bluuebunny/crossref_metadata_2025_split huggingface dataset:
SVCollector: Optimized sample selection for validating and long-read resequencing of structural variants
Authors: Sedlazeck Fritz J. , Lemmon Zachary , Soyk Sebastian , Salerno William J. , Lippman Zachary , Schatz Michael C. 
Published: June 2018

AbstractSummaryStructural Variations (SVs) are increasingly recognized for their importance in genomics. Short-read sequencing is the most widely-used approach for genotyping large numbers of samples for SVs but suffers from relatively poor accuracy. Here we present SVCollector, an open-source method that optimally selects samples to maximize variant discovery and validation using long read resequencing or PCR-based validation. SVCollector has two modes: selecting those samples that are individually the most diverse or those that collectively capture the largest number of variations.Availabilityhttps://github.com/fritzsedlazeck/SVCollectorContactfritz.sedlazeck@bcm.eduSupplementary informationSupplementary data are available at Bioinformatics online.
Genome-Wide Association Study of Brain Connectivity Changes for Alzheimer’s Disease
Authors: Elsheikh Samar S. M. , Chimusa Emile R. , Mulder Nicola J. , Crimi Alessandro 
Published: June 2018

ABSTRACTVariations in the human genome have been found to be an essential factor that affects susceptibility to Alzheimer’s disease. Genome-wide association studies (GWAS) have identified genetic loci that significantly contribute to the risk of Alzheimers. The availability of genetic data, coupled with brain imaging technologies have opened the door for further discoveries, by using data integration methodologies and new study designs. Although methods have been proposed for integrating image characteristics and genetic information for studying Alzheimers, the measurement of disease is often taken at a single time point, therefore, not allowing the disease progression to be taken into consideration. In longitudinal settings, we analyzed neuroimaging and single nucleotide polymorphism datasets obtained from the Alzheimer’s Disease Neuroimaging Initiative for three clinical stages of the disease, including healthy control, early mild cognitive impairment and Alzheimer’s disease subjects. We conducted a GWAS regressing the absolute change of global connectivity metrics on the genetic variants, and used the GWAS summary statistics to compute the gene and pathway scores. We observed significant associations between the change in structural brain connectivity defined by tractography and genes, which have previously been reported to biologically manipulate the risk and progression of certain neurodegenerative disorders, including Alzheimer’s disease.
Single-cell transcriptional analysis reveals naïve helper ILC-like cells in zebrafish
Authors: Hernández Pedro P. , Strzelecka Paulina M. , Athanasiadis Emmanouil I. , Robalo Ana F. , Collins Catherine M. , Boudinot Pierre , Levraud Jean-Pierre , Cvejic Ana 
Published: June 2018

AbstractInnate lymphoid cells (ILCs) are important mediators of the immune response and homeostasis in barrier tissues of mammals. However, the existence and function of ILCs in other vertebrates is poorly understood. Here, we use single-cell RNA sequencing to generate a comprehensive atlas of zebrafish lymphocytes during tissue homeostasis and following immune challenge. We profiled 14,080 individual cells from the gut of wild-type zebrafish, as well as of rag1-deficient fish which lack T and B cells, and discovered diverse populations of helper ILC-like cells. Unexpectedly, fish displayed a rorc-positive, naïve subset that established a Type 3 or Type 2 response only upon immune challenge. Specifically, naïve ILC-like cells expressed il22 and tnfa following exposure to inactivated bacteria, or il13 following exposure to helminth extract. Cytokine-producing ILC-like cells express a specific repertoire of novel immune-type receptors, likely involved in recognition of environmental cues. We identified additional novel markers of zebrafish ILCs and generated a cloud repository for their in-depth exploration.
Recording and reproducing the diurnal oviposition rhythms of wild populations of the soft- and stone- fruit pest Drosophila suzukii
Authors: Shaw Bethan , Fountain Michelle T. , Wijnen Herman 
Published: June 2018

AbstractDrosophila suzukii is a horticultural pest on a global scale which causes both yield and economic losses on a range of soft- and stone-fruit. Tackling this pest is problematic but exploiting behavioral rhythms could increase the impact of control. To do this, a better understanding of behavioral patterns is needed. Within this study we aimed to investigate rhythms in reproductive behavior of wild D. suzukii under natural conditions in the field. Environmental parameters were also recorded to decipher how they influence these rhythms. Assays were then performed on laboratory cultures, housed under artificial conditions mimicking the temperature and light cycles, to see if these patterns were reproducible and rhythmic. We were able to promote field like oviposition patterns within the laboratory using realistic temperature and light cycles regardless of variations in other factors including substrate, humidity, and lighting type. Locomotion activity was also recorded under these mimicked conditions to identify how this behavior interacts with oviposition rhythms. Both our field and laboratory assays show that oviposition behavior is likely under the control of the circadian clock and primarily occurs during the day, but these patterns will be disrupted by unfavorable temperature conditions. This was also found within locomotion rhythms. With an increased understanding of how these behaviors are influenced by environmental conditions, we highlight the importance of using realistic temperature and light cycles when investigating behavioral patterns. From an increased understanding of D. suzukii behavior we increase our ability to target the pest in the field.
Contrasted hybridization patterns between two local populations of European wildcats in France
Authors: Marie-Pauline Beugin , Olivier Salvador , Guillaume Leblanc , Guillaume Queney , Eugenia Natoli , Dominique Pontier 
Published: June 2018

