bluuebunny/crossref_metadata_2025_split huggingface dataset:
Logical modeling: Combining manual curation and automated parameterization to predict drug synergies
Authors: Flobak Åsmund , Zobolas John , Vazquez Miguel , Steigedal Tonje S. , Thommesen Liv , Grislingås Asle , Niederdorfer Barbara , Folkesson Evelina , Kuiper Martin 
Published: July 2021

AbstractTreatment with drug combinations carries great promise for personalized therapy. We have previously shown that drug synergies targeting cancer can manually be identified based on a logical framework. We now demonstrate how automated adjustments of model topology and logic equations can greatly reduce the workload traditionally associated with logical model optimization. Our methodology allows the exploration of larger model ensembles that all obey a set of observations. We benchmark synergy predictions against a dataset of 153 targeted drug combinations. We show that well-performing manual models faithfully represent measured biomarker data and that their performance can be outmatched by automated parameterization using a genetic algorithm. The predictive performance of a curated model is strongly affected by simulated curation errors, while data-guided deletion of a small subset of edges can improve prediction quality. With correct topology we find some tolerance to simulated errors in the biomarker calibration data. With our framework we predict the synergy of joint inhibition of PI3K and TAK1, and further substantiate this prediction with observation in cancer cell cultures and in xenograft experiments.
First Report of Lactoria cornuta from Karnataka, West coast of India–Role of tropical cyclones in Range Extension
Authors: Muhammed Zafar Iqbal A.N. , Mali Gurudev , Dollin Raghavendra 
Published: July 2021

AbstractIndia is known for its rich biodiversity and is fortunate to have several endemic species from different classes of vertebrates. India is home to 7.5% of the global fish diversity, with 91 endemic species of ray finned fishes, the actinopterygians. Some fish species have never been reported until recently, one such example is the long-horned Cowfish (Ostracidae), best known for inhabiting only certain areas of the Indo-Pacific oceans. However, this fish has been reported from Bay of Bengal, Costs of Goa and Lakshadweep. This is the first time this fish has been found on the Coasts of Karnataka, west coast of India. Given its morphology, the migration seems highly improbable since it can only endure lethargic swimming. In this article, we have explored the role of other external forces that could have contributed to its range extension in the east and west coast of India. In this paper we are exploring the role of Super Cyclones as a vital force in determining the expansion of its range. The fact of collection longhorn cowfish for the first time from the coast of Karwar coincides with the passage of Cyclone Ockhi on the west coast of India this suggests the possible role of super cyclone in its range extension. A year later, another specimen was recovered from a location very close to the first, which indicates the successful establishment of Lacturia cornuta in its new environment. Related morphometric and meristic studies of our specimens are consistent with previous studies reported in the Bay of Bengal.
PCaDB - a comprehensive and interactive database for transcriptomes from prostate cancer population cohorts
Authors: Li Ruidong , Zhu Jianguo , Zhong Wei-De , Jia Zhenyu 
Published: July 2021

AbstractProstate cancer (PCa) is a heterogeneous disease with highly variable clinical outcomes which presents enormous challenges in the clinical management. A vast amount of transcriptomics data from large PCa cohorts have been generated, providing extraordinary opportunities for the molecular characterization of the PCa disease and the development of diagnostic and prognostic signatures. The lack of an inclusive collection and harmonization of the scattered public datasets constrains the extensive use of the valuable resources. In this study, we present a user-friendly database, PCaDB, for a comprehensive and interactive analysis and visualization of gene expression profiles from 77 transcriptomics datasets with 9,068 patient samples. PCaDB also includes a single-cell RNA-sequencing (scRNAseq) dataset for normal human prostates and 30 published PCa prognostic signatures. The comprehensive data resources and advanced analytical methods equipped in PCaDB would greatly facilitate data mining to understand the heterogeneity of PCa and to develop machine learning models for accurate PCa diagnosis and prognosis to assist on clinical decision-making. PCaDB is publicly available at http://bioinfo.jialab-ucr.org/PCaDB/.
The Genome Sequence Archive Family: Towards Explosive Data Growth and Diverse Data Types
Authors: Chen Tingting , Chen Xu , Zhang Sisi , Zhu Junwei , Tang Bixia , Wang Anke , Dong Lili , Zhang Zhewen , Yu Caixia , Sun Yanling , Chi Lianjiang , Chen Huanxin , Zhai Shuang , Sun Yubin , Lan Li , Zhang Xin , Xiao Jingfa , Bao Yiming , Wang Yanqing , Zhang Zhang , Zhao Wenming 
Published: July 2021

