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Twelve species in total are recognized for the subgenus Lasioglossum (Dialictus) Robertson, 1902 from Japan, the Korean Peninsula and Taiwan. Lasioglossum (Dialictus) alishanense sp. nov. and L. (D.) taiwanense sp. nov. from Taiwan, are described as new. Four species are recorded fromn the following localities for the first time: L. (D.) miyabei Murao, Ebmer & Tadauchi, 2006 from the Korean Peninsula (South Korea); L. (D.) ellipticeps (Blüthgen, 1923), L. (D.) virideglaucum Ebmer & Sakagami, 1994 and L. (D.) viridellum (Cockerell, 1931) from South Korea. Lasioglossum (Dialictus) atroglaucum (Strand, 1913) is redescribed, L. (D.) ellipticeps, L. (D.) problematicum (Blüthgen, 1923), L. (D.) virideglaucum, and L. (D.) viridellum are supplementary described. A key to species is provided. Bionomical data, such as fl ight and fl ower records or habitat, are reported for some species. The distributions of all species are mapped. DNA barcodes of L. (D.) miyabei, L. (D.) pseudannulipes (Blüthgen, 1925), and L. (D.) virideglaucum are provided.
Two new genera and nine new species of hydroids are described based on deep-water material collected from off New Caledonia during various expeditions of the French Tropical Deep-Sea Benthos program. Caledoniana gen. nov., provisionally included in the family Sertulariidae Lamouroux, 1812, presently comprises three new species, viz. C. alata sp. nov., C. decussata sp. nov., and C. microgona sp. nov., while an additional group of three new species, is accommodated in the new sertulariid genus Solenoscyphus gen. nov.: S. candelabrum sp. nov., S. decidualis sp. nov., and S. striatus sp. nov. Furthermore, three new species of Hincksella Billard, 1918 (family Syntheciidae Marktanner- Turneretscher, 1890) are described, namely H. cornuta sp. nov., H. neocaledonica sp. nov., and H. similis sp. nov.
Morphological (shell) and molecular examination of a large suite of specimens of pleurotomariids from around New Caledonia and the Coral Sea reveals the existence of four species in the complex of Perotrochus caledonicus: Perotrochus deforgesi Métivier, 1990 and P. pseudogranulosus sp. nov. live allopatrically on the plateaus and guyots of the Coral Sea; Perotrochus caledonicus Bouchet & Métivier, 1982 and Perotrochus wareni sp. nov. live sympatrically - but essentially not syntopically - on the slopes of New Caledonia, Norfolk Ridge and the Loyalty Ridge. All species live in the 300–500 m interval, and together form a significant component of the mollusc fauna living on hard bottoms in the SW Pacific, with individual dredge hauls containing up to 25 specimens of Perotrochus.
New and interesting Surirella taxa (Surirellaceae, Bacillariophyta) from the Congo Basin (DR Congo)
(2015)
Two new diatom taxa belonging to the genus Surirella, S. ebalensis and S. congolensis, are described from material of the Congo Basin, downstream Kisangani, DR Congo. The first taxon is a small, rather common species in the studied material; the second a somewhat larger diatom that was only sporadically observed. The morphology of both taxa is examined with light and scanning electron microscopy. The differences between the new and other closely related taxa such as S. agonaensis and S. bonsaensis, and S. takoradiensis, S. tenuissima and S. pseudotenuissima, respectively, are discussed.
Pardosa benadira Caporiacco, 1940 is redescribed, including the hitherto unknown female. The species is here transferred to the genus Wadicosa Zyuzin, 1985. Previously known only from its type locality in Somalia, additional localities for P. benadira in Somalia and Kenya are given. Male and female W. cognata sp. nov. (Kenya: Lake Magadi), male and female W. jocquei sp. nov. (Comoro Islands, Aldabra, Madagascar and Mauritius) and female W. russellsmithi sp. nov. (Mauritius) are described. Pardosa oncka Lawrence, 1927, widely distributed in Africa and redescribed by Kronestedt in 1987, is formally transferred to the genus Wadicosa and new records given.
Based on intensive collecting from various sites in Sweden, the genus Dasyhelea Kieffer, 1911 was reviewed and the number of species now known from the country increased from five to twenty. Among the new species recorded there are two species described as new to science, D. dominiakae sp. nov. and D. gothlandica sp. nov., both in the subgenus Dicryptoscena Enderlein, 1936. The following subgenera are now documented from Sweden: Dasyhelea, Dicryptoscena, Pseudoculicoides Malloch, 1915, Prokempia Kieffer, 1913 and Sebessia Remm, 1979, the two latter subgenera being reported for the first time.
Ziel der vorliegenden Arbeit ist die Vorstellung einer Übersicht über die Moose und Moosgesellschaften der Kalkrasen sowie der angrenzenden Vegetationstypen im Muschelkalkgebiet des unteren Unstruttales in der Umgebung von Zscheiplitz zwischen Laucha und Freyburg/Unstrut. Bedeutungsvoll sind in einem Kalksteinbruch, in verschiedenen Trocken- und Halbtrockenrasen sowie Xerothermgebüschen die epilithischen, photophytischen Assoziationen Orthotricho anomali-Grimmietum pulvinatae, Grimmietum orbicularis, das seltene Grimmietum tergestinae, die sciophytischen Gesellschaften Homomallietum incurvati und die Homalothecium sericeum-Gesellschaft. Auf Kalkböden gedeihen häufig das Tortelletum inclinatae, vereinzelt das Barbuletum convolutae, in den Fugen der Kalkbänke das Weissietum crispatae und Aloinetum rigidae mit Aloina obliquifolia. Auf der Borke lebender Laubgehölze wachsen vereinzelt das Orthotrichetum fallacis, Syntrichio latifoliae-Leskeetum polycarpae, lokal das Ulotetum crispae, Syntrichietum pulvinatae und Orthotrichetum pallentis. Alle Gesellschaften sind durch zahlreiche Vegetationsaufnahmen in 11 Tabellen dargestellt. Insgesamt wurden 21 Moosgesellschaften und 104 Moosarten (7 Lebermoose, 97 Laubmoose) nachgewiesen. Die Diskussion betrifft die bryogeographische Situation in der Umgebung von Zscheiplitz sowie die Lebensformen, Lebensstrategien und Reproduktionsstrategien der Moose und Moosgesellschaften.
Von dreizehn Phytoflagellaten, davon zehn Euglenophyta, die aus der „Hohe Garbe“ im Naturschutzgebiet „Aland-Elbe-Niederung“ beschrieben und dokumentiert werden, sind elf Arten neu für Sachsen-Anhalt. Phacus warszewiczii wird in vorliegender Publikation erstmals nach Funden aus Deutschland abgebildet.
Buchbesprechung
(2017)
Die Autoren setzten mit der Herausgabe ihrer umfangreichen Übersicht über die Florenwerke Deutschlands eine lange Tradition fort, bekanntes Wissen übersichtlich aufzubereiten, um es so komfortabel nutzbar zu machen. Gelegentlich wird es darüber hinaus sicher ein Aha-Erlebnis geben, dass es über dieses oder jenes Gebiet überhaupt schon ein floristisches Werk gibt.
Aktuell bekannte Vorkommen von A. adiantum-nigrum L., A. ceterach L., A. ruta-muraria L., A. scolopendrium L., A. septentrionale (L.) Hoffm., A. trichomanes L. und A. viride W. Huds. im Mitteldeutschen Trockengebiet um Halle werden mitgeteilt. Erstmalig wurden Vorkommen von Asplenium trichomanes auf Unterarten untersucht und die Ergebnisse vorgestellt. Auch der intraspezifische Bastard A. trichomanes nothosubsp. lovisianum S. Jess. wurde nachgewiesen.
Eine bisher nicht erkannte heimische Scharbockskrautart, Ficaria calthifolia Rchb., wurde im Elbetal bei Pretzsch neu für Sachsen-Anhalt nachgewiesen. Da die Art nicht über Mechanismen zur aktiven Fernausbreitung verfügt, sondern räumlich-zeitlich kleine Nischen besiedelt (CSR-Strategie), ist Habitatkontinuität wichtig. In diesem Zusammenhang wird die Bedeutung von historisch altem Grünland diskutiert.
Die Fundortdaten der im Altmarkkreis Salzwedel nachgewiesenen Verwilderungen von Amelanchier alnifolia, A. lamarckii und A. spicata werden mitgeteilt. Angaben zu den Standortverhältnissen, zur Begleitflora und zum Populationsumfang ergänzen die Ausführungen. Außerdem wird auf wesentliche Unterscheidungsmerkmale der drei Arten eingegangen.
