approaches strongly depend on the development of protocols to establish 3D cell cultures, innovations in sample preparation, well-suited imaging techniques and quantitative segmentation methods.
Although 3D cell cultures and image-based systems biology provide a great potential, 2D methods are still not completely replaced by 3D methods. This is mainly due to methodical and technical hurdles. Therefore, this thesis provides a significant contribution to overcome these hurdles and to further develop 3D cell cultures. I established computational and experimental methods related to 3D aggregates and investigated fundamental, cellular processes such as adhesion, growth and differentiation.
The automatic segmentation method "PAS" and "LoS" were developed in the context of this thesis. They extract essential biological properties such as the projected area or features of cell nuclei from 2D or 3D images of 3D aggregates. Both algorithms show their accuracy robustly over image data from different samples and different microscopes. In addition, the superior performance of PAS and LoS was proven in a comparison with state-of-the-art methods.
The PAS approach served as an essential basis for investigating cellular processes such as adhesion and growth which are tightly regulated to contribute to tissue integrity. These processes are involved in the formation of spheroids. The temporally resolved data of spheroid formation of three mammary epithelial cell lines revealed differences in their formation dynamics as well as in the onset of spheroid formation phases (aggregation, compaction and growth). Despite these differences, adhesion- and growth-associated proteins such as E-cadherin, actin, microtubules, and the focal adhesion kinase show similar importance in a particular phase. Notably, certain proteins (e.g. E-Cadherin) contribute differently to spheroid formation of cells from different cell types in terms of cell adhesion and growth. Overall, analyses of the individual phases of spheroid formation revealed the temporal coordination of fundamental tissue-specific processes. The results contribute to a better understanding of the maintenance and disruption of tissue integrity.
An important but yet unknown process is how cells accomplish to arrange themselves against the gravitational force to form a spheroid. Live imaging with light sheet-based microscopy provides the best solution for a temporally and in particular spatially resolved investigation of spheroid formation. Although the imaging possibilities increase with this particular microscopy technique, available sample preparation methods are rare. Therefore, I have significantly optimized "agarose beaker" as preparation method for 3D long-term imaging of spheroid formation. The data show that upward movement of the cells takes place early. This movement is initiated in the centre of the initially flat cell layer. Subsequently, the cells move from the periphery of the cell layer toward the centre. Cells rearrange within the spheroid which is followed by growth. It is very likely that 3D aggregates form by adopting an energetically favoured, spherical shape by increasing cell-cell or cell-matrix contacts.
Besides the knowledge gained from the examination of the self-assembly process in different contexts, fully formed cellular aggregates can serve as basis to investigate differentiation processes. Differentiation guide cell fate specification during early embryonic development (i.e. preimplantation) and is not fully understood yet. Due to the lack of an in vitro system for preimplantation, I have developed "blastoids". These are 3D multicellular aggregates of mouse embryonic stem cells which represent important phases of preimplantation and beyond. In qualitative and quantitative analyses, a strong similarity was proven between blastoids and the inner cell mass of in vivo mouse embryos. Further results strongly suggest that both, the cell number and the trophectoderm play a subordinate role for cell fate decision during preimplantation. Furthermore, 3D neighbourhood analyses have shown that both, blastoids and mouse embryos, do not show a random "salt-and-pepper" pattern during differentiation. Instead, they show a yet unknown local clustering of cells with identical fates, suggesting local cell interactions that influence cell fate decision. Furthermore, the data indicate that the maturation of the epiblast in the later stages of preimplantation is initiated by an interaction between cells of the epiblast and the primitive endoderm.
Using image-based systems biology, I have investigated fundamental cellular processes such as adhesion, growth and differentiation in the context of tissue integrity and early embryonic development using 3D cellular aggregates. This highly interdisciplinary work is a major contribution to 3D cell biology and demonstrates how cells bind and interact within a complex system. The main methods developed in this thesis as well as the biological findings can be used not only in further biological but also in medical and pharmacological studies. They have the potential to advance our understanding of complex biological systems and to provide new opportunities for practical applications.
