bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADPriboDB 2.0: an updated database of ADP-ribosylated proteins
Authors: Ayyappan Vinay , Wat Ricky , Barber Calvin , Vivelo Christina A , Gauch Kathryn , Visanpattanasin Pat , Cook Garth , Sazeides Christos , Leung Anthony K L 
Published: October 2020

Abstract
ADP-ribosylation is a protein modification responsible for biological processes such as DNA repair, RNA regulation, cell cycle and biomolecular condensate formation. Dysregulation of ADP-ribosylation is implicated in cancer, neurodegeneration and viral infection. We developed ADPriboDB (adpribodb.leunglab.org) to facilitate studies in uncovering insights into the mechanisms and biological significance of ADP-ribosylation. ADPriboDB 2.0 serves as a one-stop repository comprising 48 346 entries and 9097 ADP-ribosylated proteins, of which 6708 were newly identified since the original database release. In this updated version, we provide information regarding the sites of ADP-ribosylation in 32 946 entries. The wealth of information allows us to interrogate existing databases or newly available data. For example, we found that ADP-ribosylated substrates are significantly associated with the recently identified human protein interaction networks associated with SARS-CoV-2, which encodes a conserved protein domain called macrodomain that binds and removes ADP-ribosylation. In addition, we create a new interactive tool to visualize the local context of ADP-ribosylation, such as structural and functional features as well as other post-translational modifications (e.g. phosphorylation, methylation and ubiquitination). This information provides opportunities to explore the biology of ADP-ribosylation and generate new hypotheses for experimental testing.
Assessing the Relative Effectiveness of Combining Self-Care with Practitioner-Delivered Complementary and Integrative Health Therapies to Improve Pain in a Pragmatic Trial
Authors: Zeliadt Steven B , Coggeshall Scott , Gelman Hannah , Shin Marlena H , Elwy A Rani , Bokhour Barbara G , Taylor Stephanie L 
Published: October 2020

Abstract

Background
Many health care systems are beginning to encourage patients to use complementary and integrative health (CIH) therapies for pain management. Many clinicians have anecdotally reported that patients combining self-care CIH therapies with practitioner-delivered therapies report larger health improvements than do patients using practitioner-delivered or self-care CIH therapies alone. However, we are unaware of any trials in this area.

Design
The APPROACH Study (Assessing Pain, Patient-Reported Outcomes and Complementary and Integrative Health) assesses the value of veterans participating in practitioner-delivered CIH therapies alone or self-care CIH therapies alone compared with the combination of self-care and practitioner-delivered care. The study is being conducted in 18 Veterans Health Administration sites that received funding as part of the Comprehensive Addiction and Recovery Act to expand availability of CIH therapies. Practitioner-delivered therapies under study include chiropractic care, acupuncture, and therapeutic massage, and self-care therapies include tai chi/qi gong, yoga, and meditation. The primary outcome will be improvement on the Brief Pain Inventory 6 months after initiation of CIH as compared with baseline scores. Patients will enter treatment groups on the basis of the care they receive because randomizing patients to specific CIH therapies would require withholding therapies routinely offered at VA. We will address selection bias and confounding by using sites’ variations in business practices and other encouragements to receive different types of CIH therapies as a surrogate for direct randomization by using instrumental variable econometrics methods.

Summary
Real-world evidence about the value of combining self-care and practitioner-delivered CIH therapies from this pragmatic trial will help guide the VA and other health care systems in offering specific nonpharmacological approaches to manage patients’ chronic pain.
Chemical composition and in vitro fermentation characteristics of legumes using canine fecal inoculum
Authors: Traughber Zachary T , He Fei , Hoke Jolene M , Davenport Gary M , de Godoy Maria R C 
Published: October 2020

Abstract
Legumes are a popular grain-free alternative carbohydrate source in canine diets, however, information on their fermentative characteristics have not been established. Thus, the objectives of the present study were to 1) quantify the chemical compositions and 2) fermentative profile of select legumes using canine fecal inoculum. Five legume varieties, whole yellow peas (WYP), green lentils (GL), black bean grits (BBG), navy bean powder (NBP), and garbanzo beans, were analyzed and compared to a positive control, beet pulp (BP). Substrates were analyzed for gross energy (GE), dry and organic matter, crude protein (CP), acid hydrolyzed fat, and total dietary fiber (TDF) fractions, beta-glucans, starch-free, and hydrolyzed sugars, as well as fermentative characteristics: pH, short-chain fatty acids (SCFA), branched-chain fatty acids (BCFA), total gas, hydrogen, and methane. Substrates then underwent a two-stage in vitro digestion and subsequent fermentation using canine fecal inoculum for 0, 3, 6, 9, and 12 h. All test substrates contained approximately 8% to 9% moisture and 4.5 kcal/g GE. The highest CP content was observed in GL (27%). Analyzed TDF content of test substrates was greatest for WYP (32%) and GL (36%). Total starch content was greatest for GL (58%) and WYP (56%). Sucrose and stachyose were the most predominant free sugars and glucose was the most predominant hydrolyzed sugar among test substrates. After 3 and 6 h of fermentation, a net negative change in pH was observed among most substrates with a net negative change in all substrates after 9 and 12 h. Values for SCFA did not differ among substrates after 3 or 6 h of fermentation with BP and WYP among the greatest acetate (1,656 and 1,765 umol/g, respectively) and propionate production values (157.7 and 126.1, respectively) after 9 h. All substrates produced greater total gas volumes than WYP after 3 h, with no differences observed after any other time points. However, BP hydrogen production values were greater after 9 and 12 h (P &lt; 0.0001; 726,042 and 394,675 ng/g, respectively) with greater methane production values after 12 h (P &lt; 0.0001; 54,291 ng/g) than all test substrates. These data suggest that legumes offer a diverse macronutrient profile and appear to be a source of slowly fermentable fiber, which may have beneficial implications on the ratios of saccharolytic to proteolytic fermentation toward the distal colon.
Genome-wide analysis of long noncoding RNAs affecting floral bud dormancy in pears in response to cold stress
Authors: Li Liang , Liu Jinhang , Liang Qin , Zhang Yanhui , Kang Kaiquan , Wang Wenting , Feng Yu , Wu Shaohua , Yang Chao , Li Yongyu 
Published: October 2020

AbstractThe versatile role of long noncoding RNAs (lncRNAs) in plant growth and development has been established, but a systematic identification and analysis of lncRNAs in the pear has not been reported. Bud dormancy is a crucial and complicated protective mechanism for plants in winter. The roles of lncRNAs in the dormancy process remain largely unclear. In this study, we induced pear floral buds to enter into different dormant statuses by simulating four different chilling accumulation conditions. Then, a time series of RNA-seq analysis was performed and we identified 7594 lncRNAs in Pyrus pyrifolia (Burm. F.) Nakai that have not been identified. The sequence and expression of the lncRNAs were confirmed by PCR analysis. In total, 6253 lncRNAs were predicted to target protein-coding genes including 692 cis-regulated pairs (596 lncRNAs) and 13,158 trans-regulated pairs (6181 lncRNAs). Gene Ontology analysis revealed that most of lncRNAs' target genes were involved in catalytic activity, metabolic processes and cellular processes. In the trend analysis, 124 long-term cold response lncRNAs and 80 short-term cold response lncRNAs were predicted. Regarding the lncRNA-miRNA regulatory networks, 59 lncRNAs were identified as potential precursors for miRNA members of 20 families, 586 lncRNAs were targets of 261 pear miRNAs and 53 lncRNAs were endogenous target mimics for 26 miRNAs. In addition, three cold response lncRNAs, two miRNAs and their target genes were selected for expression confirmed. The trend of their expression was consistent with the predicted relationships among them and suggested possible roles of lncRNAs in ABA metabolic pathway. Our findings not only suggest the potential roles of lncRNAs in regulating the dormancy of pear floral buds but also provide new insights into the lncRNA-miRNA-mRNA regulatory network in plants.
Revision of the higher taxonomy of Neotropical freshwater crabs of the family Pseudothelphusidae, based on multigene and morphological analyses
Authors: Álvarez Fernando , Ojeda Juan Carlos , Souza-Carvalho Edvanda , Villalobos José Luis , Magalhães Célio , Wehrtmann Ingo S , Mantelatto Fernando L 
Published: October 2020