Pulmonaria obscura ist die einzige Art des Genus Pulmonaria, die im Raum Salzwedel noch autochthone Vorkommen aufzuweisen hat. Hinzu kommen einige Verwilderungen der auch als Zierpflanze gezogenen P. officinalis s. str. Von beiden Arten werden die aktuellen Nachweisdaten mitgeteilt. Auf die Differenzierung des P. officinalis agg. und die Trennung von weiteren kultivierten Sippen wird eingegangen. Außerdem werden die historischen Aufzeichnungen über Vorkommen von P. angustifolia bei Salzwedel dargestellt. Angaben zur Bedeutung von P. officinalis s. str. in der Volksheilkunde vervollständigen die Ausführungen.
Based on newly collected material from the Kavieng Lagoon Biodiversity Survey, we describe a new species of cone snail, Conus hughmorrisoni sp. nov., from the vicinity of Kavieng, New Ireland, Papua New Guinea. It closely resembles the New Caledonian C. exiguus and the Philippine C. hanshassi, but differs from these species by having more numerous shoulder tubercles, by the shell’s sculpturing and details of the color pattern. We also sequenced a fragment of the mitochondrial COI gene of five specimens collected alive. All possessed very similar sequences (genetic distances < 0.3%), different from all the COI sequences of cone snails available in GenBank (genetic distances > 10%).
The species group effusus of the genus Pyrops Spinola, 1839 is reviewed and the nomenclatural history of the genus Pyrops is briefly summarized. One new species from eastern Borneo, Pyrops synavei sp. nov., is described. P. gunjii (Satô & Nagai, 1994) stat. nov. is proposed as a valid species instead of a subspecies of P. whiteheadi (Distant, 1889). P. maquilinganus (Baker, 1925) is removed from the effusus group and placed back into the candelaria group. P. cyanirostris (Guérin-Méneville, 1845) is removed from the group and not attributed to any of the currently defined species groups. An illustrated key to the species of the group with the addition of P. intricatus (Walker, 1857) and a distribution map are given. The effusus group is restricted to Borneo and adjacent Laut Island and presently contains 4 species: P. effusus (Distant, 1891), P. gunjii (Satô & Nagai, 1994) stat.nov., P. synavei sp. nov. and P. whiteheadi (Distant, 1889). Trophobiosis observations with the gecko Gehyra mutilata (Wiegmann, 1835) (Reptilia: Squamata: Gekkonidae) and two species of cockroaches (Insecta: Blattodea), one Dorylaea sp. and an unidentified species of Pseudophyllodromiinae, are reported and illustrated for P. whiteheadi; observation with a cockroach, Dorylaea sp., is reported for P. intricatus.
New species of Lepechinella, L. norvegica sp. nov. and L. victoriae sp. nov., from the North East Atlantic are described together with the new, closely related genus and species Lepesubchela christinae gen. et sp. nov. Lepechinella arctica Schellenberg, 1926 from north of Spitsbergen and Lepechinella schellenbergi Stephensen, 1944 from Greenland are redescribed. A key to the species of Atlantic and Arctic Lepechinella is provided. Descriptions of taxonomic characters from related species in the Atlantic and Arctic are discussed.
Evolutionary developmental biology (evo-devo) suggests a distinction between modular and systemic variation. In the case of modular change, the conservation of the overall structure helps recognizing affinities, while a single, fast evolving module is likely to produce a bonanza for the taxonomist, while systemic changes produce strongly deviating morphologies that cause problems in tracing homologies. Similarly, changes affecting the whole life cycle are more challenging than those limited to one stage. Developmental modularity is a precondition for heterochrony. Analyzing a matrix of morphological data for paedomorphic taxa requires special care. It is, however, possible to extract phylogenetic signal from heterochronic patterns. The taxonomist should pay attention to the intricacies of the genotype→phenotype map. When using genetic data to infer phylogeny, a comparison of gene sequences is just a first step. To bridge the gap between genes and morphology we should consider the spatial and temporal patterns of gene expression, and their regulation. Minor genetic change can have major phenotypic effects, sometimes suggesting saltational evolution. Evo-devo is also relevant in respect to speciation: changes in developmental schedules are often implicated in the divergence between sympatric morphs, and a developmental modulation of ‘temporal phenotypes’ appears to be responsible for many cases of speciation.
We revised the species of the genus Pristomerus Curtis, 1836 in the Afrotropical Region. Fortynine species are recognized, of which 31 are newly described. The following new species are described: P. afrikaner, P. aka, P. babinga, P. bemba, P. dikidiki, P. herero, P. hutu, P. kagga, P. khoikhoi, P. kuku, P. masai, P. mbaka, P. mbama, P. mboum, P. nzakara, P. protea, P. restio, P. san, P. sara, P. sotho, P. swahili, P. teke, P. tutsi, P. venda, P. wolof, P. xhosa, P. yakoma, P. yangere, P. yoccolo, P. zande and P. zulu spp. nov. New synonyms: P. africator, P. cunctator and P. luteolus are new junior synonyms of P. pallidus. New records: new host records are reported for the widespread P. pallidus; new country-level distribution records are added for P. bullis, P. keyka, P. kelikely and P. pallidus; and reports of Trathala concolor and P. veloma in South Africa are shown to have been erroneous. An illustrated dichotomous key to females is provided; an online Lucid interactive matrix key is also available at www.waspweb.org. Finally, the ecological and geographical correlates of colour patterns exhibited by Pristomerus in the Afrotropical region are discussed.
Two new species of jumping spiders, Thiratoscirtus oberleuthneri (♂) and Th. lamboji (♀), are described from Gabon, one of the least explored areas of the Afrotropics. Both species live in rainforest, at the forest fl oor. They are members of a very poorly known subfamily of salticids, the Thiratoscirtinae.
Four species of Bradysia Winnertz (Diptera, Sciaridae) from the Northern Holarctic are described and illustrated for the first time: Bradysia bigeminata sp. nov. (Finland, Canada), B. falciceps sp. nov. (Finland, Canada), B. oelandica sp. nov. (Sweden) and B. plusiospina sp. nov. (Finland). A few Bradysia species, described previously and now found in Northern Europe, are also redefined and illustrated.
The new ctenid genus Afroneutria is proposed to include five species: Afroneutria velox (Blackwall, 1865) comb. nov. (type species), A. immortalis (Arts, 1912) comb. nov., A. erythrochelis (Simon, 1876) comb. nov., A. quadrimaculata sp. nov. and A. hybrida sp. nov., all collected in central to southeast Africa. Afroneutria species can be distinguished from the remaining Ctenidae by the presence of a synapomorphic laminar projection on the embolus tip. The genus can also be distinguished by the presence of the following set of characters: elongated cup-shaped median apophysis and elongated and laminar embolus on the male palp; large lateral projections on the epigynum and the spermathecae divided into two parts, dorsal and ventral, in the vulva.
The diagnosis of the Formicidae is revised, including five new, unreversed apomorphies, of which one is a unique synapomorphy. The first global male-based key to all subfamilies is provided and illustrated, and all ant subfamilies are diagnosed for males on a global scale for the first time. Three lineages of “basal ants” are assessed in detail: the Amblyoponinae, Leptanillinae, and Martialinae. The males of Martialis heureka (Martialinae) and Apomyrma (Amblyoponinae) are described. The Martialinae and Leptanillinae are diagnosed based on males, and additional diagnostic traits for the male of Amblyoponinae and worker of Martialis are provided. The placement of Scyphodon and Noonilla in the Formicidae and Leptanillinae is confirmed. Morphological characters of the Amblyoponinae, the Leptanillinae, and the Martialinae are contrasted, and potentially homologous apomorphies are signaled.
Two new species of the family Desmodoridae are described from the upper continental slope of New Zealand, Southwest Pacific, and the genera Spirinia, Chromaspirina and Perspiria are revised. Spirinia verecunda sp. nov. is characterised by a short, stout body, cuticle covered in minute, hair-like structures, unispiral amphideal aperture and cryptospiral amphideal fovea, buccal cavity with small dorsal tooth and minute subventral teeth, eight oblong glands surrounding anterior portion of pharynx, large sperm cells, spicules with weak capitulum, and the absence of precloacal supplements. Stygodesmodora confusa sp. nov. is characterised by a relatively short body, spiral amphids with 1.2– 1.4 turns, cephalic setae situated at or slightly posterior to mid-level of amphid, and males with four precloacal supplements consisting of short setae on wide bases. Like other species of the genus, S. confusa sp. nov. is characterised by an annulated head region, but in some specimens the cuticle annulations are restricted to the dorsal and ventral sides of the head. S. confusa sp. nov. shows similarities with species of other desmodorid genera (i.e., Echinodesmodora, Bolbonema), but can be differentiated from them by the presence of an annulated head region and amphideal plates. The genera Spirinia, Chromaspirina and Perspiria have very similar morphologies and differ mainly in the size and structure of the buccal cavity (Spirinia vs Chromaspirina) or the shape of the tail and placement of the amphids relative to the cuticle annulations (Spirinia vs Perspiria); their diagnoses are clarified and some nomenclatural changes are proposed to eliminate overlap in the definitions of these genera.
