bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drosophila menthol sensitivity and the Precambrian origins of TRP-dependent chemosensation
Authors: Himmel Nathaniel J. , Letcher Jamin M. , Sakurai Akira , Gray Thomas R. , Benson Maggie N. , Cox Daniel N. 
Published: July 2019

AbstractTransient receptor potential (TRP) cation channels are highly conserved, polymodal sensors which respond to a wide variety of stimuli. Perhaps most notably, TRP channels serve critical functions in nociception and pain. A growing body of evidence suggests that TRPM (Melastatin) and TRPA (Ankyrin) thermal and electrophile sensitivities predate the protostome-deuterostome split (>550 million years ago). However, TRPM and TRPA channels are also thought to detect modified terpenes (e.g., menthol). Although terpenoids like menthol are thought to be aversive and/or harmful to insects, mechanistic sensitivity studies have been largely restricted to chordates. Furthermore, it is unknown if TRP-menthol sensing is as ancient as thermal and/or electrophile sensitivity. Combining genetic, optical, electrophysiological, behavioural, and phylogenetic approaches, we tested the hypothesis that insect TRP channels play a conserved role in menthol sensing. We found that topical application of menthol to Drosophila melanogaster larvae elicits a Trpm- and TrpA1-dependent nocifensive rolling behaviour, which requires activation of Class IV nociceptor neurons. Further, in characterizing the evolution of TRP channels, we put forth the hypotheses that 3 previously undescribed TRPM channel clades (basal, αTRPM, and βTRPM), as well as TRPs with residues critical for menthol sensing, were present in ancestral bilaterians.
Evaluating three different adaptive decomposition methods for EEG signal seizure detection and classification
Authors: Carvalho Vinícius R. , Moraes Márcio F.D. , Braga Antônio P. , Mendes Eduardo M.A.M. 
Published: July 2019

AbstractSignal processing and machine learning methods are valuable tools in epilepsy research, potentially assisting in diagnosis, seizure detection, prediction and real-time event detection during long term monitoring. Recent approaches involve the decomposition of these signals in different modes or functions in a data-dependent and adaptive way. These approaches may provide advantages over commonly used Fourier based methods due to their ability to work with nonlinear and non-stationary data. In this work, three adaptive decomposition methods (Empirical Mode Decomposition, Empirical Wavelet Transform and Variational Mode Decomposition) are evaluated for the classification of normal, ictal and inter-ictal EEG signals using a freely available database. We provide a previously unavailable common methodology for comparing the performance of these methods for EEG seizure detection, with the use of the same classifiers, parameters and spectral and time domain features. It is shown that the outcomes using the three methods are quite similar, with maximum accuracies of 97.5% for Empirical Mode Decomposition, 96.7% for Empirical Wavelet Transform and 98.2% for Variational Mode Decomposition. Features were also extracted from the original non-decomposed signals, yielding inferior, but still fairly accurate (95.3%) results. The evaluated decomposition methods are promising approaches for seizure detection, but their use should be judiciously analysed, especially in situations that require real-time processing and computational power is an issue. An additional methodological contribution of this work is the development of two python packages, already available at the PyPI repository: One for the Empirical Wavelet Transform (ewtpy) and another for Variational Mode Decomposition (vmdpy).
The Role of Evolving Interfacial Substrate Properties on Heterogeneous Cellulose Hydrolysis Kinetics
Authors: Nill Jennifer , Jeoh Tina 
Published: July 2019

