bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probabilistic variable-length segmentation of protein sequences for discriminative motif discovery (DiMotif) and sequence embedding (ProtVecX)
Authors: Asgari Ehsaneddin , McHardy Alice , Mofrad Mohammad R.K. 
Published: June 2018

ABSTRACTIn this paper, we present peptide-pair encoding (PPE), a general-purpose probabilistic segmentation of protein sequences into commonly occurring variable-length sub-sequences. The idea of PPE segmentation is inspired by the byte-pair encoding (BPE) text compression algorithm, which has recently gained popularity in subword neural machine translation. We modify this algorithm by adding a sampling framework allowing for multiple ways of segmenting a sequence. PPE segmentation steps can be learned over a large set of protein sequences (Swiss-Prot) or even a domain-specific dataset and then applied to a set of unseen sequences. This representation can be widely used as the input to any downstream machine learning tasks in protein bioinformatics. In particular, here, we introduce this representation through protein motif discovery and protein sequence embedding. (i) DiMotif: we present DiMotif as an alignment-free discriminative motif discovery method and evaluate the method for finding protein motifs in three different settings: (1) comparison of DiMotif with two existing approaches on 20 distinct motif discovery problems which are experimentally verified, (2) classification-based approach for the motifs extracted for integrins, integrin-binding proteins, and biofilm formation, and (3) in sequence pattern searching for nuclear localization signal. The DiMotif, in general, obtained high recall scores, while having a comparable F1 score with other methods in the discovery of experimentally verified motifs. Having high recall suggests that the DiMotif can be used for short-list creation for further experimental investigations on motifs. In the classification-based evaluation, the extracted motifs could reliably detect the integrins, integrin-binding, and biofilm formation-related proteins on a reserved set of sequences with high F1 scores. (ii) ProtVecX: we extend k-mer based protein vector (ProtVec) embedding to variable-length protein embedding using PPE sub-sequences. We show that the new method of embedding can marginally outperform ProtVec in enzyme prediction as well as toxin prediction tasks. In addition, we conclude that the embeddings are beneficial in protein classification tasks when they are combined with raw k-mer features.AvailabilityImplementations of our method will be available under the Apache 2 licence athttp://llp.berkeley.edu/dimotifandhttp://llp.berkeley.edu/protvecx.
Researchers collaborate with same-gendered colleagues more often than expected across the life sciences
Authors: Holman Luke , Morandin Claire 
Published: June 2018

AbstractEvidence suggests that women in academia are hindered by conscious and unconscious biases, and often feel excluded from formal and informal opportunities for research collaboration. In addition to ensuring fairness and helping to redress gender imbalance in the academic workforce, increasing women’s access to collaboration could help scientific progress by drawing on more of the available human capital. Here, we test whether researchers tend to collaborate with same-gendered colleagues, using more stringent methods and a larger dataset than in past work. Our results reaffirm that researchers co-publish with colleagues of the same gender more often than expected by chance, and show that this ‘gender homophily’ is slightly stronger today than it was 10 years ago. Contrary to our expectations, we found no evidence that homophily is driven mostly by senior academics, and no evidence that homophily is stronger in fields where women are in the minority. Interestingly, journals with a high impact factor for their discipline tended to have comparatively low homophily, as predicted if mixed-gender teams produce better research. We discuss some potential causes of gender homophily in science.
Common recruitment of angular gyrus in episodic autobiographical memory and bodily self-consciousness
Authors: Bréchet Lucie , Grivaz Petr , Gauthier Baptiste , Blanke Olaf 
Published: June 2018

ABSTRACTParietal cortex and adjacent parts of the temporal cortex have recently been involved in bodily self-consciousness (BSC) and in episodic autobiographical memory (EAM). However, the neuroanatomical relationship between both fundamental aspects of self-related processing remains currently unexplored. Here we investigated whether regions in the inferior parietal lobule (IPL) that have been involved in BSC (self-location and first-person perspective) are also activate in studies investigating autobiographical memory. To examine this relation, we performed a meta-analytical study based on functional neuroimaging studies on EAM and SAM and compared them with BSC activations. We report an anatomical overlap bilaterally in the angular gyrus (AG), but not in other parietal or temporal lobe structures between BSC and EAM. Moreover, there was no overlap between BSC and SAM, suggesting that the bilateral AG is a key structure for the conscious re-experiencing of past life episodes (EAM) and the conscious on-line experience of being located and experiencing the world in first-person (BSC).
Capturing the spatiotemporal dynamics of task-initiated thoughts with combined EEG and fMRI
Authors: Bréchet Lucie , Brunet Denis , Birot Gwénaël , Gruetter Rolf , Michel Christoph M. , Jorge João 
Published: June 2018

