bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biodiversity Soup II: A bulk-sample metabarcoding pipeline emphasizing error reduction
Authors: Yang Chunyan , Bohmann Kristine , Wang Xiaoyang , Cai Wang , Wales Nathan , Ding Zhaoli , Gopalakrishnan Shyam , Yu Douglas W. 
Published: July 2020

AbstractDespite widespread recognition of its great promise to aid decision-making in environmental management, the applied use of metabarcoding requires improvements to reduce the multiple errors that arise during PCR amplification, sequencing, and library generation. We present a co-designed wet-lab and bioinformatic workflow for metabarcoding bulk samples that removes both false-positive (tag jumps, chimeras, erroneous sequences) and false-negative (‘dropout’) errors. However, we find that it is not possible to recover relative-abundance information from amplicon data, due to persistent species-specific biases.To present and validate our workflow, we created eight mock arthropod soups, all containing the same 248 arthropod morphospecies but differing in absolute and relative DNA concentrations, and we ran them under five different PCR conditions. Our pipeline includes qPCR-optimized PCR annealing temperature and cycle number, twin-tagging, multiple independent PCR replicates per sample, and negative and positive controls. In the bioinformatic portion, we introduceBegum, which is a new version ofDAMe(Zepeda-Mendozaet al. 2016.BMC Res. Notes9:255) that ignores heterogeneity spacers, allows primer mismatches when demultiplexing samples, and is more efficient. LikeDAMe, Begumremoves tag-jumped reads and removes sequence errors by keeping only sequences that appear in more than one PCR above a minimum copy number per PCR. The filtering thresholds are user-configurable.We report that OTU dropout frequency and taxonomic amplification bias are both reduced by using a PCR annealing temperature and cycle number on the low ends of the ranges currently used for the Leray-FolDegenRev primers. We also report that tag jumps and erroneous sequences can be nearly eliminated withBegumfiltering, at the cost of only a small rise in dropouts. We replicate published findings that uneven size distribution of input biomasses leads to greater dropout frequency and that OTU size is a poor predictor of species input biomass. Finally, we find no evidence for ‘tag-biased’ PCR amplification.To aid learning, reproducibility, and the design and testing of alternative metabarcoding pipelines, we provide our Illumina and input-species sequence datasets, scripts, a spreadsheet for designing primer tags, and a tutorial.
Bedtk: Finding Interval Overlap with Implicit Interval Tree
Authors: Li Heng , Rong Jiazhen 
Published: July 2020

AbstractSummaryWe present bedtk, a new toolkit for manipulating genomic intervals in the BED format. It supports sorting, merging, intersection, subtraction and the calculation of the breadth of coverage. Bedtk employs implicit interval tree, a new data structure for fast interval overlap queries. It is several to tens of times faster than existing tools and tends to use less memory.Availabilityhttps://github.com/lh3/bedtkContacthli@jimmy.harvard.edu,jiazhen_rong@hms.harvard.edu
Muscle activation patterns are more constrained and regular in treadmill than in overground human locomotion
Authors: Mileti Ilaria , Serra Aurora , Wolf Nerses , Munoz-Martel Victor , Ekizos Antonis , Palermo Eduardo , Arampatzis Adamantios , Santuz Alessandro 
Published: July 2020

AbstractThe use of motorized treadmills as convenient tools for the study of locomotion has been in vogue for many decades. However, despite the widespread presence of these devices in many scientific and clinical environments, a full consensus on their validity to faithfully substitute free overground locomotion is still missing. Specifically, little information is available on whether and how the neural control of movement is affected when humans walk and run on a treadmill as compared to overground. Here, we made use of linear and nonlinear analysis tools to extract information from electromyographic recordings during walking and running overground, and on an instrumented treadmill. We extracted synergistic activation patterns from the muscles of the lower limb via non-negative matrix factorization. We then investigated how the motor modules (or time-invariant muscle weightings) were used in the two locomotion environments. Subsequently, we examined the timing of motor primitives (or time-dependent coefficients of muscle synergies) by calculating their duration, the time of main activation, and their Hurst exponent, a nonlinear metric derived from fractal analysis. We found that motor modules were not influenced by the locomotion environment, while motor primitives resulted overall more regular in treadmill than in overground locomotion, with the main activity of the primitive for propulsion shifted earlier in time. Our results suggest that the spatial and sensory constraints imposed by the treadmill environment forced the central nervous system to adopt a different neural control strategy than that used for free overground locomotion. A data-driven indication that treadmills induce perturbations to the neural control of locomotion.
Age Influences on the Molecular Presentation of Tumours
Authors: Li Constance H. , Haider Syed , Boutros Paul C. 
Published: July 2020

AbstractCancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterize them, we analyzed age-associations in the nuclear and mitochondrial somatic mutational landscape of 20,033 tumours across 35 tumour-types. Age influences both the number of mutations in a tumour and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes such as a greater influence of tobacco use in the tumours of younger patients, but more activity of DNA damage repair signatures in those of older patients. We find that known cancer driver genes are mutated in age-associated frequencies, and these alter the transcriptome and predict for clinical outcomes. These effects are most striking in brain cancers where alterations likeSUFUloss andATRXmutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.
Effects of Different Microplastics on Nematodes in the Soil Environment: Tracking the Extractable Additives using an Ecotoxicological Approach
Authors: Kim Shin Woong , Waldman Walter R. , Rillig Matthias C. 
Published: July 2020

ABSTRACTWith an increasing interest in the effects of microplastic in the soil environment, there is a need to thoroughly evaluate potential adverse effects of these particles as a function of their characteristics (size, shape, and composition). In addition, extractable chemical additives from microplastic have been identified as an important toxicity pathway in the aquatic environment. However, we currently know little about effects of such additives in the soil environment. In this study on nematodes (Caenorhabditis elegans), we adopted an ecotoxicological approach to assess the potential effects of thirteen different microplastics with different characteristics and extractable additives. We found that toxic effects appear to increase in the order of low-density polyethylene (LDPE) film < polypropylene (PP) fragments < high-density polyethylene (HDPE) fragments ≈ polystyrene (PS) fragments < polyethylene terephthalate (PET) fragments ≈ polyacrylicnitrile (PAN) fibers. Acute toxicity was mainly attributed to the extractable additives: when the additives were extracted, the toxic effects of each microplastic disappeared in the acute soil toxicity test. The harmful effects of LDPE film and PAN fibers increased when the microplastics were maintained in soil for a long-term period with frequent wet-dry cycles. We here provide clear evidence that microplastic toxicity in the soil is highly related to particle characteristics and extractable additives. Our results suggest that future experiments consider extractable additives as a key explanatory variable.Abstract art/Table of contents
A direct interareal feedback-to-feedforward circuit in primate visual cortex
Authors: Siu Caitlin , Balsor Justin , Merlin Sam , Federer Frederick , Angelucci Alessandra 
Published: July 2020

ABSTRACTThe mammalian sensory neocortex consists of hierarchically organized areas reciprocally connected via feedforward (FF) and feedback (FB) circuits. Several theories of hierarchical computation ascribe the bulk of the computational work of the cortex to looped FF-FB circuits between pairs of cortical areas. However, whether such corticocortical loops exist remains unclear. In higher mammals, individual FF-projection neurons send afferents almost exclusively to a single higher-level area. However, it is unclear whether FB-projection neurons show similar area specificity, and whether they influence FF-projection neurons directly or indirectly. Using viral-mediated monosynaptic circuit tracing in macaque primary visual cortex (V1), we show that V1 neurons sending FF projections to area V2 receive monosynaptic FB inputs from V2, but not other V1-projecting areas. We also find monosynaptic FB-to-FB neuron contacts as a second motif of FB connectivity. Our results support the existence of FF-FB loops in primate cortex, and suggest that FB can rapidly and selectively influence the activity of incoming FF signals.
CTCF Mediates Dosage and Sequence-context-dependent Transcriptional Insulation through Formation of Local Chromatin Domains
Authors: Huang Hui , Zhu Quan , Jussila Adam , Han Yuanyuan , Bintu Bogdan , Kern Colin , Conte Mattia , Zhang Yanxiao , Bianco Simona , Chiariello Andrea , Yu Miao , Hu Rong , Juric Ivan , Hu Ming , Nicodemi Mario , Zhuang Xiaowei , Ren Bing 
Published: July 2020