AbstractInterfacial enzyme reactions require formation of an enzyme-substrate complex at the surface of a heterogeneous substrate, but often multiple modes of enzyme binding and types of binding sites complicate analysis of their kinetics. Excess of heterogeneous substrate is often used as a justification to model the substrate as unchanging; but using the study of the enzymatic hydrolysis of insoluble cellulose as an example, we argue that reaction rates are dependent on evolving substrate interfacial properties. We hypothesize that the relative abundance of binding sites on cellulose where hydrolysis can occur (productive binding sites) and binding sites where hydrolysis cannot be initiated or is inhibited (non-productive binding sites) contribute to rate limitations. We show that the initial total number of productive binding sites (the productive binding capacity) determines the magnitude of the initial burst phase of cellulose hydrolysis, while productive binding site depletion explains overall hydrolysis kinetics. Furthermore, we show that irreversibly bound surface enzymes contribute to the depletion of productive binding sites. Our model shows that increasing the ratio of productive- to non-productive binding sites promotes hydrolysis, while maintaining an elevated productive binding capacity throughout conversion is key to preventing hydrolysis slowdown.
Maternal effects and environmental filtering shape seed fungal communities in oak trees
Authors: Fort Tania , Pauvert Charlie , Zanne Amy E. , Ovaskainen Otso , Caignard Thomas , Barret Matthieu , Compant Stéphane , Hampe Arndt , Delzon Sylvain , Vacher Corinne 
Published: July 2019

SummaryTrees, as foundation species, play a pivotal role in the species interaction networks that constitute forest ecosystems. From the seed stage, they interact with microbial communities that affect their growth, health and fitness. Despite their eco-evolutionary importance, the processes shaping seed microbial communities in natural forests have received little attention.To unravel these processes, we analyzed the microbial communities of seeds collected in populations of sessile oak (Quercus petraea) growing along elevation gradients. We focused on the fungal communities as this group includes seed pathogens. Ecological processes shaping the communities were quantified using joint species distribution models.Fungi were present in all seed tissues, including the embryo. Fungal communities differed significantly among oak populations along the elevation gradients, and among mother trees within the same population. These maternal effects remained significant after seed fall, despite colonization by fungal species on the ground. Associations between tree pathogens and their antagonists were detected in the seeds.Our results demonstrate that both maternal effects and environmental filtering shape seed microbial communities of sessile oak. They provide a starting point for future research aimed at identifying the seed extended phenotypic traits that influence seed dispersal and germination, and seedling survival and growth across environments.
Interictal discharges spread along local recurrent networks between tubers and surrounding cortex
Authors: Tumpa S , Thornton R , Tisdall M , Baldeweg T , Friston KJ , Rosch RE 
Published: July 2019

AbstractThe presence of interictal epileptiform discharges on electroencephalography (EEG) may indicate increased epileptic seizure risk and on invasive EEG are the signature of the irritative zone. In highly epileptogenic lesions – such as cortical tubers in tuberous sclerosis – these discharges can be recorded with intracranial stereotactic EEG as part of the evaluation for epilepsy surgery. Yet the network mechanisms that underwrite the generation and spread of these discharges remain poorly understood, limiting their current diagnostic use.Here, we investigate the dynamics of interictal epileptiform discharges using a combination of quantitative analysis of invasive EEG recordings and mesoscale neural mass modelling of cortical dynamics. We first characterise spatially organised local dynamics of discharges recorded from 36 separate tubers in 8 patients with tuberous sclerosis. We characterise these dynamics with a set of competing explanatory network models using dynamic causal modelling. Bayesian model comparison of plausible network architectures suggests that the recurrent coupling between neuronal populations within – and adjacent to – the tuber core explains the travelling wave dynamics observed in these patient recordings.Our results – based on interictal activity – unify competing theories about the pathological organisation of epileptic foci and surrounding cortex in patients with tuberous sclerosis. Coupled oscillator dynamics have previously been used to describe ictal activity, where fast travelling ictal discharges are commonly observed within the recruited seizure network. The interictal data analysed here add the insight that this functional architecture is already established in the interictal state. This links observations of interictal EEG abnormalities directly to pathological network coupling in epilepsy, with possible implications for epilepsy surgery approaches in tuberous sclerosis.Significance StatementInterictal epileptiform discharges (IEDs) are clinically important markers of an epileptic brain. Here we link local IED spread to network coupling through a combination of clinical recordings in paediatric patients with tuberous sclerosis complex, quantitative EEG analysis of interictal discharges spread, and Bayesian inference on coupled neural mass model parameters. We show that the kinds of interictal discharges seen in our patients require recurrent local network coupling extending beyond the putative seizure focus and that in fact only those recurrent coupled networks can support seizure-like and interictal dynamics when run in simulation. Our findings provide a novel integrated perspective on emergent epileptic dynamics in human patients.
A common polymorphism in the druggable ion channel PIEZO1 is associated with protection from severe malaria
Authors: Nguetse Christian N. , Purington Natasha , Shakya Bikash , Ebel Emily R. , Kremsner Peter G. , Velavan Thirumalaisamy P. , Egan Elizabeth S. 
Published: July 2019