A new species of Paracrobeles, P. kelsodunensis sp. nov. is described from the Kelso Dunes area, Mojave National Preserve, southern California. Paracrobeles kelsodunensis sp. nov. is particularly characterised by a body length of 469–626 μm in females and 463–569 μm in males; lateral field with four incisures, extending almost to tail terminus; three pairs of asymmetrical lips, separated by U-shaped primary axils with two long guarding processes, each lip usually with four tines along its margin; three long labial probolae, deeply bifurcated, with slender prongs without tines; metastegostom with a strong anteriorly directed dorsal tooth; pharyngeal corpus anteriorly spindle-shaped, posteriorly elongate bulbous with dilated lumen; spermatheca 24–87 μm long; postvulval uterine sac 60–133 μm long; vulva in a sunken area; spicules 33–38 μm long; and male tail with a 5–8 μm long mucro. The generic diagnosis is emended on the basis of recently described species and a key to the species of Paracrobeles is provided.
The osteology of Acrorhinichthys poyatoi gen. et sp. nov., a pycnodontid fish from the marine Cenomanian (Late Cretaceous) of Lebanon, is studied in detail. The new fossil genus belongs to the order Pycnodontiformes, but is less evolved than the Pycnodontidae. It still exhibits a few bony plates (= tesserae) in the gular region, 3 teeth on the premaxilla and 5 teeth on the dentary, and its parietal is devoid of a brush-like process. It shares a few characters with Akromystax, the most primitive taxon within Pycnodontidae, characters lost in the other members of the family.
The new genus Lobofemora gen. nov. is described from Vietnam to accommodate three new species: L. bachmaensis sp. nov. (Bach Ma National Park, central Vietnam), L. bidoupensis sp. nov. (Bidoup-Nui Ba National Park, central Vietnam) and L. scheirei sp. nov., the type species (Cat Tien National Park and Dong Nai Biosphere Reserve, south Vietnam). It is provisionally placed in the tribe Clitumnini Brunner von Wattenwyl, 1893. The genus is the only known Clitumnini which shows tegmina and sometimes alae in the males. Females show conspicuous foliaceous lobes on the median femora. Males and females of all species and the eggs of L. scheirei sp. nov. and L. bidoupensis sp. nov. are described and illustrated. An identification key to the species and a distribution map are provided. The definition of the tribe Clitumnini sensu Hennemann & Conle (2008) is slightly adapted to include the new genus and the tribal placement is discussed. The male of L. scheirei sp. nov. is able to stridulate by rubbing the outer margins of the tegmina against the subcostal and radial veins of the alae.
The genus name Acanthinozodium Denis, 1966 is considered available and valid, with A. spinulosum Denis, 1966 as its type species. The genus is characterized by the presence of ventral rows of long setae on the femora, large anterior median eyes and a large, dorsal, crater-like pit on the cymbium. Zodariellum Andreeva & Tyschenko, 1968 is removed from its synonymy and now only contains its type species Z. surprisum Andreeva & Tyschenko, 1968. Three new Acanthinozodium species are described: A. crateriferum sp. nov. (♂♀) from Ethiopia, A. sahelense sp. nov. (♂♀) from a wide range in the Sahel region and A. quercicola sp. nov. (♂) from Morocco. The genus appears to have a large distribution in and around the Sahara. The possible function of the cymbial pit is discussed.
Two new forest species, Eugenia sapoensis sp. nov. and Eugenia breteleri sp. nov., from Liberia and Gabon respectively, are described and illustrated here. Both are shrubs with comparatively large red fruits. They resemble each other, but E. breteleri differs from E. sapoensis in having twigs with conspicuously peeling bark, 6–8 pairs of main lateral nerves, versus 4–6 pairs, and fruits with a peduncle of 3–5 mm rather than 1– 2 mm long. Eugenia breteleri grows up to 3 m high while E. sapoensis does not grow higher than 1.4 m.
Two new species of Elaphropeza Macquart, 1827 are described from the northeast coast of Bali (Indonesia): Elaphropeza triseta sp. nov. belonging to the ephippiata-group and E. balinensis sp. nov. belonging to the biuncinata-group. A COI Neighbour-Joining tree is given for the Southeast Asian Elaphropeza species showing large genetic distances between the species. The morphological characterisation of the ephippiata-group and the biuncinata-group sensu Shamshev & Grootaert 2007 is confirmed.
The ostracod genus Bennelongia De Deckker & McKenzie, 1981 occurs in Australia and New Zealand. We redescribe B. nimala from the Northern Territory and describe six new species from Western Australia belonging to the B. nimala (five species) and B. triangulata sp. nov. (one species) lineages: B. tirigie sp. nov., B. koendersae sp. nov., B. pinderi sp. nov., B. muggon sp. nov., B. shieli sp. nov. and B. triangulata sp. nov. For six of these seven species, we could construct molecular phylogenies and parsimonious networks based on COI sequences. We tested for specific status and for potential cryptic diversity of clades with Birky’s 4 theta rule. The analyses support the existence of these six species and the absence of cryptic species in these lineages. Bennelongia triangulata sp. nov. is a common species in the turbid claypans of the Murchison/Gascoyne region. Bennelongia nimala itself is thus far known only from the Northern Territory. Bennelongia tirigie sp. nov., B. pinderi sp. nov. and B. muggon sp. nov. occur in the Murchison/Gascoyne region, whereas B. koendersae sp. nov. and B. shieli sp. nov. are described from the Pilbara. With the six new species described here, the genus Bennelongia now comprises 31 nominal species.
The species of the genus Polydictya Guérin-Méneville, 1844 from Sulawesi and adjacent islands are reviewed and three new species are described: P. bantimurung sp. nov. (Sulawesi), P. basirubra sp. nov. (Sulawesi, Wowoni and Buton) and P. pelengana sp. nov. (Peleng). An identification key for the 6 species recorded in the area is given. Habitus, detailed illustrations and a distribution map are provided for all species. The male genitalia of the three new species are illustrated and described, and the male genitalia of P. thanatos Chew Kea Foo, Porion & Audibert, 2010 are figured and described for the first time. The genus Polydictya now contains 24 species.
We report here on recent collections of freshwater crabs from Antsiranana Province, northern Madagascar. The specimens belong to three species, one of which is new to science and is described here. This raises the number of species of freshwater crabs found in Madagascar to 17. All are endemic to the island and all belong to the Afrotropical family Potamonautidae Bott, 1970. The new species, Foza manonae sp. nov., is compared to the other species in this genus, and an updated key is provided. It is distinguished from the other three congeners by characters of the male first gonopod, sternum, carapace, and cheliped. The conservation status of the Malagasy freshwater crab fauna is summarized and discussed in light of the new material reported on here belonging to two other species, Madagapotamon humberti Bott, 1965 and Foza ambohitra Cumberlidge & Meyer, 2009.
In 1796, Thomas Hardwicke travelled through northern India between what is now Fatehgarh in Uttar Pradesh and Srinagar in Uttarakhand. Hardwicke collected and described plants encountered and had many of the plants illustrated from life. He published an account of the journey in 1799 including a list of plant species. I review the names validated in the original paper, and also those published subsequently by Sir James Edward Smith and William Roxburgh based partly or wholly on the material or drawings acquired by Hardwicke on the journey to Srinagar. The large collection of Hardwicke plant drawings now held in the British Library, and a smaller set in the Botany Library of the Natural History Museum, are considered in relation to the application and typification of plant names related to Hardwicke’s botanical exploration in India. The names of seven plant species were validly published in the 1799 paper (Androsace rotundifolia Hardw., Ficus laminosa Hardw., Justicia thyrsiformis Roxb. ex Hardw., Linum trigynum Roxb. ex Hardw., Lonicera quinquelocularis Hardw., Salvia integrifolia Roxb. ex Hardw. and Volkameria bicolor Hardw.), plus one new combination (Echites antidysentericus (L.) Roxb. ex Hardw.). As concluded by Britten more than a century ago, Ficus laminosa is the correct name for the fig variously referred to F. saemocarpa Miq. or F. squamosa Roxb. Smith based Rhododendron arboreum Sm. and Bignonia undulata Sm. on Hardwicke plants. At least a dozen Roxburgh names, including Crataegus integrifolia Roxb., Gardenia tetrasperma Roxb. and Morus serrata Roxb., are based, at least partly, on Hardwicke’s collections. In total, 23 names are lectotypified here and one neotype is designated.
Die am Wochenende beschlossene Verfassungsänderung gibt Chinas Präsident Xi Jinping die Möglichkeit auf Lebenszeit im Amt zu bleiben. Das wird als Zeichen des wachsenden Autoritarismus und Xis zunehmender Macht gewertet. Doch ein genauerer Blick lässt zweifeln: Die Entscheidung ist eher Ausdruck von Zukunftssorgen und Selbstzweifeln der Regierenden in Peking.
