bluuebunny/crossref_metadata_2025_split huggingface dataset:
IBD analysis of Australian amyotrophic lateral sclerosis SOD1-mutation carriers identifies five founder events and links sporadic cases to existing ALS families
Authors: Henden Lyndal , Twine Natalie A. , Szul Piotr , McCann Emily P. , Nicholson Garth A. , Rowe Dominic B. , Kiernan Matthew C. , Bauer Denis C. , Blair Ian P. , Williams Kelly L. 
Published: June 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by the loss of upper and lower motor neurons resulting in paralysis and eventual death. Approximately 10% of ALS cases have a family history of disease, while the remaining cases present as apparently sporadic. Heritability studies suggest a significant genetic component to sporadic ALS, and although most sporadic cases have an unknown genetic etiology, some familial ALS mutations have also been found in sporadic cases. This suggests that some sporadic cases may be unrecognised familial cases with reduced disease penetrance. Identifying a familial basis of disease in apparently sporadic ALS cases has significant genetic counselling implications for immediate relatives. A powerful strategy to uncover a familial link is identity-by-descent (IBD) analysis which detects genomic regions that have been inherited from a common ancestor. We performed IBD analysis on 90 Australian familial ALS cases from 25 families and three sporadic ALS cases, each of whom carried one of three SOD1 mutations (p.I114T, p.V149G and p.E101G). We identified five unique haplotypes that carry these mutations in our cohort, indicative of five founder events. This included two different haplotypes that carry SOD1 p.I114T, where one haplotype was present in one sporadic case and 20 families, while the second haplotype was found in the remaining two sporadic cases and one family, thus linking these familial and sporadic cases. Furthermore, we linked two families that carry SOD1 p.V149G and found that SOD1 p.E101G arose independently in each family that carries this mutation.
Striking differences in virulence, transmission, and sporocyst growth dynamics between two schistosome populations
Authors: Clec’h Winka Le , Diaz Robbie , Chevalier Frédéric D. , McDew-White Marina , Anderson Timothy J.C. 
Published: June 2019

ABSTRACTBackgroundParasite traits associated with transmission success, such as the number of infective stages released from the host, are expected to be optimized by natural selection. However, in the trematode parasite Schistosoma mansoni, a key transmission trait – the number of cercariae larvae shed from infected Biomphalaria spp. snails – varies significantly within and between different parasite populations and selection experiments demonstrate that this variation has a strong genetic basis. In this study, we compared the transmission strategies of two laboratory schistosome population and their consequences for their snail host.MethodsWe infected inbred Biomphalaria glabrata snails using two Schistosoma mansoni parasite populations (SmBRE and SmLE), both isolated from Brazil and maintained in the laboratory for decades. We compared life history traits of these two parasite populations by quantifying sporocyst growth within infected snails (assayed using qPCR), output of cercaria larvae, and impact on snail host physiological response (i.e. hemoglobin rate, laccase-like activity) and survival.ResultsWe identified striking differences in virulence and transmission between the two studied parasite populations. SmBRE (low shedder (LS) parasite population) sheds very low numbers of cercariae, and causes minimal impact on the snail physiological response (i.e. laccase-like activity, hemoglobin rate and snail survival). In contrast, SmLE (high shedder (HS) parasite population) sheds 8-fold more cercariae (mean ± se cercariae per shedding: 284±19 vs 2352±113), causes high snail mortality, and has strong impact on snail physiology. We found that HS sporocysts grow more rapidly inside the snail host, comprising up to 60% of cells within infected snails, compared to LS sporocysts which comprised up to 31%. Cercarial production is strongly correlated to the number of S. mansoni sporocyst cells present within the snail host tissue, although the proportion of sporocyst cells alone does not explain the low cercarial shedding of SmBRE.ConclusionsWe demonstrated the existence of alternative transmission strategies in the S. mansoni parasite consistent with trade-offs between parasite transmission and host survival: a “boom-bust” strategy characterized by high virulence, high transmission and short duration infections and a “slow and steady” strategy with low virulence, low transmission but long duration of snail host infections.
Extramacrochaete promotes branch and bouton number via the sequestration of Daughterless in the cytoplasm of neurons
Authors: Waddell Edward A. , Viveiros Jennifer M. , Robinson Erin L. , Sharoni Michal A. , Latcheva Nina K. , Marenda Daniel R. 
Published: June 2019

