bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproducibility2020: Progress and Priorities
Authors: Freedman Leonard P. , Venugopalan Gautham , Wisman Rosann 
Published: February 2017

ABSTRACTThe preclinical research process is a cycle of idea generation, experimentation, and reporting of results. The biomedical research community relies on the reproducibility of published discoveries to create new lines of research and to translate research findings into therapeutic applications. Since 2012, when scientists from Amgen reported that they were able to reproduce only 6 of 53 “landmark” preclinical studies, the biomedical research community began discussing the scale of the reproducibility problem and developing initiatives to address critical challenges. GBSI released the “Case for Standards” in 2013, one of the first comprehensive reports to address the rising concern of irreproducible biomedical research. Further attention was drawn to issues that limit scientific self-correction including reporting and publication bias, underpowered studies, lack of open access to methods and data, and lack of clearly defined standards and guidelines in areas such as reagent validation. To evaluate the progress made towards reproducibility since 2013, GBSI identified and examined initiatives designed to advance quality and reproducibility. Through this process, we identified key roles for funders, journals, researchers and other stakeholders and recommended actions for future progress. This paper describes our findings and conclusions.
The Stochastic Early Reaction, Inhibition, and Late Action (SERIA) Model for Antisaccades
Authors: Aponte Eduardo A. , Schoebi Dario , Stephan Klaas E. , Heinzle Jakob 
Published: February 2017

AbstractThe antisaccade task is a classic paradigm used to study the voluntary control of eye movements. It requires participants to suppress a reactive eye movement to a visual target and to concurrently initiate a saccade in the opposite direction. Although several models have been proposed to explain error rates and reaction times in this task, no formal model comparison has yet been performed. Here, we describe a Bayesian modeling approach to the antisaccade task that allows us to formally compare different models on the basis of their evidence. First, we provide a formal likelihood function of actions (pro- and antisaccades) and reaction times based on previously published models. Second, we introduce theStochastic Early Reaction, Inhibition, and late Action model(SERIA), a novel model postulating two different mechanisms that interact in the antisaccade task: an early GO/NO-GO race decision process and a late GO/GO decision process. Third, we apply these models to a data set from an experiment with three mixed blocks of pro- and antisaccade trials. Bayesian model comparison demonstrates that the SERIA model explains the data better than competing models that do not incorporate a late decision process. Moreover, we show that the race decision processes postulated by the SERIA model are, to a large extent, insensitive to the cue presented on a single trial. Finally, we use parameter estimates to demonstrate that changes in reaction time and error rate due to the probability of a trial type (prosaccade or antisaccade) are best explained by faster or slower inhibition and the probability of generating late voluntary prosaccades.Author summaryOne widely replicated finding in schizophrenia research is that patients tend to make more errors in the antisaccade task, a psychometric paradigm in which participants are required to look in the opposite direction of a visual cue. This deficit has been suggested to be an endophenotype of schizophrenia, as first order relatives of patients tend to show similar but milder deficits. Currently, most models applied to experimental findings in this task are limited to fit average reaction times and error rates. Here, we propose a novel statistical model that fits experimental data from the antisaccade task, beyond summary statistics. The model is inspired by the hypothesis that antisaccades are the result of several competing decision processes that interact nonlinearly with each other. In applying this model to a relatively large experimental data set, we show that mean reaction times and error rates do not fully reflect the complexity of the processes that are likely to underlie experimental findings. In the future, our model could help to understand the nature of the deficits observed in schizophrenia by providing a statistical tool to study their biological underpinnings.
Holographic deep learning for rapid optical screening of anthrax spores
Authors: Jo YoungJu , Park Sangjin , Jung JaeHwang , Yoon Jonghee , Joo Hosung , Kim Min-hyeok , Kang Suk-Jo , Choi Myung Chul , Lee Sang Yup , Park YongKeun 
Published: February 2017

AbstractEstablishing early warning systems for anthrax attacks is crucial in biodefense. Here we present an optical method for rapid screening ofBacillus anthracisspores through the synergistic application of holographic microscopy and deep learning. A deep convolutional neural network is designed to classify holographic images of unlabeled living cells. After training, the network outperforms previous techniques in all accuracy measures, achieving single-spore sensitivity and sub-genus specificity. The unique ‘representation learning’ capability of deep learning enables direct training fromraw imagesinstead of manually extracted features. The method automatically recognizes key biological traits encoded in the images and exploits them as fingerprints. This remarkable learning ability makes the proposed method readily applicable to classifying various single cells in addition toB. anthracis, as demonstrated for the diagnosis ofListeria monocytogenes, without any modification. We believe that our strategy will make holographic microscopy more accessible to medical doctors and biomedical scientists for easy, rapid, and accurate diagnosis of pathogens, and facilitate exciting new applications.
Whole exome sequencing reveals a mutation inARMC9as a cause of mental retardation, ptosis and polydactyly
Authors: Kar Anjana , Phadke Shubha R , Bhowmik Aneek Das , Dalal Ashwin 
Published: February 2017

ABSTRACTIntellectual disability (ID) refers to deficits in mental abilities, social behaviour and motor skills to perform activities of daily living as compared to peers. Numerous genetic and environmental factors may be responsible for ID. We report on identification of a novel gene for syndromic ID, using homozygosity mapping followed by exome sequencing in a family with mental retardation, ptosis and polydactyly. The analysis revealed a synonymous mutation c.879G>A which leads to a splicing defect inARMC9gene. The variant is present in conserved region of ARM domain of ARMC9 protein which is predicted to form a platform for protein interaction. This domain is likely to be altered in patients due to splicing defect caused by this synonymous mutation. Our study was helpful in elucidation of molecular basis of mental retardation, ptosis and polydactyly phenotype and addition ofARMC9to group of genes leading to syndromic ID.
A Fluorescent Split Aptamer for Visualizing RNA-RNA AssemblyIn Vivo
Authors: Alam Khalid K. , Tawiah Kwaku D. , Lichte Matthew F. , Porciani David , Burke Donald H. 
Published: February 2017

AbstractRNA-RNA assembly governs key biological processes and is a powerful tool for engineering synthetic genetic circuits. Characterizing RNA assembly in living cells often involves monitoring fluorescent reporter proteins, which are at best indirect measures of underlying RNA-RNA hybridization events and are subject to additional temporal and load constraints associated with translation and activation of reporter proteins. In contrast, RNA aptamers that sequester small molecule dyes and activate their fluorescence are increasingly utilized in genetically-encoded strategies to report on RNA-level events. Split-aptamer systems have been rationally designed to generate signal upon hybridization of two or more discrete RNA transcripts, but none directly function when expressedin vivo. We reasoned that the improved physiological properties of the Broccoli aptamer enable construction of a split-aptamer system that could function in living cells. Here we present the Split-Broccoli system, in which self-assembly is nucleated by a thermostable, three-way junction RNA architecture and fluorescence activation requires both strands. Functional assembly of the system approximately follows second order kineticsin vitroand improves when cotranscribed, rather than when assembled from purified components. Split-Broccoli fluorescence is digitalin vivoand retains functional modularity when fused to RNAs that regulate circuit function through RNA-RNA hybridization, as demonstrated with an RNA Toehold switch. Split-Broccoli represents the first functional split-aptamer system to operatein vivo. It offers a genetically-encoded and nondestructive platform to monitor and exploit RNA-RNA hybridization, whether as an all-RNA, stand-alone AND gate or as a tool for monitoring assembly of RNA-RNA hybrids.
Linking soil biology and chemistry using bacterial isolate exometabolite profiles
Authors: Swenson Tami L. , Karaoz Ulas , Swenson Joel M. , Bowen Benjamin P. , Northen Trent 
Published: February 2017

ABSTRACTSequencing provides a window into microbial community structure and metabolic potential; however, linking these data to exogenous metabolites that microorganisms process and produce (the exometabolome) remains challenging. Previously, we observed strong exometabolite niche partitioning among bacterial isolates from biological soil crust (biocrust). Here we examine native biocrust to determine if these patterns are reproduced in the environment. Overall, most soil metabolites displayed the expected relationship (positive or negative correlation) with four dominant bacteria following a wetting event and across biocrust developmental stages. For metabolites that were previously found to be consumed by an isolate, 78% were negatively correlated with the abundance ofin situisolate phylotypes whereas for released metabolites, 73% were positively correlated. Our results demonstrate that metabolite profiling, sequencing and exometabolomics can be successfully integrated to functionally link metagenomes and microbial community structure with environmental chemistry.
Patterns of shared signatures of recent positive selection across human populations
Authors: Johnson Kelsey Elizabeth , Voight Benjamin F. 
Published: February 2017

ABSTRACTScans for positive selection in human populations have identified hundreds of sites across the genome with evidence of recent adaptation. These signatures often overlap across populations, but the question of how often these overlaps represent a single ancestral event remains unresolved. If a single positive selection event spread across many populations, the same sweeping haplotype should appear in each population and the selective pressure could be common across diverse populations and environments. Identifying such shared selective events would be of fundamental interest, pointing to genomic loci and human traits important in recent history across the globe. Additionally, genomic annotations that recently became available could help attach these signatures to a potential gene and molecular phenotype that may have been selected across multiple populations. We performed a scan for positive selection using the integrated haplotype score on 20 populations, and compared sweeping haplotypes using the haplotype-clustering capability of fastPHASE to create a catalog of shared and unshared overlapping selective sweeps in these populations. Using additional genomic annotations, we connect these multi-population sweep overlaps with potential biological mechanisms at several loci, including potential new sites of adaptive introgression, the glycophorin locus associated with malarial resistance, and the alcohol dehydrogenase cluster associated with alcohol dependency.
Significance estimation for large scale untargeted metabolomics annotations
Authors: Scheubert Kerstin , Hufsky Franziska , Petras Daniel , Wang Mingxun , Nothias Louis-Félix , Dührkop Kai , Bandeira Nuno , Dorrestein Pieter C , Bocker Sebastian 
Published: February 2017

AbstractThe annotation of small molecules in untargeted mass spectrometry relies on the matching of fragment spectra to reference library spectra. While various spectrum-spectrum match scores exist, the field lacks statistical methods for estimating the false discovery rates (FDR) of these annotations. We present empirical Bayes and target-decoy based methods to estimate the false discovery rate. Relying on estimations of false discovery rates, we explore the effect of different spectrum-spectrum match criteria on the number and the nature of the molecules annotated. We show that the spectral matching settings needs to be adjusted for each project. By adjusting the scoring parameters and thresholds, the number of annotations rose, on average, by +139% (ranging from −92% up to +5705%) when compared to a default parameter set available at GNPS. The FDR estimation methods presented will enable a user to define the scoring criteria for large scale analysis of untargeted small molecule data that has been essential in the advancement of large scale proteomics, transcriptomics, and genomics science.
A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress
Authors: Drummond Nicola J. , Davies Nick O. , Lovett Janet E. , Miller Mark R. , Cook Graeme , Becker Thomas , Becker Catherina G. , McPhail Donald B. , Kunath Tilo 
Published: February 2017

AbstractExcessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson’s disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range ofin vitroandin vivoapproaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and mitochondrial localisation of Proxison. Importantly,in vivoadministration of Proxison demonstrated effective and well tolerated neuroprotection against oxidative stress in a zebrafish model of dopaminergic neuronal loss.
HistMapR: Rapid digitization of historical land-use maps in R
Authors: Auffret Alistair G. , Kimberley Adam , Plue Jan , Skånes Helle , Jakobsson Simon , Waldén Emelie , Wennbom Marika , Wood Heather , Bullock James M. , Cousins Sara A. O. , Gartz Mira , Hooftman Danny A. P. , Tränk Louise 
Published: February 2017

Abstract1.Habitat destruction and degradation represent serious threats to biodiversity, and quantification of land-use change over time is important for understanding the consequences of these changes to organisms and ecosystem service provision.2.Comparing land use between maps from different time periods allows estimation of the magnitude of habitat change in an area. However, digitizing historical maps manually is time-consuming and analyses of change are usually carried out at small spatial extents or at low resolutions.3.We developed a method to semi-automatically digitize historical land-use maps using the R environment. We created a number of functions that use the existingrasterpackage to classify land use according to a map’s colours, as defined by the RGB channels of the raster image. The method was tested on three different types of historical land-use map and results were compared to manual digitisations.4.Our method is fast, and agreement with manually-digitised maps of around 80-92% meets common targets for image classification. We hope that the ability to quickly classify large areas of historical land-use will promote the inclusion of land-use change into analyses of biodiversity, species distributions and ecosystem services.
Using remote camera traps to assess mammal and bird assemblages across a complex environmental landscape
Authors: Cloyed Carl S. , Cappelli Laura R. , Tilson David A. , Crawford John A. , Dell Anthony I. 
Published: February 2017

AbstractAnimals must navigate a complex mosaic of habitat types, both natural and artificial. As artificial habitats (e.g., agricultural fields) become increasingly abundant in many landscapes, species will be affected differently, depending on their habitat preferences. We investigated the diversity, richness, abundance, and biomass of mammals and birds with remote camera traps that optimized the capture of both large and small animals. Camera traps allowed us to capture natural rates of mammals and birds, which is difficult to obtain using human observers who can affect the behavior of animals and are limited in their spatio-temporal scope and ability to assess nocturnal communities. Our camera trap arrays were established along two transects in a local conservation reserve; one transect ran from an agricultural field to an upland forest and another from a wetland to an upland forest. Over the 6-week study our cameras recorded 2,245 images, within which we observed 483 individuals comprising 16 species of mammals and birds. Our data showed that species composition and abundances were only marginally different between the two transects, with species common to both transects not exhibiting any statistical difference in abundances. Coyotes and armadillos were unique to the riparian transect, and many more bird species were present along the riparian transect than the agricultural transect. Diversity, richness, and total community biomass did not differ significantly between the two transects nor along each transect but there were non-significant trends in predicted directions. Our results revealed that fewer species use the forest immediately adjacent to the agricultural field, but more species use the wetland and the forest immediately adjacent to the wetland. Our results corroborate other studies revealing that certain species are more common in forested areas but also that some species thought to prefer forested areas may actually be more habitat generalists than previously thought.
Zebrafish models for human ALA-dehydratase-deficient porphyria (ADP) and hereditary coproporphyria (HCP) generated with TALEN and CRISPR-Cas9
Authors: Zhang Shuqing , Meng Jiao , Niu Zhijie , Huang Yikai , Wang Jingjing , Su Xiong , Zhou Yi , Wang Han 
Published: February 2017

ABSTRACTDefects in the enzymes involved in heme biosynthesis result in a group of human metabolic genetic disorders known as porphyrias. Using a zebrafish model for human hepatoerythropoietic porphyria (HEP), caused by defective uroporphyrinogen decarboxylase (Urod), the fifth enzyme in the heme biosynthesis pathway, we recently have found a novel aspect of porphyria pathogenesis. However, no hereditable zebrafish models with genetic mutations ofaladandcpox, encoding the second enzyme delta-aminolevulinate dehydratase (Alad) and the sixth enzyme coproporphyrinogen oxidase (Cpox), have been established to date. Here we employed site-specific genome-editing tools transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) to generate zebrafish mutants foraladandcpox. These zebrafish mutants display phenotypes of heme deficiency, hypochromia, abnormal erythrocytic maturation and accumulation of heme precursor intermediates, reminiscent of human ALA-dehydratase-deficient porphyria (ADP) and hereditary coproporphyrian (HCP), respectively. Further, we observed altered expression of genes involved in heme biosynthesis and degradation and particularly down-regulation of exocrine pancreatic zymogens in ADP (alad-/-) and HCP (cpox-/-) fishes. These two zebrafish porphyria models can survive at least 7 days and thus provide invaluable resources for elucidating novel pathological aspects of porphyrias, evaluating mutated forms of humanALADandCPOX, discovering new therapeutic targets and developing effective drugs for these complex genetic diseases. Our studies also highlight generation of zebrafish models for human diseases with two versatile genome-editing tools.
The third moments of the site frequency spectrum
Authors: Klassmann A. , Ferretti L. 
Published: February 2017

AbstractThe analysis of patterns of segregating (i.e. polymorphic) sites in aligned sequences is routine in population genetics. Quantities of interest include the total number of segregating sites and the number of sites with mutations of different frequencies, the so-calledsite frequency spectrum. For neutrally evolving sequences, some classical results are available, including the expected value and variance of the spectrum in the Kingman coalescent model without recombination as calculated by Fu(1995).In this work, we use similar techniques to compute the third moments of the site frequency spectrum without recombination. We also account for the linkage pattern of mutations, yielding the full haplotype spectrum of three polymorphic sites. Based on these results, we derive analytical results for the bias of Tajima’sDand other neutrality tests.As an application, we obtain the second moments of the spectrum of linked sites, which is related to the neutral spectrum of chromosomal inversions and other structural variants. These moments can be used for the normalisation of new neutrality tests relying on these spectra.