AbstractA new classification for the freshwater crabs of the Americas, the superfamily Pseudothelphusoidea¸ is presented based on a multigene phylogeny complemented by morphological analyses. We propose that the superfamily Pseudothelphusoidea be composed of two families, the Epiloboceridae and the Pseudothelphusidae, with the subsequent reorganization of the latter into eight subfamilies, of which five (Hypolobocerinae, Kingsleyinae, Potamocarcininae, Pseudothelphusinae, Strengerianinae) represent previously recognized tribes. We erect three new subfamilies: Guinotiinae, Ptychophallinae and Raddausinae, to reflect relationships that have become clear with the new analyses. The new classification scheme has a high level of congruence with the geographical distribution of species and genera. A divergence time estimate suggests that the Pseudothelphusoidea originated in the late Cretaceous around 68 Mya. Subsequent divergence events can be correlated with emergent landmasses throughout the range of the superfamily. There is high concordance among several elements of our proposal: (1) the main morphological types of male gonopods correspond to well defined clades obtained with molecular analyses; (2) the geographic distribution of the subfamilies has a structured pattern; and (3) the estimated times of divergence of each group can be associated to the geological history of each region. The combination of these elements results in a robust new classification scheme.
Open Science Discovery of Potent Non-Covalent SARS-CoV-2 Main Protease Inhibitors
Authors: Boby Melissa L. , Fearon Daren , Ferla Matteo , Filep Mihajlo , Koekemoer Lizbé , Robinson Matthew C. ,   The COVID Moonshot Consortium, Chodera John D. , Lee Alpha A , London Nir , von Delft Annette , von Delft Frank 
Published: October 2020

AbstractWe report the results of theCOVID Moonshot, a fully open-science, crowd sourced, structure-enabled drug discovery campaign targeting the SARS-CoV-2 main protease. We discovered a non-covalent, non-peptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>840 ligand-bound X-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledgebase for future anti-coronavirus drug discovery.
Ribosome-linked mRNA-rRNA chimeras reveal active novel virus host associations
Authors: Ignacio-Espinoza J. Cesar , Laperriere Sarah M. , Yeh Yi-Chun , Weissman Jake , Hou Shengwei , Long Andrew M. , Fuhrman Jed A. 
Published: October 2020

AbstractViruses of prokaryotes greatly outnumber their hosts1and impact microbial processes across scales, including community assembly, evolution, and metabolism1. Metagenomic discovery of novel viruses has greatly expanded viral sequence databases, but only rarely can viral sequences be linked to specific hosts. Here, we adapt proximity ligation methods to ligate ribosomal RNA to transcripts, including viral ones, during translation. We sequenced the resulting chimeras, directly linking marine viral gene expression to specific hosts by transcript association with rRNA sequences. With a sample from the San Pedro Ocean Time-series (SPOT), we found viral-host links to Cyanobacteria, SAR11, SAR116, SAR86, OM75, and Rhodobacteracae hosts, some being the first viruses reported for these groups. We used the SPOT viral and cellular DNA database to track abundances of multiple virus-host pairs monthly over 5 years, e.g. withRoseovariusphages tracking the host. Because the vast majority of proximity ligations should occur between an organism’s ribosomes and its own transcripts, we validated our method by looking for self- vs non-self mRNA-rRNA chimeras, by read recruitment to marine single amplified genomes; verifiable non-self chimeras, suggesting off-target linkages, were very rare, indicating host-virus hits were very unlikely to occur by mistake. This approach in practice could link any transcript and its associated processes to specific microorganisms.
Archaeogenomic Distinctiveness of the Isthmo-Colombian Area
Authors: Capodiferro Marco Rosario , Aram Bethany , Raveane Alessandro , Migliore Nicola Rambaldi , Colombo Giulia , Ongaro Linda , Rivera Javier , Mendizábal Tomás , Hernández-Mora Iosvany , Tribaldos Maribel , Perego Ugo Alessandro , Li Hongjie , Scheib Christiana Lyn , Modi Alessandra , Gòmez-Carballa Alberto , Grugni Viola , Lombardo Gianluca , Hellenthal Garrett , Pascale Juan Miguel , Bertolini Francesco , Grieco Gaetano , Cereda Cristina , Lari Martina , Caramelli David , Pagani Luca , Metspalu Mait , Friedrich Ronny , Knipper Corina , Olivieri Anna , Salas Antonio , Cooke Richard , Montinaro Francesco , Motta Jorge , Torroni Antonio , Martín Juan Guillermo , Semino Ornella , Malhi Ripan Singh , Achilli Alessandro 
Published: October 2020