AbstractThe Genome Sequence Archive (GSA) is a data repository for archiving raw sequence data, which provides data storing and sharing services for worldwide scientific communities. Considering explosive data growth with diverse data types, here we present the GSA family by expanding into a set of resources for raw data archive with different purposes, namely, GSA (https://ngdc.cncb.ac.cn/gsa/), GSA for Human (GSA-Human, https://ngdc.cncb.ac.cn/gsa-human/), and Open Archive for Miscellaneous Data (OMIX, https://ngdc.cncb.ac.cn/omix/). Compared with the 2017 version, GSA has been significantly updated in data model, online functionalities, and web interfaces. GSA-Human, as a new partner of GSA, is a data repository specialized in human genetics-related data with controlled access and security. OMIX, as a critical complement to the two resources mentioned above, is an open archive for miscellaneous data. Together, all these resources form a family of resources dedicated to archiving explosive data with diverse types, accept data submissions from all over the world and provide free open access to all publicly available data in support of worldwide research activities.
Taming the massive genome of Scots pine with PiSy50k, a new genotyping array for conifer research
Authors: Kastally Chedly , Niskanen Alina K. , Perry Annika , Kujala Sonja T. , Avia Komlan , Cervantes Sandra , Haapanen Matti , Kesälahti Robert , Kumpula Timo A. , Mattila Tiina M. , Ojeda Dario I. , Tyrmi Jaakko S. , Wachowiak Witold , Cavers Stephen , Kärkkäinen Katri , Savolainen Outi , Pyhäjärvi Tanja 
Published: July 2021

SummaryScots pine (Pinus sylvestris) is the most widespread coniferous tree in the boreal forests of Eurasia and has major economic and ecological importance. However, its large and repetitive genome presents a challenge for conducting genome-wide analyses such as association studies and genomic selection. We present a new 50K SNP genotyping array for Scots pine research, breeding programs, and other applications. To select the SNP set, we first genotyped 480 Scots pine samples on a 407 540 SNP screening array, and identified 47 712 high-quality SNPs for the final array (called ‘PiSy50k’). Here, we provide details of the design and testing, as well as allele frequency estimates from the discovery panel, functional annotation, tissue-specific expression patterns, and expression level information for the SNPs or corresponding genes, when available. We validated the performance of the PiSy50k array using samples from breeding populations from Finland and Scotland. Overall, 39 678 (83.2%) SNPs showed low error rates (mean = 0.92%). Relatedness estimates based on array genotypes were consistent with the expected pedigrees, and the amount of Mendelian error was negligible. In addition, array genotypes successfully discriminate Scots pine populations from different geographic origins. The PiSy50k array will be a valuable tool for future genetic studies and forestry applications.Significance statementScots pine is an evolutionary, economically and ecologically impressive coniferous species but its gigantic genome has limited studying e.g. the genetic basis of its functional trait variation. We have developed a genotyping array that facilitates Scots pine genetic research and linking its trait variation to genetic polymorphisms and gene expression levels across the genome.
SLOW5: a new file format enables massive acceleration of nanopore sequencing data analysis
Authors: Gamaarachchi Hasindu , Samarakoon Hiruna , Jenner Sasha P. , Ferguson James M. , Amos Timothy G. , Hammond Jillian M. , Saadat Hassaan , Smith Martin A. , Parameswaran Sri , Deveson Ira W. 
Published: July 2021