ABSTRACTThe European wildcat (Felis silvestris silvestris) is threatened across the totality of its area of distribution by hybridization with the domestic catF.s. catus. The underlying ecological processes promoting hybridization, remain largely unknown. In France, wildcats are mainly present in the North-East but signs of their presence in the Pyrenees have been recently provided. However, no studies have been carried out in the French Pyrenees to assess the genetic status of wildcats. We have compared a local population of wildcats living in a continuous habitat in the French Pyrenees and a local population of wildcats living in a fragmented habitat in Northeastern France to evaluate how habitat fragmentation influence the population structure of European wildcats. Close kin were not found in the same geographic location contrary to what was observed for females in the Northeastern wildcat population. Furthermore, there was no evidence of hybridization in the Pyrenean wildcats and only one domestic cat raised suspicions while hybridization was categorically detected in northeastern France. The two wildcat populations were significantly differentiated (Fst= 0.08) and the genetic diversity of the Pyrenean wildcats was lower than that of other wildcat populations in France and in Europe. Taken together, these results suggest that habitat fragmentation, and in particular the absence of agricultural fields, may play an important role in lowering the probability of hybridization by reducing the likelihood of contact with domestic cats. Moreover, our results suggest that the French Pyrenean wildcat populations is isolated and may be threatened by a lack of genetic diversity.
A Narrative Systematic Review of Coaching Interventions to Improve Dyslexia at Work
Authors: Doyle Nancy , McDowall Almuth 
Published: June 2018

AbstractAlthough dyslexia affects 5-8% of the workforce this developmental disorder is insufficiently researched within adult psychological research. Dyslexia confers legal protections wherein employers must provide ‘accommodations’ to support work performance, including coaching activities. Implementation of accommodations has moved forward without an evidence-base to date. The present systematic review investigates to what extent face-to-face learning interventions improve the working memory capacity and self-efficacy of adults with dyslexia guided by a realist, narrative framework. We extracted 25 studies from eleven countries, prioritizing relevant learning intervention protocols above population context, synthesizing the delivery context and impact on mechanisms of working memory (N=501) and self-efficacy (N=1211) also contextual, work-related outcomes such as comprehension. Though limited by inadequate intervention descriptions in primary papers, a narrative synthesis determined that learning interventions compliant with Social Cognitive Learning Theory elicited reliable outcomes for not only self-efficacy, as would be expected, but also improved working memory and workplace contextualized variables. Development of metacognition, stress management and fidelity to Goal Setting Theory were also inferred as valuable intervention features. Implications include the need for population-specific evaluation of the emergent conceptual framework to further our understanding of disability accommodations, and questioning the ecological validity of working memory as an intervening mechanism.
14-3-3 proteins activatePseudomonasexotoxins-S and –T by chaperoning a hydrophobic surface
Authors: Karlberg Tobias , Hornyak Peter , Filipa Pinto Ana , Milanova Stefina , Ebrahimi Mahsa , Lindberg Mikael , Püllen Nikolai , Nordström Axel , Löverli Elinor , Caraballo Rémi , Wong Emily V. , Näreoja Katja , Thorsell Ann-Gerd , Elofsson Mikael , De La Cruz Enrique M. , Björkegren Camilla , Schüler Herwig 
Published: June 2018

AbstractPseudomonasare a common cause of hospital acquired infections that may be lethal. ADP-ribosyltransferase activities ofPseudomonasexotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, a hydrophobic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3β:ExoS and -ExoT complexes presented here reveal an extensive novel binding interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the hydrophobic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the hydrophobic C-terminus with a fragment fromVibrioVis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the hydrophobic C-terminal segment.Short summaryCrystal structures of Pseudomonas exotoxins-S and –T identify a novel hydrophobic interface with 14-3-3 proteins, and we show that 14-3-3 activates these toxins independent of their phosphopeptide groove binding C-termini, by preventing their aggregation.
Dietary Advanced Glycation End-Product Consumption Leads to Mechanical Stiffening of Murine Intervertebral Discs
Authors: Krishnamoorthy Divya , Hoy Robert C. , Natelson Devorah M , Torre Olivia M. , Laudier Damien M , Iatridis James C. , Illien-Jünger Svenja 
Published: June 2018