AbstractInsulators play a critical role in spatiotemporal gene expression in metazoans by separating active and repressive chromatin domains and preventing inappropriate enhancer-promoter contacts. The evolutionarily conserved CCCTC-binding factor (CTCF) is required for insulator function in mammals, but not all of its binding sites act as insulators. Here, we explore the sequence requirements of CTCF-mediated transcriptional insulation with the use of a sensitive insulator reporter assay in mouse embryonic stem cells. We find that insulation potency depends on the number of CTCF binding sites in tandem. Furthermore, CTCF-mediated insulation is dependent on DNA sequences flanking its core binding motifs, and CTCF binding sites at topologically associating domain(TAD) boundaries are more likely to function as insulators than those outside TAD boundaries, independent of binding strength. Using chromosomal conformation capture assays and high-resolution chromatin imaging techniques, we demonstrate that insulators form local chromatin domain boundaries and reduce enhancer-promoter contacts. Taken together, our results provide strong genetic, molecular, and structural evidence connecting chromatin topology to the action of insulators in the mammalian genome.
A Pseudo-Temporal Causality Approach to Identifying miRNA-mRNA Interactions During Biological Processes
Authors: Cifuentes-Bernal Andres M. , Pham Vu VH , Li Xiaomei , Liu Lin , Li Jiuyong , Le Thuc Duy 
Published: July 2020

AbstractMotivationmicroRNAs (miRNAs) are important gene regulators and they are involved in many biological processes, including cancer progression. Therefore, correctly identifying miRNA-mRNA interactions is a crucial task. To this end, a huge number of computational methods has been developed, but they mainly use the data at one snapshot and ignore the dynamics of a biological process. The recent development of single cell data and the booming of the exploration of cell trajectories using “pseudo-time” concept have inspired us to develop a pseudo-time based method to infer the miRNA-mRNA relationships characterising a biological process by taking into account the temporal aspect of the process.ResultsWe have developed a novel approach, called pseudo-time causality (PTC), to find the causal relationships between miRNAs and mRNAs during a biological process. We have applied the proposed method to both single cell and bulk sequencing datasets for Epithelia to Mesenchymal Transition (EMT), a key process in cancer metastasis. The evaluation results show that our method significantly outperforms existing methods in finding miRNA-mRNA interactions in both single cell and bulk data. The results suggest that utilising the pseudo-temporal information from the data helps reveal the gene regulation in a biological process much better than using the static information.AvailabilityR scripts and datasets can be found athttps://github.com/AndresMCB/PTC
Unconventional ER to Endosomal Trafficking by a Retroviral Protein
Authors: Xu Wendy Kaichun , Gou Yongqiang , Lozano Mary M. , Dudley Jaquelin P. 
Published: July 2020

