bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Experimental Test of Adaptive Introgression in Locally Adapted Populations of Splash Pool Copepods
Authors: Griffiths Joanna S , Kawji Yasmeen , Kelly Morgan W 
Published: November 2020

AbstractAs species struggle to keep pace with the rapidly warming climate, adaptive introgression of beneficial alleles from closely related species or populations provides a possible avenue for rapid adaptation. We investigate the potential for adaptive introgression in the copepod, Tigriopus californicus, by hybridizing two populations with divergent heat tolerance limits. We subjected hybrids to strong heat selection for 15 generations followed by whole-genome resequencing. Utilizing a hybridize evolve and resequence (HER) technique, we can identify loci responding to heat selection via a change in allele frequency. We successfully increased the heat tolerance (measured as LT50) in selected lines, which was coupled with higher frequencies of alleles from the southern (heat tolerant) population. These repeatable changes in allele frequencies occurred on all 12 chromosomes across all independent selected lines, providing evidence that heat tolerance is polygenic. These loci contained genes with lower protein-coding sequence divergence than the genome-wide average, indicating that these loci are highly conserved between the two populations. In addition, these loci were enriched in genes that changed expression patterns between selected and control lines in response to a nonlethal heat shock. Therefore, we hypothesize that the mechanism of heat tolerance divergence is explained by differential gene expression of highly conserved genes. The HER approach offers a unique solution to identifying genetic variants contributing to polygenic traits, especially variants that might be missed through other population genomic approaches.
Bacterial tRNA 2′-O-methylation is dynamically regulated under stress conditions and modulates innate immune response
Authors: Galvanin Adeline , Vogt Lea-Marie , Grober Antonia , Freund Isabel , Ayadi Lilia , Bourguignon-Igel Valerie , Bessler Larissa , Jacob Dominik , Eigenbrod Tatjana , Marchand Virginie , Dalpke Alexander , Helm Mark , Motorin Yuri 
Published: November 2020

Abstract
RNA modifications are a well-recognized way of gene expression regulation at the post-transcriptional level. Despite the importance of this level of regulation, current knowledge on modulation of tRNA modification status in response to stress conditions is far from being complete. While it is widely accepted that tRNA modifications are rather dynamic, such variations are mostly assessed in terms of total tRNA, with only a few instances where changes could be traced to single isoacceptor species. Using Escherichia coli as a model system, we explored stress-induced modulation of 2′-O-methylations in tRNAs by RiboMethSeq. This analysis and orthogonal analytical measurements by LC-MS show substantial, but not uniform, increase of the Gm18 level in selected tRNAs under mild bacteriostatic antibiotic stress, while other Nm modifications remain relatively constant. The absence of Gm18 modification in tRNAs leads to moderate alterations in E. coli mRNA transcriptome, but does not affect polysomal association of mRNAs. Interestingly, the subset of motility/chemiotaxis genes is significantly overexpressed in ΔTrmH mutant, this corroborates with increased swarming motility of the mutant strain. The stress-induced increase of tRNA Gm18 level, in turn, reduced immunostimulation properties of bacterial tRNAs, which is concordant with the previous observation that Gm18 is a suppressor of Toll-like receptor 7 (TLR7)-mediated interferon release. This documents an effect of stress induced modulation of tRNA modification that acts outside protein translation.
Repressor Activity of SqrR, a Master Regulator of Persulfide-Responsive Genes, Is Regulated by Heme Coordination
Authors: Shimizu Takayuki , Hayashi Yuuki , Arai Munehito , McGlynn Shawn E , Masuda Tatsuru , Masuda Shinji 
Published: November 2020

Abstract
Reactive sulfur species (RSS) are involved in bioactive regulation via persulfidation of proteins. However, how cells regulate RSS-based signaling and RSS metabolism is poorly understood, despite the importance of universal regulation systems in biology. We previously showed that the persulfide-responsive transcriptional factor SqrR acts as a master regulator of sulfide-dependent photosynthesis in proteobacteria. Here, we demonstrated that SqrR also binds heme at a near one-to-one ratio with a binding constant similar to other heme-binding proteins. Heme does not change the DNA-binding pattern of SqrR to the target gene promoter region; however, DNA-binding affinity of SqrR is reduced by the binding of heme, altering its regulatory activity. Circular dichroism spectroscopy clearly showed secondary structural changes in SqrR by the heme binding. Incremental change in the intracellular heme concentration is associated with small, but significant reduction in the transcriptional repression by SqrR. Overall, these results indicate that SqrR has an ability to bind heme to modulate its DNA-binding activity, which may be important for the precise regulation of RSS metabolism in vivo.
Effects of a novel E. coli phytase expressed in Pseudomonas fluorescens on growth, bone mineralization, and nutrient digestibility in pigs fed corn–soybean meal diets
Authors: Ren Ping , Blavi Laia , González-Vega Caroline , Liu Yanhong , Hancock Deana , Vazquez-Añón Mercedes , Almeida Ferdinando N , Stein Hans H 
Published: November 2020

