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The genus Profundiconus Kuroda, 1956 is reviewed. The morphological characters of the shell, radular tooth and internal anatomy of species in Profundiconus are discussed. In particular, we studied Profundiconus material collected by dredging in deep water during different scientific campaigns carried out in the Solomon Islands, Madagascar, Papua New Guinea and New Caledonia. We reconstructed a phylogeny of 55 individuals based on partial mitochondrial cox1 gene sequences. The phylogeny shows several clades containing individuals that do not match any of the known species of Profundiconus based on their shell and radular morphologies, and are introduced here as five new species: Profundiconus maribelae sp. nov. from the Solomon Islands; P. virginiae sp. nov. from Chesterfield Plateau (New Caledonia); P. barazeri sp. nov. from Chesterfield Plateau and the Grand Passage area (New Caledonia); P. puillandrei sp. nov. from Norfolk Ridge (New Caledonia), Kermadec Ridge (New Zealand) and possibly Balut Island (Philippines); and P. neocaledonicus sp. nov. from New Caledonia. Furthermore, Profundiconus teramachii forma neotorquatus (da Motta, 1984) is raised to specific status as P. neotorquatus (da Motta, 1984).
DNA sequences disclose a new species of Africonus cone snail from São Vicente (Gastropoda: Conidae)
(2017)
The sequencing of complete mitochondrial genomes of cone species belonging to the (sub)genus Africonus, which is endemic to Cabo Verde, has allowed the reconstruction of phylogenetic relationships among these species, as well as delimitation and validation of their taxonomic status. While several species were found to be synonyms, some populations had enough DNA sequence divergence to merit the species status. This is the case of some populations inhabiting São Vicente, which are hereby described as a new species. The new species shares similarity in shell morphology to Africonus miruchae (Röckel, Rolán & Monteiro, 1980), endemic to Sal, due to convergence, and with Africonus denizi Afonso & Tenorio, 2011, endemic to São Vicente, due to close phylogenetic relationship. Additionally, the three species have significant differences in radular morphology.
In the last few years, a sharp increase in the number of descriptions of new species of West African cone snails, particularly from the Cabo Verde Archipelago, has taken place. In previous studies, we used mitogenome sequences for reconstructing robust phylogenies, which comprised in total 120 individuals representing the majority of species (69.7%) described from this biogeographical region (except Angolan endemics) and grouped into seven genera within the family Conidae. Here, we add another 12 individuals representing endemic species that were missing in the previous studies. We use the phylogenies to identify monophyletic groups and a genetic divergence threshold (0.2% uncorrected p distance) to determine the number of valid species. As a result, the number of valid West African cone species could be drastically reduced to at least 40%, indicating that some recent poor-quality descriptions loosely based on phenotypic characters prone to convergence such as the shape and color patterns of the shell have contributed substantially to taxonomic inflation. Several previously accepted species with a reduced geographical distribution now become phenotypic forms of the remaining valid species, which increase their distribution ranges. In contrast, several cryptic species are now uncovered and described. For instance, Africonus insulae sp. nov. and Kalloconus canariensis sp. nov. are hereby introduced as new species. A detailed systematic account with illustrations and relevant information is presented. Lectotypes are designated for Conus trochulus and Conus irregularis, and neotypes for Conus crotchii and Conus diminutus. According to our results, it is strongly recommended that any future introduction of new taxa names for cone snails from West Africa should be supported by molecular and/or anatomical rather than exclusively shell morphological data. The taxonomic decisions here taken have direct implications for conservation and will eventually require re-evaluation of the Red List risk status of an important number of species.
Cardiac trabeculation is one of the essential processes required for the formation of a competent ventricular wall, whereby clusters of ventricular cardiomyocytes (CMs) from a single layer delaminate and expand into the cardiac jelly to form sheet-like projections in the developing heart (Samsa et al., 2013). Several congenital heart diseases are associated with defects in the formation of these trabeculae and lead to embryonic lethality (Jenni et al., 1999; Zhang et al., 2013, Jenni et al., 2001; Towbin 2010). It has been experimentally shown that lack of Nrg1/ErbB2/ErbB4, Angipoetin1/Tie2, EphrinB2/B4, BMP10, or any component of the Notch signaling pathway can cause defective trabeculation. Moreover, changes in blood flow and/or contractility can also affect trabeculation (Samsa et al., 2013). Together, these observations demonstrate that cardiac trabeculation is a highly dynamic and regulated process.
