bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting shared independent selection
Authors: Harris Nathan S. , Rogers Alan R. 
Published: April 2020

AbstractSignals of selection are not often shared between populations. When a mutual signal is detected, it is often not known if selection occurred before or after populations split. Here we develop a method to detect genomic regions at which selection has favored different haplotypes in two populations. This method is verified through simulations and tested on small regions of the genome. This method was then expanded to scan the phase 3 genomes of the 1000 Genomes Project populations for regions in which the evidence for independent selection is strongest. We identify several genes which likely underwent selection independently in different populations.
TMPRSS2 and TMPRSS4 mediate SARS-CoV-2 infection of human small intestinal enterocytes
Authors: Zang Ruochen , Castro Maria F.G. , McCune Broc T. , Zeng Qiru , Rothlauf Paul W. , Sonnek Naomi M. , Liu Zhuoming , Brulois Kevin F. , Wang Xin , Greenberg Harry B. , Diamond Michael S. , Ciorba Matthew A. , Whelan Sean P.J. , Ding Siyuan 
Published: April 2020

AbstractBoth gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA have been frequently observed in COVID-19 patients. However, whether SARS-CoV-2 replicate in the human intestine and its clinical relevance to potential fecal-oral transmission remain unclear. Here, we demonstrate productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids. In addition to TMPRSS2, another mucosa-specific serine protease, TMPRSS4, also enhanced SARS-CoV-2 spike fusogenic activity and mediated viral entry into host cells. However, newly synthesized viruses released into the intestinal lumen were rapidly inactivated by human colonic fluids and no infectious virus was recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression.
Four Families of Folate-independent Methionine Synthases
Authors: Price Morgan N. , Deutschbauer Adam M. , Arkin Adam P. 
Published: April 2020

AbstractAlthough most organisms synthesize methionine from homocysteine and methyl folates, some have “core” methionine synthases that lack folate-binding domains and use other methyl donors.In vitro, the characterized core synthases use methylcobalamin as a methyl donor, butin vivo, they probably rely on corrinoid (vitamin B12-binding) proteins. We identified four families of core methionine synthases that are distantly related to each other (under 30% pairwise amino acid identity). From the characterized enzymes, we identified the families MesA, which is found in methanogens, and MesB, which is found in anaerobic bacteria and archaea with the Wood-Ljungdahl pathway. A third uncharacterized family, MesC, is found in anaerobic archaea that have the Wood-Ljungdahl pathway and lack known forms of methionine synthase. We predict that most members of the MesB and MesC families accept methyl groups from the iron-sulfur corrinoid protein of that pathway. The fourth family, MesD, is found only in aerobic bacteria. Using transposon mutants and complementation, we show that MesD does not require 5-methyltetrahydrofolate or cobalamin. Instead, MesD requires an uncharacterized protein family (DUF1852) and oxygen for activity.
Aerial High-Throughput Phenotyping Enabling Indirect Selection for Grain Yield at the Early-generation Seed-limited Stages in Breeding Programs
Authors: Krause Margaret R. , Mondal Suchismita , Crossa José , Singh Ravi P. , Pinto Francisco , Haghighattalab Atena , Shrestha Sandesh , Rutkoski Jessica , Gore Michael A. , Sorrells Mark E. , Poland Jesse 
Published: April 2020