Abstract
Two studies were conducted to determine the effects of a novel Escherichia coli phytase expressed in Pseudomonas fluorescens on growth performance, bone mineralization, and nutrient digestibility in pigs fed corn-soybean meal diets. In experiment 1, 160 nursery pigs (9.79 ± 1.22 kg) were randomly allotted to one of four treatments with 10 pens per treatment and four pigs per pen. Phase I and phase II diets were provided from d 0 to d 14 and d 14 to d 28, respectively. Treatments included: positive control (PC) with all nutrients meeting requirements; negative control (NC) with standardized total tract digestible (STTD) P reduced by 0.15% and 0.14% compared with PC in phase I and phase II, respectively; and NC diets containing 250 or 500 units of phytase (FTU) per kilogram. Results demonstrated that pigs fed PC had greater (P &lt; 0.01) ADG and G:F for the overall experimental period, and greater (P &lt; 0.01) bone ash and P concentrations, compared with pigs fed NC or diets with phytase supplementation. Pigs fed diets containing phytase had greater (P &lt; 0.01) ADG and G:F for the overall experimental period compared with pigs fed the NC diet without phytase, and bone ash and P weights were increased (P &lt; 0.01) as well. In experiment 2, 63 growing barrows (56.25 ± 2.54 kg) were blocked by BW and randomly allotted to one of seven treatments with nine pens per treatment and one pig per pen. A basal corn–soybean meal diet was formulated to meet nutrient requirements for growing pigs with the exception that STTD P was reduced by 0.18% compared with the requirement, and Ca was included to achieve a Ca:STTD P ratio of 2.15. Six additional diets were formulated by adding 250, 500, 750, 1,000, 1,500, or 2,000 FTU/kg of phytase to the basal diet. Pigs were fed experimental diets for 12 d with 7 d of adaptation and 5 d of fecal sample collection. Results indicated that there was a linear (P &lt; 0.01) increase in apparent total tract digestibility of ash and ether extract, and STTD of Ca and P also increased (linear, P &lt; 0.05) in response to increasing doses of phytase. Increasing phytase levels in the diets resulted in increase (quadratic, P &lt; 0.05) in apparent ileal digestibility of Arg, His, Ile, Lys, Trp, Asp, and Glu. In conclusion, the novel E. coli phytase was effective in increasing growth performance, bone mineralization, and Ca and P digestibility in pigs fed corn–soybean meal-based diets. Results also indicated that this phytase had the potential to enhance the digestibility of fat and certain AA.
Patterns of dengue in Nepal from 2010–2019 in relation to elevation and climate
Authors: Gyawali Narayan , Johnson Brian J , Dixit Sameer M , Devine Gregor J 
Published: November 2020

AbstractBackgroundUnderstanding and describing the regional and climatic patterns associated with increasing dengue epidemics in Nepal is critical to improving vector and disease surveillance and targeting control efforts.MethodsWe investigated the spatial and temporal patterns of annual dengue incidence in Nepal from 2010 to 2019, and the impacts of seasonal meteorological conditions (mean maximum, minimum temperature and precipitation) and elevation on those patterns.ResultsMore than 25 000 laboratory-confirmed dengue cases were reported from 2010 to 2019. Epidemiological trends suggest that dengue epidemics are cyclical with major outbreaks occurring at 2- to 3-y intervals. A significant negative relationship between dengue incidence and increasing elevation (metres above sea level) driven by temperature was observed (p&lt;0.05) with dengue risk being greatest below 500 m. Risk was moderate between 500 and 1500 m and decreased substantially above 1500 m. Over the last decade, increased nightly temperatures during the monsoon months correlated with increased transmission (p&lt;0.05). No other significant relationship was observed between annual dengue cases or incidence and climatological factors.ConclusionsThe spatial analysis and interpretation of dengue incidence over the last decade in Nepal confirms that dengue is now a well-established public health threat of increasing importance, particularly in low elevation zones and urbanised areas with a tropical or subtropical climate. Seasonal variations in temperature during the monsoon months are associated with increased transmission.
β-hydroxy-β-methylbutyrate supplementation in older persons – an update
Authors: Bear Danielle E. , Cruz-Jentoft Alfonso J. , Stout Jeffrey R. 
Published: November 2020

Purpose of review
The interest in the use of beta-hydroxy-beta-methylbutyrate (HMB) as an intervention to prevent and treat sarcopenia has increased over recent years. The purpose of this review is to explore recent evidence pertaining to the mechanism of action of HMB and how this may influence changes in lean mass and strength in older persons who are both hospitalized and living in the community.