ABSTRACTMouse mammary tumor virus (MMTV) encodes a Rem precursor protein that specifies both regulatory and accessory functions. Rem is cleaved at the ER membrane into a functional N-terminal signal peptide (SP) and the C-terminus (Rem-CT). Rem-CT lacks a membrane-spanning domain and a known ER retention signal, yet was not detectably secreted into cell supernatants. Inhibition of intracellular trafficking by the drug Brefeldin A (BFA), which interferes with the ER to Golgi secretory pathway, resulted in dramatically reduced intracellular Rem-CT levels. A Rem mutant lacking glycosylation sites was cleaved into SP and Rem-CT, but was insensitive to BFA, suggesting that unglycosylated Rem-CT does not exit the ER or reach a degradative compartment. BFA reduction of Rem-CT levels was not rescued by proteasome or lysosomal inhibitors. Rem-CT has simple glycans, which are necessary for Rem-CT stability and trafficking, but indicate that Rem-CT does not traffic through the Golgi. Analysis of wild-type Rem-CT and its glycosylation mutant by confocal microscopy revealed that both were primarily localized to the ER lumen. A small fraction of wild-type Rem-CT, but not the unglycosylated mutant, were co-localized with Rab5+ endosomes. Expression of a dominant-negative (DN) form of ADP ribosylation factor 1 (Arf1) (T31N) mimicked the effects of BFA by reducing Rem-CT levels, suggesting that Arf1 prevents Rem-CT localization to a degradative compartment. A DN form of the AAA ATPase, p97/VCP, rescued Rem-CT in the presence of BFA or DN Arf1. Thus, Rem-CT uses an unconventional trafficking scheme, perhaps to thwart innate immunity to MMTV infection.IMPORTANCEMouse mammary tumor virus is a complex retrovirus that encodes a regulatory/accessory protein, Rem. Rem is a precursor protein that is processed at the endoplasmic reticulum (ER) membrane by signal peptidase. The N-terminal SP eludes ER-associated degradation to traffic to the nucleus and serve a human immunodeficiency virus Rev-like function. In contrast, the function of the C-terminal glycosylated cleavage product (Rem-CT) is unknown. Since localization is critical for protein function, we used multiple methods to localize Rem-CT. Surprisingly, Rem-CT, which lacks a transmembrane domain or an ER retention signal, was detected primarily within the ER and required glycosylation for trafficking to endosomes. Blocking of retrograde trafficking through Arf1 reduced Rem-CT levels, but was not restored by lysosomal or proteasomal inhibitors. The unique trafficking of Rem-CT suggests a novel intracellular trafficking pathway, potentially impacting host anti-viral immunity.
A clinical specific BERT developed with huge size of Japanese clinical narrative
Authors: Kawazoe Yoshimasa , Shibata Daisaku , Shinohara Emiko , Aramaki Eiji , Ohe Kazuhiko 
Published: July 2020

AbstractGeneralized language models that pre-trained with a large corpus have achieved great performance on natural language tasks. While many pre-trained transformers for English are published, few models are available for Japanese text, especially in clinical medicine. In this work, we demonstrate a development of a clinical specific BERT model with a huge size of Japanese clinical narrative and evaluated it on the NTCIR-13 MedWeb that has pseudo-Twitter messages about medical concerns with eight labels. Approximately 120 millions of clinical text stored at the University of Tokyo Hospital were used as dataset. The BERT-base was pre-trained with the entire dataset and a vocabulary including 25,000 tokens. The pre-training was almost saturated at about 4 epochs, and the accuracies of Masked LM and Next Sentence Prediction were 0.773 and 0.975, respectively. The developed BERT tends to show higher performances on the MedWeb task than the other nonspecific BERTs, however, no significant differences were found. The advantage of training on domain-specific texts may become apparent in the more complex tasks on actual clinical text, and such corpus for the evaluation is required to be developed.
Statistically correcting dynamical electron scattering improves refinement of protein nanocrystals, including charge refinement of coordinated metals
Authors: Blum Thorsten B. , Housset Dominique , Clabbers Max T.B. , van Genderen Eric , Bacia-Verloop Maria , Zander Ulrich , McCarthy Andrew A. , Schoehn Guy , Li Ling Wai , Abrahams Jan Pieter 
Published: July 2020