ABSTRACTNanopore sequencing is an emerging genomic technology with great potential. However, the storage and analysis of nanopore sequencing data have become major bottlenecks preventing more widespread adoption in research and clinical genomics. Here, we elucidate an inherent limitation in the file format used to store raw nanopore data – known as FAST5 – that prevents efficient analysis on high-performance computing (HPC) systems. To overcome this, we have developed SLOW5, an alternative file format that permits efficient parallelisation and, thereby, acceleration of nanopore data analysis. For example, we show that using SLOW5 format, instead of FAST5, reduces the time and cost of genome-wide DNA methylation profiling by an order of magnitude on common HPC systems, and delivers consistent improvements on a wide range of different architectures. With a simple, accessible file structure and a ~25% reduction in size compared to FAST5, SLOW5 format will deliver substantial benefits to all areas of the nanopore community.
A dinucleotide tag-based parallel reporter gene assay method
Authors: Ren Naixia , Li Bo , Liu Qingqing , Yang Lele , Liu Xiaodan , Huang Qilai 
Published: July 2021

AbstractThe causal SNPs leading to increased cancer predisposition mainly function as gene regulatory elements, the evaluation of which largely rely on the parallel reporter gene assay system. However, the common DNA barcode-based parallel reporter gene assay systems are troubled with tag bias, mainly due to the tag nucleotide composition. Here we describe a versatile dinucleotide-tag reporter system (DiR) that enables parallel analysis of regulatory elements with minimized bias based on the next-generation sequencing. The DiR system is also more robust than the classical luciferase assay method, especially in the investigation of moderate-level regulatory elements. We applied DiR-seq assay in the functional evaluation of the prostate cancer risk SNPs in prostate cancer cell lines and disclosed 2, and 6 regulatory SNPs in PC-3 and LNCaP cells. The DiR system has great potential to advance the functional study of risk SNPs that have associations with polygenic diseases.
Quercetin ameliorates mitochondrial dysfunction and mitigates methamphetamine-induced anxiety-like behavior
Authors: Chen Fengrong , Sun Jiaxue , Zhang Yongjin , Dai Yicong , Zhang Zherui , Chen Cheng , Zou Lei , Zhang Zunyue , Wu Hongjin , Tian Weiwei , Xu Yu , Luo Huayou , Yu Juehua , Wang Kunhua 
Published: July 2021

ABSTRACTMethamphetamine (MA) abuse results in neurotoxic outcomes, including increased anxiety and depression, during both MA use and withdrawal. Although numerous studies have reported an association between MA exposure and anxiety, the underlying mechanism remains elusive. In this study, escalating dose of MA was used to establish an MA-treated mouse model presenting anxiety behavior. RNA seq was then performed to profile the gene expression patterns in the hippocampus (HIPP). Differentially expressed genes (DEGs) were identified and function enrichment analysis was conducted to explore the underlying mechanisms. Quercetin as an mitochondria protector was usedin vivoandin vitro. The C57BL/6J mice were co-treated with 50 mg/kg Quercetin and escalating MA. Anxiety behavior was evaluated by utilizing the elevated plus maze and the open field test. Transmission electron microscopy and immunohistochemistry were conducted to study the pathology of MA-inducced anxiety. The effects of MA and Quercetin on astrocytes were investigated by fluorescence staining, transmission electron microscopy, flow cytometry, and oxygen consumption rate. Western blot and qPCR were performed to analyze altered protein and gene levels of HIPP in mice and astrtocytes. The results demonstrated that forteen upregulated differentially expressed genes were identified and significantly enriched in signaling pathways related to psychiatric disorders and mitochondrial function. Interestingly, we found that quercetin was able to alleviate MA-induced anxiety-like behavior by improving neuron number and mitochondria injury. Mechanistically, quercetin can mitigate aberrant mitochondrial morphology and mitochondrial dysfunction not only by decreasing the levels of total cytoplasmic reactive oxygen species (ROS), mitochondria-derived ROS (mtROS), and mitochondrial membrane potential (MMP), but also increasing the oxygen consumption rate (OCR) and mitochondrial ATP productionin vitro, indicating Quercetin ameliorated MA-induced anxiety-like behavior by modifying mitochondrial morphology and function. Furthermore, quercetin reversed OPA1 and DRP1 expression in astrocytes, and mitigated astrocyte activation and the release of inflammatory factors, which can trigger neuronal apoptosis and synaptic loss. Taken together, we provided evidence showing that MA can induce anxiety-like behavior via the induction of oxidative stress and mitochondrial dysfunction. Quercetin exerted antipsychotic activity through mitochondrial modulation, suggesting its potential for further therapeutic development in MA-induced anxiety.
Transcriptional profiling of sequentially generated septal neuron fates
Authors: García Miguel Turrero , Stegmann Sarah K , Lacey Tiara E , Reid Christopher M , Hrvatin Sinisa , Weinreb Caleb , Adam Manal A , Aurel Nagy M , Harwell Corey C 
Published: July 2021

