bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with Autism risk genes
Authors: Jin Xin , Simmons Sean K. , Guo Amy X. , Shetty Ashwin S. , Ko Michelle , Nguyen Lan , Robinson Elise , Oyler Paul , Curry Nathan , Deangeli Giulio , Lodato Simona , Levin Joshua Z. , Regev Aviv , Zhang Feng , Arlotta Paola 
Published: October 2019

AbstractThe thousands of disease risk genes and loci identified through human genetic studies far outstrip our current capacity to systematically study their functions. New experimental approaches are needed for functional investigations of large panels of genes in a biologically relevant context. Here, we developed a scalable genetic screen approach, in vivo Perturb-Seq, and applied this method to the functional evaluation of 35 autism spectrum disorder (ASD) de novo loss-of-function risk genes. Using CRISPR-Cas9, we introduced frameshift mutations in these risk genes in pools, within the developing brain in utero, and then performed single-cell RNA-Seq in the postnatal brain. We identified cell type-specific gene signatures from both neuronal and glial cell classes that are affected by genetic perturbations, and pointed at elements of both convergent and divergent cellular effects across this cohort of ASD risk genes. In vivo Perturb-Seq pioneers a systems genetics approach to investigate at scale how diverse mutations affect cell types and states in the biologically relevant context of the developing organism.
Differential protein metabolism and regeneration in hypertrophic diaphragm and atrophic gastrocnemius muscles in hibernating Daurian ground squirrels
Authors: Yan Xia , Gao Xuli , Peng Xin , Zhang Jie , Ma Xiufeng , Wei Yanhong , Wang Huiping , Gao Yunfang , Chang Hui 
Published: October 2019

AbstractWhether differences in regulation of protein metabolism and regeneration are involved in the different phenotypic adaptation mechanisms of muscle hypertrophy and atrophy in hibernators? Two fast-type muscles (diaphragm and gastrocnemius) in summer active and hibernating Daurian ground squirrels were selected to detect changes in cross-sectional area (CSA), fiber type distribution, and protein expression indicative of protein synthesis metabolism (protein expression of P-Akt, P-mTORC1, P-S6K1, and P-4E-BP1), protein degradation metabolism (MuRF1, atrogin-1, calpain-1, calpain-2, calpastatin, desmin, troponin T, Beclin1, and LC3-II), and muscle regeneration (MyoD, myogenin, and myostatin). Results showed the CSA of the diaphragm muscle increased significantly by 26.1%, whereas the CSA of the gastrocnemius muscle decreased significantly by 20.4% in the hibernation group compared with the summer active group. Both muscles displayed a significant fast-to-slow fiber-type transition in hibernation. Our study further indicated that increased protein synthesis, decreased protein degradation, and increased muscle regeneration potential contributed to diaphragm muscle hypertrophy, whereas decreased protein synthesis, increased protein degradation, and decreased muscle regeneration potential contributed to gastrocnemius muscle atrophy. In conclusion, the differences in muscle regeneration and regulatory pattern of protein metabolism may contribute to the different adaptive changes observed in the diaphragm and gastrocnemius muscles of ground squirrels.
Discordant bioinformatic predictions of antimicrobial resistance from whole-genome sequencing data of bacterial isolates: An inter-laboratory study
Authors: Doyle Ronan M. , O’Sullivan Denise M. , Aller Sean D. , Bruchmann Sebastian , Clark Taane , Pelegrin Andreu Coello , Cormican Martin , Benavente Ernest Diez , Ellington Matthew J. , McGrath Elaine , Motro Yair , Thuy Nguyen Thi Phuong , Phelan Jody , Shaw Liam P. , Stabler Richard A. , van Belkum Alex , van Dorp Lucy , Woodford Neil , Moran-Gilad Jacob , Huggett Jim F. , Harris Kathryn A. 
Published: October 2019

AbstractBackgroundAntimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as a ‘one-stop’ test for epidemiological and predictive AST results. Few published comparisons exist for the myriad analytical pipelines used for predicting AMR. To address this, we performed an inter-laboratory study providing sets of participating researchers with identical short-read WGS data sequenced from clinical isolates, allowing us to assess the reproducibility of the bioinformatic prediction of AMR between participants and identify problem cases and factors that lead to discordant results.MethodsWe produced ten WGS datasets of varying quality from cultured carbapenem-resistant organisms obtained from clinical samples sequenced on either an Illumina NextSeq or HiSeq instrument. Nine participating teams (‘participants’) were provided these sequence data without any other contextual information. Each participant used their own pipeline to determine the species, the presence of resistance-associated genes, and to predict susceptibility or resistance to amikacin, gentamicin, ciprofloxacin and cefotaxime.ResultsIndividual participants predicted different numbers of AMR-associated genes and different gene variants from the same clinical samples. The quality of the sequence data, choice of bioinformatic pipeline and interpretation of the results all contributed to discordance between participants. Although much of the inaccurate gene variant annotation did not affect genotypic resistance predictions, we observed low specificity when compared to phenotypic AST results but this improved in samples with higher read depths. Had the results been used to predict AST and guide treatment a different antibiotic would have been recommended for each isolate by at least one participant.ConclusionsWe found that participants produced discordant predictions from identical WGS data. These challenges, at the final analytical stage of using WGS to predict AMR, suggest the need for refinements when using this technology in clinical settings. Comprehensive public resistance sequence databases and standardisation in the comparisons between genotype and resistance phenotypes will be fundamental before AST prediction using WGS can be successfully implemented in standard clinical microbiology laboratories.
Knowledge-primed neural networks enable biologically interpretable deep learning on single-cell sequencing data
Authors: Fortelny Nikolaus , Bock Christoph 
Published: October 2019

ABSTRACTDeep learning has emerged as a powerful methodology for predicting a variety of complex biological phenomena. However, its utility for biological discovery has so far been limited, given that generic deep neural networks provide little insight into the biological mechanisms that underlie a successful prediction. Here we demonstrate deep learning on biological networks, where every node has a molecular equivalent (such as a protein or gene) and every edge has a mechanistic interpretation (e.g., a regulatory interaction along a signaling pathway).With knowledge-primed neural networks (KPNNs), we exploit the ability of deep learning algorithms to assign meaningful weights to multi-layered networks for interpretable deep learning. We introduce three methodological advances in the learning algorithm that enhance interpretability of the learnt KPNNs: Stabilizing node weights in the presence of redundancy, enhancing the quantitative interpretability of node weights, and controlling for the uneven connectivity inherent to biological networks. We demonstrate the power of our approach on two single-cell RNA-seq datasets, predicting T cell receptor stimulation in a standardizedin vitromodel and inferring cell type in Human Cell Atlas reference data comprising 483,084 immune cells.In summary, we introduce KPNNs as a method that combines the predictive power of deep learning with the interpretability of biological networks. While demonstrated here on single-cell sequencing data, this method is broadly relevant to other research areas where prior domain knowledge can be represented as networks.
An artistic approach to neurofeedback for emotion regulation
Authors: Gabriel Damien , Chabin Thibault , Joucla Coralie , Bussière Thomas , Tarka Aleksandra , Galmes Nathan , Comte Alexandre , Bertrand Guillaume , Giustiniani Julie , Haffen Emmanuel 
Published: October 2019