Acute myeloid leukemia (AML) is a clonal malignancy of hematopoietic stem cells (HSCs) characterized by expansion of myeloid blasts in the bone marrow. It has been shown that autophagy is a degradative process, which delivers cytoplasmic components to lysosomes to prevent malignant transformation by maintaining HSC integrity. Besides its function as a bulk degradation machinery to recycle cytoplasmic components during limited energy supply, autophagy also serves as an intracellular quality control mechanism. Selective autophagy requires autophagy receptors such as p62 to specifically bridge the targeted cargos into autophagosomes. p62 is known as a central signaling hub involved in pro-oncogenic signaling pathways and autophagic degradation pathways. However, little is known about the role of p62 as a selective autophagy receptor in AML. This study aims to elucidate the precise function of p62 as an autophagy receptor in leukemia development and maintenance.
In silico analysis revealed that high p62 expression was significantly associated with poor overall survival of adult patients with de novo AML, suggesting that p62 may promote leukemia maintenance. To address the functional role of p62 in leukemia, genome editing by CRISPR/Cas9 was used to knockout p62 in four human AML cell lines. Importantly, p62 loss reduced cell proliferation in all four cell lines. This observation could be transferred to a murine leukemia cell model in which leukemic transformation of lineage-depleted bone marrow (ldMBM) cells was induced by overexpression of the human transcriptional coactivator MN1. Knockdown of p62 by shRNA in MN1-driven leukemia cells impaired proliferation and decreased colony forming ability without altering apoptosis. This indicates that p62 is crucial for leukemia proliferation in vitro. To further characterize the role of p62 in leukemia development and maintenance a murine AML transplantation model was established. Therefore, ldMBM cells isolated from WT and p62-/- mice were transduced with MN1 and transplanted into lethally irradiated mice. As expected, all mice developed fatal myeloid proliferation. Notably, p62 loss in MN1-driven leukemia significantly prolonged survival in mice and caused a more immature phenotype. Consistent with the in vitro results, ex vivo analysis of p62-/- leukemic cells displayed decreased colony-forming ability, although p62 loss did not affect composition and function of HSCs. Moreover, re-transplantation of primary MN1-driven leukemia cells attenuated leukemia progression upon p62 loss. These findings support a decisive role of p62 in leukemia development and maintenance.
To gain molecular insight into the function of p62 during myeloid transformation an interactome analysis of murine MN1-driven leukemia cells was performed. This revealed first that p62 predominantly interacts with mitochondrial proteins and second that inhibition of autophagic degradation causes accumulation of p62-bound mitochondria. This leads to the first assumption that loss of p62 may provoke mitochondrial accumulation with increasing mitochondrial damage and second that p62 may mediate degradation of mitochondria by mitophagy. Indeed, in the absence of p62, accumulation of dysfunctional mitochondria was detected by morphological changes of the mitochondria, increased mitochondrial ROS and impaired mitochondrial respiration capacity. Furthermore, induction of PINK1/Parkin-independent mitophagy revealed that loss of p62 caused impaired degradation of mitochondrial proteins and reduced translocation of damaged mitochondria into autophagosomes. Taken together, p62 is required for effective degradation of dysfunctional mitochondria by mitophagy in AML.
Due to the fact that p62 is a multifunctional protein, rescue experiments with different mutants of p62 were performed to clarify if p62-mediated mitophagy contributes to leukemia proliferation. Notably, the autophagy-deficient mutant (disabled to bind autophagosomes) reduced cell growth and colony-forming ability to the same extent as knockdown of p62, as the clustering-deficient mutant (disabled to form aggregates) displayed an intermediate phenotype. Strikingly, only the autophagy-deficient mutant failed to rescue mitophagy.
In conclusion, this study demonstrates the prominent role of p62 as a selective autophagy receptor for mitochondrial quality control which contributes to leukemia development and maintenance. Therefore, targeting selective autophagy opens new venues in the treatment of AML.
The pyrrolobenzodiazepine tilivalline (1) was originally identified in the human gut pathobiont Klebsiella oxytoca, the causative agent of antibiotic-associated hemorrhagic colitis. Here we show the identification of tilivalline and analogs thereof in the entomopathogenic bacterium Xenorhabdus eapokensis as well as the identification of its biosynthesis gene cluster encoding a bimodular non-ribosomal peptide synthetase. Heterologous expression of both genes in E. coli resulted in the production of 1 and from mutasynthesis and precursor directed biosynthesis 11 new tilivalline analogs were identified in X. eapokensis. These results allowed the prediction of the tilivalline biosynthesis being similar to that in K. oxytoca.