AbstractThe class I basic Helix Loop Helix (bHLH) proteins are highly conserved transcription factors that are ubiquitously expressed. A wealth of literature on class I bHLH proteins have shown that these proteins must homodimerize or heterodimerize with tissue specific HLH proteins in order to bind DNA at E box (CANNTG) consensus sequences to control tissue specific transcription. Due to its ubiquitous expression, class I bHLH proteins are also extensively regulated post-translationally, mostly through dimerization. Previously, we reported that in addition to its role in promoting neurogenesis, the class I bHLH protein Daughterless also functions in mature neurons to restrict axon branching and synapse number. Here, we show that part of the molecular logic that specifies how Daughterless functions in neurogenesis is also conserved in neurons. We show that the type V HLH protein Extramacrochaete binds to and represses Daughterless function by sequestering Daughterless to the cytoplasm. This work provides initial insights into the mechanisms underlying the function of Daughterless and Extramacrochatae in neurons while providing a novel understanding of how Extramacrochaetae functions to restricts Daughterless activity within the cell.
Unsupervised decoding of single-trial EEG reveals unique states of functional brain connectivity that drive rapid speech categorization decisions
Authors: Al-Fahad Rakib , Yeasin Mohammed , Bidelman Gavin M. 
Published: June 2019

ABSTRACTCategorical perception (CP) is an inherent property of speech perception. The response time (RT) of listeners’ perceptual speech identification are highly sensitive to individual differences. While the neural correlates of CP have been well studied in terms of the regional contributions of the brain to behavior, functional connectivity patterns that signify individual differences in listeners’ speed (RT) for speech categorization is less clear. To address these questions, we applied several computational approaches to the EEG including graph mining, machine learning (i.e., support vector machine), and stability selection to investigate the unique brain states (functional neural connectivity) that predict the speed of listeners’ behavioral decisions. We infer that (i) the listeners’ perceptual speed is directly related to dynamic variations in their brain connectomics, (ii) global network assortativity and efficiency distinguished fast, medium, and slow RT, (iii) the functional network underlying speeded decisions increases in negative assortativity (i.e., became disassortative) for slower RTs, (iv) slower categorical speech decisions cause excessive use of neural resources and more aberrant information flow within the CP circuitry, (v) slower perceivers tended to utilize functional brain networks excessively (or inappropriately) whereas fast perceivers (with lower global efficiency) utilized the same neural pathways but with more restricted organization. Our results showed that neural classifiers (SVM) coupled with stability selection correctly classify behavioral RTs from functional connectivity alone with over 90% accuracy (AUC=0.9). Our results corroborate previous studies by confirming the engagement of similar temporal (STG), parietal, motor, and prefrontal regions in CP using an entirely data-driven approach.
Diffusion of kinesin motors on cargo can enhance binding and run lengths during intracellular transport
Authors: Bovyn Matthew , Reddy Babu , Gross Steven , Allard Jun 
Published: June 2019

AbstractCellular cargos, including lipid droplets and mitochondria, are transported along microtubules using molecular motors such as kinesins. Many experimental and computational studies of cargos with rigidly attached motors, in contrast to many biological cargos that have lipid surfaces that may allow surface mobility of motors. We extend a mechanochemical 3D computational model by adding coupled-viscosity effects to compare different motor arrangements and mobilities. We show that organizational changes can optimize for different objectives: Cargos with clustered motors are transported efficiently, but are slow to bind to microtubules, whereas those with motors dispersed rigidly on their surface bind microtubules quickly, but are transported inefficiently. Finally, cargos with freely-diffusing motors have both fast binding and efficient transport, although less efficient than clustered motors. These results suggest that experimentally observed changes in motor organization may be a control point for transport.
A “feet digging” swash zone sampling method for the sandy beach bivalveDonax deltoides(Bivalvia: Donacidae)
Authors: Totterman Stephen 
Published: June 2019