Trabeculation is a morphogenetic process that requires control over cell shape changes and rearrangements, similar to those observed during EMT. Epithelial cells within an epithelium are polarized and establish cell-cell junctions with the neighboring cells (Ikenouchi et al., 2003; Ferrer-vaquer et al., 2010), thus epithelial cell polarity is an important feature to maintain cell shape and tissue structure. During developmental processes such as cell migration and cell division or in disease states epithelial polarity might be disrupted. As a consequence of this alteration, cells lose their tight cell-cell adhesions, undergo cytoskeletal rearrangements, change their shape and gain migratory properties becoming mesenchymal cells (Micalizzi et al., 2010). In epithelial cells, apicobasal polarity is regulated by a conserved set of core complexes, including the PAR, Scribble and Crumbs complexes (Kemphues et al., 1988; Bilder and Perrimon, 2000; Teppas et al., 1984). The polarity proteins composing these complexes interact in a well organized and coordinated-manner creating molecular asymmetry along the apicobasal axis of the cell. In turn, this crosstalk regulates the maturation and stabilization of the junctions between cells and cytoskeleton in order to strengthen cell polarization (Roignot et al., 2013). Amongst the different polarity complex, Crumbs has been shown to be a key regulator of apicobasal polarity during development in both vertebrates and invertebrates (Tepass et al., 1990; Fan et al., 2004).
Here, taking advantage of zebrafish as a model organism, I study in vivo at single cell resolution changes in CM apicobasal polarity during cardiac trabeculation. Moreover, I show which factors regulate CM apicobasal polarity during this process. In addition, I dissect the role of the polarity complex Crumbs in regulating CM junctional rearrangements and the formation of the trabecular network.
Baryonic models of ultra-low-mass compact stars for the central compact object in HESS J1731-347
(2023)
The recent attempt on mass and radius inference of the central compact object within the supernova remnant HESS J1731-347 suggests for this object an unusually low mass of M=0.77−0.17+0.20M⊙ and a small radius of R=10.4−0.78+0.86km. We explore the ways such a result can be accommodated within models of dense matter with heavy baryonic degrees of freedom which are constrained by the multi-messenger observations. We find that to do so using only purely nucleonic models, one needs to assume a rather small value of the slope of symmetry energy Lsym. Once heavy baryons are included higher values of the slope Lsym become acceptable at the cost of a slightly reduced maximum mass of static configuration. These two scenarios are distinguished by the particle composition and will undergo different cooling scenarios. In addition, we show that the universalities of the I-Love-Q relations for static configurations can be extended to very low masses without loss in their accuracy.
Intrinsically disordered protein (IDP) duplexes composed of two IDP chains cross-linked by bivalent partner proteins form scaffolds for assembly of multiprotein complexes. The N-terminal domain of dynein intermediate chain (N-IC) is one such IDP that forms a bivalent scaffold with multiple dynein light chains including LC8, a hub protein that promotes duplex formation of diverse IDP partners. N-IC also binds a subunit of the dynein regulator, dynactin. Here we characterize interactions of a yeast ortholog of N-IC (N-Pac11) with yeast LC8 (Dyn2) or with the intermediate chain-binding subunit of yeast dynactin (Nip100). Residue level changes in Pac11 structure are monitored by NMR spectroscopy, and binding energetics are monitored by isothermal titration calorimetry (ITC). N-Pac11 is monomeric and primarily disordered except for a single α-helix (SAH) at the N terminus and a short nascent helix, LH, flanked by the two Dyn2 recognition motifs. Upon binding Dyn2, the only Pac11 residues making direct protein-protein interactions are in and immediately flanking the recognition motifs. Dyn2 binding also orders LH residues of Pac11. Upon binding Nip100, only Pac11 SAH residues make direct protein-protein interactions, but LH residues at a distant sequence position and L1 residues in an adjacent linker are also ordered. The long distance, ligand-dependent ordering of residues reveals new elements of dynamic structure within IDP linker regions.