Due to immigration influxes, Germany’s ethnic diversity is on steady rise. Although citizens of immigrant origin make up a high percentage of the population in all Western European countries, they are descriptively underrepresented in most legislative bodies. As widely acknowledged, political parties form the key channels through which societal developments are fed into parliament. By selecting parliamentary candidates, they constitute the most crucial nexus of the population to be represented and legislative bodies. Despite the pivotal role of the intra-party candidate selection in shaping who runs for election, the question of how candidates of immigrant background fare in the candidate selection and whether the criteria political parties use for selecting candidates of immigrant background are the same as for native-born candidates remained a blind spot of the research on minority representation. Therefore, the dissertation scrutinizes the thresholds candidates of immigrant background need to overcome to run for legislative office. It thus tackles the questions of how political parties go about selecting candidates of immigrant background in comparison to native-born candidates and which contextual factors drive their choice of selection behavior. For this purpose, the dissertation develops three ideal-typical selection strategies political parties can adopt towards candidates of immigrant background, which are referred to as neutrality, opening or closure, and empirically tests which selection strategy is in use. To explore parties’ selection behavior towards candidates of immigrant background, the dissertation combines the advantages of quantitative analysis by employing candidate surveys at the state and national level, with advantages of qualitative analysis by conducting interviews with candidates of immigrant background. As the analysis reveals, neutrality is the predominant selection strategy that political parties use towards candidates of immigrant background, the reason being that neutral selection practices involve the fewest intra-party conflicts.
Determining the age of juvenile blow flies is one of the key tasks of forensic entomology when providing evidence for the minimum post mortem interval. While the age determination of blow fly larvae is well established using morphological parameters, the current study focuses on molecular methods for estimating the age of blow flies during the metamorphosis in the pupal stage, which lasts about half the total juvenile development. It has already been demonstrated in several studies that the intraspecific variance in expression of so far used genes in blow flies is often too high to assign a certain expression level to a distinct age, leading to an inaccurate prediction. To overcome this problem, we previously identified new markers, which show a very sharp age dependent expression course during pupal development of the forensically-important blow fly Calliphora vicina Robineau–Desvoidy 1830 (Diptera: Calliphoridae) by analyzing massive parallel sequencing (MPS) generated transcriptome data. We initially designed and validated two quantitative polymerase chain reaction (qPCR) assays for each of 15 defined pupal ages representing a daily progress during the total pupal development if grown at 17 °C. We also investigated whether the performance of these assays is affected by the ambient temperature, when rearing pupae of C. vicina at three different constant temperatures—namely 17 °C, 20 °C and 25 °C. A temperature dependency of the performance could not be observed, except for one marker. Hence, for each of the defined development landmarks, we can present gene expression profiles of one to two markers defining the mentioned progress in development.
We used electron cryo-tomography and subtomogram averaging to investigate the structure of complex I and its supramolecular assemblies in the inner mitochondrial membrane of mammals, fungi, and plants. Tomographic volumes containing complex I were averaged at ∼4 nm resolution. Principal component analysis indicated that ∼60% of complex I formed a supercomplex with dimeric complex III, while ∼40% were not associated with other respiratory chain complexes. The mutual arrangement of complex I and III2 was essentially conserved in all supercomplexes investigated. In addition, up to two copies of monomeric complex IV were associated with the complex I1III2 assembly in bovine heart and the yeast Yarrowia lipolytica, but their positions varied. No complex IV was detected in the respiratory supercomplex of the plant Asparagus officinalis. Instead, an ∼4.5-nm globular protein density was observed on the matrix side of the complex I membrane arm, which we assign to γ-carbonic anhydrase. Our results demonstrate that respiratory chain supercomplexes in situ have a conserved core of complex I and III2, but otherwise their stoichiometry and structure varies. The conserved features of supercomplex assemblies indicate an important role in respiratory electron transfer.
The major obstacle in the clinical use of the antitumor drug cisplatin is inherent and acquired resistance. Typically, cisplatin resistance is not restricted to a single mechanism demanding for a systems pharmacology approach to understand a whole cell’s reaction to the drug. In this study, the cellular transcriptome of untreated and cisplatin-treated A549 non-small cell lung cancer cells and their cisplatin-resistant sub-line A549rCDDP2000 was screened with a whole genome array for relevant gene candidates. By combining statistical methods with available gene annotations and without a previously defined hypothesis HRas, MAPK14 (p38), CCL2, DOK1 and PTK2B were identified as genes possibly relevant for cisplatin resistance. These and related genes were further validated on transcriptome (qRT-PCR) and proteome (Western blot) level to select candidates contributing to resistance. HRas, p38, CCL2, DOK1, PTK2B and JNK3 were integrated into a model of resistance-associated signalling alterations describing differential gene and protein expression between cisplatin-sensitive and -resistant cells in reaction to cisplatin exposure.