ABSTRACTBack pain is a leading cause of disability strongly associated with intervertebral disc (IVD) degeneration. Reducing structural disruption and catabolism in IVD degeneration remains an important clinical challenge. Pro-oxidant and structure-modifying advanced glycation end-products (AGEs) contribute to obesity and diabetes, which are associated with increased back pain, and accumulate in tissues due to hyperglycemia or ingestion of foods processed at high heat. Collagen-rich IVDs are particularly susceptible to AGE accumulation due to their slow metabolic rates yet it is unclear if dietary AGEs can cross the endplates to accumulate in IVDs. We apply a dietary mouse model to test the hypothesis that chronic consumption of high AGE diets results in sex-specific IVD structural disruption and functional changes. High AGE diet resulted in AGE accumulation in IVDs and increased IVD compressive stiffness, torque range, and failure torque, particularly for females. These biomechanical changes were likely caused by significantly increased AGE crosslinking in the annulus fibrosus, measured by multiphoton imaging. Increased collagen damage measured with collagen hybridizing peptide may be a risk factor for IVD degeneration as these animals age. The greater influence of high AGE diet on females is an important area of future investigation that may involve AGE receptors, known to interact with estrogen. We conclude high AGE diets can be a source for IVD crosslinking and collagen damage known to be important in IVD degeneration. This suggests dietary and other interventions that modify AGEs warrant further investigation and may be particularly important for diabetics where AGEs accumulate more rapidly.Summary StatementDietary advanced glycation end-products (AGE) lead to sex-specific intervertebral disc structural and functional changes and may be targeted for promoting spinal health especially in diabetes where AGEs form rapidly.
Association between Parkinson’s Disease subtypes and tests of physical function: the 360-degree turn test is most predictive
Authors: Prime Morgane , McKay J. Lucas , Bay Allison , Hart Ariel , Kim Chaejin , Abraham Amit , Hackney Madeleine E. 
Published: June 2018

ABSTRACTBACKGROUND AND PURPOSEPeople with Parkinson’s disease (PD) present phenotypes that can be characterized as tremor-dominant (TD) or postural instability / gait difficulty (PIGD) subtypes. Differentiation of subtypes allows clinicians to predict the disease course and adjust treatment accordingly. We examined whether brief mobility and balance measures can discriminate PIGD from TD phenotypes.METHODSWe performed a cross-sectional study with individuals with PD (N=104). Blinded raters assessed participants with the UPDRS or MDS-UPDRS, and potential predictor variables: 360-degree turn test, one-leg stance, backward perturbation test and tandem walk. Participant were classified as PIGD or TD based on the Unified Parkinson’s Disease Rating Scale or the Movement Disorder Society revision (UPDRS or MDS-UPDRS) assessment results. Differences in study variables between subtype groups were assessed with univariate analyses. Receiver operating characteristic (ROC) curve analyses were performed to investigate the ability of candidate predictor variables to differentiate PD subtypes.RESULTSMean age and disease duration were 68±9 and 7±5 years, respectively, and Hoehn & Yahr Stages I-IV median (1st,3rd quartile) = II (II, III). No differences between subtypes were observed for tandem walk or reactive postural control. PIGD participants performed worse on number of steps (p<0.001) and time to complete (p=0.003) the 360-degree turn test and one-leg stance (p=0.006). ROC curves showed only the 360-degree turn test could discriminate PIGD from TD with high sensitivity.CONCLUSIONSThe 360-degree turn test requires minimal time to administer and may be useful in mild-moderate PD for distinguishing PIGD from TD subtypes.
Altered Stool Microbiota of Infants with Cystic Fibrosis Shows Reduction in Genera Associated with Immune Programming
Authors: Antosca Katherine M. , Chernikova Diana A. , Ruoff Kathryn L. , Li Kewei , Guill Margaret F. , MacKenzie Todd A. , Dorman Dana B. , Moulton Lisa A. , Williams Molly A. , Aldrich Brian J. , Yuan Irene H. , Karagas Margaret R. , O’Toole George A. , Madan Juliette C. 
Published: June 2018