ABSTRACTThe septum is a ventral forebrain structure known to regulate innate behaviors. During embryonic development, septal neurons are produced in multiple proliferative areas from neural progenitors following transcriptional programs that are still largely unknown. Here, we use a combination of single cell RNA sequencing, histology and genetic models to address how septal neuron diversity is established during neurogenesis. We find that the transcriptional profiles of septal progenitors change along neurogenesis, coinciding with the generation of distinct neuron types. We characterize the septal eminence, a spatially distinct and transient proliferative zone composed of progenitors with distinctive molecular profiles, proliferative capacity and fate potential compared to the rostral septal progenitor zone. We show that Nkx2.1-expressing septal eminence progenitors give rise to neurons belonging to at least three morphological classes, born in temporal cohorts that are distributed across different septal nuclei in a sequential fountain-like pattern. Our study provides insight into the molecular programs that control the sequential production of different neuronal types in the septum, a structure with important roles in regulating mood and motivation.
Atrazine induced In vivo immunotoxicity in Bivalves
Authors: Muhammed Zafar Iqbal A.N , Iqbal Navalgund M. Azhar 
Published: July 2021

AbstractAtrazine is ubiquitously used broad-spectrum herbicide to control the weeds in agriculture. The present study aimed to evaluate the acute toxicity and immunotoxicity of Atrazine in two ecologically and economically important bivalves. Acute toxicity of atrazine evaluated in triplicates by taking control and six experimental groups each comprising of 30 animals and treated with a range of atrazine from 2 PPM to 12 PPM for 96 hours. Mortalities were recorded for every 24 hours until 96 hours and data analyzed by one-way ANOVA and Dunnett T-test. The results indicated a significant increase in mortalities with increase in dose and time of exposure in both species. The values of LC50 were determined as 6.10 PPM and 4.90 PPM respectively for Perna viridis and Paphia malabarica. Furthermore, the immunotoxic potential of atrazine assessed by treating mussels and clams with the five sub-lethal doses of atrazine for 14 days and quantifying the viability of hemocytes by using simple yet reliable Tryphan blue exclusion assay. The results of the present study suggest atrazine-induced immunotoxicity by decreasing the number of viable hemocytes in bivalves. Hemocytes with phagocytic function are indispensable to confer innate immunity in bivalves, decreased viability of these cells leads to compromised immunity. This study is first of its kind to implicate atrazine with the immunotoxicity in bivalves.
HMMploidy: inference of ploidy levels from short-read sequencing data
Authors: Soraggi Samuele , Rhodes Johanna , Altinkaya Isin , Tarrant Oliver , Balloux François , Fisher Matthew C. , Fumagalli Matteo 
Published: July 2021

AbstractThe inference of ploidy levels from genomic data is important to understand molecular mechanisms underpinning genome evolution. However, current methods based on allele frequency and sequencing depth variation do not have power to infer ploidy levels at low-and mid-depth sequencing data, as they do not account for data uncertainty. Here we introduce HMMploidy, a novel tool that leverages the information from multiple samples and combines the information from sequencing depth and genotype likelihoods. We demonstrate that HMMploidy outperforms existing methods in most tested scenarios, especially at low-depth with large sample size. We apply HMMploidy to sequencing data from the pathogenic fungus Cryptococcus neoformans and retrieve pervasive patterns of aneuploidy, even when artificially downsampling the sequencing data. We envisage that HMMploidy will have wide applicability to low-depth sequencing data from polyploid and aneuploid species.
Children are full of optimism, but those rose-tinted glasses are fading – reduced learning from negative outcomes drives hyperoptimism in children
Authors: Habicht Johanna , Bowler Aislinn , Moses-Payne Madeleine E , Hauser Tobias U 
Published: July 2021