Natural Killer T cells (NKT cells) are emerging as critical regulators of pro- and anti-tumor immunity, both at baseline and in therapeutic settings. While type I NKT cells can promote anti-tumor immunity, their activity in the tumor microenvironment may be limited by negative regulators such as inhibitory immune checkpoints. We observed dominant expression of B- and T-lymphocyte attenuator (BTLA) on type I NKT cells in polyoma middle T oncogene-driven (PyMT) murine autochthonous mammary tumors. Other immune checkpoint receptors, such as programmed cell death 1 (PD-1) were equally distributed among T cell populations. Interference with BTLA using neutralizing antibodies limited tumor growth and pulmonary metastasis in the PyMT model in a therapeutic setting, correlating with an increase in type I NKT cells and expression of cytotoxic marker genes. While therapeutic application of an anti-PD-1 antibody increased the number of CD8+ cytotoxic T cells and elevated IL-12 expression, tumor control was not established. Expression of ZBTB16, the lineage-determining transcription factor of type I NKT cells, was correlated with a favorable patient prognosis in the METABRIC dataset, and BTLA levels were instrumental to further distinguish prognosis in patents with high ZBTB16 expression. Taken together, these data support a role of BTLA on type I NKT cells in limiting anti-tumor immunity.
kurz und kn@pp news : Nr. 42
(2018)
Even if the importance of micro data transparency is a well-established fact, European institutions are still lacking behind the US when it comes to the provision of financial market data to academics. In this Policy Letter we discuss five different types of micro data that are crucial for monitoring (systemic) risk in the financial system, identifying and understanding inter-linkages in financial markets and thus have important implications for policymakers and regulatory authorities. We come to the conclusion that for all five areas of micro data, outlined in this Policy Letter (bank balance sheet data, asset portfolio data, market transaction data, market high frequency data and central bank data), the benefits of increased transparency greatly offset potential downsides. Hence, European policymakers would do well to follow the US example and close the sizeable gap in micro data transparency. For most cases, relevant data is already collected (at least on national level), but just not made available to academics for partly incomprehensible reasons. Overcoming these obstacles could foster financial stability in Europe and assure level playing fields with US regulators and policymakers.
Does economic policy uncertainty affect household stockholding? To answer this question we create a novel measure of household exposure to economic policy uncertainty news by combining survey information on the hours a household spends in reading newspapers and the frequency of such news in the popular press during a household’s pre-interview period. After controlling for household fixed effects, month-year fixed effects and time-varying cognitive skills, we find that households with a higher exposure to economic policy uncertainty news are less likely to invest in stocks held directly or through mutual funds. This effect is independent from the market volatility index and household (first-moment) expectations about the stock market index.
Objectives: Within a randomized controlled trial contrasting the outcome of manualized cognitive-behavioral (CBT) and short term psychodynamic therapy (PDT) compared to a waiting list condition (the SOPHO-Net trial), we set out to test whether self-reported attachment characteristics change during the treatments and if these changes differ between treatments.
Research design and methods: 495 patients from the SOPHO-Net trial (54.5% female, mean age 35.2 years) who were randomized to either CBT, PDT or waiting list (WL) completed the partner-related revised Experiences in Close Relationships Questionnaire (ECR-R) before and after treatment and at 6 and 12 months follow-up. The Liebowitz Social Anxiety Scale (LSAS) was administered at pre-treatment, post-treatment, and at 6-month and 1-year follow-up. ECR-R scores were first compared to a representative healthy sample (n = 2508) in order to demonstrate that the clinical sample differed significantly from the non-clinical sample with respect to attachment anxiety and avoidance.
Results: LSAS scores correlated significantly with both ECR-R subscales. Post-therapy, patients treated with CBT revealed significant changes in attachment anxiety and avoidance whereas patients treated with PDT showed no significant changes. Changes between post-treatment and the two follow-ups were significant in both conditions, with minimal (insignificant) differences between treatments at the 12- month follow-up.