AbstractPrevious work from our group indicated a connection between the gastrointestinal microbiota of infants and children with cystic fibrosis (CF) and airway disease in this population. Here we examine the stool microbiota of infants with CF and from the general population who did not have CF over the first year of life. CF children had reduced gastrointestinal Bacteroides and Bifidobacterium beginning in infancy, even after adjusting for antibiotic treatment. We also identify several metabolic pathways that are enriched or under represented among the microbial communities in the stool of these young patients with CF as compared to children without CF. In vitro studies demonstrated that exposure of the apical face of a polarized Intestinal cell line to Bacteroides thetaiotaomicron significantly reduced production of IL-8 secreted from both the apical and basolateral face of these cells, suggesting a mechanism whereby changes in the intestinal microflora could impact systemic inflammation. This work further establishes a link between gastrointestinal microbiota, systemic inflammation and airway disease, and presents the opportunity for therapeutic probiotic interventions.Significance statementThere is a surprising link between gastrointestinal microbial communities and airway disease progression in CF. Here we show that infants with CF ≤1 year of age show a distinct stool microbiota compared with children of a comparable age from a general population cohort. We detect associations between stool microbes and airway exacerbation events in the cohort of infants with CF, and in vitro studies provide a possible mechanism for this observation. These data argue that current therapeutics do not establish a healthy-like gastrointestinal microbiota in young patients with CF, and we suggest that interventions that direct the gastrointestinal microbiota closer to a healthy state may provide benefit to these patients.
Can Drosophila melanogaster tell who’s who?
Authors: Schneider Jonathan , Murali Nihal , Taylor Graham , Levine Joel 
Published: June 2018

AbstractDrosophila melanogaster are known to live in a social but cryptic world of touch and odours, but the extent to which they can perceive and integrate visual information is a hotly debated topic. Some researchers fixate on the limited resolution of D. melanogaster’s optics, other’s on their seemingly identical appearance; yet there is evidence of individual recognition and surprising visual learning in flies. Here, we apply machine learning and show that individual D. melanogaster are visually distinct. We also use the striking similarity of Drosophila’s visual system to current convolutional neural networks to theoretically investigate D. melanogaster’s capacity for visual understanding. We find that, despite their limited optical resolution, D. melanogaster’s neuronal architecture has the capability to extract and encode a rich feature set that allows flies to re-identify individual conspecifics with surprising accuracy. These experiments provide a proof of principle that Drosophila inhabit in a much more complex visual world than previously appreciated.Author summaryIn this paper, we determine a proof of principle for inter-individual recognition in two parts; is there enough information contained in low resolution pictures for inter-fly discrimination, and if so does Drosophila’s visual system have enough capacity to use it. We show that the information contained in a 29×29 pixel image (number of ommatidia in a fly eye) is sufficient to achieve 94% accuracy in fly re-identification. Further, we show that the fly eye has the theoretical capacity to identify another fly with about 75% accuracy. Although it is unlikely that flies use the exact algorithm we tested, our results show that, in principle, flies may be using visual perception in ways that are not usually appreciated.
Towards building an automated bioinformatician: more accurate transcript assembly via parameter advising
Authors: DeBlasio Dan , Kim Kwanho , Kingsford Carl 
Published: June 2018

AbstractComputational tools used for genomic analyses are becoming increasingly sophisticated and complex. While these applications often provide more accurate results than their predecessors, a new problem is emerging in that these pieces of software have a large number of tunable parameters. Choosing the wrong parameter values for an application may lead to significant results being overlooked or false results being reported. We take some first steps towards generating a truly automated genomic analysis pipeline by developing a method for automatically choosing input-specific parameter values for reference-based transcript assembly. We extend the parameter advising framework, first developed for multiple sequence alignment, to optimize parameter choices for the Scallop transcript assembler. In doing so, we provide the first method for finding advisor sets for applications with large numbers of tunable parameters. By choosing parameter values for each input, the area under the curve (AUC) when comparing assembled transcripts to a reference transcriptome is increased by 28.9% over using only the default parameter choices on 1595 RNA-Seq samples in the Sequence Read Archive. This approach is general, and when applied to StringTie it increases AUC by 13.1% on a set of 65 RNA-Seq experiments from ENCODE. Parameter advisors for both Scallop and StringTie are available on Github1.
AlleleAnalyzer: a tool for personalized and allele-specific sgRNA design
Authors: Keough Kathleen C. , Lyalina Svetlana , Olvera Michael P. , Whalen Sean , Conklin Bruce R. , Pollard Katherine S. 
Published: June 2018

AbstractThe CRISPR/Cas system is a highly specific genome editing tool capable of distinguishing alleles differing by even a single base pair. However, current tools only design sgRNAs for a reference genome, not taking into account individual variants which may generate, remove, or modify CRISPR/Cas sgRNA sites. This may cause mismatches between designed sgRNAs and the individual genome they are intended to target, leading to decreased experimental performance. Here we describe AlleleAnalyzer, a tool for designing personalized and allele-specific sgRNAs for genome editing. We leverage >2,500 human genomes to identify optimized pairs of sgRNAs that can be used for human therapeutic editing in large populations in the future.