julilili42/papers huggingface dataset:
Evidence for heterochrony in the cranial evolution of fossil crocodyliforms
2018-03-08

Abstract The southern supercontinent of Gondwana was home to an extraordinary diversity of stem‐crocodylians (Crocodyliformes) during the Late Cretaceous. The remarkable morphological disparity of notosuchian crocodyliforms indicates that this group filled a wide range of ecological roles more frequently occupied by other vertebrates. Among notosuchians, the distinctive cranial morphology and large body sizes of Baurusuchidae suggest a role as apex predators in ecosystems in which the otherwise dominant predatory theropod dinosaurs were scarce. Large‐bodied crocodyliforms, modern and extinct, are known to have reached large sizes by extending their growth period. In a similar way, peramorphic heterochronic processes may have driven the evolution of the similarly large baurusuchids. To assess the presence of peramorphic processes in the cranial evolution of baurusuchids, we applied a geometric morphometric approach to investigate ontogenetic cranial shape variation in a comprehensive sample of notosuchians. Our results provide quantitative morphological evidence that peramorphic processes influenced the cranial evolution of baurusuchids. After applying size and ancestral ontogenetic allometry corrections to our data, we found no support for the action of either hypermorphosis or acceleration, indicating that these two processes alone cannot explain the shape variation observed in Notosuchia. Nevertheless, the strong link between cranial shape variation and size increase in baurusuchids suggests that peramorphic processes were involved in the emergence of hypercarnivory in these animals. Our findings illustrate the role of heterochrony as a macroevolutionary driver, and stress, once more, the usefulness of geometric morphometric techniques for identifying heterochronic processes behind evolutionary trends.
Comprehensive Molecular Approach for Characterization of Hepatitis E Virus Genotype 3 Variants
2018-03-08

ABSTRACT Autochthonous hepatitis E virus genotype 3 (HEV-3) infections in industrialized countries are more frequent than previously assumed. HEV-3 is zoonotic and the causal pathogen of chronic hepatitis E. According to the latest classification of the family Hepeviridae , 10 designated HEV-3 subtypes (HEV-3a to HEV-3j) and 7 unassigned HEV-3 subtypes are proposed. In order to identify and characterize the HEV-3 variants in circulation, we developed a molecular approach combining a sensitive HEV-specific real-time reverse transcription-PCR (RT-PCR) targeting the overlapping region of HEV ORF2 and ORF3 (the ORF2/3 region) and two newly designed consensus nested RT-PCRs targeting the HEV ORF1 and ORF2 genes, respectively. Since complete genome sequences are required for new HEV-3 subtype assignment, we implemented a straightforward approach for full-length HEV-3 genome amplification. Twenty-nine human serum samples and six human feces samples from chronic hepatitis E patients were selected for evaluation of the system. Viral loads ranged from 1 × 10 4 to 1.9 × 10 10 copies/ml of serum and from 1.8 × 10 4 to 1 × 10 12 copies/g of feces. Sequence and phylogenetic analyses of partial ORF1 and ORF2 sequences showed that HEV strains had considerable genetic diversity and clustered into the HEV-3c (29/35), HEV-3e (2/35), HEV-3f (2/35), and unassigned HEV-3 (2/35) subtypes. Moreover, from these strains, three full-length HEV-3 genome sequences were generated and characterized. DE/15-0030 represents a typical HEV-3c strain (95.7% nucleotide identity to wbGER27), while DE/15-0031 and SW/16-0282 have &lt;89.2% homology to known HEV-3 strains and are phylogenetically divergent, indicating novel HEV-3 subtypes. In summary, our approach will significantly facilitate the detection, quantification, and determination of HEV-3 strains and will thus help to improve molecular diagnostics and our knowledge of HEV diversity and evolution.
A systematic review and meta-analysis of the relationship between brain data and the outcome in Disorders of Consciousness
2018-03-08