AbstractElectron diffraction allows protein structure determination when only nanosized crystals are available. Nevertheless, multiple elastic (or dynamical) scattering, prominent in electron diffraction, is a concern. Current methods for modeling dynamical scattering by multi-slice or Bloch wave approaches are not suitable for protein crystals because they are not designed to cope with large molecules. Here, we limited dynamical scattering of nanocrystals of insulin, thermolysin, and thaumatin by collecting data from thin crystals. To accurately measure the weak diffraction signal from the few unit cells in the thin crystals, we used a low-noise hybrid-pixel Timepix electron counting detector. The remaining dynamical component was further reduced in refinement using a likelihood-based correction, which we introduced previously for analyzing electron diffraction data of small molecule nanocrystals and adapted here for protein crystals. We show that the procedure notably improved the structural refinement, allowing in one case the location of solvent molecules. It also allowed the refinement of the charge state of bound metal atoms, an important element in protein functions, through B-factor analysis of the metal atoms and their ligands. Our results clearly increase the value of macromolecular electron crystallography as a complementary structural biology technique.
HIF1α is an essential regulator of steroidogenesis in the adrenal gland
Authors: Watts Deepika , Stein Johanna , Meneses Ana , Bechmann Nicole , Neuwirth Ales , Kaden Denise , Krüger Anja , Sinha Anupam , Alexaki Vasileia Ismini , Perez-Rivas Luis Gustavo , Kircher Stefan , Martinez Antoine , Theodoropoulou Marily , Eisenhofer Graeme , Peitzsch Mirko , El-Armouche Ali , Chavakis Triantafyllos , Wielockx Ben 
Published: July 2020

AbstractEndogenous steroid hormones, especially glucocorticoids and mineralocorticoids, are essential for life regulating numerous physiological and pathological processes. These hormones derive from the adrenal cortex, and drastic or sustained changes in their circulatory levels affect multiple organ systems. Although a role for hypoxia pathway proteins (HPP) in steroidogenesis has been suggested, knowledge on the true impact of the HIFs (Hypoxia Inducible Factors) and oxygen sensors (HIF-prolyl hydroxylase domain-containing enzymes; PHDs) in the adrenocortical cells of vertebrates is scant. By creating a unique set of transgenic mouse lines, we reveal a prominent role for HIF1α in the synthesis of virtually all steroids under steady state conditions. Specifically, mice deficient in HIF1α in a part of the adrenocortical cells displayed enhanced levels of enzymes responsible for steroidogenesis and a cognate increase in circulatory steroid levels. These changes resulted in cytokine alterations and changes in the profile of circulatory mature hematopoietic cells. Conversely, HIF1α overexpression due to combined PHD2 and PHD3 deficiency in the adrenal cortex resulted in the opposite phenotype of insufficient steroid production due to impaired transcription of necessary enzymes. Based on these results, we propose HIF1α to be a central and vital regulator of steroidogenesis as its modulation in adrenocortical cells dramatically impacts hormone synthesis with systemic consequences. Additionally, these mice can have potential clinical significances as they may serve as essential tools to understand the pathophysiology of hormone modulations in a number of diseases associated with metabolic syndrome, auto-immunity or even cancer.
Chromatin Accessibility Reveals Potential Prognostic Value of the Peak Set Associated with Smoking History in Patients with Lung Adenocarcinoma
Authors: Liang Han , Deng Jianlian , Luo Tian , Luo Huijuan , Wu Xuan , Ye Yiwang , Wang Shubin , Li Fuqiang , Wu Kui , Lin Cong 
Published: July 2020

AbstractConsiderable differences in molecular characteristics have been defined between non-smoker and smokers in patients with lung adenocarcinoma (LUAD), yet study of open chromatin patterns associated with LUAD progression caused by smoking is still lacking. Here, we constructed a novel network based on correlations between each ATAC-seq peak from TCGA data using our previously developed algorithm. Subsequently, principal component analysis was performed on LUAD samples with retained peaks filtered by the correlation network and pathway analysis was conducted for potential pathways identification. Results were verified in an independent dataset from primary LUAD samples. We identified a set of peaks that clearly differentiated long-term from short-term smokers in LUAD patients and also significantly associated with overall survival of these patients. We then investigated the gene set related to those peaks and found that the comprising genes are strongly associated with LUAD development, such asB3GNT3, ACTN4andCLDN3. They are consistent with the important roles for the associated pathways in LUAD oncogenesis induced by smoking, including glycosphingolipid biosynthesis and tight junction pathways.In summary, our study may provide valuable insights on exploration of ATAC-seq peaks and on smoking-related LUAD carcinogenesis from a perspective of open chromatin changes.