AbstractWhen at rest, our mind wanders from thought to thought in distinct mental states. Despite the marked importance of ongoing mental processes, it is challenging to capture and relate these states to specific cognitive contents. In this work, we employed ultra-high field functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG) to study the ongoing thoughts of participants instructed to retrieve self-relevant past episodes for periods of 20s. These task-initiated, participant-driven activity patterns were compared to a distinct condition where participants performed serial mental arithmetic operations, thereby shifting from self-related to self-unrelated thoughts. BOLD activity mapping revealed selective activity changes in temporal, parietal and occipital areas (“posterior hot zone”), evincing their role in integrating the re-experienced past events into conscious representations during memory retrieval. Functional connectivity analysis showed that these regions were organized in two major subparts of the default mode network, previously associated to “scene-reconstruction” and “self-experience” subsystems. EEG microstate analysis allowed studying these participant-driven thoughts in the millisecond range by determining the temporal dynamics of brief periods of stable scalp potential fields. This analysis revealed selective modulation of occurrence and duration of specific microstates in both conditions. EEG source analysis revealed similar spatial distributions between the sources of these microstates and the regions identified with fMRI. These findings support growing evidence that specific fMRI networks can be captured with EEG as repeatedly occurring, integrated brief periods of synchronized neuronal activity, lasting only fractions of seconds.SignificanceWe investigated the spatiotemporal dynamics of large-scale brain networks related to specific conscious thoughts. We demonstrate here that instructing participants to direct their thoughts to either episodic autobiographic memory or to mental arithmetic modulates distinct networks both in terms of highly spatially-specific BOLD signal oscillations as well as fast sub-second dynamics of EEG microstates. The combined findings from the two modalities evince a clear link between hemodynamic and electrophysiological signatures of spontaneous brain activity by the occurrence of thoughts that last for fractions of seconds, repeatedly appearing over time as integrated coherent activities of specific large-scale networks.
A matrix protein acts as a cue to preserve collective motility ofB. subtilisbiofilm cells
Authors: Steinberg Nitai , Doron Shany , Jain Rakeshkumar , Rosenberg Gili , Teeffelen Sven van , Kolodkin-Gal Ilana 
Published: June 2018

SummaryBacteria in nature are usually found in complex multicellular communities, termed biofilms. Biofilms are generally seen as sessile structures, resulting from downregulation of motility. However, during interspecies competition and predation, biofilm cells were shown to migrate towards competitor colonies. Here, we show that a specific extracellular matrix (ECM) protein, TasA, is essential for collective migration toward potential competitors and serves as a developmental cue that increases the formation of motile offspring from sessile chains. We reveal an effective strategy to maintain migration capacities in bacterial biofilms: besides providing a three-dimensional adhesive scaffold for the cells, TasA acts as a signal within the bacterial community.
Unique molecular markers for GC-D-expressing olfactory sensory neurons and chemosensory neurons of the Grueneberg ganglion
Authors: Huang Zhi , Zimmerman Arthur D. , Munger Steven D. 
Published: June 2018