AbstractMalaria caused by the Apicomplexan parasite Plasmodium falciparum has served as a strong evolutionary force throughout human history, selecting for red blood cell polymorphisms that confer innate protection against severe disease. Recently, gain-of-function mutations in the mechanosensitive ion channel PIEZO1 were shown to ameliorate Plasmodium parasite growth, blood-brain barrier dysfunction, and mortality in a mouse model of malaria. In humans, the gain-of-function allele PIEZO1 E756del is highly prevalent and enriched in Africans, raising the possibility that it is under positive selection due to malaria. Here we used a case-control study design to test for an association between PIEZO1 E756del and malaria severity among children in Gabon. We found that the E756del variant is strongly associated with protection against severe malaria in heterozygotes, independent of the protection conferred by the sickle cell trait (hemoglobin AS). In vitro experiments using donor red blood cells failed to find an effect of E756del on parasite growth, suggesting this variant confers a mild channel defect and/or that its protective effect may be mediated by other tissue types in vivo. Nonetheless, we show that Yoda1, a small molecule agonist of PIEZO1, has potent antimalarial activity in both E756del and wild-type red blood cells. Our findings demonstrate that PIEZO1 is an important innate determinant of malaria susceptibility in humans and holds potential as druggable host target for malaria control.
IDR2D identifies reproducible genomic interactions
Authors: Krismer Konstantin , Guo Yuchun , Gifford David K. 
Published: July 2019

AbstractChromatin interaction data from protocols such as ChIA-PET, HiChIP, and HiC provide valuable insights into genome organization and gene regulation, but can include spurious interactions that do not reflect underlying genome biology. We introduce a generalization of the Irreproducible Discovery Rate (IDR) method called IDR2D that identifies replicable interactions shared by chromatin interaction experiments. IDR2D provides a principled set of interactions and eliminates artifacts from single experiments. The method is available as a Bioconductor package for the R community, as well as an online service at https://idr2d.mit.edu.
LKB1 negatively regulates AKT1 signaling via DBC1 and TRB3
Authors: Sarwar Zarka , Bhat Sameer , Gillani Qaaifah , Reshi Irfana , Nisa Misbah Un , Adelmant Guillaume , Marto Jarrod , Andrabi Shaida 
Published: July 2019

AbstractDBC1 plays a critical role in various cellular functions notably cell proliferation, transcription, histone modification and adipogenesis. Current reports about the role of DBC1 in tumorigenesis are paradoxical and designate DBC1 both as a tumor suppressor or an oncogene. Here, using small T antigen of polyoma virus (PyST) as a tool, we have delineated a signaling mechanism that connects LKB1 to AKT1 via DBC1. We report that PyST associates with DBC1 and leads to its down-regulation. Our results also show that PyST expression promotes LKB1 activation which in turn leads to in the downregulation of DBC1 protein. Absence of DBC1 results in transcriptional upregulation and consequently enhanced protein levels of TRB3. TRB3 sequesters AKT1, and consequently the phosphorylation and activity of AKT1 is compromised. This ultimately results in inactivation of pro-survival pathways triggered via AKT1 signaling. Our studies thus provide an insight into a signaling pathway that connects LKB1, DBC1, TRB3 and AKT1.
Plasticity in aDrosophilawing circuit supports an adaptive sleep function
Authors: Melnattur K. , Zhang B. , Shaw P.J. 
Published: July 2019