ABSTRACTA “feet digging” method for sampling the sandy beach bivalveDonax deltoideswas evaluated by comparison to quadrat-based results from eleven beaches in subtropical eastern Australia. The method was developed from a recreational fishing technique that involves twisting one’s feet into the thixotropic sand to dislodge buried clams which are then recovered by hand. Several plots are sampled across the swash zone in one five-minute sampling unit and the process is replicated at several locations along the beach. Mean feet digging clam counts were proportional to mean transect linear clam densities (r= 0.98). Clam length-frequency distributions from feet digging were similar to those from quadrat sampling except that feet digging was not effective for clams < 16 mm. Feet digging counts are sensitive to both across shore (tidal) and alongshore variation in clam abundance and were less precise than those from quadrat-based methods (CV1.2× larger). However, feet digging is fast and the method should be useful for low cost surveys ofDonax deltoidesand similar “surf clams”.
On-scalp MEG SQUIDs are sensitive to early somatosensory activity unseen by conventional MEG
Authors: Andersen Lau M. , Pfeiffer Christoph , Ruffieux Silvia , Riaz Bushra , Winkler Dag , Schneiderman Justin F. , Lundqvist Daniel 
Published: June 2019

AbstractMagnetoencephalography (MEG) has a unique capacity to resolve the spatio-temporal development of brain activity from non-invasive measurements. Conventional MEG, however, relies on sensors that sample from a distance (20-40 mm) to the head due to thermal insulation requirements (the MEG sensors function at 4 K in a helmet). A gain in signal strength and spatial resolution may be achieved if sensors are moved closer to the head. Here, we report a study comparing measurements from a seven-channel on-scalp SQUID MEG system to those from a conventional (in-helmet) SQUID MEG system.We compared spatio-temporal resolution between on-scalp and conventional MEG by comparing the discrimination accuracy for neural activity patterns resulting from stimulating five different phalanges of the right hand. Because of proximity and sensor density differences between on-scalp and conventional MEG, we hypothesized that on-scalp MEG would allow for a more high-resolved assessment of these activity patterns, and therefore also a better classification performance in discriminating between neural activations from the different phalanges.We observed that on-scalp MEG provided better classification performance during an early post-stimulus period (15-30 ms). This corresponded to electroencephalographic (EEG) response components N16 and P23, and was an unexpected observation as these components are usually not observed in conventional MEG. They indicate that on-scalp MEG opens up for a richer registration of the cortical signal, allowing for sensitivity to what are potentially sources in the thalamo-cortical radiation and to quasi-radial sources.We had originally expected that on-scalp MEG would provide better classification accuracy based on activity in proximity to the P60m component compared to conventional MEG. This component indeed allowed for the best classification performance for both MEG systems (60-75%, chance 50%). However, we did not find that on-scalp MEG allowed for better classification than conventional MEG at this latency. We believe this may be due to the limited sensor coverage in the recording, in combination with our strategy for positioning the on-scalp MEG sensors. We discuss how sensor density and coverage as well as between-phalange source field dissimilarities may influence our hypothesis testing, which we believe to be useful for future benchmarking measurements.
Non-invasive prenatal testing by low coverage genomic sequencing: Detection limits of screened chromosomal microdeletions
Authors: Kucharik Marcel , Gnip Andrej , Hyblova Michaela , Budis Jaroslav , Strieskova Lucia , Harsanyova Maria , Duris Frantisek , Radvanszky Jan , Minarik Gabriel , Szemes Tomas 
Published: June 2019

