bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species
Authors: Shefchek Kent A , Harris Nomi L , Gargano Michael , Matentzoglu Nicolas , Unni Deepak , Brush Matthew , Keith Daniel , Conlin Tom , Vasilevsky Nicole , Zhang Xingmin Aaron , Balhoff James P , Babb Larry , Bello Susan M , Blau Hannah , Bradford Yvonne , Carbon Seth , Carmody Leigh , Chan Lauren E , Cipriani Valentina , Cuzick Alayne , Della Rocca Maria , Dunn Nathan , Essaid Shahim , Fey Petra , Grove Chris , Gourdine Jean-Phillipe , Hamosh Ada , Harris Midori , Helbig Ingo , Hoatlin Maureen , Joachimiak Marcin , Jupp Simon , Lett Kenneth B , Lewis Suzanna E , McNamara Craig , Pendlington Zoë M , Pilgrim Clare , Putman Tim , Ravanmehr Vida , Reese Justin , Riggs Erin , Robb Sofia , Roncaglia Paola , Seager James , Segerdell Erik , Similuk Morgan , Storm Andrea L , Thaxon Courtney , Thessen Anne , Jacobsen Julius O B , McMurry Julie A , Groza Tudor , Köhler Sebastian , Smedley Damian , Robinson Peter N , Mungall Christopher J , Haendel Melissa A , Munoz-Torres Monica C , Osumi-Sutherland David 
Published: October 2019

Abstract
In biology and biomedicine, relating phenotypic outcomes with genetic variation and environmental factors remains a challenge: patient phenotypes may not match known diseases, candidate variants may be in genes that haven’t been characterized, research organisms may not recapitulate human or veterinary diseases, environmental factors affecting disease outcomes are unknown or undocumented, and many resources must be queried to find potentially significant phenotypic associations. The Monarch Initiative (https://monarchinitiative.org) integrates information on genes, variants, genotypes, phenotypes and diseases in a variety of species, and allows powerful ontology-based search. We develop many widely adopted ontologies that together enable sophisticated computational analysis, mechanistic discovery and diagnostics of Mendelian diseases. Our algorithms and tools are widely used to identify animal models of human disease through phenotypic similarity, for differential diagnostics and to facilitate translational research. Launched in 2015, Monarch has grown with regards to data (new organisms, more sources, better modeling); new API and standards; ontologies (new Mondo unified disease ontology, improvements to ontologies such as HPO and uPheno); user interface (a redesigned website); and community development. Monarch data, algorithms and tools are being used and extended by resources such as GA4GH and NCATS Translator, among others, to aid mechanistic discovery and diagnostics.
The (PATAN)-CheY-Like Response Regulator PixE Interacts with the Motor ATPase PilB1 to Control Negative Phototaxis in the Cyanobacterium Synechocystis sp. PCC 6803
Authors: Jakob Annik , Nakamura Hiroshi , Kobayashi Atsuko , Sugimoto Yuki , Wilde Annegret , Masuda Shinji 
Published: October 2019

AbstractThe cyanobacterium Synechocystis sp. PCC 6803 can move directionally on a moist surface toward or away from a light source to reach optimal light conditions for its photosynthetic lifestyle. This behavior, called phototaxis, is mediated by type IV pili (T4P), which can pull a single cell into a certain direction. Several photoreceptors and their downstream signal transduction elements are involved in the control of phototaxis. However, the critical steps of local pilus assembly in positive and negative phototaxis remain elusive. One of the photoreceptors controlling negative phototaxis in Synechocystis is the blue-light sensor PixD. PixD forms a complex with the CheY-like response regulator PixE that dissociates upon illumination with blue light. In this study, we investigate the phototactic behavior of pixE deletion and overexpression mutants in response to unidirectional red light with or without additional blue-light irradiation. Furthermore, we show that PixD and PixE partly localize in spots close to the cytoplasmic membrane. Interaction studies of PixE with the motor ATPase PilB1, demonstrated by in vivo colocalization, yeast two-hybrid and coimmunoprecipitation analysis, suggest that the PixD–PixE signal transduction system targets the T4P directly, thereby controlling blue-light-dependent negative phototaxis. An intriguing feature of PixE is its distinctive structure with a PATAN (PatA N-terminus) domain. This domain is found in several other regulators, which are known to control directional phototaxis. As our PilB1 coimmunoprecipitation analysis revealed an enrichment of PATAN domain response regulators in the eluate, we suggest that multiple environmental signals can be integrated via these regulators to control pilus function.
Nitric Oxide in Post-cardiac Arrest Syndrome
Authors: Miyazaki Yusuke , Ichinose Fumito 
Published: October 2019