AbstractSleep is a near universal phenomenon whose function remains controversial. An influential theory of sleep function posits that ecological factors that place animals in harm’s way increase sleep as a state of adaptive inactivity. Here we find that manipulations that impair flight inDrosophilaincrease sleep. Further, we identify a novel neural pathway from peripheral wing sensory neurons to the central brain that mediates the change in sleep. Moreover, we show that flight impairments activate and induce structural plasticity in specific projection neurons to support increases in sleep over days. Thus, chemosensory neurons do not only signal sensory cues but also appear to provide information on wing-integrity to support behavioural adaptability. Together, these data provide mechanistic support of adaptive increases in sleep and highlight the importance of behavioural flexibility for fitness and survival.
The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes
Authors: de Greef Peter C. , Oakes Theres , Gerritsen Bram , Ismail Mazlina , Heather James M. , Hermsen Rutger , Chain Benjamin , de Boer Rob J. 
Published: July 2019

AbstractThe human naive T-cell receptor (TCR) repertoire is extremely diverse and accurately estimating its distribution is challenging. We address this challenge by combining a quantitative sequencing protocol of TCRA and TCRB sequences with computational modelling. We observed the vast majority of TCR chains only once in our samples, confirming the enormous diversity of the naive repertoire. However, a substantial number of sequences were observed multiple times within samples, and we demonstrated that this is due to expression by many cells in the naive pool. We reason that α and β chains are frequently observed due to a combination of selective processes and summation over multiple clones expressing these chains. We test the contribution of both mechanisms by predicting samples from phenomenological and mechanistically modelled repertoire distributions. By comparing these with sequencing data, we show that frequently observed chains are likely to be derived from multiple clones. Still, a neutral model of T-cell homeostasis cannot account for the observed distributions. We conclude that the data are only compatible with distributions of many small clones in combination with a sufficient number of very large naive T-cell clones, the latter most likely as a result of peripheral selection.
Genome-wide Association study of facial morphology identifies novel genetic loci in Han Chinese
Authors: Huang Yin , Li Dan , Qiao Lu , Liu Yu , Peng Qianqian , Wu Sijie , Zhang Manfei , Yang Yajun , Tan Jingze , Xu Shuhua , Jin Li , Wang Sijia , Tang Kun , Grünewald Stefan 
Published: July 2019

AbstractHuman face is a heritable surface with many complex sensory organs. In recent years, many genetic loci associated with facial features have been reported in different populations, yet there is a lack for the Han Chinese population. We report a genome-wide association analysis of 3D normal human faces in 2659 Han Chinese with two groups of phenotypes, the partial and whole face phenotypes and the distance and angle phenotypes. We found significant signals in five genomic regions with traits related to nose or eyes, including rs970797 in 2q31.1 near HOXD1 and MTX2, rs16897517 in 8q22.2 at intron of VPS13B, rs9995821 in 4q31.3 near DCHS2 and SFRP2, rs12636297 in 3q23 near PISRT1, and rs12948076 in 17q24.3 near SOX9 and CASC17. We visualized changes in facial morphology by comparing the volume of local areas and observed that these nose-related loci were associated with different features of the nose, including nose prominence, nasion height, and nostril shape, suggesting that the nose underlies precise genetic regulation. These results provide a more comprehensive understanding of the relationship between genetic loci and human facial morphology.Author SummaryHuman face as a combination of delicate sensory organs has a strong genetic component, as evidenced by the identical appearance in twins and shared facial features in close relatives. Although facial genetics have been studied in different populations, our knowledge between genetic markers with facial features is still limited. In this paper, we found genetic variants associated with nose and eyes through a large-scale high-resolution 3D facial genetic study on the Han Chinese population. We observed that these nose-related loci were associated with different features of the nose, including nose prominence, nasion height, and nostril shape, which suggests the nose underlies precise genetic regulation. Intriguingly, we noted that genes (DCHS2 and SFRP2) related to one of these loci are differentially expressed in human and chimp cranial neural crest cells, which plays a crucial role in the early formation of facial morphology. The ongoing genetic studies of facial morphology will improve our understanding of human craniofacial development, and provide potential evolution evidence of human facial features.
Identifying maintenance hosts and risk factors for infection with Dichelobacter nodosus in free-ranging wild ruminants in Switzerland: a prevalence study
Authors: Moore-Jones Gaia , Ardüser Flurin , Dürr Salome , Brawand Stefanie Gobeli , Steiner Adrian , Zanolari Patrik , Ryser-Degiorgis Marie-Pierre 
Published: July 2019