AbstractNeurofeedback has been shown to be a promising tool for learning to regulate one’s own emotions in healthy populations and in neuropsychiatric disorders. While it has been suggested that neurofeedback performance improves when sensory feedback is related to the pathology under consideration, it is still difficult to represent in real time a proper feedback representative of our emotional state. Since emotion is a central part of people’s dealings with artworks, we have initiated a collaboration between neuroscientists and artists to develop a visual representation of emotions that can be used in neurofeedback experiences. As a result of this collaboration, emotions were represented as particles, moving in a white sphere according to valence and arousal levels. In this study, several possibilities for particle control were explored: direction of particles, their concentration in a specific place, or their gravity. 107 participants evaluated these performances, either in laboratory condition or at various scientific and artistic events. At the end of the experiment, questionnaires were distributed to participants who were asked to indicate on scales ranging from 0 to 5 how artistic the different representations were and could be used as a clinical activity, whether they thought they had successfully controlled the particles during the neurofeedback exercise, and whether they had appreciated the experience. We found that influing on the direction and concentration of particles was considered the most artistic with an average score around 3/5. 47% of the participants considered the concentration of particles as artistic. In addition, although this is not the purpose of this study, we found that participants could significantly control the direction of particles during this session. These encouraging results constitute a first step before evaluating the effectiveness of our emotional neurofeedback over several sessions in healthy, then pathological populations.
Dynamics of Heat Shock Detection and Response in the Intestine ofCaenorhabditis elegans
Authors: Dahlstrom Erin K. , Levine Erel 
Published: October 2019

AbstractThe heat shock response is the organized molecular response to stressors which disrupt proteostasis, potentially leading to protein misfolding and aggregation. While the regulation of the heat shock response is well-studied in single cells, its coordination at the cell, tissue, and systemic levels of a multicellular organism is poorly understood. To probe the interplay between systemic and cell-autonomous responses, we studied the upregulation of HSP-16.2, a molecular chaperone induced throughout the intestine ofCaenorhabditis elegansfollowing a heat shock, by taking longitudinal measurements in a microfluidic environment. Based on the dynamics of HSP-16.2 accumulation, we showed that a combination of heat shock temperature and duration define the intensity of stress inflicted on the worm and identified two regimes of low and high intensity stress. Modeling the underlying regulatory dynamics implicated the saturation of heat shock protein mRNA production in defining these two regimes and emphasized the importance of time separation between transcription and translation in establishing these dynamics. By applying a heat shock and measuring the response in separate parts of the animals, we implicated thermosensory neurons in accelerating the response and transducing information within the animal. We discuss possible implications of the systemic and cell level aspects and how they coordinate to facilitate the organismal response.
Broadly Conserved TMEM-131 Family Proteins in Collagen Production and Secretory Cargo Trafficking
Authors: Zhang Zhe , Bai Meirong , Barbosa Guilherme Oliveira , Chen Andrew , Wei Yuehua , Luo Shuo , Wang Xin , Wang Bingying , Tsukui Tatsuya , Li Hao , Sheppard Dean , Kornberg Thomas B. , Ma Dengke K. 
Published: October 2019

AbstractCollagen is the most abundant protein in animals. Its dysregulation contributes to ageing and human disorders including tissue fibrosis in major organs. How premature collagens in the endoplasmic reticulum (ER) assemble and route for secretion remains molecularly undefined. From an RNAi screen, we identified an uncharacterized C. elegans gene tmem-131, deficiency of which impairs collagen production and activates ER stress response. TMEM-131 N-termini contain bacterial PapD chaperone-like (PapD-L) domains essential for collagen assembly and secretion. Human TMEM131 binds to COL1A2 and TRAPPC8 via N-terminal PapD-L and C-terminal domain, respectively, to drive collagen production. We provide evidence that previously undescribed roles of TMEM131 in collagen recruitment and secretion are evolutionarily conserved in C. elegans, Drosophila and humans.
Class I histone deacetylase HDA-3 is required for full maintenance of locomotor ability in Caenorhabditis elegans
Authors: Kawamura Kazuto , Maruyama Ichiro N. 
Published: October 2019