ABSTRACTBreeding programs for wheat and many other crops require one or more generations of seed increase before replicated yield trials can be sown. Extensive phenotyping at this stage of the breeding cycle is challenging due to the small plot size and large number of lines under evaluation. Therefore, breeders typically rely on visual selection of small, unreplicated seed increase plots for the promotion of breeding lines to replicated yield trials. With the development of aerial high-throughput phenotyping technologies, breeders now have the ability to rapidly phenotype thousands of breeding lines for traits that may be useful for indirect selection of grain yield. We evaluated early generation material in the irrigated bread wheat (Triticum aestivumL.) breeding program at the International Maize and Wheat Improvement Center to determine if aerial measurements of vegetation indices assessed on small, unreplicated plots were predictive of grain yield. To test this approach, two sets of 1,008 breeding lines were sown both as replicated yield trials and as small, unreplicated plots during two breeding cycles. Vegetation indices collected with an unmanned aerial vehicle in the small plots were observed to be heritable and moderately correlated with grain yield assessed in replicated yield trials. Furthermore, vegetation indices were more predictive of grain yield than univariate genomic selection, while multi-trait genomic selection approaches that combined genomic information with the aerial phenotypes were found to have the highest predictive abilities overall. A related experiment showed that selection approaches for grain yield based on vegetation indices could be more effective than visual selection; however, selection on the vegetation indices alone would have also driven a directional response in phenology due to confounding between those traits. A restricted selection index was proposed for improving grain yield without affecting the distribution of phenology in the breeding population. The results of these experiments provide a promising outlook for the use of aerial high-throughput phenotyping traits to improve selection at the early-generation seed-limited stage of wheat breeding programs.
The genomic variation landscape of globally-circulating clades of SARS-CoV-2 defines a genetic barcoding scheme
Authors: Guan Qingtian , Sadykov Mukhtar , Nugmanova Raushan , Carr Michael J. , Arold Stefan T. , Pain Arnab 
Published: April 2020

ABSTRACTWe describe fifteen major mutation events from 2,058 high-quality SARS-CoV-2 genomes deposited up to March 31st, 2020. These events define five major clades (G, I, S, D and V) of globally-circulating viral populations, representing 85.7% of all sequenced cases, which we can identify using a 10 nucleotide genetic classifier or barcode. We applied this barcode to 4,000 additional genomes deposited between March 31stand April 15thand classified successfully 95.6% of the clades demonstrating the utility of this approach. An analysis of amino acid variation in SARS-CoV-2 ORFs provided evidence of substitution events in the viral proteins involved in both host-entry and genome replication. The systematic monitoring of dynamic changes in the SARS-CoV-2 genomes of circulating virus populations over time can guide therapeutic and prophylactic strategies to manage and contain the virus and, also, with available efficacious antivirals and vaccines, aid in the monitoring of circulating genetic diversity as we proceed towards elimination of the agent. The barcode will add the necessary genetic resolution to facilitate tracking and monitoring of infection clusters to distinguish imported and indigenous cases and thereby aid public health measures seeking to interrupt transmission chains without the requirement for real-time complete genomes sequencing.
Cytotoxic lymphocytes use mechanosurveillance to target biophysical vulnerabilities in cancer
Authors: Tello-Lafoz Maria , Srpan Katja , Hu Jing , Romin Yevgeniy , Calò Annalisa , Hsu Katharine C. , Massagué Joan , Huse Morgan , Er Ekrem Emrah 
Published: April 2020

ABSTRACTImmune cells identify cancer cells by recognizing characteristic biochemical features indicative of oncogenic transformation. Cancer cells have characteristic mechanical features, as well, but whether these biophysical properties also contribute to destruction by the immune system is not known. In the present study, we found that enhanced expression of myocardin related transcription factors (MRTFs), which promote migration and metastatic invasion, paradoxically compromised lung colonization by melanoma and breast carcinoma cells in an immune-mediated manner. Cancer cells with increased MRTF signaling were also more sensitive to immune checkpoint blockade therapy in mice and humans. The basis for this vulnerability was not biochemical, but biophysical. MRTF expression strengthened the actin cytoskeleton, increasing the rigidity of cancer cells and thereby making them more vulnerable to cytotoxic T lymphocytes and natural killer cells. These results reveal a mechanical dimension of immunosurveillance, which we call mechanosurveillance, that is particularly relevant to the targeting of metastatic disease.
Human iPSC-derived cerebral organoids model features of Leigh Syndrome and reveal abnormal corticogenesis
Authors: Romero-Morales Alejandra I. , Robertson Gabriella L. , Rastogi Anuj , Rasmussen Megan L. , Temuri Hoor , McElroy Gregory Scott , Chakrabarty Ram Prosad , Hsu Lawrence , Almonacid Paula M. , Millis Bryan A. , Chandel Navdeep S. , Cartailler Jean-Philippe , Gama Vivian 
Published: April 2020

SummaryLeigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents with bilateral brain lesions, caused by defects in the mitochondrial respiratory chain and associated nuclear-encoded proteins. We generated iPSCs from three patient-derived LS fibroblast lines and identified, by whole-exome and mitochondrial sequencing, unreported mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and dihydrolipoyl dehydrogenase (GM01503, DLD). LS-derived iPSC lines were viable and generally capable of differentiating into key progenitor populations, but we identified several abnormalities in three-dimensional differentiation models of brain development. LS-derived cerebral organoids showed defects in neural epithelial bud generation, size, and cortical architecture at 100 days. The double mutant MT-ATP6/PDH line produced organoid neural progenitor cells with abnormal mitochondrial morphology characterized by fragmentation and disorganization and showed an increased generation of astrocytes. These studies aim to provide a comprehensive phenotypic characterization of available patient-derived cell lines that can be used as LS model systems.
Structural basis for active-site probes targetingStaphylococcus aureusserine hydrolase virulence factors
Authors: Fellner Matthias , Lentz Christian S. , Jamieson Sam A. , Brewster Jodi L. , Chen Linhai , Bogyo Matthew , Mace Peter D. 
Published: April 2020

SummaryStaphylococcus aureusis a major cause of infection in the community and in hospitals. Serine hydrolases play key roles in bacterial homeostasis, in particular biofilms. Activity-based profiling has previously identified a family of serine hydrolases, designated fluorophosphonate-binding hydrolases (Fphs), which contribute to virulence ofS. aureusin the biofilm niche. Here we report structures of the putative tributyrin esterase FphF, alone and covalently bound by a substrate analog, and small molecule inhibitors that occupy the hydrophobic substrate-binding pocket. We show that FphF has promiscuous esterase activity. Building from this, we extended our analysis to the wider Fph protein family using homology modeling and docking tools. We predict that other Fph enzymes, including FphB which was linked directly to virulence, may be more specific than FphF. This study provides insight into Fph function and a template for designing new imaging agents, diagnostic probes, and inhibitors to treatS. aureusinfections.
Chronic IL-1 exposure drives LNCaP cells to evolve androgen and AR independence
Authors: Dahl H.C. , Kanchwala M. , Thomas-Jardin S.E. , Sandhu A. , Kanumuri P. , Nawas A.F. , Xing C. , Lin C. , Frigo D.E. , Delk N.A. 
Published: April 2020

AbstractChronic inflammation promotes prostate cancer (PCa) initiation and progression. We previously reported that acute intereluekin-1 (IL-1) exposure represses androgen receptor (AR) accumulation and activity, providing a possible mechanism for IL-1-mediated development of androgen- and AR-independent PCa. Given that acute inflammation is quickly resolved, and chronic inflammation is, instead, co-opted by cancer cells to promote tumorigenicity, we set out to determine if chronic IL-1 exposure leads to similar repression of AR and AR activity observed for acute IL-1 exposure and to determine if chronic IL-1 exposure selects for androgen- and AR- independent PCa cells. We generated isogenic sublines from LNCaP cells chronically exposed to IL-1α or IL-1β. Cells were treated with IL-1α, IL-1β, TNFα or HS-5 bone marrow stromal cells conditioned medium to assess cell viability in the presence of cytotoxic inflammatory cytokines. Cell viability was also assessed following serum starvation,ARsiRNA silencing and enzalutamide treatment. Finally, RNA sequencing was performed for the IL-1 sublines. MTT, RT-qPCR and western blot analysis show that the sublines evolved resistance to inflammation- induced cytotoxicity and intracellular signaling and evolved reduced sensitivity to siRNA- mediated loss ofAR, serum deprivation and enzalutamide. Differential gene expression reveals that canonical AR signaling is aberrant in the IL-1 sublines, where the cells show constitutivePSArepression and basally highKLK2andNKX3.1mRNA levels and bioinformatics analysis predicts that pro-survival and pro-tumorigenic pathways are activated in the sublines. Our data provide evidence that chronic IL-1 exposure promotes PCa cell androgen and AR independence and, thus, supports CRPCa development.
Laboratory sprayer for testing of microbial biocontrol agents: design and calibration
Authors: Erdos Z. , Halswell P. , Matthews A. , Raymond B. 
Published: April 2020