Eine 1-1-Korrespondenz zwischen einer Klasse von Leftist-Bäumen und erweiterten t-nären Bäumen
(2006)
Leftist-Bäume sind eine Teilmenge der geordneten Bäume mit der Eigenschaft, daß der [kürzeste] Weg von jedem inneren Knoten zu einem Blatt des Teilbaums mit diesem Knoten als Wurzel immer über den am weitesten links stehenden Sohn dieses Knotens verläuft.
In der vorliegenden Arbeit wird eine 1-1-Korrespondenz zwischen erweiterten t-nären Bäumen und der Klasse der Leftist-Bäumen mit erlaubten Knotengraden 0, t, 2t-1, ... 1+t(t-1) präsentiert. Diese 1-1-Korrespondenz verallgemeinert ein Ergebnis von R. Kemp.
Die vorliegende Arbeit befasst sich damit, wie die spezifische Durchführung eines besonderen psychologischen Laborexperiments in eine allgemeine, kausale Form übersetzt wird. Anstatt dazu formale Kriterien der Validität heranzuziehen, wird ein experimenteller Forschungsprozess ethnographisch begleitet.
Forschungsgegenstand ist ein Verhaltensexperiment aus der allgemeinen Psychologie zur Trainierbarkeit des Arbeitsgedächtnisses. Im Rahmen der Ethnographie werden teilnehmende Beobachtungen, Interviews und Dokumentensammlung kombiniert eingesetzt. Die Auswertung der Materialien erfolgt mithilfe der Situationsanalyse nach Clarke (2012), einer qualitativen Auswertungsmethode im Anschluss an die Grounded Theory.
In dieser Arbeit wird das Verhalten der Versuchsperson ins Zentrum gerückt, das die Messung in Gang setzt und hält und die Entstehung von zahlenförmigen Daten ermöglicht. Dazu wird in Orientierung an neueren Science & Technology Studies eine begriffliche Systematisierung der Experimentalpraxis aus dem empirischen Material herausgearbeitet, mit dem die Konstruktion und Transformation des Verhaltens der Versuchsperson im Verlauf des Datenerhebungs- Auswertungs- und Interpretationsprozesses beschrieben werden kann.
Die Ergebnisse der Ethnographie legen nahe, dass dieses Verhalten der Versuchsperson - korrespondierend zum kausal verfassten Endprodukt des Experiments - von der komplexen Erhebungssituation abhängig und paradoxerweise gleichzeitig unabhängig ist. Damit wird in Anlehnung an Latour (2002) zwischen konstruktivistischen und objektivistischen Positionen vermittelt. Zudem weisen die erforschten Praktiken die epistemische Stellung der Versuchsperson aus. Diese wird im Anschluss an die Terminologie von Rheinberger (2001/ 2006) als Mischform von epistemischem Ding (Neues) und technischem Ding (Bekanntes) bestimmt.
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.
Tumor-associated macrophages, angiogenesis, and tumor cell migration in oral squamous cell carcinoma
(2017)
Objective: To investigate the relationship between tumor-associated macrophages (TAMs), neovascularization, and tumor cell migration in oral squamous cell carcinoma (OSCC) of an African subpopulation.
Materials and Methods: Twenty OSCC paraffin blocks underwent immunohistochemistry to TAM1 (CCR7), TAM2 (CD206), Twist, E-cadherin, N-cadherin, and CD34. The relative percentage of CCR7 + and CD206 + cells to overall immune cell population was calculated for three high power fields and an average was taken. TAM-related microvessel density (MVD) was determined as the mean of the three recorded values. Cases that had no CD34 + vessels adjacent to the TAMs region were regarded as having an MVD score of 0.
Results: Ten cases (50%) expressed greater CCR7 activity than CD206, seven cases (35%) expressed approximately equal activity of CCR7 and CD206, while three cases (15%) expressed greater activity of CD206 than CCR7. Twist expression was strong in some cases with strong N-cadherin and weak E-cadherin, but the expression of Twist was not consistently high in all cases that expressed strong N-cadherin and weak E-cadherin.
Conclusions: TAMs distribution suggested antitumor activity and the potential for tumor metastasis was only partly due to Twist-mediated epithelial–mesenchymal transition.
Androgen receptor deregulation drives bromodomain-mediated chromatin alterations in prostate cancer
(2017)
Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses.
More than 30% of the world's population are anemic with serious economic consequences including reduced work capacity and other obstacles to national welfare and development. Red blood cell transfusion is the mainstay to correct anemia, but it is also 1 of the top 5 overused procedures. Patient blood management (PBM) is a proactive, patient-centered, and multidisciplinary approach to manage anemia, optimize hemostasis, minimize iatrogenic blood loss, and harness tolerance to anemia. Although the World Health Organization has endorsed PBM in 2010, many hospitals still seek guidance with the implementation of PBM in clinical routine. Given the use of proven change management principles, we propose simple, cost-effective measures enabling any hospital to reduce both anemia and red blood cell transfusions in surgical and medical patients. This article provides comprehensive bundles of PBM components encompassing 107 different PBM measures, divided into 6 bundle blocks acting as a working template to develop institutions' individual PBM practices for hospitals beginning a program or trying to improve an already existing program. A stepwise selection of the most feasible measures will facilitate the implementation of PBM. In this manner, PBM represents a new quality and safety standard.
NADPH oxidases of the Nox family are important enzymatic sources of reactive oxygen species (ROS) in the cardiovascular system. Of the 7 members of the Nox family, at least three depend for their activation on specific cytosolic proteins. These are p47phox and its homologue NoxO1 and p67phox and its homologue NoxA1. Also the Rho-GTPase Rac is important but as this protein has many additional functions, it will not be covered here. The Nox1 enzyme is preferentially activated by the combination of NoxO1 with NoxA1, whereas Nox2 gains highest activity with p47phox together with p67phox. As p47phox, different to NoxO1 contains an auto inhibitory region it has to be phosphorylated prior to complex formation. In the cardio-vascular system, all cytosolic Nox proteins are expressed but the evidence for their contribution to ROS production is not well established. Most data have been collected for p47phox, whereas NoxA1 has basically not yet been studied. In this article the specific aspects of cytosolic Nox proteins in the cardiovascular system with respect to Nox activation, their expression and their importance will be reviewed. Finally, it will be discussed whether cytosolic Nox proteins are suitable pharmacological targets to tamper with vascular ROS production.
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.
The abiotic and biotic drivers of rapid diversification in Andean bellflowers (Campanulaceae)
(2016)
The tropical Andes of South America, the world's richest biodiversity hotspot, are home to many rapid radiations. While geological, climatic, and ecological processes collectively explain such radiations, their relative contributions are seldom examined within a single clade. We explore the contribution of these factors by applying a series of diversification models that incorporate mountain building, climate change, and trait evolution to the first dated phylogeny of Andean bellflowers (Campanulaceae: Lobelioideae). Our framework is novel for its direct incorporation of geological data on Andean uplift into a macroevolutionary model. We show that speciation and extinction are differentially influenced by abiotic factors: speciation rates rose concurrently with Andean elevation, while extinction rates decreased during global cooling. Pollination syndrome and fruit type, both biotic traits known to facilitate mutualisms, played an additional role in driving diversification. These abiotic and biotic factors resulted in one of the fastest radiations reported to date: the centropogonids, whose 550 species arose in the last 5 million yr. Our study represents a significant advance in our understanding of plant evolution in Andean cloud forests. It further highlights the power of combining phylogenetic and Earth science models to explore the interplay of geology, climate, and ecology in generating the world's biodiversity.
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: The possible etiologic relevance of occupational factors such as cadmium, cutting oils, diesel fuel and fumes, herbicides, polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls, soot, tar, mineral oil, and solvents to prostate cancer was studied.
Methods: A case-referent study design was used to recruit 192 subjects with histologically confirmed prostate cancer and 210 referents who had prostate cancer histologically excluded either in one of two urologic practices (Hamburg and Frankfurt) or in the urological policlinic of the Frankfurt University. Data were gathered with a self-administered questionnaire and analyzed using logistic regression to control for age, region, and cigarette smoking. A job-exposure matrix was used for assigning exposure. For the calculation of dose-years, the duration of contact with specific substances was weighted by the intensity and probability of exposure according to a job-exposure matrix.
Results: The analysis of dose-years yielded a statistically significant association between occupational exposure to diesel fuel or fumes and prostate cancer (odds ratio 3.7, 95% confidence interval 1.4-9.8, for subjects exposed to more than 25 dose-years in a comparison with subjects never exposed). For the other substances, no statistically significant differences in exposure were found between the cases and referents. When only jobs with a high exposure probability were used to classify the participants as exposed, only exposure to PAH was significantly associated with prostate cancer.