A systematic search revealed 68 empirical studies of neurophysiological (EEG, ERP, fMRI, PET) variables as potential outcome predictors in patients with Disorders of Consciousness (diagnoses Unresponsive Wakefulness Syndrome [UWS] and Minimally Conscious State [MCS]). Data of 47 publications could be presented in a quantitative manner and systematically reviewed. Insufficient power and the lack of an appropriate description of patient selection each characterized about a half of all publications. In more than 80% studies, neurologists who evaluated the patients’ outcome were familiar with the results of neurophysiological tests conducted before, and may, therefore, have been influenced by this knowledge. In most subsamples of data sets effect size significantly correlated with its standard error, indicating publication bias toward positive results. Neurophysiological data predicted the transition from UWS to MCS substantially better than they predicted the recovery of consciousness (i.e., the transition from UWS or MCS to exit-MCS). A meta-analysis was carried out for predictor groups including at least three independent studies with N &amp;gt; 10 per predictor per improvement criterion (i.e., transition to MCS versus recovery). Oscillatory EEG responses were the only predictor group whose effect attained significance for both improvement criteria. Other perspective variables, whose true prognostic value should be explored in future studies, are sleep spindles in the EEG and the somatosensory cortical response N20. Contrary to what could be expected on the basis of neuroscience theory, the poorest prognostic effects were shown for fMRI responses to stimulation and for the ERP component P300. The meta-analytic results should be regarded as preliminary given the presence of numerous biases in the data.
Gene panel testing of 5589 BRCA1/2‐negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer
2018-03-09

Abstract The prevalence of germ line mutations in non‐ BRCA 1/2 genes associated with hereditary breast cancer ( BC ) is low, and the role of some of these genes in BC predisposition and pathogenesis is conflicting. In this study, 5589 consecutive BC index patients negative for pathogenic BRCA 1/2 mutations and 2189 female controls were screened for germ line mutations in eight cancer predisposition genes ( ATM , CDH 1 , CHEK 2 , NBN , PALB 2 , RAD 51C , RAD 51D, and TP 53 ). All patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germ line testing. The highest mutation prevalence was observed in the CHEK 2 gene (2.5%), followed by ATM (1.5%) and PALB 2 (1.2%). The mutation prevalence in each of the remaining genes was 0.3% or lower. Using Exome Aggregation Consortium control data, we confirm significant associations of heterozygous germ line mutations with BC for ATM ( OR : 3.63, 95% CI : 2.67–4.94), CDH 1 ( OR : 17.04, 95% CI : 3.54–82), CHEK 2 ( OR : 2.93, 95% CI : 2.29–3.75), PALB 2 ( OR : 9.53, 95% CI : 6.25–14.51), and TP 53 ( OR : 7.30, 95% CI : 1.22–43.68). NBN germ line mutations were not significantly associated with BC risk ( OR :1.39, 95% CI : 0.73–2.64). Due to their low mutation prevalence, the RAD 51C and RAD 51D genes require further investigation. Compared with control datasets, predicted damaging rare missense variants were significantly more prevalent in CHEK 2 and TP 53 in BC index patients. Compared with the overall sample, only TP 53 mutation carriers show a significantly younger age at first BC diagnosis. We demonstrate a significant association of deleterious variants in the CHEK 2 , PALB 2, and TP 53 genes with bilateral BC . Both, ATM and CHEK 2 , were negatively associated with triple‐negative breast cancer ( TNBC ) and estrogen receptor ( ER )‐negative tumor phenotypes. A particularly high CHEK 2 mutation prevalence (5.2%) was observed in patients with human epidermal growth factor receptor 2 ( HER 2)‐positive tumors.
Intercomparison of cosmic-ray neutron sensors and water balance monitoring in an urban environment
2018-03-09

Abstract. Sensor-to-sensor variability is a source of error common to all geoscientific instruments that needs to be assessed before comparative and applied research can be performed with multiple sensors. Consistency among sensor systems is especially critical when subtle features of the surrounding terrain are to be identified. Cosmic-ray neutron sensors (CRNSs) are a recent technology used to monitor hectometre-scale environmental water storages, for which a rigorous comparison study of numerous co-located sensors has not yet been performed. In this work, nine stationary CRNS probes of type “CRS1000” were installed in relative proximity on a grass patch surrounded by trees, buildings, and sealed areas. While the dynamics of the neutron count rates were found to be similar, offsets of a few percent from the absolute average neutron count rates were found. Technical adjustments of the individual detection parameters brought all instruments into good agreement. Furthermore, we found a critical integration time of 6 h above which all sensors showed consistent dynamics in the data and their RMSE fell below 1 % of gravimetric water content. The residual differences between the nine signals indicated local effects of the complex urban terrain on the scale of several metres. Mobile CRNS measurements and spatial simulations with the URANOS neutron transport code in the surrounding area (25 ha) have revealed substantial sub-footprint heterogeneity to which CRNS detectors are sensitive despite their large averaging volume. The sealed and constantly dry structures in the footprint furthermore damped the dynamics of the CRNS-derived soil moisture. We developed strategies to correct for the sealed-area effect based on theoretical insights about the spatial sensitivity of the sensor. This procedure not only led to reliable soil moisture estimation during dry-out periods, it further revealed a strong signal of intercepted water that emerged over the sealed surfaces during rain events. The presented arrangement offered a unique opportunity to demonstrate the CRNS performance in complex terrain, and the results indicated great potential for further applications in urban climate research.
The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 2 Core
2018-03-09