AbstractObjectiveTo study the detection limits of chromosomal microaberrations in non-invasive prenatal testing with aim for five target microdeletion syndromes, including DiGeorge, Prader-Willi/Angelman, 1p36, Cri-Du-Chat, and Wolf-Hirschhorn syndromes.MethodWe used known cases of pathogenic deletions from ISCA database to specifically define regions critical for the target syndromes. Our approach to detect microdeletions, from whole genome sequencing data, is based on sample normalization and read counting for individual bins. We performed both an in-silico study using artificially created data sets and a laboratory test on mixed DNA samples, with known microdeletions, to assess the sensitivity of prediction for varying fetal fractions, deletion lengths, and sequencing read counts.ResultsThe in-silico study showed sensitivity of 79.3% for 10% fetal fraction with 20M read count, which further increased to 98.4% if we searched only for deletions longer than 3Mb. The test on laboratory-prepared mixed samples was in agreement with in-silico results, while we were able to correctly detect 24 out of 29 control samples.ConclusionOur results suggest that it is possible to incorporate microaberration detection into basic NIPT as part of the offered screening/diagnostics procedure, however, accuracy and reliability depends on several specific factors.What’s already known about this topic?Microdeletion detection accuracy, similarly to most common trisomies detection, was found to be dependent mostly on technical and biological parameters of the test and tested samples, such as coverage of target region, fetal fraction, size and positions of the deletions.What does this study add?Estimation of relevant regions for five chosen microdeletion syndromes. Confirmation and improvement upon previous methods. Systematic evaluation of sensitivity of microdeletion detection with read counts from 10M to 20M.
Basicity of N5 in semiquinone enhances the rate of respiratory electron outflow inShewanella oneidensisMR-1
Authors: Tokunou Yoshihide , Saito Keisuke , Hasegawa Ryo , Nealson Kenneth H. , Hashimoto Kazuhito , Ishikita Hiroshi , Okamoto Akihiro 
Published: June 2019

AbstractExtracellular electron transport (EET) occurs in environmental iron-reducing bacteria and is mediated by an outer membrane multi-heme cytochrome complex (Cyts). It has critical implications for global mineral cycling and electrochemical microbial catalysis. The rate of EET mediated by multiple heme redox centers significantly increases in the presence of flavins and quinones. Their electron free energy does not entirely account for the fact that differential effects on EET rate enhancement vary significantly by factors ≥100. Here, we report on whole-cell electrochemical analysis ofShewanella oneidensisMR-1 using six flavin analogs and four quinones. We demonstrated that protonation of the nitrogen atom at position 5 (N5) of the isoalloxazine ring is essential for electron outflow acceleration as a bound non-covalent cofactor of Cyts. EET mediated by Cyts was accelerated at a rate dependent on pKa(N5). The EET rate largely decreased in response to the addition of deuterated water (D2O), while low concentration of D2O (4 %) had little impact on electron free energy difference of the heme and non-covalent bound cofactors, strongly suggesting that the protonation of N5 limits the rate of EET. Our findings directly link EET kinetics to proton transport reaction via N5 and provide a basis for the development of novel strategies for controlling EET-associated biological reactions.Significance statementThe potential of various small molecules such as flavins and quinones to enhance the rate of extracellular electron transport (EET) has been exploited to develop environmental energy conversion systems. Flavins and quinones have similar molecular structures but their abilities to enhance EET vary by >100× inShewanella oneidensisMR-1. These large differences are inconsistent with conventional models, which rely on redox potentials or diffusion constant of shuttling electron mediators. In this study, we demonstrated that the basicity of the nitrogen atom of the isoalloxazine ring (N5) enhances the rate of electron outflow when a flavin or quinone is a non-covalent cofactor ofS. oneidensisMR-1 outer membranec-type cytochromes.
Relation Extraction Between Bacteria and Biotopes from Biomedical Texts with Attention Mechanisms and Domain-Specific Contextual Representations
Authors: Jettakul Amarin , Wichadakul Duangdao , Vateekul Peerapon 
Published: June 2019