ABSTRACTThe main olfactory bulb (MOB) is differentiated into subregions based on their innervation by molecularly distinct chemosensory neurons. For example, olfactory sensory neurons (OSNs) that employ a cGMP-mediated transduction cascade – guanylyl-cyclase D-expressing (GC-D+) OSNs of the main olfactory epithelium (MOE) and chemosensory neurons of the Grueneberg ganglion (GGNs) – project to distinct groups of “necklace” glomeruli encircling the caudal MOB. To better understand the unique functionality and neural circuitry of the necklace glomeruli and their associated sensory neurons, we sought to identify additional molecular markers that would differentiate GC-D+ OSNs and GGNs as well as their target glomeruli. We found in mouse that GC-D+ OSNs, but not other MOE OSNs or GGNs, express the neuropeptide CART (cocaine- and amphetamine-regulated transcript). Both GC-D+ OSNs and GGNs, but not other MOE OSNs, express the Ca2+/calmodulin-dependent phosphodiesterase Pde1a, which is immunolocalized throughout the dendrites, somata and axons of these neurons. Stronger Pde1a immunolabeling in necklace glomeruli innervated by GGNs than in those innervated by GC-D+ OSNs suggests either greater Pde1a expression in individual GGNs than in GC-D+ OSNs or a difference in sensory neuron innervation density between the two types of necklace glomeruli. Together, the unique molecular signatures of GC-D+ OSNs, GGNs and their MOB targets offer important tools for understanding the processing of chemosensory information by olfactory subsystems associated with the necklace glomeruli.
Computer Simulations of the Humoral Immune System Reveal How Imprinting Can Affect Responses to Influenza HA Stalk with Implications for the Design of Universal Vaccines
Authors: Anderson Christopher S. , Sangster Mark Y. , Yang Hongmei , Chaudhury Sidhartha , Topham David J. 
Published: June 2018

AbstractBackgroundSuccessful vaccination against the H1N1 Influenza A virus has required the continuous development of new vaccines that are antigenically similar to currently circulating strains. Vaccine strategies that can increase the cross-reactivity of the antibody response, especially to conserved regions, are essential to creating long-lasting immunity to H1N1 viruses. How pre-existing immunity affects vaccine-induced antibody cross-reactivity is still not well understood.MethodsAn immunological shape space of antigenic sites of hemagglutinin (HA) was constructed using viral sequence data. A Gillespie Algorithm-based model of the humoral immune system was used to simulate B cell responses to A/California/07/2009 (CA09) HA antigen after prior immunization with an antigenically similar or dissimilar strain. The effect of pre-existing memory B cells and antibody on the resulting antibody responses was interrogated.ResultsWe found increased levels of highly-cross-reactive antibodies after immunization with antigenically dissimilar strains. This increase was dependent on pre-existing memory B cells. Furthermore, pre-existing antibody also interfered with the cross-reactive antibody response, but this effect occurred irrespective of the priming antigen.ConclusionThese findings suggest that vaccination by divergent strains will boost highly-cross-reactive antibodies by selectively targeting memory B cells specific to conserved antigenic sites and by reducing the negative interference caused by pre-existing antibody.
GONST2 transports GDP-Mannose for sphingolipid glycosylation in the Golgi apparatus of Arabidopsis
Authors: Jing Beibei , Ishikawa Toshiki , Soltis Nicole , Inada Noriko , Liang Yan , Murawska Gosia , Andeberhan Fekadu , Pidatala Ramana , Yu Xiaolan , Baidoo Edward , Kawai-Yamada Maki , Loque Dominique , Kliebenstein Daniel J. , Dupree Paul , Mortimer Jenny C. 
Published: June 2018

AbstractThe Golgi lumen is the site of many different glycosylation events, including cell wall polysaccharide biosynthesis and lipid glycosylation. Transporters are necessary for the import of the substrates required for glycosylation (nucleotide sugars) from the cytosol where they are synthesized. Plants use four GDP-linked sugars to glycosylate macromolecules: GDP-L-Fucose, GDP-D-Mannose, GDP-L-Galactose and GDP-D-Glucose. Of the predicted fifty-one members of the nucleotide sugar transporter/triose phosphate transporter family in Arabidopsis, only four appear to contain the conserved motif needed for the transport of GDP-linked sugars, GOLGI LOCALIZED NUCLEOTIDE SUGAR TRANSPORTER (GONST) 1-4. Previously, we have demonstrated that GONST1 provides GDP-D-Mannose for glycosylation of a class of sphingolipids, the glycosylinositolphosphorylceramides (GIPCs). Here, we characterize its closest homologue, GONST2, and conclude that it also specifically provides substrate for GIPC glycosylation. Expression ofGONST2driven by theGONST1promoter is able to rescue the severe growth phenotype ofgonst1. Loss of GONST2 exacerbates thegonst1constitutive hypersensitive response, as well as the reduced cell wall cellulose content. Thegonst2mutant grows normally under standard conditions, but has enhanced resistance to the powdery mildew-causing fungusGolovinomyces orontii.
Inducible gene switches with memory in human T cells for cellular immunotherapy
Authors: Chakravarti Deboki , Caraballo Leidy D , Weinberg Benjamin H. , Wong Wilson W. 
Published: June 2018