AbstractFootrot is a worldwide economically important, painful, contagious bacterial hoof disease of domestic and wild ungulates caused by Dichelobacter nodosus (D. nodosus). Benign and virulent strains have been identified in sheep presenting mild and severe lesions, respectively. However, in Alpine ibex (Capra ibex) both strains have been associated with severe, fatal lesions. In Switzerland a nationwide footrot control program for sheep focusing on the virulent strain shall soon be implemented. The aim of this cross-sectional study was to estimate the nationwide prevalence of both strains of D. nodosus in four wild indigenous ruminant species and to identify potential susceptible maintenance hosts that could be a reinfection source for sheep. During two years (2017-2018), interdigital swabs of 1,821 wild indigenous ruminants species (Alpine ibex; Alpine chamois, Rupicapra rupicapra; roe deer, Capreolus capreolus; red deer, Cervus elaphus) were analysed by Real-Time PCR. Furthermore, observed interspecies interactions were documented for each sample. Overall, we report a low prevalence of D. nodosus in all four indigenous wild ruminants, for both the benign (1.97%, N = 36, of which 31 red deer) and virulent (0.05%, N = 1) strain of D. nodosus. Footrot lesions were documented in one ibex with the virulent strain, and in one ibex with the benign strain. Interactions with domestic livestock occurred mainly with cattle and sheep. In conclusion, the data suggest that domestic ungulates represent a significant source of infection for wild ungulates, while wild ruminants are likely irrelevant for the maintenance and spread of D. nodosus. Furthermore, we add evidence that both D. nodosus strains can be associated with severe disease in Alpine ibex. These data are crucial for the upcoming nationwide control program and reveal that wild ruminants should not be considered as a threat to footrot control in sheep in this context.
Resistome metagenomics from plate to farm: the resistome and microbial composition during food waste feeding and composting on a Vermont poultry farm
Authors: Eckstrom Korin , Barlow John W. 
Published: July 2019

AbstractFood waste diversion and composting, either mandated or voluntary, are growing alternatives to traditional waste disposal. An acceptable source of agricultural feed and composting material, methane-emitting food residuals, including post-consumer food scraps, are diverted from landfills allowing recapture of nutrients that would otherwise be lost. However, risk associated with the transfer of antimicrobial resistant bacteria (ARB), antibiotic resistance genes (ARGs), or pathogens from food waste is not well characterized. Using shotgun metagenomic sequencing, ARGs, microbial content, and associated virulence factors were successfully identified across samples from an integrated poultry farm that feeds post-consumer food waste. A total of 495 distinct bacterial species or sub-species, 50 ARGs, and 54 virulence gene sequences were found. ARG sequences related to aminoglycoside, tetracycline, and macrolide resistance were most prominent, while most virulence gene sequences were related to transposon or integron activity. Microbiome content was distinct between on-farm samples and off-farm food waste collection sites, with a reduction in pathogens throughout the composting process. While most samples contained some level of resistance, only 3 resistance gene sequences occurred in both on- and off-farm samples and no multidrug resistance (MDR) gene sequences persisted once on the farm. The risk of incorporating novel or multi-drug resistance from human sources appears to be minimal and the practice of utilizing post-consumer food scraps as feed for poultry and composting material may not present a significant risk for human or animal health. Pearson correlation and co-inertia analysis identified a significant interaction between resistance and virulence genes (P = 0.05, RV = 0.67), indicating that ability to undergo gene transfer may be a better marker for ARG risk than presence of specific bacterial species. This work expands the knowledge of ARG fate during food scrap animal feeding and composting and provides a methodology for reproducible analysis.