Conclusion: In keeping with results from other studies, this study provides further evidence that exposure to diesel fuel or fumes - possibly mediated through PAH - may be associated with the development of prostate cancer.
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.
Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury
(2018)
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) to be upregulated in renal I/R injury. We here elucidated the functional role of Malat1 in vitro and its potential contribution to kidney injury in vivo. Malat1 was upregulated in kidney biopsies and plasma of patients with AKI, in murine hypoxic kidney tissue as well as in cultured and ex vivo sorted hypoxic endothelial cells and tubular epithelial cells. Malat1 was transcriptionally activated by hypoxia-inducible factor 1-α. In vitro, Malat1 inhibition reduced proliferation and the number of endothelial cells in the S-phase of the cell cycle. In vivo, Malat1 knockout and wildtype mice showed similar degrees of outer medullary tubular epithelial injury, proliferation, capillary rarefaction, inflammation and fibrosis, survival and kidney function. Small-RNA sequencing and whole genome expression analysis revealed only minor changes between ischemic Malat1 knockout and wildtype mice. Contrary to previous studies, which suggested a prominent role of Malat1 in the induction of disease, we did not confirm an in vivo role of Malat1 concerning renal I/R-injury.
Background: In this study we evaluated the interactions of human adipose tissue-derived stem cells (ADSCs) and different human breast cancer cell lines (BRCAs) with regard to the safety of cell-assisted lipotransfers for breast reconstruction and a thereby unintended co-localization of ADSCs and BRCAs.
Methods: ADSCs were co-cultured with five different human BRCAs (MCF-7, MDA-MB-231, SK-BR-3, ZR-75-30, and EVSA-T) and primary BRCAs from one patient in a transwell system, and cell-cell-interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real-time polymerase chain reaction (PCR) of more than 300 tumor-associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPs). Results of co-culture were compared to those of the respective monoculture.
Results: Quantitative real-time PCR revealed remarkable changes in the expression of multiple tumor-associated genes in co-culture compared to monocultures of both ADSCs and BRCAs. Concomitantly, the concentration of several tumor-associated proteins, such as cytokines and MMPs, were strongly increased in co-culture. Furthermore, exclusively in co-culture with ADSCs, the different BRCAs were exposed to several important tumor-modulating proteins, such as CCL2, HGF, or interleukins.
Co-culture did not significantly affect cellular proliferation of either ADSCs or BRCAs (p > 0.05). The migration of MCF-7 and MDA-MB-231 BRCAs was significantly increased in co-culture with ADSCs by a mean of 11% and 23%, respectively (p = 0.04 and 0.012), as well as that of ADSCs in co-culture with MDA-MB-231, ZR-75-30, and EVSA-T (+11–15%, p = 0.035–0.045). Co-culture with MDA-MB-231, SK-BR-3, and EVSA-T BRCAs significantly increased the invasive behavior of ADSCs by a mean of 24–41% (p = 0.014–0.039). There were no significant differences in the in vitro invasive properties of BRCAs in co-culture compared to monoculture. An in vitro angiogenesis assay revealed an increased tube formation of conditioned media from co-cultured BRCAs and ADSCs compared to the respective monocultures.
Conclusion: This study further elucidates the possible interactions of primary human ADSCs with human BRCAs, pointing towards a potential increased oncological risk which should not be neglected when considering a clinical use of cell-assisted lipoaspirates in breast reconstruction.
Background: Denosumab treatment for up to 8 years in the FREEDOM study and Extension was associated with low fracture incidence. It was not clear whether subjects who discontinued during the study conduct had a higher risk of fracture than those who remained enrolled, thereby underestimating the true fracture risk for the entire trial cohort. Thus, we explored the influence of early withdrawals on nonvertebral fracture incidence during the Extension study.
Methods: To understand the potential effect of depletion of susceptible subjects on fracture incidence, we first evaluated subject characteristics in patients who were enrolled in the Extension vs those who were not. We subsequently employed a Kaplan-Meier multiple imputation (KMMI) approach to consider subjects who discontinued as if they remained enrolled with a 0%, 20%, 50%, and 100% increase in fracture risk compared with participants remaining on study.
Results: Extension enrollees were generally similar to nonparticipants in median age (71.9 and 73.1 years, respectively), mean total hip bone mineral density T-score (–1.9 and –2.0, respectively), and probability of fracture risk by Fracture Risk Assessment Tool (FRAX®) at FREEDOM baseline (16.9% and 17.7% for major osteoporotic fracture and 6.7% and 7.4% for hip fracture, respectively). When we assumed a doubled fracture risk (100% increase) after discontinuation in KMMI analyses, nonvertebral fracture rate estimates were only marginally higher than the observed rates for both the crossover group (10.32% vs 9.16%, respectively) and the long-term group (7.63% vs 6.63%, respectively).
Conclusion: The observation of continued denosumab efficacy over 8 years of treatment was robust and does not seem to be explained by depletion of susceptible subjects.
Trial registration: ClincalTrials.gov registration number NCT00523341; registered August 30, 2007
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent lymphoma, but can transform into diffuse large B cell lymphoma (DLBCL), showing a more aggressive clinical behavior. Little is known about these cases on the molecular level. Therefore, the aim of the present study was to characterize DLBCL transformed from NLPHL (LP-DLBCL) by gene expression profiling (GEP). GEP revealed an inflammatory signature pinpointing to a specific host response. In a coculture model resembling this host response, DEV tumor cells showed an impaired growth behavior. Mechanisms involved in the reduced tumor cell proliferation included a downregulation of MYC and its target genes. Lack of MYC expression was also confirmed in 12/16 LP-DLBCL by immunohistochemistry. Furthermore, CD274/PD-L1 was upregulated in DEV tumor cells after coculture with T cells or monocytes and its expression was validated in 12/19 cases of LP-DLBCL. Thereby, our data provide new insights into the pathogenesis of LP-DLBCL and an explanation for the relatively low tumor cell content. Moreover, the findings suggest that treatment of these patients with immune checkpoint inhibitors may enhance an already ongoing host response in these patients.
Purpose: Advanced Ewing sarcomas have poor prognosis. They are defined by early relapse (<24 months after diagnosis) and/or by metastasis to multiple bones or bone marrow (BM). We analyzed risk factors, toxicity and survival in advanced Ewing sarcoma patients treated with the MetaEICESS vs. EICESS92 protocols.
Design: Of 44 patients, 18 patients were enrolled into two subsequent MetaEICESS protocols between 1992 and 2014, and compared to outcomes of 26 advanced Ewing sarcoma patients treated with EICESS 1992 between 1992 and 1996. MetaEICESS 1992 consisted of induction chemotherapy, whole body imaging directed radiotherapy to the primary tumor and metastases, tandem high-dose chemotherapy and autologous rescue. In MetaEICESS 2007 this treatment was complemented by allogeneic stem cell transplantation. EICESS 1992 comprised induction chemotherapy, local therapy to the primary tumor only followed by consolidation chemotherapy.
Results: In MetaEICESS 8/18 patients survived in complete remission vs. 2/26 in EICESS 1992 (p<0.05). Survival did not differ between MetaEICESS 2007 and MetaEICESS 1992. Three MetaEICESS patients died of complications, all in MetaEICESS 1992. After exclusion of patients succumbing to treatment related complications (n=3), 7/10 patients survived without BM involvement, in contrast to 0/5 patients with BM involvement. This was confirmed in a multivariate analysis. There was no correlation between BM involvement and the number of metastases at diagnosis.
Conclusion: The MetaEICESS protocols yield long-term disease-free survival in patients with advanced Ewing sarcoma. Allogeneic stem cell transplantation was not associated with increased death of complications. Bone marrow involvement is a risk factor distinct from multiple bone metastases.
Apoptosis is deregulated in most, if not all, cancers, including hematological malignancies. Smac mimetics that antagonize Inhibitor of Apoptosis (IAP) proteins have so far largely been investigated in acute myeloid leukemia (AML) cell lines; however, little is yet known on the therapeutic potential of Smac mimetics in primary AML samples. In this study, we therefore investigated the antileukemic activity of the Smac mimetic BV6 in diagnostic samples of 67 adult AML patients and correlated the response to clinical, cytogenetic and molecular markers and gene expression profiles. Treatment with cytarabine (ara-C) was used as a standard chemotherapeutic agent. Interestingly, about half (51%) of primary AML samples are sensitive to BV6 and 21% intermediate responsive, while 28% are resistant. Notably, 69% of ara-C-resistant samples show a good to fair response to BV6. Furthermore, combination treatment with ara-C and BV6 exerts additive effects in most samples. Whole-genome gene expression profiling identifies cell death, TNFR1 and NF-κB signaling among the top pathways that are activated by BV6 in BV6-sensitive, but not in BV6-resistant cases. Furthermore, sensitivity of primary AML blasts to BV6 correlates with significantly elevated expression levels of TNF and lower levels of XIAP in diagnostic samples, as well as with NPM1 mutation. In a large set of primary AML samples, these data provide novel insights into factors regulating Smac mimetic response in AML and have important implications for the development of Smac mimetic-based therapies and related diagnostics in AML.