Conclusions: The current study supports recent reviews of mostly naturalistic studies indicating changes in attachment as a result of psychotherapy. Although there were differences between conditions at the end of treatment, these largely disappeared during the follow-up period which is line with the other results of the SOPHO-NET trial.
Trial registration: Controlled-trials.com ISRCTN53517394
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the US and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H (FH). To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds FH to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because FH-binding cloaks potentially protective epitopes. We modified CspZ by conjugating to virus-like particles (VLP-CspZ) and eliminating FH binding (modified VLP-CspZ) to increase immunogenicity. We observed greater bactericidal antibody titers in mice vaccinated with modified VLP-CspZ: A serum dilution of 1:395 (modified VLP-CspZ) vs 1:143 (VLP-CspZ) yielded 50% borreliacidal activity. Immunizing mice with modified VLP-CspZ cleared spirochete infection, as did passive transfer of elicited antibodies. This work developed a novel Lyme disease vaccine candidate by conjugating CspZ to VLP and eliminating FH-binding ability. Such a strategy of conjugating an antigen to a VLP and eliminating binding to the target ligand can serve as a general model for developing vaccines against other bacterial infectious agents.
Acetaminophen [paracetamol, N-acetyl-p-aminophenol (APAP)]-induced acute liver injury (ALI) not only remains a persistent clinical challenge but likewise stands out as well-characterized paradigmatic model of drug-induced liver damage. APAP intoxication associates with robust hepatic necroinflammation the role of which remains elusive with pathogenic but also pro-regenerative/-resolving functions being ascribed to leukocyte activation. Here, we shine a light on and put forward a unique role of the interleukin (IL)-1 family member IL-18 in experimental APAP-induced ALI. Indeed, amelioration of disease as previously observed in IL-18-deficient mice was further substantiated herein by application of the IL-18 opponent IL-18-binding protein (IL-18BPd:Fc) to wild-type mice. Data altogether emphasize crucial pathological action of this cytokine in APAP toxicity. Adding recombinant IL-22 to IL-18BPd:Fc further enhanced protection from liver injury. In contrast to IL-18, the role of prototypic pro-inflammatory IL-1 and tumor necrosis factor-α is controversially discussed with lack of effects or even protective action being repeatedly reported. A prominent detrimental function for IL-18 in APAP-induced ALI as proposed herein should relate to its pivotal role for hepatic expression of interferon-γ and Fas ligand, both of which aggravate APAP toxicity. As IL-18 serum levels increase in patients after APAP overdosing, targeting IL-18 may evolve as novel therapeutic option in those hard-to-treat patients where standard therapy with N-acetylcysteine is unsuccessful. Being a paradigmatic experimental model of ALI, current knowledge on ill-fated properties of IL-18 in APAP intoxication likewise emphasizes the potential of this cytokine to serve as therapeutic target in other entities of inflammatory liver diseases.
A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI (Npr2fl/fl;Wnt1Cre and cGKIKO/fl;Wnt1Cre) that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice. Cholera toxin labeling in digits of the hind paw demonstrated an altered shape of sensory neuron termination fields in the spinal cord of conditional Npr2 mouse mutants. Behavioral testing of both sexes indicated that noxious heat sensation and nociception induced by chemical irritants are impaired in the mutants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are not affected. Recordings from C-fiber nociceptors in the hind limb skin showed that Npr2 function was not required to maintain normal heat sensitivity of peripheral nociceptors. Thus, the altered behavioral responses to noxious heat found in Npr2fl/fl;Wnt1Cre mice is not due to an impaired C-fiber function. Overall, these data point to a critical role of axonal bifurcation for the processing of pain induced by heat or chemical stimuli.
Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model (Cln3Δex7/8 mice) for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3Δex7/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both biochemical and cytochemical methods. However, quantitative high-performance liquid chromatography analysis revealed a highly significant increase in GM3, suggesting a metabolic blockade in the conversion of GM3 to more complex gangliosides. Quantitative real-time PCR analysis revealed a significant reduction in the transcripts of the interconverting enzymes, especially of β-1,4-N-acetyl-galactosaminyl transferase 1 (GM2 synthase), which is the enzyme converting GM3 to GM2. Thus, our data suggest that the complex a-series gangliosides are reduced in Cln3Δex7/8 mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis.