bluuebunny/crossref_metadata_2025_split huggingface dataset:
Software-assisted manual review of clinical NGS data: an alternative to routine Sanger sequencing confirmation with equivalent results in >15,000 hereditary cancer screens
Authors: Muzzey Dale , Kash Shera , Johnson Jillian I. , Melroy Laura M. , Kaleta Piotr , Pierce Kelly A. , Ready Kaylene , Kang Hyunseok P. , Haas Kevin R. 
Published: April 2018

ABSTRACTClinical genomic tests increasingly utilize a next generation sequencing (NGS) platform due in part to the high fidelity of variant calls, yet rare errors are still possible. In hereditary cancer screening, failure to correct such errors could have serious consequences for patients, who may follow an unwarranted screening or surgical-management path. It has been suggested that routine orthogonal confirmation via Sanger sequencing is required to verify NGS results, especially low-confidence positives with depressed allele fraction (<30% of alternate allele). We evaluated whether an alternative method of confirmation—software-assisted manual call review—performed comparably to Sanger confirmation in >15,000 samples. Licensed reviewers manually inspected both raw and processed data at the batch-, sample-, and variant-level, including raw NGS read pileups. Of ambiguous variant calls with <30% allele fraction (1,707 total calls at 38 unique sites), manual call review classified >99% (1,701) as true positives (enriched for long insertions or deletions (“indels”) and homopolymers) or true negatives (often conspicuous NGS artifacts), with the remaining <1% (6) being mosaic. Critically, results from software-assisted manual review and retrospective Sanger sequencing were concordant for samples selected from all ambiguous sites. We conclude that the confirmation required for high confidence in NGS-based germline testing can manifest in different ways: a trained NGS expert operating platform-tailored review software achieves quality comparable to routine Sanger confirmation.
Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development
Authors: Madissoon Elo , Damdimopoulos Anastasios , Katayama Shintaro , Krjutškov Kaarel , Einarsdottir Elisabet , Mamia Katariina , De Groef Bert , Hovatta Outi , Kere Juha , Damdimopoulou Pauliina 
Published: April 2018

ABSTRACTPleomorphic adenoma gene 1 (PLAG1) is a transcription factor involved in cancer and growth. We discovered a de novo DNA motif containing a PLAG1 binding site in the promoters of genes activated during zygotic genome activation (ZGA) in human embryos. This motif was located within an Alu element in a region that was conserved in the murine B1 element. We show that maternally provided Plag1 is essential for timely mouse preimplantation embryo development. Heterozygous mouse embryos lacking maternal Plag1 showed disrupted regulation of 1,089 genes, spent significantly longer time in the 2-cell stage, and started expressing Plag1 ectopically from the paternal allele. The de novo PLAG1 motif was enriched in the promoters of the genes whose activation was delayed in the absence of Plag1. Further, these mouse genes showed a significant overlap with genes upregulated during human ZGA that also contain the motif. By gene ontology, the mouse and human ZGA genes with de novo PLAG1 motifs were involved in ribosome biogenesis and protein synthesis. Collectively, our data suggest that PLAG1 affects embryo development in mice and humans through a conserved DNA motif within Alu/B1 elements located in the promoters of a subset of ZGA genes.
The effect of acquisition resolution on orientation decoding from V1: comparison of 3T and 7T
Authors: Sengupta Ayan , Speck Oliver , Yakupov Renat , Kanowski Martin , Tempelmann Claus , Pollmann Stefan , Hanke Michael 
Published: April 2018

AbstractPreviously published results indicate that the accuracy of decoding visual orientation from 7 Tesla fMRI data of V1 peaks at spatial acquisition resolutions that are routinely accessible with more conventional 3 Tesla scanners. This study directly compares the decoding performance between a 3 Tesla and a 7 Tesla dataset that were acquired using the same stimulation paradigm by applying an identical analysis procedure. The results indicate that decoding models built on 3 Tesla data are comparatively impaired. Moreover, we found no evidence for a strong coupling of BOLD signal change magnitude or temporal signal to noise ratio (tSNR) with decoding performance. Direct enhancement of tSNR via multiband fMRI acquisition at the same resolution did not translate into improved decoding performance. Additional voxel selection can boost 3 Tesla decoding performance to the 7 Tesla level only at a 3 mm acquisition resolution. In both datasets the BOLD signal available for orientation decoding is spatially broadband, but, consistent with the size of the BOLD point-spread-function, decoding models at 3 Tesla utilize spatially coarser image components.
Virtual navigation tested on a mobile app is predictive of real-world wayfinding navigation performance
Authors: Coutrot A. , Schmidt S. , Coutrot L. , Pittman J. , Hong L. , Wiener J. M. , Hölscher C. , Dalton R.C. , Hornberger M. , Spiers H. J. 
Published: April 2018

AbstractVirtual reality environments presented on tablets and smartphones have potential to aid the early diagnosis of conditions such as Alzheimer’s dementia by quantifying impairments in navigation performance. However, it is unclear whether performance on mobile devices can predict navigation errors in the real world. We compared the performance of 60 participants (30 females, 18-35 years old) at wayfinding and path integration tasks designed in our mobile app ‘Sea Hero Quest’ with their performance at similar tasks in a real-world environment. We first performed this experiment in the streets of London (UK) and replicated it in Paris (France). In both cities, we found a significant correlation between virtual and real-world wayfinding performance and a male advantage in both environments, although smaller in the real world (Cohen’s d in the game = 0.89, in the real world = 0.59). Results in London and Paris were highly similar, and controlling for familiarity with video games did not change the results. The strength of the correlation between real world and virtual environment increased with the difficulty of the virtual wayfinding task, indicating that Sea Hero Quest does not merely capture video gaming skills. The fact that the Sea Hero Quest wayfinding task has real-world ecological validity constitutes a step toward controllable, sensitive, safe, low-cost, and easy to administer digital cognitive assessment of navigation ability.
Sex-specific co-expression networks and sex-biased gene expression in the salmonid Brook Charr Salvelinus fontinalis
Authors: Sutherland Ben J. G. , Prokkola Jenni M. , Audet Céline , Bernatchez Louis 
Published: April 2018

ABSTRACTNetworks of co-expressed genes produce complex phenotypes associated with functional novelty. Sex differences in gene expression levels or in the structure of gene co-expression networks can cause sexual dimorphism and may resolve sexually antagonistic selection. Here we used RNA-sequencing in the paleopolyploid salmonid Brook Charr Salvelinus fontinalis to characterize sex-specific co-expression networks in the liver of 47 female and 53 male offspring. In both networks, modules were characterized for functional enrichment, hub gene identification, and associations with 15 growth, reproduction, and stress-related phenotypes. Modules were then evaluated for preservation in the opposite sex, and in the congener Arctic Charr Salvelinus alpinus. Overall, more transcripts were assigned to a module in the female network than in the male network, which coincided with higher inter-individual gene expression and phenotype variation in the females. Most modules were preserved between sexes and species, including those involved in conserved cellular processes (e.g. translation, immune pathways). However, two sex-specific male modules were identified, and these may contribute to sexual dimorphism. To compare with the network analysis, differentially expressed transcripts were identified between the sexes, finding a total of 16% of expressed transcripts as sex-biased. For both sexes, there was no overrepresentation of sex-biased genes or sex-specific modules on the putative sex chromosome. Sex-biased transcripts were also not overrepresented in sex-specific modules, and in fact highly male-biased transcripts were enriched in preserved modules. Comparative network analysis and differential expression analyses identified different aspects of sex differences in gene expression, and both provided new insights on the genes underlying sexual dimorphism in the salmonid Brook Charr.
Circuit mechanisms for the maintenance and manipulation of information in working memory
Authors: Masse Nicolas Y. , Yang Guangyu R. , Song H. Francis , Wang Xiao-Jing , Freedman David J. 
Published: April 2018

SummaryRecently it has been proposed that information in short-term memory may not always be stored in persistent neuronal activity, but can be maintained in “activity-silent” hidden states such as synaptic efficacies endowed with short-term plasticity (STP). However, working memory involves manipulation as well as maintenance of information in the absence of external stimuli. In this work, we investigated working memory representation using recurrent neural network (RNN) models trained to perform several working memory dependent tasks. We found that STP can support the short-term maintenance of information provided that the memory delay period is sufficiently short. However, in tasks that require actively manipulating information, persistent neuronal activity naturally emerges from learning, and the amount of persistent neuronal activity scales with the degree of manipulation required. These results shed insight into the current debate on working memory encoding, and suggest that persistent neural activity can vary markedly between tasks used in different experiments.
Multi-model inference of non-random mating from an information theoretic approach
Authors: Carvajal-Rodriguez Antonio 
Published: April 2018

AbstractNon-random mating has a significant impact on the evolution of organisms. Here, I developed a modelling framework for discrete traits (with any number of phenotypes) to explore different models connecting the non-random mating causes (intra sexual competition and/or mate choice) and their consequences (sexual selection and/or assortative mating).I derived the formulas for the maximum likelihood estimates of each model and used information criteria for performing multimodel inference. Simulation results showed a good performance of both model selection and parameter estimation. The methodology was applied to data from GalicianLittorina saxatilisecotypes, to show that the mating pattern is better described by models with two parameters that involve both mate choice and intrasexual competition, generating positive assortative mating plus female sexual selection.As far as I know, this is the first standardized methodology for model selection and multimodel inference of mating parameters for discrete traits. The advantages of this framework include the ability of setting up models from which the parameters connect causes, as intrasexual competition and mate choice, with their outcome in the form of data patterns of sexual selection and assortative mating. For some models, the parameters may have a double effect i.e. they cause both kind of patterns, while for others models there are separated parameters for one kind of pattern or another.The full methodology was implemented in a software called InfoMating (available athttp://acraaj.webs6.uvigo.es/InfoMating/Infomating.htm).
Geminivirus Replication Protein impairs SUMO conjugation of PCNA at two acceptor sites
Authors: Arroyo-Mateos Manuel , Sabarit Blanca , Maio Francesca , Sánchez-Durán Miguel A. , Rosas-Díaz Tabata , Prins Marcel , Ruiz-Albert Javier , Luna Ana P , van den Burg Harrold A. , Bejarano Eduardo R. 
Published: April 2018

ABSTRACTGeminiviruses are DNA viruses that replicate in nuclei of infected plant cells using the plant DNA replication machinery, including PCNA (Proliferating cellular nuclear antigen), a cofactor that orchestrates genome duplication and maintenance by recruiting crucial players to replication forks. These viruses encode a multifunctional protein, Rep, which is essential for viral replication, induces the accumulation of the host replication machinery and interacts with several host proteins, including PCNA and the SUMO E2 conjugation enzyme (SCE1). Post-translational modification of PCNA by ubiquitin or SUMO plays an essential role in the switching of PCNA between interacting partners during DNA metabolism processes (e.g. replication, recombination, repair, etc.). In yeast, PCNA sumoylation has been associated to DNA repair involving homologous recombination (HR). Previously, we reported that ectopic Rep expression results in very specific changes in the sumoylation pattern of plant cells. In this work, we show, using a reconstituted sumoylation system inEscherichia coli, that tomato PCNA is sumoylated at two residues, K254 and K164, and that co-expression of the geminivirus protein Rep suppresses sumoylation at these lysines. Finally, we confirm that PCNA is sumoylatedin plantaand that Rep also interferes with PCNA sumoylation in plant cells.ImportanceSUMO adducts have a key role in regulating the activity of animal and yeast PCNA on DNA repair and replication. Our work demonstrates for the first time that sumoylation of plant PCNA occurs in plant cells and that a plant virus interferes with this modification. This work marks the importance of sumoylation in allowing viral infection and replication in plants. Moreover, it constitutes a prime example of viral proteins interfering with post-translational modifications of selected host factors to create a proper environment for infection.
Proteins in the periplasmic space and outer membrane vesicles ofRhizobium etliCE3 grown in minimal medium are largely distinct and change with growth phase
Authors: Taboada Hermenegildo , Meneses Niurka , Dunn Michael F. , Vargas-Lagunas Carmen , Buchs Natasha , Castro-Mondragon Jaime A. , Heller Manfred , Encarnación Sergio 
Published: April 2018

ABSTRACTRhizobium etliCE3 grown in succinate-ammonium minimal medium (MM) excreted outer membrane vesicles (OMVs) with diameters of 40 to 100 nm. Proteins from the OMVs and the periplasmic space were isolated from 6 and 24 h cultures and identified by proteome analysis. A total 770 proteins were identified: 73.8 and 21.3 % of these proteins occurred only in the periplasm and OMVs, respectively, and only 4.9 % were found in both locations. The majority of proteins found in either location were present only at 6 or 24 h: in the periplasm and OMVs, only 24 and 9 % of proteins, respectively, were present at both sampling times, indicating a time-dependent differential sorting of proteins into the two compartments. The OMVs contained proteins with physiologically varied roles, includingRhizobiumadhering proteins (Rap), polysaccharidases, polysaccharide export proteins, autoaggregation and adherence proteins, glycosyl transferases, peptidoglycan binding and cross-linking enzymes, potential cell wall modifying enzymes, porins, multidrug efflux RND family proteins, ABC transporter proteins, and heat shock proteins. As expected, proteins with known periplasmic localizations (phosphatases, phosphodiesterases, pyrophosphatases) were found only in the periplasm, along with numerous proteins involved in amino acid and carbohydrate metabolism and transport. Nearly one-quarter of the proteins present in the OMVs were also found in our previous analysis of theR. etlitotal exproteome of MM-grown cells, indicating that these nanoparticles are an important mechanism for protein excretion in this species.IMPORTANCEThe reduction of atmospheric nitrogen to ammonia by rhizobia symbiotically associated with legumes is of major importance in sustainable agricultural. Rhizobia excrete a variety of symbiotically important proteins using canonical secretion systems. In this work, we show thatRhizobium etligrown in culture also excretes proteins in membrane-enclosed structures called outer membrane vesicles (OMVs). This study reports OMV production by rhizobia. Proteins identified in the OMVs included Rhizobium adhering (Rap) and autoaggregation proteins, polysaccharidases, RTX toxins, porins and multidrug efflux proteins. Some of these proteins have important roles in theR. etli-common bean symbiosis, and their packaging into OMVs could deliver them to the environment in a concentrated yet diffusible form protected from degradation. The work described here provides a basis for future studies on the function of rhizobial OMVs in free life and symbiosis.
T cell responses to nonstructural protein 3 distinguish infections by Dengue and Zika viruses
Authors: Herrera Bobby Brooke , Tsai Wen-Yang , Brites Carlos , Luz Estela , Pedroso Celia , Drexler Jan Felix , Wang Wei-Kung , Kanki Phyllis J. 
Published: April 2018

ABSTRACTThe 2015-16 Zika virus (ZIKV) epidemic in the Americas and the Caribbean demonstrates that clinical assays to detect, distinguish, and characterize immune responses to flaviviral infections are needed. ZIKV and dengue virus (DENV) are mosquito-transmitted flaviviruses sharing overlapping geographical distribution and have significant sequence similarity that can increase the potential for antibody and T cell cross-reaction. Using nonstructural protein 1-based enzyme-linked immunosorbent assays (ELISAs), we determine the serostatus of individuals living in a DENV- and ZIKV-endemic region in Brazil, identifying individuals with primary DENV (pDENV) and ZIKV (pZIKV), ZIKV with primary DENV (ZIKVwpDENV), and secondary DENV (sDENV) infections; pDENV and pZIKV were further confirmed by neutralization tests. Development of an enzyme-linked immunospot (ELISPOT) assay for DENV and ZIKV structural and nonstructural (NS) protein antigens enables us to distinguish infections by these viruses based on T cells and to characterize those responses. We find that IFN-γ and TNF-α T cell responses to NS3 differentiates DENV and ZIKV infections with 94% sensitivity and 92% specificity. In general, we also show that pDENV and sDENV cases and pZIKV and ZIKVwpDENV cases elicit similar T cell response patterns, and that HIV-infected individuals have T cell responses that are lower in magnitude compared to HIV-negative individuals. These results have important implications for DENV and ZIKV diagnostic and vaccine development and provide critical insights into the T cell response in individuals with multiple flaviviral infections.
Large-scale organization of the hand action observation network in individuals born without hands
Authors: Vannuscorps Gilles , Wurm Moritz , Striem-Amit Ella , Caramazza Alfonso 
Published: April 2018

AbstractThe human high-level visual cortex comprises regions specialized for the processing of distinct types of stimuli, such as objects, animals, and human actions. How does this specialization emerge? Here, we investigated the role of sensorimotor experience in shaping the organization of the action observation network as a window on this question. Observed body movements are frequently coupled with corresponding motor codes, e.g. during monitoring one’s own movements and imitation, resulting in bidirectionally connected circuits between areas involved in body movements observation (e.g., of the hand) and the motor codes involved in their execution. If the organization of the action observation network is shaped by this sensorimotor coupling, then, it should not form for body movements that do not belong to individuals’ motor repertoire. To test this prediction, we used fMRI to investigate the spatial arrangement and functional properties of the hand and foot action observation circuits in individuals born without upper limbs. Multivoxel pattern decoding, pattern similarity, and univariate analyses revealed an intact hand action observation network in the individuals born without upper limbs. This suggests that the organization of the action observation network does not require effector-specific visuomotor coupling.
Modelling the emergence of an egalitarian society in the n-player game framework
Authors: Tamura Kohei , Takikawa Hiroki 
Published: April 2018

AbstractUnlike other primates, human foragers have an egalitarian society. Therefore, the evolution of egalitarian behaviour has been the subject of long-standing debate in a wide variety of disciplines. A recent hypothesis states that a social control against potentially dominant individuals played an important role in the emergence of an egalitarian society, although this has not been modelled directly. In the present study, we modelled this hypothesis based on the n-player game framework, in which the owner, who may attempt to monopolise resources, could be punished by a coalition of other group members. Our results suggest that a potentially despotic payoff structure can promote the evolution of egalitarian behaviour. Besides, large group size, small cost of competition, and variation in the strengths of individuals can promote the evolution of egalitarian behaviour. Our results suggest the importance of both social control against dominant individuals and benefits of a coalition for the evolution of egalitarian behaviour.
Differential valuation and learning from social and non-social cues in Borderline Personality Disorder
Authors: Fineberg Sarah K , Leavitt Jacob , Stahl Dylan S , Kronemer Sharif , Landry Christopher D. , Alexander-Bloch Aaron , Hunt Laurence T , Corlett Philip R 
Published: April 2018

AbstractBackgroundVolatile interpersonal relationships are a core feature of Borderline Personality Disorder (BPD), and lead to devastating disruption of patients’ personal and professional lives. Quantitative models of social decision making and learning hold promise for defining the underlying mechanisms of this problem. In this study, we tested BPD and control subject weighting of social versus non-social information, and their learning about choices under stable and volatile conditions. We compared behavior using quantitative models.MethodsSubjects (n=20 BPD, n=23 control) played an extended reward learning task with a partner (confederate) that requires learning about non-social and social cue reward probability (The Social Valuation Task). Task experience was measured using language metrics: explicit emotions/beliefs, talk about the confederate, and implicit distress (using the previously established marker self-referentiality). Subjects’ weighting of social and non-social cues was tested in mixed-effects regression models. Subjects’ learning rates under stable and volatile conditions were modelled (Rescorla-Wagner approach) and group x condition interactions tested.ResultsCompared to controls, BPD subject debriefings included more mentions of the confederate and less distress language. BPD subjects also weighted social cues more heavily, but had blunted learning responses to (non-social and social) volatility.ConclusionsThis is the first report of patient behavior in the Social Valuation Task. The results suggest that BPD subjects expect higher volatility than do controls. These findings lay the groundwork for a neuro-computational dissection of social and non-social belief updating in BPD, which holds promise for the development of novel clinical interventions that more directly target pathophysiology.