Abstract:
Sudden cardiac arrest is a leading cause of death worldwide. Although the methods of cardiopulmonary resuscitation have been improved, mortality is still unacceptably high, and many survivors suffer from lasting neurological deficits due to the post-cardiac arrest syndrome (PCAS). Pathophysiologically, generalized vascular endothelial dysfunction accompanied by platelet activation and systemic inflammation has been implicated in the pathogenesis of PCAS. Because endothelial-derived nitric oxide (NO) plays a central role in maintaining vascular homeostasis, the role of NO-dependent signaling has been a focus of the intense investigation. Recent preclinical studies showed that therapeutic interventions that increase vascular NO bioavailability may improve outcomes after cardiac arrest complicated with PCAS. In particular, NO inhalation therapy has been shown to improve neurological outcomes and survival in multiple species. Clinical studies examining the safety and efficacy of inhaled NO in patients sustaining PCAS are warranted.
Exploring factors that impact uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO) in high-risk women
Authors: Hickey Martha , Rio Ines , Trainer Alison , Marino Jennifer L. , Wrede C. David , Peate Michelle 
Published: October 2019

Abstract

Objective:
Only risk-reducing bilateral salpingo-oophorectomy (RRBSO) has been shown to reduce ovarian cancer deaths in high-risk women. Uptake of RRBSO is, however, suboptimal and reasons are not well defined. More information is needed about the barriers to RRBSO and patient needs for information and care.

Methods:
Cross-sectional study including the Perception of Cancer Risk Scale, factors affecting decision-making about RRBSO, and unmet information needs were measured using a purpose-designed questionnaire.

Results:
Of the 193 high-risk women aged 30 to 50 approached, 60 (31%) agreed to participate. Respondents were either considering or had recently undergone premenopausal RRBSO. Most (49/60) had no personal history of cancer; 11/60 had previous breast cancer. Overall, responses did not differ between pre- and post-RRBSO participants. The main barriers to RRBSO were surgical menopause and loss of fertility. Other concerns included the impact on sexual function and bone health. Reduction in ovarian cancer risk and prolonged life expectancy were the main drivers for RRBSO. Participants understood that RRBSO reduced cancer risk, although most substantially overestimated their personal ovarian cancer risk. High-risk women wanted more information about how to manage the short- and long-term consequences of surgical menopause.

Conclusions:
Concerns about surgical menopause and loss of fertility are barriers to RRBSO for high-risk women despite understanding the benefits of reduced cancer risk. There is an unmet need for more information about effectively managing the noncancer consequences of RRBSO in premenopausal women.

Video Summary:
http://links.lww.com/MENO/A478.
SMOKING STATUS AND TREATMENT OUTCOMES OF VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Vittorio Alexander F. , Nguyen Vuong , Barthelmes Daniel , Arnold Jennifer J. , Cheung Chui M. G. , Murray Neil , Gillies Mark C. ,   the Fight Retinal Blindness! Study Group
Published: October 2019

Purpose:
To assess whether smoking status affects 1-year visual outcomes in eyes treated with vascular endothelial growth factor inhibitors for neovascular age-related macular degeneration.

Methods:
Retrospective analysis of data from a prospectively designed, multicenter, observational database. Nine hundred and eighty seven treatment-naive eyes of patients with neovascular age-related macular degeneration were tracked by the Fight Retinal Blindness! outcome registry in Australia, New Zealand, Singapore, and Switzerland who had documented smoking status at baseline and commenced vascular endothelial growth factor inhibitor therapy from January 2006 to December 2016. Generalized additive models were used to display visual acuity results.

Results:
There was a significant difference in mean improvement in visual acuity at 12 months between nonsmokers, ex-smokers, and current smokers (7.7 vs. 6.1 vs. 3.5 letters of change; P = 0.046) among patients who completed 12 months of treatment when adjusted for age, baseline visual acuity, and choroidal neovascular membrane lesion type and nested for practice. There was no significant difference in the median number of injections over 12 months of treatment by smoking status. Current smokers were a mean of 6.2 years younger than nonsmokers when they started treatment (P < 0.001).

Conclusion:
This study found inferior 12-month visual outcomes in patients who continued to smoke while receiving vascular endothelial growth factor inhibitor therapy for neovascular age-related macular degeneration.
Intraoperative methadone administration and postoperative pain control: a systematic review and meta-analysis
Authors: D'Souza Ryan S. , Gurrieri Carmelina , Johnson Rebecca L. , Warner Nafisseh , Wittwer Erica 
Published: October 2019

Abstract
Postoperative pain is not adequately managed in greater than 40% of surgical patients and is a high priority for perioperative research. In this meta-analysis, we examined studies comparing postoperative opioid consumption and pain scores in surgical patients who received methadone by any route vs those who received another opioid by any route. Studies were identified from PubMed, Cochrane, Web of Science, EMBASE, and Scopus from January 1966 to November 2018. Pooled odds ratios were calculated for a primary outcome of postoperative opioid consumption and secondary outcomes of time-to-extubation, time-to-first postoperative analgesia request, satisfaction, hospital length-of-stay, and complications. Postoperative pain scores were assessed qualitatively. Ten studies (617 patients) were included. Postoperative opioid consumption at 24 hours was lower in the methadone group vs control (mean difference = −15.22 mg oral morphine equivalents, 95% confidence interval −27.05 to −3.38; P = 0.01). Patients in the methadone group generally reported lower postoperative pain scores in 7 of 10 studies. Meta-analysis revealed greater satisfaction scores with analgesia in the methadone group vs control (0-100 visual analog scale; mean difference = 7.16, 95% confidence interval 2.30-12.01; P = 0.004). There was no difference in time-to-extubation, time-to-first analgesia request, hospital length-of-stay, or complications (nausea, sedation, respiratory depression, and hypoxemia). The results demonstrate that surgical patients who received intraoperative methadone had lower postoperative opioid consumption, generally reported lower pain scores and experienced better satisfaction with analgesia. However, these advantages need to be weighed carefully against dangerous risks with perioperative methadone, specifically respiratory depression and arrhythmia. Future studies should explore logistics, safety, and cost effectiveness.
The deubiquitinating enzymes UBP12 and UBP13 negatively regulate the activity of the ubiquitin-dependent peptidases DA1, DAR1 and DAR2
Authors: Vanhaeren Hannes , Chen Ying , Vermeersch Mattias , De Vleeschhauwer Valerie , Persiau Geert , Eeckhout Dominique , De Jaeger Geert , Gevaert Kris , Inzé Dirk 
Published: October 2019

AbstractProtein ubiquitination is a very diverse post-translational modification leading to protein degradation or delocalization, or altering protein activity. InArabidopsis thaliana, two E3 ligases, BIG BROTHER (BB) and DA2, activate the latent peptidases DA1, DAR1 and DAR2 by mono-ubiquitination at multiple sites. Subsequently, these activated peptidases destabilize various positive regulators of growth. Here, we show that two ubiquitin-specific proteases, UBP12 and UBP13, deubiquitinate DA1, DAR1 and DAR2, hence reducing their peptidase activity. Overexpression ofUBP12orUBP13strongly decreased leaf size and cell area, and resulted in lower ploidy levels. Mutants in whichUBP12andUBP13were downregulated produced smaller leaves that contained fewer and smaller cells. Remarkably, neither UBP12 nor UBP13 were found to be cleavage substrates of the activated DA1. Our results therefore suggest that UBP12 and UBP13 work upstream of DA1, DAR1 and DAR2 to restrict their protease activity and hence fine-tune plant growth and development.
Metage2Metabo: metabolic complementarity applied to genomes of large-scale microbiotas for the identification of keystone species
Authors: Belcour Arnaud , Frioux Clémence , Aite Méziane , Bretaudeau Anthony , Siegel Anne 
Published: October 2019

AbstractCapturing the functional diversity of microbiotas entails identifying metabolic functions and species of interest within hundreds or thousands. Starting from genomes, a way to functionally analyse genetic information is to build metabolic networks. Yet, no method enables a functional screening of such a large number of metabolic networks nor the identification of critical species with respect to metabolic cooperation.Metage2Metabo (M2M) addresses scalability issues raised by metagenomics datasets to identify keystone, essential and alternative symbionts in large microbiotas communities with respect to individual metabolism and collective metabolic complementarity. Genome-scale metabolic networks for the community can be either provided by the user or very efficiently reconstructed from a large family of genomes thanks to a multi-processing solution to run the Pathway Tools software. The pipeline was applied to 1,520 genomes from the gut microbiota and 913 metagenome-assembled genomes of the rumen microbiota. Reconstruction of metabolic networks and subsequent metabolic analyses were performed in a reasonable time.M2M identifies keystone, essential and alternative organisms by reducing the complexity of a large-scale microbiota into minimal communities with equivalent properties, suitable for further analyses.
Community Standards for Open Cell Migration Data
Authors: Gonzalez-Beltran Alejandra N. , Masuzzo Paola , Ampe Christophe , Bakker Gert-Jan , Besson Sébastien , Eibl Robert H. , Friedl Peter , Gunzer Matthias , Kittisopikul Mark , Le Dévédec Sylvia E. , Leo Simone , Moore Josh , Paran Yael , Prilusky Jaime , Rocca-Serra Philippe , Roudot Philippe , Schuster Marc , Sergeant Gwendolien , Strömblad Staffan , Swedlow Jason R. , van Erp Merijn , Troys Marleen Van , Zaritsky Assaf , Sansone Susanna-Assunta , Martens Lennart 
Published: October 2019

AbstractCell migration research has become a high-content field. However, the quantitative information encapsulated in these complex and high-dimensional datasets is not fully exploited due to the diversity of experimental protocols and non-standardised output formats. In addition, typically the datasets are not open for reuse. Making the data open and Findable, Accessible, Interoperable, and Reusable (FAIR) will enable meta-analysis, data integration, and data mining. Standardised data formats and controlled vocabularies are essential for building a suitable infrastructure for that purpose but are not available in the cell migration domain. We here present standardisation efforts by the Cell Migration Standardisation Organization, CMSO, an open community-driven organisation to facilitate the development of standards for cell migration data. This work will foster the development of improved algorithms and tools, and enable secondary analysis of public datasets, ultimately unlocking new knowledge of the complex biological process of cell migration.
T-Gene: Improved target gene prediction
Authors: O’Connor Timothy , Grant Charles E. , Bodén Mikael , Bailey Timothy L. 
Published: October 2019

AbstractMotivationIdentifying the genes regulated by a given transcription factor (its “target genes”) is a key step in developing a comprehensive understanding of gene regulation. Previously we developed a method for predicting the target genes of a transcription factor (TF) based solely on the correlation between a histone modification at the TF’s binding site and the expression of the gene across a set of tissues. That approach is limited to organisms for which extensive histone and expression data is available, and does not explicitly incorporate the genomic distance between the TF and the gene.ResultsWe present the T-Gene algorithm, which overcomes these limitations. T-Gene can be used to predict which genes are most likely to be regulated by a TF, and which of the TF’s binding sites are most likely involved in regulating particular genes. T-Gene calculates a novel score that combines distance and histone/expression correlation, and we show that this score accurately predicts when a regulatory element bound by a TF is in contact with a gene’s promoter, achieving median positive predictive value (PPV) above 50%. T-Gene is easy to use via its web server or as a command-line tool, and can also make accurate predictions (median PPV above 40%) based on distance alone when extensive histone/expression data is not available for the organism. T-Gene provides an estimate of the statistical significance of each of its predictions.AvailabilityThe T-Gene web server, source code, histone/expression data and genome annotation files are provided at http://meme-suite.org.Contacttimothybailey@unr.edu
Biallelic mutations in M1AP are a frequent cause of meiotic arrest leading to male infertility
Authors: Wyrwoll Margot J. , Temel Şehime G. , Nagirnaja Liina , Oud Manon S. , Lopes Alexandra M. , van der Heijden Godfried W. , Rotte Nadja , Wistuba Joachim , Wöste Marius , Ledig Susanne , Krenz Henrike , Smits Roos M. , Carvalho Filipa , Gonçalves João , Fietz Daniela , Türkgenç Burcu , Ergören Mahmut C. , Çetinkaya Murat , Başar Murad , Kahraman Semra , Pilatz Adrian , Röpke Albrecht , Dugas Martin , Kliesch Sabine , Neuhaus Nina ,   GEMINI Consortium, Aston Kenneth I. , Conrad Donald F. , Veltman Joris A. , Friedrich Corinna , Tüttelmann Frank 
Published: October 2019

AbstractMale infertility affects ∼7% of men in Western societies, but its causes remain poorly understood. The most clinically severe form of male infertility is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis, but so far only few genes have been reported to cause germ cell arrest in males. To address this gap, whole exome sequencing was performed in 60 German men with complete meiotic arrest, and we identified in three unrelated men the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 arresting protein. Then, with collaborators from the International Male Infertility Genomics Consortium (IMIGC), we screened a Dutch cohort comprising 99 infertile men and detected the same homozygous variant c.676dup in a man with hypospermatogenesis predominantly displaying meiotic arrest. We also identified two Portuguese men with NOA carrying likely biallelic loss-of-function (LoF) and missense variants in M1AP among men screened by the Genetics of Male Infertility Initiative (GEMINI). Moreover, we discovered a homozygous missense variant p.(Pro389Leu) in M1AP in a consanguineous Turkish family comprising five infertile men. M1AP is predominantly expressed in human and mouse spermatogonia up to secondary spermatocytes and previous studies have shown that knockout male mice are infertile due to meiotic arrest. Collectively, these findings demonstrate that both LoF and missense M1AP variants that impair its protein cause autosomal-recessive meiotic arrest, non-obstructive azoospermia and male infertility. In view of the evidence from several independent groups and populations, M1AP should be included in the growing list of validated NOA genes.
Molecular mechanism of attenuation of heat shock transcription factor 1 activity
Authors: Kmiecik Szymon W. , Breton Laura Le , Mayer Matthias P. 
Published: October 2019

AbstractThe heat shock response is a universal transcriptional response to proteotoxic stress orchestrated by heat shock transcription factor Hsf1 in all eukaryotic cells. Despite over 40 years of intense research, the mechanism of HSF1 activity regulation remains poorly understood at a molecular level. In metazoa Hsf1 trimerizes upon heat shock through a leucin-zipper domain and binds to DNA. How Hsf1 is dislodged from DNA and monomerized remained enigmatic. Here, we demonstrate that trimeric Hsf1 is dissociated from DNA in vitro by Hsc70 and DnaJB1. Hsc70 acts at two distinct sites on Hsf1. Hsf1 trimers are monomerized by successive cycles of entropic pulling, unzipping the triple leucine-zipper. This process directly monitors the concentration of Hsc70 and DnaJB1. During heat shock adaptation Hsc70 first binds to the transactivation domain leading to partial attenuation of the response and subsequently, at higher concentrations, Hsc70 removes Hsf1 from DNA to restore the resting state.
An adhesion code ensures robust pattern formation during tissue morphogenesis
Authors: Tsai Tony Y.-C. , Sikora Mateusz , Xia Peng , Colak-Champollion Tugba , Knaut Holger , Heisenberg Carl-Philipp , Megason Sean G. 
Published: October 2019

ABSTRACTAn outstanding question in embryo development is how spatial patterns are formed robustly. In the zebrafish spinal cord, neural progenitors form stereotypic stripe-like patterns despite noisy morphogen signaling and large-scale cellular rearrangement required for tissue growth and morphogenesis. We set out to understand the mechanisms underlying this patterning robustness. Our adhesion assays revealed a preference for three neural progenitor types to stabilize contacts with cells of the same type. Genetic analysis uncovered a three-molecule adhesion code, composed of N-cadherin, Cadherin 11, and Protocadherin 19, with unique gene expression profiles for each cell type. Perturbation of the adhesion code results in loss of homotypic preferenceex vivoand patterning errorsin vivo. Both the cell fate and adhesion code are co-regulated by the common upstream morphogen signal Shh. We propose that robust patterning in tissues undergoing morphogenesis results from a previously unappreciated interplay between morphogen gradient-based patterning and adhesion-based self-organization.