ABSTRACTLocomotor ability declines with old age. A person’s capacity to maintain locomotor ability depends on genetic and environmental factors. Currently, the specific genetic factors that work to maintain locomotor ability are not well understood. Here we report the involvement of hda-3, encoding a class I histone deacetylase, as a specific genetic factor that contributes to the maintenance of locomotor ability in C. elegans. From a forward genetic approach, we identified a missense mutation in HDA-3 as the causative mutation for progressive decline in locomotor ability in one of the isolated strains. From transcriptome analysis, we found downregulated expression of two clusters of genes on Chromosome II and IV in this strain. Genes carrying CUB-like domains and genes carrying BATH domains were found on Chromosome II and IV, respectively. Knockdown of CUB-like genes, K08D8.5 and dod-17, and BATH genes, bath-1, bath-21 and bath-24 led to a progressive decline in locomotor ability. Our study identifies specific genetic factors that work to maintain locomotor ability and reveals potential targets for delaying age-related locomotor decline.
Amyloid precursor protein-b facilitates cell adhesion during early development in zebrafish
Authors: Banote Rakesh Kumar , Chebli Jasmine , Şatır Tuğçe Munise , Varshney Gaurav K. , Camacho Rafael , Ledin Johan , Burgess Shawn M. , Abramsson Alexandra , Zetterberg Henrik 
Published: October 2019

AbstractUnderstanding the biological function of amyloid beta (Aβ) precursor protein (APP) beyond its role in Alzheimer’s disease is emerging. Yet, its function during embryonic development is poorly understood. The zebrafish APP homologue, Appb, is strongly expressed during early development but thus far has only been studied via morpholino-mediated knockdown. Zebrafish enables analysis of cellular processes in an ontogenic context, which is limited in many other vertebrates. We characterized zebrafish carrying a homozygous mutation that introduces a premature stop in exon 2 of the appb gene. We report that appb mutants are significantly smaller until 2dpf and display perturbed enveloping layer (EVL) integrity and cell protrusions at the blastula stage.Moreover, appb mutants surviving beyond 48 hpf exhibited no behavioral defects at 6 dpf and developed into healthy and fertile adults. The expression of the app-family members, appa and aplp2, was found to be altered in appb mutants. Taken together, we show that appb orchestrates the initial development by supporting the integrity of the EVL, likely by mediating cell adhesion properties. The loss of Appb might be compensated for by other app family members to be able to implement continued normal development.
Agent-based Modeling of Asian Corn Borer Resistance to BT Corn
Authors: Jacildo Arian J. , Rabajante Jomar F. , Alcantara Edwin P. 
Published: October 2019

1.Overview and PurposeWe present ABM-IRM, an agent-based modeling approach to insect resistance management. ABM-IRM is one of the agent-based models that we have developed to simulate the insect resistance of Asian Corn Borer (ACB) to BT corn. The model was implemented using NetLogo, an agent-based programming environment (Wilensky, 1999). We created our model using simple rules to find emergent patterns (Wilensky and Rand, 2015) based on refuge types and pyramid BT events that may aid in controlling the resistance of ACB to BT Corn. Following how the Overview, Design concepts, and Details (ODD) protocol was used in presenting a related ABM paper as guide (Anderson and Dragićević, 2015), the following sections are organized as follows: Section 2 covers the typologies of the agents, Section 3 discusses the process overview, and Section 4 highlights our results and emergent patterns.
Electroencephalographic evidence for the involvement of mirror neuron and error monitoring related processes in virtual body ownership
Authors: Raz Gal , Gurevitch Guy , Vaknin Tom , Aazamy Araz , Gefen Iddo , Grunstein Stanislaw , Azouri Gal , Goldway Noam 
Published: October 2019