AbstractThe lack of commercially available low-cost laboratory spraying equipment for testing microbial control agents can hinder advancement in the field of biocontrol. This study presents an inexpensive, portable sprayer that is calibrated utilizing laboratory consumables. The computer aided design files are made available so that it is freely modifiable and can be used for machine routing or 3D printing. Bioassay data was obtained by sprayingMyzus persicaewith spores of entomopathogenic fungi. Observed variation in droplet deposition within tested pressure and volume settings, and spore deposition within sprayed concentrations were low. Bioassay results show reproducible mortality for the tested doses.
STAT5 regulation of sex-dependent hepatic CpG methylation at distal regulatory elements mapping to sex-biased genes
Authors: Hao Pengying , Waxman David J. 
Published: April 2020

AbstractGrowth hormone-activated STAT5b is an essential regulator of sex-differential gene expression in mouse liver, however, its impact on hepatic gene expression and epigenetic responses is poorly understood. Here, we found a substantial, albeit incomplete loss of liver sex bias in hepatocyte-specific STAT5a/STAT5b (collectively, STAT5)-deficient mouse liver. In male liver, many male-biased genes were down regulated in direct association with the loss of STAT5 binding; many female-biased genes, which show low STAT5 binding, were de-repressed, indicating an indirect mechanism for repression by STAT5. Extensive changes in CpG-methylation were seen in STAT5-deficient liver, where sex differences in DNA methylation were abolished at 88% of ~1,500 differentially-methylated regions, largely due to an increase in methylation at the hypomethylated sites. STAT5-dependent CpG-hypomethylation was rarely found at proximal promoters of STAT5-dependent genes. Rather, STAT5 primarily regulated the methylation of distal enhancers, where STAT5 deficiency induced widespread hypermethylation at genomic regions enriched for accessible chromatin, enhancer histone marks (H3K4me1, H3K27ac), STAT5 binding, and DNA motifs for STAT5 and other transcription factors implicated in liver sex differences. In conclusion, the sex-dependent binding of STAT5 to liver chromatin is closely linked to sex-dependent demethylation of distal regulatory elements mapping to STAT5-dependent genes important for liver sex bias.
Megaevolutionary dynamics in reptiles and the role of adaptive radiations in evolutionary innovation
Authors: Simões Tiago R. , Vernygora Oksana , Caldwell Michael W. , Pierce Stephanie E. 
Published: April 2020

AbstractAdaptive radiations are long believed to be responsible for the origin of phenotypic diversity and new body plans among higher clades in the fossil record. However, few studies have assessed rates of phenotypic evolution and disparity across broad scales of time to understand the evolutionary dynamics behind the origin of major clades, or how they relate to rates of molecular evolution. Here, we provide a total evidence approach to this problem using the largest available data set on diapsid reptiles. We find a strong decoupling between phenotypic and molecular rates of evolution, with many periods of accelerated phenotypic evolution or expansion of phenotypic disparity at the origin of major reptile clades and body plans that do not correspond to periods of adaptive radiation. We find heterogeneous rates of evolution during the acquisition of similarly adapted functional types, and that the origin of snakes is marked by exceptionally high evolutionary rates.
Seasonal weight changes in laboratory ferrets
Authors: Jones Eleanor J. , Poole Katarina , Sollini Joseph , Town Stephen M. , Bizley Jennifer K. 
Published: April 2020

AbstractFerrets (Mustela putorius furo) are a valuable animal model used in biomedical research. Ferrets undergo significant variation in body weight seasonally, affected by photoperiod, and these variations make it difficult to use weight as an indicator of health status. To overcome this requires a better understanding of these seasonal weight changes. We provide a normative weight data set for the female ferret accounting for seasonal changes, and also investigate the effect of fluid regulation on weight change. Female ferrets (n=39) underwent behavioural testing from May 2017 to August 2019 and were weighed daily while housed in an animal care facility with controlled light exposure. In the winter (October to March), animals experienced 10 hours of light and 14 hours of dark, while in summer (March to October), this contingency was reversed. Individual animals varied in their body weight from approximately 700 to 1200 g. However, weights fluctuated with light cycle, with animals losing weight in summer, and gaining weight in winter such that they fluctuated between approximately 80% and 120% of their long term average weight. Ferrets were weighed as part of their health assessment while experiencing water regulation for behavioural training. Water regulation superimposed additional weight changes on these seasonal fluctuations, with weight loss during the 5 day water regulation period being greater in summer than winter. These data establish a normative benchmark for seasonal weight variation in female ferrets that can be incorporated into the health assessment of an animal’s condition.
Decreased torsinA or LINC Complex Function Rescues a Laminopathy inCaenorhabditis elegans
Authors: Huelgas-Morales Gabriela , Sanders Mark , Mekonnen Gemechu , Tsukamoto Tatsuya , Greenstein David 
Published: April 2020