The use of phylogenies in ecology is increasingly common and has broadened our understanding of biological diversity. Ecological sub-disciplines, particularly conservation, community ecology and macroecology, all recognize the value of evolutionary relationships but the resulting development of phylogenetic approaches has led to a proliferation of phylogenetic diversity metrics. The use of many metrics across the sub-disciplines hampers potential meta-analyses, syntheses, and generalizations of existing results. Further, there is no guide for selecting the appropriate metric for a given question, and different metrics are frequently used to address similar questions. To improve the choice, application, and interpretation of phylo-diversity metrics, we organize existing metrics by expanding on a unifying framework for phylogenetic information.
Generally, questions about phylogenetic relationships within or between assemblages tend to ask three types of question: how much; how different; or how regular? We show that these questions reflect three dimensions of a phylogenetic tree: richness, divergence, and regularity. We classify 70 existing phylo-diversity metrics based on their mathematical form within these three dimensions and identify ‘anchor’ representatives: for α-diversity metrics these are PD (Faith's phylogenetic diversity), MPD (mean pairwise distance), and VPD (variation of pairwise distances). By analysing mathematical formulae and using simulations, we use this framework to identify metrics that mix dimensions, and we provide a guide to choosing and using the most appropriate metrics. We show that metric choice requires connecting the research question with the correct dimension of the framework and that there are logical approaches to selecting and interpreting metrics. The guide outlined herein will help researchers navigate the current jungle of indices.
The multifunctional protein p21Cip1/CDKN1A (p21) is an important and universal Cdk-interacting protein. Recently, we have reported that p21 is involved in the regulation of the mitotic kinase Cdk1/cyclin B1 and critical for successful mitosis and cytokinesis. In the present work we show that S130 of p21 is phosphorylated by Cdk1/cyclin B1 during mitosis, which reduces p21’s stability and binding affinity to Cdk1/cyclin B1. Interfering with this phosphorylation results in extended mitotic duration and defective chromosome segregation, indicating that this regulation ensures proper mitotic progression. Given that p53, the major transcriptional activator of p21, is the most frequently mutated gene in human cancer and that deregulated Cdk1 associates with the development of different types of cancer, this work provides new insight into the understanding of how deregulated p21 contributes to chromosomal instability and oncogenesis.
Nichts anderes geschieht dem Bauernsohn Helmbrecht, als dass er sich die heldenhaften Erzählungen und kunstvollen Lebweisen des Adels über den Kopf respektive über die Weltwahrnehmung streift. So erschafft er sich ein halb-holographisches 'Second Life', in dem er sich wider seinen Stand die Ehrhaftigkeit der adligen Aventürewelten angedeihen lässt. Die Holo-Haube (als 'textura' wie Text) 'infiziert' sein Denken, belegt mit ihren Abbildern (so könnte man es mittelalterlich verstehen) die vier in seinem Kopf gelagerten Kammern der 'imaginatio', 'memoria', 'ratio' und des 'intellectus' mit dem hofliterarischen Wertsystem.
Die Schuluniform ist bis heute umstritten. Befürworter betonen, sie überbrücke soziale Unterschiede, nivelliere den Konkurrenzdruck durch die Fixierung auf teure Markenartikel und fördere so den Zusammenhalt der Kinder untereinander. Kritiker hingegen sehen in der Schuluniform ein Instrument der Disziplinierung und folglich das Bestreben, Kindern ihre Individualität zu nehmen. Im Russischen Imperium wurde die einheitliche Schuluniform für Gymnasiasten - russisch: 'mundir' (von 'Montur' bzw. Uniformrock) - 1834 eingeführt, im Zuge der Kodifizierung von Ziviluniformen für Staatsbeamte. Eine entsprechende Verfügung für Mädchen folgte erst Ende des 19. Jahrhunderts.
"Wer trägt heute noch Trainingsanzüge in der Öffentlichkeit?", titelt die "Stilkritik" der Süddeutschen Zeitung im Mai 2010. Sportler jedenfalls nicht. Der aktuelle Bundestrainer der deutschen Fußballnationalmannschaft kleidet sich - "modisch top", "Stilikone" - selbst im Stadion in Designer-Anzüge. Dabei waren Sportler ursprünglich die einzige Zielgruppe des Ende der 1920er Jahre in den USA erfundenen 'tracksuit'. Die Kombination aus locker sitzender Hose mit Gummizug und Beinbündchen sowie Blouson mit Reißverschluss oder Sweatshirt sollte sie vor und nach ihren Aktivitäten wärmen. Ein Einsatz von Trainingsanzügen außerhalb des Sports war lange Zeit undenkbar. Die Modifizierung des Trainingsanzugs begann erst fünf Jahrzehnte nach seiner Erfindung.
Im Weltall existieren hunderte sehr helle Objekte, die eine hohe konstante Leuchtkraft im Wellenlängenbereich von Gammastrahlung besitzen. Die konstante Leuchtkraft mancher dieser Objekte wird in regelmäßigen Abständen von starken Ausbrüchen, den sogenannten X-Ray-Bursts, unterbrochen. Hauptenergiequelle dieser X-RayBursts ist der „rapid-proton-capture“-Prozess (rp-Prozess). Dieser zeichnet sich durch eine Abfolge von (p,γ)-Reaktionen und β+-Zerfällen aus, die die charakteristischen Lichtkurven produzieren. Für viele am Prozess beteiligte Reaktionen ist der Q-Wert sehr klein, wodurch die Rate der einzelnen Reaktionen von den resonanten Einfängen in die ungebundenen Zustände dominiert wird. Die Unsicherheiten in der Beschreibung der Lichtkurve sind derzeit aufgrund fehlender kernphysikalischer Informationen von vielen am Prozess beteiligten Isotopen sehr groß. Sensitivitätsstudien zeigen, dass dabei die Unsicherheiten der 23Al(p,γ)24Si-Reaktion eine der größten Auswirkungen auf die Lichtkurve hat. Diese werden durch ungenaue und widersprüchliche Informationen zu den ungebundenen Zuständen im kurzlebigen 24Si hervorgerufen.
Um Informationen über die Kernstruktur von 24Si zu erhalten, wurde am National Superconducting Cyclotron Laboratory (NSCL), Michigan, USA, die 23Al(d,n)24Si Transferreaktion untersucht. Der in dieser Form erstmals umgesetzte Versuchsaufbau bestand aus einem Gammadetektor zur Messung der Übergangsenergien des produzierten 24Si, einem Neutronendetektor zur Messung der Winkelverteilung der emittierten Neutronen und einem Massensprektrometer zur Identifikation des produzierten Isotops. Mit diesem Aufbau, der eine Detektion der kompletten Kinematik der (d,nγ)-Reaktion ermöglichte, konnten folgende Erkentnisse gewonnen werden:
Aus der Energie der nachgewiesenen Gammas konnten die Übergänge zwischen den Kernniveaus von 24Si bestimmt und daraus die Energien der einzelnen Zustände ermittelt werden. Dabei konnte neben dem bereits bekannten gebundenen 2+-Zustand (in dieser Arbeit gemessen bei 1874 ± 2,9keV) und dem ungebundenen 2+-Zustand (3448,8 ± 4,6keV), erstmals ein weiterer ungebundener (4+,0+)-Zustand bei 3470,6 ± 6,2 keV beobachtet werden. Zusätzlich konnte die Diskrepanz, die bezüglich der Energie des ungebundenen 2+-Zustands aufgrund früherer Messungen bestand, beseitigt und die Energieunsicherheit reduziert werden.