AbstractThe Bacteria Biotope (BB) task is biomedical relation extraction (RE) that aims to study the interaction between bacteria and their locations. This task is considered to pertain to fundamental knowledge in applied microbiology. Some previous investigations have used feature-based models; others have presented deep-learning-based models such as convolutional and recurrent neural networks used with the shortest dependency paths (SDPs). Although SDPs contain valuable and concise information, sections of significant information necessary to define bacterial location relationships are often neglected. In addition, the traditional word embedding used in previous studies may suffer from word ambiguation across linguistic contexts.Here, we present a deep learning model for biomedical RE. The model incorporates feature combinations of SDPs and full sentences with various attention mechanisms. We also used pre-trained contextual representations based on domain-specific vocabularies. In order to assess the model’s robustness, we introduced a mean F1 score on many models using different random seeds. The experiments were conducted on the standard BB corpus in BioNLP-ST’16. Our experimental results revealed that the model performed better (in terms of both maximum and average F1 scores; 60.77% and 57.63%, respectively) compared with other existing models.We demonstrated that our proposed contributions to this task can be used to extract rich lexical, syntactic, and semantic features that effectively boost the model’s performance. Moreover, we analyzed the trade-off between precision and recall in order to choose the proper cut-off to use in real-world applications.
Transposable element over-accumulation in autopolyploids results from relaxed purifying selection and provides variants for rapid local adaptation
Authors: Baduel P. , Quadrana L. , Hunter B. , Bomblies K. , Colot V. 
Published: June 2019

AbstractPolyploidization is frequently associated with increased transposable element (TE) content. However, what drives TE dynamics following whole genome duplication (WGD) and the evolutionary implications remain unclear. Here, we leveraged whole-genome resequencing data of ∼300 individual Arabidopsis arenosa plants, a well characterized natural diploid-autotetraploid species, to address these questions. Based on 43,176 polymorphic TE insertions we detected in these genomes, we demonstrate that relaxed purifying selection rather than transposition bursts is the main driver of TE over-accumulation after WGD. Furthermore, the increased pool of TE insertions in tetraploids is especially enriched within or near abiotic and biotic stress response genes. Notably, we uncovered one such insertion in a major flowering-time repressor gene and found that the resulting allele is specific to the rapid-cycling tetraploid lineage that colonized mainland railways. Together, our findings indicate that tetrasomy by itself leads to an enhanced tolerance to accumulating genic TE variants, some of which can potentially contribute to local adaptation.
Feedback regulation of BMP signaling byC. eleganscuticle collagens
Authors: Madaan Uday , Faure Lionel , Chowdhury Albar , Ahmed Shahrear , Ciccarelli Emma J. , Gumienny Tina L. , Savage-Dunn Cathy 
Published: June 2019

AbstractCellular responsiveness to environmental cues, including changes in extracellular matrix (ECM), is critical for normal processes such as development and wound healing, but can go awry, as in oncogenesis and fibrosis. One type of molecular pathway allowing this responsiveness is the bone morphogenetic protein (BMP) signaling pathway. Due to their broad and potent functions, BMPs and their signaling pathways are highly regulated at multiple levels. InCaenorhabditis elegans, the BMP ligand DBL-1 is a major regulator of body size. We have previously shown that DBL-1/BMP signaling determines body size through transcriptional regulation of cuticle collagen genes. We have now obtained evidence of feedback regulation of DBL-1/BMP by collagen genes. We analyzed four DBL-1-regulated collagen genes that affect body size. Here we show that inactivation of any one of these cuticle collagen genes reduces DBL-1/BMP signaling, as measured by a Smad activity reporter. Furthermore, we find that depletion of these collagens reduces GFP::DBL-1 fluorescence, and acts unexpectedly at the level ofdbl-1transcription. We therefore conclude that cuticle, a type of ECM, impinges on DBL-1/BMP expression and signaling. In contrast to other characterized examples, however, the feedback regulation of DBL-1/BMP signaling by collagens is likely to be contact-independent, due to the physical separation of the cuticle from DBL-1-expressing cells in the ventral nerve cord. Our results provide an entry point into a novel mechanism of regulation of BMP signaling, with broader implications for mechanical regulation of gene expression in general.