AbstractCell-based therapies that employ engineered T cells—including the expression of chimeric antigen receptors (CARs)—to target cancer cells have demonstrated promising responses in clinical trials. However, engineered T cell responses must be regulated to prevent severe side effects such as cytokine storms and off-target responses. Here we present a class of recombinase-based gene circuits that will enable inducible switching between two states of adoptive T cell therapy using an FDA-approved drug, creating a generalizable platform that can be used to control when and how strongly a gene is expressed. These circuits exhibit memory such that induced T cells will maintain any changes made even when the drug inducer is removed. This memory feature avoids prolonged drug inducer exposure, thus reducing the complexity and potential side effect associated with the drug inducer. We have utilized these circuits to control the expression of an anti-Her2-CAR, demonstrating the ability of these circuits to regulate CAR expression and T cell activity. We envision this platform can be extended to regulate other genes in T cell behavior for various adoptive T cell therapies.
Machine learning to classify animal species in camera trap images: applications in ecology
Authors: Tabak Michael A. , Norouzzadeh Mohammad S. , Wolfson David W. , Sweeney Steven J. , VerCauteren Kurt C. , Snow Nathan P. , Halseth Joseph M. , Di Salvo Paul A. , Lewis Jesse S. , White Michael D. , Teton Ben , Beasley James C. , Schlichting Peter E. , Boughton Raoul K. , Wight Bethany , Newkirk Eric S. , Ivan Jacob S. , Odell Eric A. , Brook Ryan K. , Lukacs Paul M. , Moeller Anna K. , Mandeville Elizabeth G. , Clune Jeff , Miller Ryan S. 
Published: June 2018

Abstract1. Motion-activated cameras (“camera traps”) are increasingly used in ecological and management studies for remotely observing wildlife and have been regarded as among the most powerful tools for wildlife research. However, studies involving camera traps result in millions of images that need to be analyzed, typically by visually observing each image, in order to extract data that can be used in ecological analyses.2. We trained machine learning models using convolutional neural networks with the ResNet-18 architecture and 3,367,383 images to automatically classify wildlife species from camera trap images obtained from five states across the United States. We tested our model on an independent subset of images not seen during training from the United States and on an out-of-sample (or “out-of-distribution” in the machine learning literature) dataset of ungulate images from Canada. We also tested the ability of our model to distinguish empty images from those with animals in another out-of-sample dataset from Tanzania, containing a faunal community that was novel to the model.3. The trained model classified approximately 2,000 images per minute on a laptop computer with 16 gigabytes of RAM. The trained model achieved 98% accuracy at identifying species in the United States, the highest accuracy of such a model to date. Out-of-sample validation from Canada achieved 82% accuracy, and correctly identified 94% of images containing an animal in the dataset from Tanzania. We provide an R package (Machine Learning for Wildlife Image Classification; MLWIC) that allows the users to A) implement the trained model presented here and B) train their own model using classified images of wildlife from their studies.4. The use of machine learning to rapidly and accurately classify wildlife in camera trap images can facilitate non-invasive sampling designs in ecological studies by reducing the burden of manually analyzing images. We present an R package making these methods accessible to ecologists. We discuss the implications of this technology for ecology and considerations that should be addressed in future implementations of these methods.
Capturing variation impact on molecular interactions: the IMEx Consortium mutations data set
Authors:   The IMEx Consortium Curators, del Toro N , Duesbury M , Koch M , Perfetto L , Shrivastava A , Ochoa D , Wagih O , Piñero J , Kotlyar M , Pastrello C , Beltrao P , Furlong LI , Jurisica I , Hermjakob H , Orchard S , Porras P 
Published: June 2018