AbstractBelieving that good things will happen in life is essential to maintain motivation and achieve highly ambitious goals. This optimism bias, the overestimation of positive outcomes, may be particularly important during childhood when motivation must be maintained in the face of negative outcomes. In a learning task, we have thus studied the mechanisms underlying the development of optimism bias. Investigating children (8-9 year-olds), early (12-13 year-olds) and late adolescents (16-17 year-olds), we find a consistent optimism bias across age groups. However, children were particularly hyperoptimistic, with the optimism bias decreasing with age. Using computational modelling, we show that this was driven by a reduced learning from worse-than-expected outcomes, and this reduced learning explains why children are hyperoptimistic. Our findings thus show that insensitivity to bad outcomes in childhood helps to prevent taking on an overly realistic perspective and maintain motivation.
Single-cell analyses of immune thrombocytopenic patients reveal multiorgan dissemination of high-affinity autoreactive plasma cells
Authors: Canales-Herrerias Pablo , Crickx Etienne , Broketa Matteo , Sokal Aurélien , Chenon Guilhem , Azzaoui Imane , Vandenberghe Alexis , Perima Angga , Iannascoli Bruno , Goff Odile Richard-Le , Castrillon Carlos , Mottet Guillaume , Sterlin Delphine , Robbins Ailsa , Michel Marc , England Patrick , Millot Gael A. , Eyer Klaus , Baudry Jean , Mahevas Matthieu , Bruhns Pierre 
Published: July 2021

AbstractThe major therapeutic goal for immune thrombocytopenia (ITP) is to restore normal platelet counts using drugs to promote platelet production or by interfering with mechanisms responsible for platelet destruction. 80% of patients possess anti-integrin αIIbβ3 (GPIIbIIIa) IgG autoantibodies causing platelet opsonization and phagocytosis. The spleen is considered the primary site of autoantibody production by autoreactive B cells and platelet destruction. The immediate failure in ~50% of patients to recover a normal platelet count after anti-CD20 Rituximab-mediated B cell depletion and splenectomy suggest that autoreactive, rituximab-resistant, IgG-secreting B cells (IgG-SC) reside in other anatomical compartments. We analyzed >3,300 single IgG-SC from spleen, bone marrow and/or blood of 27 patients with ITP revealing high inter-individual variability in affinity for GPIIbIIIa with variations over 3 logs. IgG-SC dissemination and range of affinities were however similar per patient. Longitudinal analysis of autoreactive IgG-SC upon treatment with anti-CD38 mAb daratumumab demonstrated variable outcomes, from complete remission to failure with persistence of high-affinity anti-GPIIbIIIa IgG-SC in the bone marrow. This study demonstrates the existence and dissemination of high-affinity autoreactive plasma cells in multiple anatomical compartments of patients with ITP that may cause the failure of current therapies.
Using wearable biosensors and ecological momentary assessments for the detection of prolonged stress in real life
Authors: Tutunji Rayyan , Kogias Nikos , Kapteijns Bob , Krentz Martin , Krause Florian , Vassena Eliana , Hermans Erno J. 
Published: July 2021

AbstractBackgroundIncreasing efforts toward prevention of stress-related mental disorders have created a need for unobtrusive real-life monitoring of stress-related symptoms. Wearable devices have emerged as a possible solution to aid in this process, but their use in real-life stress detection has not been systematically investigated.MethodsUsing ecological momentary assessments (EMA) combined with wearable biosensors for ecological physiological assessments (EPA), we investigated the impact of an ecological stressor (i.e., an exam week) on physiological arousal and affect. With this paradigm we investigated whether we could use wearable devices to detect stress states using machine learning models.ResultsDuring stressful high-stake exam (versus control) weeks, participants reported increased negative affect and decreased positive affect. Intriguingly, physiological arousal was decreased on average during the exam week. Time-resolved analyses revealed peaks in physiological arousal associated with both self-reported stress and self-reported positive affect, while the overall decrease in physiological arousal was mediated by lower positive affect during the stress period. We then used machine learning to show that a combination of EMA and physiology yields optimal identification of stress states.ConclusionsOur findings highlight the potential of wearable biosensors in stress-related mental-health monitoring, but critically show that psychological context is essential for interpreting physiological arousal detected using these devices.