SUMMARYThe recently enriched genomic history of Indigenous groups in the Americas is still meagre concerning continental Central America. Here, we report ten pre-Hispanic (plus two early colonial) genomes and 84 genome-wide profiles from seven groups presently living in Panama. Our analyses reveal that pre-Hispanic demographic changes and isolation events contributed to create the extensive genetic structure currently seen in the area, which is also characterized by a distinctive Isthmo-Colombian Indigenous component. This component drives these populations on a specific variability axis and derives from the local admixture of different ancestries of northern North American origin(s). Two of these ancestries were differentially associated to Pleistocene Indigenous groups that also moved into South America leaving heterogenous footprints. An additional Pleistocene ancestry was brought by UPopI, a still unsampled population that remained restricted to the Isthmian area, expanded locally during the early Holocene, and left genomic traces up to the present.
The prophase oocyte nucleus is a homeostatic G-actin buffer
Authors: Scheffler Kathleen , Giannini Federica , Mogessie Binyam 
Published: October 2020

AbstractFormation of healthy mammalian eggs from oocytes requires specialised F-actin structures. F-actin disruption produces aneuploid eggs, which are a leading cause of human embryo deaths, genetic disorders, and infertility. We found that oocytes regulate F-actin organisation and function by promptly transferring excess monomeric G-actin from the cytoplasm to the nucleus. Inside healthy oocyte nuclei, transferred monomers form dynamic F-actin structures, a conserved feature that significantly declines with maternal age. Monomer transfer must be controlled tightly. Blocked nuclear import of G-actin triggers assembly of a dense cytoplasmic F-actin network, while excess G-actin in the nucleus dramatically stabilises nuclear F-actin. Imbalances in either direction predispose oocytes to aneuploidy. The large oocyte nucleus is thus a homeostatic G-actin buffer that is used to maintain cytoplasmic F-actin form and function.One Sentence SummaryMammalian oocyte nuclei buffer cytosolic G-actin
Flower Power: Floral reversion as a viable alternative to nodal micropropagation inCannabis sativa
Authors: Monthony A.S. , Bagheri S. , Zheng Y. , Jones A.M.P. 
Published: October 2020

AbstractThe legalization ofCannabis sativaL. for recreational and medical purposes has been gaining global momentum, leading to a rise in interest inCannabistissue culture as growers look for large-scale solutions to germplasm storage and clean plant propagation. Mother plants used in commercial propagation are susceptible to insect pests and disease and require considerable space. While micropropagation can produce disease free starting material in less space, current publishedin vitromicropropagation methods are not robust and few report high multiplication rates. Further, these micropropagation methods rely on photoperiod-sensitive plants which can be maintained in a perpetual vegetative state. Current methods are not adaptable to long-term tissue culture of day-neutral cultivars, which cannot be maintained in perpetual vegetative growth. In this study, we chose to develop a micropropagation system which usesC. sativainflorescences as starting materials. This study used two cannabis cultivars, two plant growth regulators (PGR; 6-benzylaminopurine and meta-topolin) at different concentrations, and two different numbers of florets. Here we show that floral reversion occurs from meristematic tissue inC. sativaflorets and that it can be used to enhance multiplication rates compared to existingin vitromethods. Floret number was shown to have a significant impact on percent reversion, with pairs of florets reverting more frequently and producing healthier explants than single florets, while cultivar and PGR had no significant effect on percent reversion. Compared with our previously published nodal culture studies, the current floral reversion method produced up to eight times more explants per tissue culture cycle. Floral reversion provides a foundation for effective inflorescence-based micropropagation systems inC. sativa.
Global regulatory transitions at core promoters demarcate the mammalian germline cycle
Authors: Cvetesic Nevena , Borkowska Malgorzata , Hatanaka Yuki , Yu Changwei , Vincent Stéphane D. , Müller Ferenc , Tora László , Leitch Harry G. , Hajkova Petra , Lenhard Boris 
Published: October 2020

AbstractCore promoters integrate regulatory inputs of genes1–3. Global dynamics of promoter usage can reveal systemic changes in how genomic sequence is interpreted by the cell4Here we report the first analysis of promoter dynamics and code switching in the mammalian germ line, characterising the full cycle of transitions from embryonic stem cells through germline, oogenesis, and zygotic genome activation. Using Super Low Input Carrier-CAGE5,6(SLIC-CAGE) we show that mouse germline development starts with the somatic promoter code, followed by a prominent switch to the maternal code during follicular oogenesis. The sequence features underlying the shift from somatic to maternal code are conserved across vertebrates, despite large differences in promoter nucleotide compositions. In addition, we show that, prior to this major shift, the promoters of gonadal germ cells diverge from the canonical somatic transcription initiation. This divergence is distinct from the promoter code used later by developing oocytes and reveals genome-wide promoter remodelling associated with alternative nucleosome positioning during early female and male germline development. Collectively, our findings establish promoter-level regulatory transitions as a central, conserved feature of the vertebrate life cycle.
Single-PanIN-seq Unveils that ARID1A Deficiency Promotes Pancreatic Tumorigenesis by Attenuating KRAS Induced Senescence
Authors: Liu Shou , Cao Wenjian , Niu Yichi , Luo Jiayi , Zhao Yanhua , Hu Zhiying , Zong Chenghang 
Published: October 2020

ABSTRACTARID1A is one of the most frequently mutated epigenetic regulators in a wide spectrum of cancers. Recent studies have shown that ARID1A deficiency induces global changes in the epigenetic landscape of enhancers and promoters. These broad and complex effects make it challenging to identify the driving mechanisms of ARID1A deficiency in promoting cancer progression. Here we identified the anti-senescence effect of ARID1A deficiency in the progression of pancreatic intraepithelial neoplasia (PanIN) by profiling the transcriptome of individual PanINs in the mouse model. Interestingly, we found that ARID1A deficiency upregulates the expression of Aldehyde dehydrogenase ALDH1A1, which plays an essential role in attenuating the senescence induced by oncogenic KRAS. Despite that ALDH proteins have been commonly used as cancer stem cell markers, their effect in promoting attenuation of senescence is not known before. Therefore, ALDH proteins could be considered a potential adjuvant drug target in treating pancreatic cancer.
Fitting penalized regressions on very large genetic data using snpnet and bigstatsr
Authors: Privé Florian , Vilhjálmsson Bjarni J. , Aschard Hugues 
Published: October 2020

AbstractBoth R packages snpnet and bigstatsr allow for fitting penalized regressions on individual-level genetic data as large as the UK Biobank. Here we benchmark bigstatsr against snpnet for fitting penalized regressions on large genetic data. We find bigstatsr to be an order of magnitude faster than snpnet when applied to the UK Biobank data (from 4.5x to 35x). We also discuss the similarities and differences between the two packages, provide theoretical insights, and make recommendations on how to fit penalized regressions in the context of genetic data.