AbstractThe current wealth of genomic variation data identified at the nucleotide level has provided us with the challenge of understanding by which mechanisms amino acid variation affects cellular processes. These effects may manifest as distinct phenotypic differences between individuals or result in the development of disease. Physical interactions between molecules are the linking steps underlying most, if not all, cellular processes. Understanding the effects that amino acid variation of a molecule’s sequence has on its molecular interactions is a key step towards connecting a full mechanistic characterization of nonsynonymous variation to cellular phenotype. Here we present an open access resource created by IMEx database curators over 14 years, featuring 28,000 annotations fully describing the effect of individual point sequence changes on physical protein interactions. We describe how this resource was built, the formats in which the data content is provided and offer a descriptive analysis of the data set. The data set is publicly available through the IntAct website at www.ebi.ac.uk/intact/resources/datasets#mutationDs and is being enhanced with every monthly release.
Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice
Authors: Chandler Joshua D. , Hu Xin , Ko Eunju , Park Soojin , Fernandes Jolyn , Lee Young-Tae , Orr Michael L. , Hao Li , Ryan Smith M. , Neujahr David C. , Uppal Karan , Kang Sang-Moo , Jones Dean P. , Go Young-Mi 
Published: June 2018

AbstractBACKGROUNDCadmium (Cd) is a toxic, pro-inflammatory metal ubiquitous in the diet that accumulates in body organs due to inefficient elimination. Many individuals exposed to dietary Cd are also infected by seasonal influenza virus. The H1N1 strain causes mild to severe pneumonia which can be fatal.OBJECTIVESTo determine the influence of low-dose Cd exposure on inflammatory responses to H1N1 influenza A virus.METHODSWe exposed mice to low-dose (1 mg CdCl2/l) Cd or vehicle (water) for 16 weeks prior to infection with a sub-lethal dose of H1N1. Lung inflammation was assessed by histopathology and flow cytometry. We used a combination of transcriptomics, metabolomics and bioinformatics to determine the molecular associations of inflammatory cells important in Cd-exacerbated responses.RESULTSCd-treated mice had increased lung tissue inflammatory cells, including neutrophils, monocytes, T lymphocytes and dendritic cells, following H1N1 infection. Lung genetic responses to infection (increasing TNF-a, interferon and complement, and decreasing myogenesis) were also exacerbated. Global correlations with immune cell counts, leading edge gene transcripts and metabolites revealed that Cd increased correlation of myeloid immune cells with pro-inflammatory genes, particularly interferon-γ, and metabolites in amino acid, nucleobase, glycerophospholipid and vitamin B3 pathways.DISCUSSIONCd burden in mice increased inflammation in response to sub-lethal H1N1 challenge, which was coordinated by genetic and metabolic responses, and could provide new targets for intervention against lethal inflammatory pathology of clinical H1N1 infection.
Determinants of base-pair substitution patterns revealed by whole-genome sequencing of DNA mismatch repair defectiveEscherichia coli
Authors: Foster Patricia L. , Niccum Brittany A. , Popodi Ellen , Townes Jesse P. , Lee Heewook , MohammedIsmail Wazim , Tang Haixu 
Published: June 2018

ABSTRACTMismatch repair (MMR) is a major contributor to replication fidelity, but its impact varies with sequence context and the nature of the mismatch. Mutation accumulation experiments followed by whole-genome sequencing of MMR-defectiveE. colistrains yielded ≈30,000 base-pair substitutions, revealing mutational patterns across the entire chromosome. The base-pair substitution spectrum was dominated by A:T > G:C transitions, which occurred predominantly at the center base of 5′NAC3′+5′GTN3′ triplets. Surprisingly, growth on minimal medium or at low temperature attenuated these mutations. Mononucleotide runs were also hotspots for base-pair substitutions, and the rate at which these occurred increased with run length. Comparison with ≈2000 base-pair substitutions accumulated in MMR-proficient strains revealed that both kinds of hotspots appeared in the wild-type spectrum and so are likely to be sites of frequent replication errors. In MMR-defective strains transitions were strand biased, occurring twice as often when A and C rather than T and G were on the lagging-strand template. Loss of nucleotide diphosphate kinase increases the cellular concentration of dCTP, which resulted in increased rates of mutations due to misinsertion of C opposite A and T. In anmmr ndkdouble mutant strain, these mutations were more frequent when the template A and T were on the leading strand, suggesting that lagging-strand synthesis was more error-prone or less well corrected by proofreading than was leading strand synthesis.