AbstractThe illusion that an artificial or virtual object becomes part of one’s body has been demonstrated and productively investigated in the past two decades. Empirical and theoretical accounts of this phenomenon suggest that the body ownership illusion relies not on a single process, but rather on the alignment of the biological and the alternative bodies across multiple aspects. However, the portrayal of these aspects and the demarcation of their neurophysiological correlates has yet to be established.Our study examines electroencephalographic (EEG) markers of two extensively studied systems in the context of virtual body ownership illusion: the mirror neuron system (MNS) and the error monitoring system (EMS). We designed an experimental manipulation of brief involuntary virtual hand bounces, which triggers both systems, and examined how the response of EEG markers of these systems to this manipulation is modulated by three aspects of body ownership: agency, visuotactile synchronicity, and semantic congruence between the participant’s hands and its virtual representation.We found evidence for enhanced MNS-related suppression of power at the Mu band in the synchronous and semantic congruence conditions. On the other hand, the EMS-related Pe/P300 wave was reduced by semantic congruence. This Pe/P300 effect was stronger among participants who exhibited higher acceptance of the spatial illusion and increased tendency for affective empathy. Mu power and Pe/P300 were not correlated, suggesting a dissociation between the distinct aspects of body ownership they probe. The findings suggest that synchronicity and semantic congruence induce sensorimotor sensitivity to the alternative body, whereas the latter parameter also buffers minor erroneous virtual motions. These neurophysiological markers may be added to the arsenal of body ownership probes, and integrated in VR rehabilitation protocols.
Running rabid: modelling of European bat lyssavirus (EBLV) pathways in a bat population
Authors: Breeze Carys , Aegerter James , Smith Graham C 
Published: October 2019

AbstractWorldwide the 16 species of lyssaviruses all exhibit a similar pathology in most mammals, including man; with successful infections usually ending with death. Recently it has been demonstrated that European bat lyssaviruses (EBLV) are not invariably fatal in their wild reservoir host bat species, however the mechanisms and epidemiological consequences of this resistance are interesting and unexplored and the fundamental pathology in bats is still unclear. Here we modelled alternative pathological pathways to explore which appear most plausible, with respect to our limited knowledge of bat-rabies epidemiology and also host population dynamics. Two models were created, one based on a standard progression of disease (classic SEIR model) and the other modified to allow for animals to become either rabid or immune (flexible model). Of these our flexible model was found to be more plausible, demonstrating a much lower sensitivity to epidemiological parameters and by inference the more likely to represent the real-life process occurring in wild European bat populations, with a comparative state space ratio of 1:47. This result implies that it is highly probable survival and post-infection immunity is a widespread epidemiological phenomenon rather than an infrequent consequence of an aborted infection in few individuals. These results can be used to inform laboratory studies on bat immunology and future bat modelling work.
Three-dimensional super-resolution fluorescence imaging of DNA
Authors: Yardimci Sevim , Burnham Daniel R. , Terry Samantha Y. A. , Yardimci Hasan 
Published: October 2019

AbstractRecent advances in fluorescence super-resolution microscopy are providing important insights into details of cellular structures. To acquire three dimensional (3D) super-resolution images of DNA, we combined binding activated localization microscopy (BALM) using fluorescent double-stranded DNA intercalators and optical astigmatism. We quantitatively establish the advantage of mono-over bis-intercalators before demonstrating the approach by visualizing single DNA molecules stretched between microspheres at various heights. Finally, the approach is applied to the more complex environment of intact and damaged metaphase chromosomes, unravelling their structural features.
Persistent Prolate Polymersomes for Enhanced Co-Delivery of Hydrophilic and Hydrophobic Drugs
Authors: L’Amoreaux Nicholas , Ali Aon , Iqbal Shoaib , Larsen Jessica 
Published: October 2019

AbstractSelf-assembled polymersomes encapsulate, protect, and deliver hydrophobic and hydrophilic drugs. Though spherical polymersomes are effective, early studies suggest that non-spherical structures may enhance specificity of delivery and uptake due to similarity to endogenous uptake targets. Here we describe a method to obtain persistent non-spherical shapes, prolates, via osmotic pressure and the effect of prolates on uptake behavior. Polyethylene glycol-b-poly(lactic acid) polymersomes change in diameter from 175 ± 5nm to 200 ± 5nm and increase in polydispersity from 0.06 ± 0.02 to 0.122 ± 0.01 nm after addition of 50 mM salt. Transmission and scanning electron microscopy confirm changes from spheres to prolates. Prolate-like polymersomes maintain their shape in 50 mM NaCl for seven days. Nile Red and bovine serum albumin(BSA)-Fluorescein dyes are taken up in greater amounts by SH-SY5Y neural cells when encapsulated in polymersomes. Prolate polymersomes may be taken up more efficiently in neural cells than spherical polymersomes.