Abstract Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 2 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language), validation rules that determine the validity of an SBML document, and examples of models in SBML form. The design of Version 2 differs from Version 1 principally in allowing new MathML constructs, making more child elements optional, and adding identifiers to all SBML elements instead of only selected elements. Other materials and software are available from the SBML project website at http://sbml.org/ .
Can digital information literacy among undergraduates be improved? Evidence from an experimental study
2018-03-09

The Internet has become a pivotal source of information among university students. However, studies routinely show that many students lack digital information literacy skills (i.e. skills needed to find and evaluate information online). In this paper, we report results from an experimental study testing the effect of a workshop for third-year students of a German university. The workshop was designed to teach relevant information literacy skills in a computer lab. Afterwards, students were given academic search tasks and their search behavior was recorded with a tracking device. We find that, compared with the control group, workshop participants significantly increased their use of academic databases and cited more articles from scholarly journals. On the other hand, we find no effect on the relevance of the content students found online. Teaching digital information literacy is essential and feasible, but it is no panacea for increasing the academic quality of students' work.
Bulk dynamics of Brownian hard disks: Dynamical density functional theory versus experiments on two-dimensional colloidal hard spheres
2018-03-09

Using dynamical density functional theory (DDFT), we theoretically study Brownian self-diffusion and structural relaxation of hard disks and compare to experimental results on quasi two-dimensional colloidal hard spheres. To this end, we calculate the self-van Hove correlation function and distinct van Hove correlation function by extending a recently proposed DDFT-approach for three-dimensional systems to two dimensions. We find that the theoretical results for both self-part and distinct part of the van Hove function are in very good quantitative agreement with the experiments up to relatively high fluid packing fractions of roughly 0.60. However, at even higher densities, deviations between the experiment and the theoretical approach become clearly visible. Upon increasing packing fraction, in experiments, the short-time self-diffusive behavior is strongly affected by hydrodynamic effects and leads to a significant decrease in the respective mean-squared displacement. By contrast, and in accordance with previous simulation studies, the present DDFT, which neglects hydrodynamic effects, shows no dependence on the particle density for this quantity.
Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis
2018-03-09

Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. We aimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A–encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 μg/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.
Precise Doppler shift compensation in the hipposiderid bat, Hipposideros armiger
2018-03-09

Abstract Bats of the Rhinolophidae and Hipposideridae families, and Pteronotus parnellii , compensate for Doppler shifts generated by their own flight movement. They adjust their call frequency such that the frequency of echoes coming from ahead fall in a specialized frequency range of the hearing system, the auditory fovea, to evaluate amplitude and frequency modulations in echoes from fluttering prey. Some studies in hipposiderids have suggested a less sophisticated or incomplete Doppler shift compensation. To investigate the precision of Doppler shift compensation in Hipposideros armiger , we recorded the echolocation and flight behaviour of bats flying to a grid, reconstructed the flight path, measured the flight speed, calculated the echo frequency, and compared it with the resting frequency prior to each flight. Within each flight, the average echo frequency was kept constant with a standard deviation of 110 Hz, independent of the flight speed. The resting and reference frequency were coupled with an offset of 80 Hz; however, they varied slightly from flight to flight. The precision of Doppler shift compensation and the offset were similar to that seen in Rhinolophidae and P . parnellii . The described frequency variations may explain why it has been assumed that Doppler shift compensation in hipposiderids is incomplete.
Contrast gain control and retinogeniculate communication
2018-03-09

Abstract Visual information processed in the retina is transmitted to primary visual cortex via relay cells in the lateral geniculate nucleus ( LGN ) of the dorsal thalamus. Although retinal ganglion cells are the primary source of driving input to LGN neurons, not all retinal spikes are transmitted to the cortex. Here, we investigate the relationship between stimulus contrast and retinogeniculate communication and test the hypothesis that both the time course and strength of retinogeniculate interactions are dynamic and dependent on stimulus contrast. By simultaneously recording the spiking activity of synaptically connected retinal ganglion cells and LGN neurons in the cat, we show that the temporal window for retinogeniculate integration and the effectiveness of individual retinal spikes are inversely proportional to stimulus contrast. This finding provides a mechanistic understanding for the phenomenon of augmented contrast gain control in the LGN —a nonlinear receptive field property of LGN neurons whereby response gain during low‐contrast stimulation is enhanced relative to response gain during high‐contrast stimulation. In addition, these results support the view that network interactions beyond the retina play an essential role in transforming visual signals en route from retina to cortex.
Inside Back Cover: The Cysteinome of Protein Kinases as a Target in Drug Development (Angew. Chem. Int. Ed. 16/2018)
2018-03-09

Covalent and reversible covalent bond formation with cysteine residues located in the vicinity of the ATP binding site in protein kinases has led to inhibitors with high potency and exclusive isoform selectivity and now four approved kinase drugs. As outlined by S. Knapp et al. in their Review on page 4372, the successful development of these interesting inhibitors requires careful fine tuning of reactivity, precise positioning of the reactive moiety on a suitable ATP mimetic compound and careful characterization of these inhibitors in cells and in vivo.
The iris signal: blue periphery, tan collaret and freckles pattern – strong indicators for epidermal skin cancer in South‐Eastern Europe
2018-03-10

Abstract Background Eye and skin share the embryological origin. Both are established risk factors in epidermal skin cancer. There are few reports using iris colour classification scales, most of them analyse colour in general or are too complex to use in daily practice. Objectives To investigate which iris colour pattern is associated with epidermal skin cancer in a S‐E European Caucasian population. Methods A case–control study was conducted on 480 patients: 229 skin cancers patients and 251 controls (dermatological patients free of skin cancers) admitted in two medical clinics of Dermatology in Bucharest, between October 2011 and May 2014. High‐resolution iris photographs were taken for each patient. Three parameters of the iris were analysed individually and in association patterns for each patient: periphery, collaret and freckles. Results The most frequent iris colour pattern associated with epidermal skin cancer was blue periphery with light brown collaret and freckles present. In terms of individual parameters, the strongest indicators for skin cancer patients were blue periphery and blue collaret. Conclusions The results of this study sustain the hypothesis that blue periphery with light brown collaret and freckles iris pattern is a reliable phenotypic marker for epidermal skin cancer. The results of this study differ from previous reports in which skin cancer risk was associated with a homogeneous blue iris. We account these differences in the characteristics of the recruited patients (S‐E European, skin type II and III ). The assessment of iris colour patterns is an easy and inexpensive detection tool in skin cancer risk assessment.
Implantation, removal and replacement of subretinal electronic implants for restoration of vision in patients with retinitis pigmentosa
2018-03-11

The new RETINA IMPLANT Alpha AMS shows significantly improved durability compared with the predecessor model RETINA IMPLANT Alpha IMS. The subretinal implant offers excellent visual results but requires experienced surgeons. Explantation of devices is straight-forward, and reimplantations are challenging but have been successful in four patients.
Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration
2018-03-12

Significance Development of treatments for hereditary degeneration of the retina (RD) is hampered by the vast genetic heterogeneity of this group of diseases and by the delivery of the drug to an organ protected by the blood–retina barrier. Here, we present an approach for the treatment of different types of RD, combining an innovative drug therapy with a liposomal system that facilitates drug delivery into the retina. Using different animal models of RD we show that this pharmacological treatment preserved both the viability of cells in the retina as well as retinal function. Thus, our study provides an avenue for the development of therapies for hereditary diseases which cause blindness, an unmet medical need.
A novel heterozygous variant in ERLIN2 causes autosomal dominant pure hereditary spastic paraplegia
2018-03-12

Background and purpose Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous monogenic disorders. To date, nearly 70 genes are known to be causative. The aim of this project was to identify the genetic cause of autosomal dominantly inherited pure HSP in two large, unrelated non‐consanguineous families. Methods The two families were characterized clinically and selected members underwent whole exome sequencing. Potentially disease‐causing variants were confirmed by Sanger sequencing and their functional consequences on protein function were predicted by bioinformatic prediction tools. Results The patients presented with pure spastic paraplegia with age of onset between 9 and 46 years. In both families, a novel heterozygous missense variant in ERLIN2, c.386G&gt;C; p.Ser129Thr, was the only potentially pathogenic variant identified that segregated with the disease. Conclusions Biallelic variants in ERLIN2 are known to cause recessive HSP type SPG18. Here, the first two families with an autosomal dominant, pure form of HSP caused by a novel ERLIN2 heterozygous missense variant are described. These findings expand the mutational and inheritance spectrum of SPG18. ERLIN2 variants should also be considered in the diagnostic evaluation of patients with autosomal dominant HSP.