Aus der Anzahl der nachgewiesenen Gammas konnten ebenfalls die (d,n)-Wirkungsquerschnitte in die einzelnen Zustände von 24Si bestimmt werden. Unter Verwendung der Ergebnisse von DWBA-Rechnungen konnte mithilfe dieser die spektroskopischen Faktoren berechnet werden. Für die angeregten Zustände musste dabei zwischen verschiedenen Drehimpulsüberträgen unterschieden werden. Mittels der Winkelverteilung der nachgewiesenen Neutronen konnte gezeigt werden, dass die Gewichtung anhand der theoretischen spektroskopischen Faktoren zur Berechnung der Anteile des jeweiligen Drehimpulsübertrags am gesamten Wirkungsquerschnitt für den entsprechenden Zustand gute Ergebnisse liefert. Für eine quantitative Bestimmung der spektroskopischen Faktoren der Zustände anhand der Neutronenwinkelverteilungen in 24Si war allerdings die Statistik zu gering. Für den Fall der deutlich häufiger beobachteten 22Mg(d,n)23Al-Reaktion konnte hingegen ein spektroskopischer Faktor für den 23Al-Grundzustand von 0,29 ± 0,04 bestimmt werden. Abschließend wurden die Auswirkungen der gewonnenen Erkenntnisse zur Kernstruktur von 24Si auf die Rate der 23Al(p,γ)-Reaktion untersucht. Dabei konnte aufgrund der besseren Energiebestimmung zum einen die Diskrepanz zwischen den Raten die auf Grundlage der beiden früheren Untersuchungen berechnet wurden und bis zu einem Faktor von 20 voneinander abweichen, beseitigt werden. Zum anderen konnte aufgrund der kleineren Unsicherheit in der Energiebestimmung der Fehlerbereich der Rate verkleinert werden. Die Untersuchungen zeigen, dass die Unsicherheit in der neuen Rate von der Ungenauigkeit der Massenbestimmung der beiden beteiligten Isotope und damit dem Q-Wert der Reaktion dominiert wird. Durch eine bessere Bestimmung des Q-Werts könnte die Unsicherheit in der Rate aufgrund der neuen experimentellen Ergebnisse auf ein Zehntel gesenkt werden.
Der Pelz des Hermelins ist im Sommer braun und im Winter weiß. Das ist ein schönes Phänomen für sich, zumal das Weiß von einer Reinheit ist, die sich im Tierreich selten findet. Die Reinheit ihres weißen Fells wurde vielen Hermelinen zum Verhängnis: Sie endeten als Stück in einem adligen Mantel, ihr Weiß noch unterstrichen durch die schwarze Schwanzspitze, die mitverarbeitet wurde. Das reine Weiß des Winterpelzes machte das Hermelin auch zu einer brauchbaren Projektionsfläche des Volksglaubens. Als Symbol der Keuschheit und Reinheit erscheint es schon im antiken Aberglauben: Um sein Fell nicht zu beflecken, empfange das Hermelin durchs Ohr und gebäre durch den Mund - oder umgekehrt, wie der 'Physiologus' behauptete. Auch galt es als ein besonders kultiviertes Tier, weil es sich eher von einem Jäger fangen lasse, als durch den Kot zu gehen, sein reines Weiß also höher schätze als Freiheit und Leben. Sein Fellwechsel machte das Tier darüber hinaus zu einem beliebten Objekt für Zauber und Gegenzauber, Wetterorakel und Verwandlungssagen.
Handschuhe sind Bindungswesen. Sie sind zunächst einmal genuin dual, denn sie kommen immer im Paar. Da ein einzelner Handschuh aber viel leichter verloren geht als etwa ein einzelner Schuh, ist die Welt trotzdem voll von einsamen Handschuhen, besonders im Winter. Sie liegen auf Bürgersteigen, Parkbänken oder in Treppenhäusern und geben ein trauriges Bild ab. Der eine ist nichts ohne den anderen. Vielmehr: Er ist zu nichts nutze.
Das Leder des Schuhs
(2015)
Schuhe - schwere, wetterfeste Stiefel ebenso wie luftige, filigrane Sandalen - wurden lange Zeit aus Leder gefertigt. Robuster und langlebiger als Leinen, Seide oder Bast, aber wesentlich anschmiegsamer als das Holz rustikaler Pantinen, war Leder ein geradezu ideales Material für den Schutz der Füße vor den Widrigkeiten der Straße, vor Steinen, Schmutz, Staub, Kälte und sogar Nässe. Seine Eigenschaften lassen das Leder des Schuhs zugleich zu einem unheimlichen Material werden, speichert es doch Informationen über seinen Gebrauch und kommuniziert damit Gewohnheiten und Präferenzen seiner TrägerInnen.
Dysfunction of the NO/sGC/cGMP signaling pathway has been implicated in the pathogenesis of pulmonary hypertension (PH). Therefore, agents stimulating cGMP synthesis via sGC are important therapeutic options for treatment of PH patients. An unwanted effect of this novel class of drugs is their systemic hypotensive effect. We tested the hypothesis that aerosolized intra-tracheal delivery of the sGC stimulator BAY41-8543 could diminish its systemic vasodilating effect.
Pharmacodynamics and -kinetics of BAY41-8543 after single intra-tracheal delivery was tested in healthy rats. Four weeks after a single injection of monocrotaline (MCT, 60 mg/kg s.c.), rats were randomized to a two-week treatment with either placebo, BAY 41-8543 (10 mg/kg per os (PO)) or intra-tracheal (IT) instillation (3 mg/kg or 1 mg/kg).
Circulating concentrations of the drug 10 mg/kg PO and 3 mg/kg IT were comparable. BAY 41-8543 was detected in the lung tissue and broncho-alveolar fluid after IT delivery at higher concentrations than after PO administration. Systemic arterial pressure transiently decreased after oral BAY 41-8543 and was unaffected by intratracheal instillation of the drug. PO 10 mg/kg and IT 3 mg/kg regimens partially reversed pulmonary hypertension and improved heart function in MCT-injected rats. Minor efficacy was noted in rats treated IT with 1 mg/kg. The degree of pulmonary vascular remodeling was largely reversed in all treatment groups.
Intratracheal administration of BAY 41-8543 reverses PAH and vascular structural remodeling in MCT-treated rats. Local lung delivery is not associated with systemic blood pressure lowering and represents thus a further development of PH treatment with sGC stimulators.
T lymphocytes against tumor-specific mutated neoantigens can induce tumor regression. Also, the size of the immunogenic cancer mutanome is supposed to correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied the susceptibility of tumor cell lines from lymph node metastases occurring in a melanoma patient over several years towards blood-derived, neoantigen-specific CD8+ T cells. In contrast to a cell line established during early stage III disease, all cell lines generated at later time points from stage IV metastases exhibited partial or complete loss of HLA class I expression. Whole exome and transcriptome sequencing of the four tumor lines and a germline control were applied to identify expressed somatic single nucleotide substitutions (SNS), insertions and deletions (indels). Candidate peptides encoded by these variants and predicted to bind to the patient’s HLA class I alleles were synthesized and tested for recognition by autologous mixed lymphocyte-tumor cell cultures (MLTCs). Peptides from four mutated proteins, HERPUD1G161S, INSIG1S238F, MMS22LS437F and PRDM10S1050F, were recognized by MLTC responders and MLTC-derived T cell clones restricted by HLA-A*24:02 or HLA-B*15:01. Intracellular peptide processing was verified with transfectants. All four neoantigens could only be targeted on the cell line generated during early stage III disease. HLA loss variants of any kind were uniformly resistant. These findings corroborate that, although neoantigens represent attractive therapeutic targets, they also contribute to the process of cancer immunoediting as a serious limitation to specific T cell immunotherapy.
Der Mantel des Schweigens
(2015)
The major vault protein (MVP) is the predominant constituent of ubiquitous, evolutionarily conserved large cytoplasmic ribonucleoprotein particles of unknown function. Vaults are multimeric protein complexes with several copies of an untranslated RNA. Double labeling employing laser-assisted confocal microscopy and indirect immunofluorescence demonstrates partial colocalization of vaults with cytoskeletal elements in Chinese hamster ovary (CHO) and nerve growth factor (NGF)-treated neuronlike PC12 cells. Transfection of CHO and PC12 cells with a cDNA encoding the rat major vault protein containing a vesicular stomatitis virus glycoprotein epitope tag demonstrates that the recombinant protein is sorted into vault particles and targeted like endogenous MVPs. In neuritic extensions of differentiated PC12 cells, there is an almost complete overlap of the distribution of microtubules and vaults. A pronounced colocalization of vaults with filamentous actin can be seen in the tips of neurites. Moreover, in NGF-treated PC12 cells the location of vaults partially coincides with vesicular markers. Within the terminal tips of neurites vaults are located near secretory organelles. Our observations suggest that the vault particles are transported along cytoskeletal-based cellular tracks.
Der Mantel des Propheten
(2015)
In der Bibel, auf die sich die westlichen Religionen Judentum, Christentum und Islam auf jeweils unterschiedliche Weise beziehen, erscheint besonders eine Figur als mit besonderer Kleidermacht begabt: der Prophet Elijahu, der einen sprechenden Namen trägt, 'Mein Gott ist Jahu', wobei der Gottesname hier eine andere Form für das Tetragrammaton ist. Auf Hebräisch heißt dieser Prophet 'Elija', auf Arabisch 'Ilias', Christen ist er als 'Elia(s)' bekannt. Unter diesem Namen soll im Folgenden von ihm die Rede sein. Die Theophanie ist in den biblischen Erzählungen des Propheten der erste von insgesamt vier Fällen, in denen sein Mantel eine wichtige Rolle spielt.