Cognition requires the dynamic modulation of effective connectivity, i.e., the modulation of the postsynaptic neuronal response to a given input. If postsynaptic neurons are rhythmically active, this might entail rhythmic gain modulation, such that inputs synchronized to phases of high gain benefit from enhanced effective connectivity. We show that visually induced gamma-band activity in awake macaque area V4 rhythmically modulates responses to unpredictable stimulus events. This modulation exceeded a simple additive superposition of a constant response onto ongoing gamma-rhythmic firing, demonstrating the modulation of multiplicative gain. Gamma phases leading to strongest neuronal responses also led to shortest behavioral reaction times, suggesting functional relevance of the effect. Furthermore, we find that constant optogenetic stimulation of anesthetized cat area 21a produces gamma-band activity entailing a similar gain modulation. As the gamma rhythm in area 21a did not spread backward to area 17, this suggests that postsynaptic gamma is sufficient for gain modulation.
Cognition requires the dynamic modulation of effective connectivity, i.e. the modulation of the postsynaptic neuronal response to a given input. If postsynaptic neurons are rhythmically active, this might entail rhythmic gain modulation, such that inputs synchronized to phases of high gain benefit from enhanced effective connectivity. We show that visually induced gamma-band activity in awake macaque area V4 rhythmically modulates responses to unpredictable stimulus events. This modulation exceeded a simple additive superposition of a constant response onto ongoing gamma-rhythmic firing, demonstrating the modulation of multiplicative gain. Gamma phases leading to strongest neuronal responses also led to shortest behavioral reaction times, suggesting functional relevance of the effect. Furthermore, we find that constant optogenetic stimulation of anesthetized cat area 21a produces gamma-band activity entailing a similar gain modulation. As the gamma rhythm in area 21a did not spread backwards to area 17, this suggests that postsynaptic gamma is sufficient for gain modulation.
Die neuronalen Mechanismen, welche den meisten kognitiven Prozessen zu Grunde liegen, bestehen aus dem Zusammenspiel verschiedener Neuronen-Typen und deren spezifischen Funktionsmechanismen, sowohl in lokalen, als auch in globalen neuronalen Netzwerken. Eine funktionelle Interaktion mit diesen Netzwerken ist unumgänglich um das „kognitive“ Gehirn zu studieren, da neuronale Gruppen in einer hierarchischen, nicht linearen Weise miteinander interagieren, und dabei charakteristische raum-zeitliche Muster aufweisen. In dieser Arbeit untersuchten wir die Struktur und Funktion eines wichtigen Merkmals kortikaler Prozesse: Die neuronale gamma-Band Oszillation.
Background: For prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionation over 8 weeks or with moderate hypo-fractionation over about 5 weeks. Recent advances in radiotherapy technology have made extreme hypo-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer feasible, which has not yet been introduced as a standard treatment method in Germany. Initial results from other countries are promising, but long-term results are not yet available. The aim of this study is to investigate feasibility and effectiveness of SBRT for prostate cancer in Germany.
Methods/design: This German bi-center single group trial (HYPOSTAT) is designed to evaluate feasibility and effectiveness, as measured by toxicity and PSA-response, respectively, of an extreme hypo-fractionated SBRT regimen with five fractions of 7 Gy in treatment of localized low and intermediate risk prostate cancer. The target volume includes the prostate with or without the base of seminal vesicles depending on risk stratification and uncertainty margins that are kept at 3–5 mm. SBRT treatment is delivered with the robotic CyberKnife system, which was recently introduced in Germany. Acute and late toxicity after one year will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) Scores. The quality of life will be assessed before and after treatment with the EORTC QLQ C30 questionnaire. Hypothesizing that the proportion of patients with grade 2 side effects or higher is less or equal than 2.8%, thus markedly lower than the standard EBRT percentage (17.5%), the recruitment target is 85 patients.
Discussion: The HYPOSTAT trial aims at demonstrating short term feasibility of extreme hypo-fractioned SBRT for the treatment of prostate cancer and might be used as the pilot study for a multi-center multi-platform or for randomized-controlled trials comparing conventional radiotherapy with SBRT for localized prostate cancer in the future. The study concept of patient enrollment, follow up and evaluation by multiple public university clinics and actual patient treatment in dedicated private radiosurgery practices with high-tech radiation equipment is unique for clinical trials.
Study status: The study is ongoing and currently recruiting patients.
Trial registration: Registration number: NCT02635256 (clinicaltrials.gov). Registered 8 December 2015