AbstractThe function of the nucleus depends on the integrity of the nuclear lamina, an intermediate filament network associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex spanning the nuclear envelope. In turn, the AAA+ ATPase torsinA regulates force transmission from the cytoskeleton to the nucleus. In humans, mutations affecting nuclear envelope-associated proteins cause laminopathies, including progeria, myopathy, and dystonia. We report that decreasing the function of theC. eleganstorsinA homolog, OOC-5, rescues the sterility and premature aging caused by a null mutation in the single worm lamin homolog,lmn-1. Loss of OOC-5 activity prevents nuclear collapse inlmn-1mutants by disrupting the function of the LINC complex. These results suggest that LINC complex-transmitted forces damage nuclei with a compromised nuclear lamina.One Sentence SummaryInhibiting LINC complex activity prevents a progeric syndrome inC. elegans.
PlanktonScope: Affordable modular imaging platform for citizen oceanography
Authors: Pollina Thibaut , Larson Adam G. , Lombard Fabien , Li Hongquan , Colin Sebastien , de Vargas Colomban , Prakash Manu 
Published: April 2020

AbstractThe planktonic communities within our oceans represent one of the most diverse and understudied ecosystems on the planet. A major hurdle in describing these systems is the sheer scale of the oceans along with logistical and economic constraints associated with their sampling. This is due to the limited amount of scientifically equipped fleets and affordable equipment. Here we demonstrate a modular approach for building a versatile, re-configurable imaging platform that can be adapted to a number of field applications, specifically focusing on oceanography. By using a modular hardware/software approach for building microscopes, we demonstrate high-throughput imaging of lab and field samples while enabling rapid device reconfiguration in order to match diverse applications and the evolving needs of the sampler. The presented versions of PlanktonScope are capable of autonomously imaging 1.7 ml per minute with a 1.5 µm resolution, and are built with under $400 in parts. This low cost enables new applications in laboratory settings such as the continuous imaging of suspension cultures, and in-field settings with the ability to scale up for long-term deployment on an international fleet of sailing boats enabling citizens based oceanographic research
Banks’ CSR reporting – Do women have a say?
Authors: Tapver Triinu , Laidroo Laivi , Gurvitš-Suits Natalie Aleksandra 
Published: April 2020

PurposeThis paper aims to determine the association between corporate social responsibility (CSR) reporting of listed banks and female representation on boards while controlling for the impact of gender quotas.Design/methodology/approachLogistic regressions are used with bank fixed effects on a global sample of 285 commercial banks from 2005 to 2017.FindingsThere exists a positive association between the proportion of women on board and banks’ CSR disclosure. Positive association remains also after quota corrections for banks with either below- or above-quota female representation. Further, adding more women to boards than required by quota could affect boards’ CSR reporting in masculine countries but not in feminine countries.Research limitations/implicationsThe results are not generalizable to smaller listed banks and the used estimation approach does not enable to detect causality.Practical implicationsPolicymakers interested in improving banks’ CSR reporting could introduce gender quotas.Social implicationsGender quotas can enforce banks’ sustainable behaviour.Originality/valueFirst, it is the first study to thoroughly control for gender quotas while investigating the association between female representation on boards and CSR disclosure. Second, this paper moves forward from the so-far predominant concentration on single-country studies on banks’ CSR reporting. Third, this paper covers the aspect of a country’s masculinity-femininity as a factor that could influence the association between CSR disclosure and female representation.