Impact of Polo-like kinase 1 inhibitors on human adipose tissue-derived mesenchymal stem cells
(2016)
Polo-like kinase 1 (Plk1) has been established as one of the most promising targets for molecular anticancer intervention. In fact, various Plk1 inhibitors have been identified and characterized. While the data derived from the bench are prospective, the clinical outcomes are less encouraging by showing modest efficacy. One of the explanations for this discrepancy could be unintendedly targeting of non-malignant cells by Plk1 inhibitors. In this work, we have addressed the effect of Plk1 inhibition in adipose tissue-derived mesenchymal stem cells (ASCs). We show that both visceral and subcutaneous ASCs display monopolar spindles, reduced viability and strong apoptosis induction upon treatment with BI 2536 and BI 6727, the Plk1 kinase domain inhibitors, and with Poloxin, the regulatory Polo-box domain inhibitor. While Poloxin triggers quickly apoptosis, BI 2536 and BI 6727 result in mitotic arrest in ASCs. Importantly, survived ASCs exhibit DNA damage and a pronounced senescent phenotype. In addition, Plk1 inhibition impairs ASCs’ motility and homing ability. These results show that Plk1 inhibitors target slowly proliferating ASCs, an important population of anti-inflammation and immune modulation. The toxic effects on primary cells like ASCs could be partially responsible for the reported moderate antitumor activity in patients treated with Plk1 inhibitors.
Chanel - metaphysisch
(2015)
Objectives: Investigate the effectiveness of a complex intervention aimed at improving the appropriateness of medication in older patients with multimorbidity in general practice.
Design: Pragmatic, cluster randomised controlled trial with general practice as unit of randomisation.
Setting: 72 general practices in Hesse, Germany.
Participants: 505 randomly sampled, cognitively intact patients (≥60 years, ≥3 chronic conditions under pharmacological treatment, ≥5 long-term drug prescriptions with systemic effects); 465 patients and 71 practices completed the study.
Interventions: Intervention group (IG): The healthcare assistant conducted a checklist-based interview with patients on medication-related problems and reconciled their medications. Assisted by a computerised decision support system, the general practitioner optimised medication, discussed it with patients and adjusted it accordingly. The control group (CG) continued with usual care.
Outcome measures: The primary outcome was a modified Medication Appropriateness Index (MAI, excluding item 10 on cost-effectiveness), assessed in blinded medication reviews and calculated as the difference between baseline and after 6 months; secondary outcomes after 6 and 9 months’ follow-up: quality of life, functioning, medication adherence, and so on.
Results: At baseline, a high proportion of patients had appropriate to mildly inappropriate prescriptions (MAI 0–5 points: n=350 patients). Randomisation revealed balanced groups (IG: 36 practices/252 patients; CG: 36/253). Intervention had no significant effect on primary outcome: mean MAI sum scores decreased by 0.3 points in IG and 0.8 points in CG, resulting in a non-significant adjusted mean difference of 0.7 (95% CI −0.2 to 1.6) points in favour of CG. Secondary outcomes showed non-significant changes (quality of life slightly improved in IG but continued to decline in CG) or remained stable (functioning, medication adherence).
Conclusions: The intervention had no significant effects. Many patients already received appropriate prescriptions and enjoyed good quality of life and functional status. We can therefore conclude that in our study, there was not enough scope for improvement.
Trial registration number: ISRCTN99526053. NCT01171339; Results.
Although the mechanistic target of rapamycin (mTOR) inhibitor, everolimus, has improved the outcome of patients with renal cell carcinoma (RCC), improvement is temporary due to the development of drug resistance. Since many patients encountering resistance turn to alternative/complementary treatment options, an investigation was initiated to evaluate whether the natural compound, sulforaphane (SFN), influences growth and invasive activity of everolimus-resistant (RCCres) compared to everolimus-sensitive (RCCpar) RCC cell lines in vitro. RCC cells were exposed to different concentrations of SFN and cell growth, cell proliferation, apoptosis, cell cycle, cell cycle regulating proteins, the mTOR-akt signaling axis, adhesion to human vascular endothelium and immobilized collagen, chemotactic activity, and influence on surface integrin receptor expression were investigated. SFN caused a significant reduction in both RCCres and RCCpar cell growth and proliferation, which correlated with an elevation in G2/M- and S-phase cells. SFN induced a marked decrease in the cell cycle activating proteins cdk1 and cyclin B and siRNA knock-down of cdk1 and cyclin B resulted in significantly diminished RCC cell growth. SFN also modulated adhesion and chemotaxis, which was associated with reduced expression of the integrin subtypes α5, α6, and β4. Distinct differences were seen in RCCres adhesion and chemotaxis (diminished by SFN) and RCCpar adhesion (enhanced by SFN) and chemotaxis (not influenced by SFN). Functional blocking of integrin subtypes demonstrated divergent action on RCC binding and invasion, depending on RCC cell sensitivity to everolimus. Therefore, SFN administration could hold potential for treating RCC patients with established resistance towards everolimus.
We explore a combinatorial framework which efficiently quantifies the asymmetries between minima and maxima in local fluctuations of time series. We first showcase its performance by applying it to a battery of synthetic cases. We find rigorous results on some canonical dynamical models (stochastic processes with and without correlations, chaotic processes) complemented by extensive numerical simulations for a range of processes which indicate that the methodology correctly distinguishes different complex dynamics and outperforms state of the art metrics in several cases. Subsequently, we apply this methodology to real-world problems emerging across several disciplines including cases in neurobiology, finance and climate science. We conclude that differences between the statistics of local maxima and local minima in time series are highly informative of the complex underlying dynamics and a graph-theoretic extraction procedure allows to use these features for statistical learning purposes.
Es sind weit mehr als jene sprichwörtlichen Siebensachen, die ein ghanaischer Oberschüler beim Eintritt in eines der zahlreichen Internate des Landes mitzubringen hat. Ein zuvor ausgehändigter "prospectus" verzeichnet so nützliche und notwendige Dinge wie Bügeleisen, Wassereimer, Buschmesser, Scheuerbürste, Schaumstoffmatratze und einiges andere mehr. Was die Bekleidung betrifft, so findet sich auf dieser Liste neben "white trousers for church service" und "khaki trousers" auch ein ausdrücklich mit dem Zusatz "school supply" versehenes "pair of khaki shorts": Bis heute identifizieren sich "school boys" in Ghana durch sowohl den klimatischen Bedingungen als auch einer impliziten sozialen Hierarchie genügende kurze Hosen, für die sich im informellen Idiom die Bezeichnung 'school knickers' durchgesetzt hat.
The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose. Pharmacological inhibition of 20-HETE formation and blockade of FFAR1 in islets inhibits GSIS. In islets from type-2 diabetic humans and mice, glucose-stimulated 20-HETE formation and 20-HETE-dependent stimulation of GSIS are strongly reduced. We show that 20-HETE is an FFAR1 agonist, which functions as an autocrine positive feed-forward regulator of GSIS, and that a reduced glucose-induced 20-HETE formation contributes to inefficient GSIS in type-2 diabetes.
Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications, and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischaemia, putting it in the context of the human ‘diseasome’. Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischaemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischaemia/reperfusion injury and ischaemic heart failure in the post-genomic era.
EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50–69 years taking up the invitation while the probability of false-positive needle biopsy is <1 % per round and overdiagnosis is only 1–10 % for a 20-year screening. Mortality reduction was also observed for the age groups 40–49 years and 70–74 years, although with “limited evidence”. Thus, we firstly recommend biennial screening mammography for average-risk women aged 50–69 years; extension up to 73 or 75 years, biennially, is a second priority, from 40–45 to 49 years, annually, a third priority. Screening with thermography or other optical tools as alternatives to mammography is discouraged. Preference should be given to population screening programmes on a territorial basis, with double reading. Adoption of digital mammography (not film-screen or phosphor-plate computer radiography) is a priority, which also improves sensitivity in dense breasts. Radiologists qualified as screening readers should be involved in programmes. Digital breast tomosynthesis is also set to become “routine mammography” in the screening setting in the next future. Dedicated pathways for high-risk women offering breast MRI according to national or international guidelines and recommendations are encouraged.
Während einer Recherchereise nach Moskau im Sommer 2014 fiel mir auf, dass in den Transferbereichen der U-Bahn-Stationen unverblümt und in riesigen Mengen Damenunterwäsche ausgestellt und verkauft wurde. Wer in aller Welt kauft zwischendurch und im öffentlichen Gedränge Unterwäsche? Und warum wird Unterwäsche gerade in einer solchen Umgebung gehandelt, im kalten Neonlicht des Moskauer Untergrunds? Auch meine russischen Kollegen wussten keine Antwort auf diese Fragen. Vielleicht hilft ein Blick in die russische Geschichte, um das Rätsel der Unterwäsche zu lösen.