Recent findings
No new studies have been published over the last 2 years investigating the effect of HMB in older persons who are hospitalized, aside from one posthoc analysis of a randomized controlled trial exploring the effect of a high protein oral nutrition supplement containing HMB on handgrip strength and nutritional status. Three studies recruiting community-dwelling older adults have been published, but results are influenced by suboptimal methodological quality.

Summary
Recent data suggest the need for high-quality studies investigating the effectiveness of HMB to improve outcomes related to sarcopenia in both hospitalized and community-dwelling older persons.
Stem-cell-derived models: tools for studying role of microbiota in intestinal homeostasis and disease
Authors: Dheer Rishu , Young Vincent B. 
Published: November 2020

Purpose of review
In this review, we will summarize the recent progress made in generating stem-cell-based organoid and enteroid models of the gastrointestinal tract and their importance in understanding the role of microbes in intestinal epithelial homeostasis and disease.

Recent finding
Intestinal stem-cell-derived culture systems are self-organizing three-dimensional organotypic cultures that recapitulate many cellular, architectural and functional aspects of the human intestine. Progress has been made in the development of methods to incorporate additional cell lineages and physiological cues to better mimic the complexity of the intestine. Current model systems have facilitated both the study of gastrointestinal infections and interactions with normally nonpathogenic microbial residents of the gastrointestinal tract. These studies have illustrated how live microbes, or their metabolites, ligands and virulence factors influence epithelial cell differentiation, maintenance, repair, function and intestine development.

Summary
Organotypic models are invaluable tools for studying host–microbe interactions that complement in-vivo experimental model systems. These models have evolved in terms of complexity and fidelity. The stem-cell-based models are already at forefront for studying host–microbe interactions and with continued development, the future looks even more promising.
Applicability of Magnetic Resonance Imaging of the Knee in Forensic Age Estimation
Authors: Uygun Besim , Kaya Kenan , Köse Sevgül , Ekizoğlu Oğuzhan , Hilal Ahmet 
Published: November 2020

Abstract
Age estimation in forensic medicine practice is of particular importance to the legal systems, and it is one of the current research topics in forensic medicine. Age determination is most frequently performed by radiological methods, but recently, nonionized methods are preferred for nonmedical indications. Therefore, we aimed to examine feasibility of MRI imaging, which provides nonionized, noninvasive, and detailed images, in forensic age estimation and to expand the database on this subject. The MRI images of the patients between the ages of 10 and 25 years, who visited Cukurova University Faculty of Medicine between January 2012 and April 2018 for any reason, were retrospectively analyzed according to the staging method described by Dedouit et al. The stage 5 ossification in distal femoral epiphysis indicated an age over 18 years in both sexes (except for 2 cases of 14 and 15 years). The stage 5 ossification in proximal tibial epiphysis indicated an age older than 18 years (except for 1 male case at the age of 15 years and 2 female cases at the age of 14 and 17 years, respectively). It was determined that stage 1 and stage 2 in both distal femur and proximal tibial epiphysis were last seen in younger than 18 years in both sexes. Our study data show that MRI imaging is a nonionized method that can be used in addition to other radiological methods in determining the age limit of 18 years.
PBRM1 loss-of-function mutations and response to immune checkpoint blockade in clear cell renal cell carcinoma
Authors: Conway Jake , Taylor-Weiner Amaro , Braun David , Bakouny Ziad , Choueiri Toni K. , Van Allen Eliezer M. 
Published: November 2020

ABSTRACTThe biological role of PBRM1 loss-of-function (LOF) mutations mediating response to immune checkpoint blockade (ICB) in clear cell renal cell carcinoma (ccRCC) remains an area of active investigation. A recent study (hereafter, ‘the MSK study’) evaluated this hypothesis in a clinically heterogeneous single institution retrospective ccRCC cohort using targeted sequencing and did not find a univariable statistically significant association for PBRM1 LOF and time-to-treatment failure (TTF), but did report a significant association between continuous tumor mutational burden (TMB) and ICB TTF. We re-analyzed this cohort to (i) match the methodology from previous studies and (ii) account for differences in cohort development, statistical approaches, mutation classifications, and outcome measurements. Univariable analysis of the PBRM1 LOF mutation hypothesis, when performed analogously to prior studies, demonstrated a modest statistically significant association with TTF on ICB (p = 0.047; HR = 0.7, 95% CI = 0.49 - 0.99). By contrast, when using the different methodology presented in the MSK study, statistical modeling demonstrated that there was insufficient power to detect this association given the altered classification scheme and modest effect size. In addition, after appropriately normalizing TMB to account for anomalous outliers, TMB was not significantly associated with ICB response in ccRCC. Thus, this study provides further support for the biological association between PBRM1 LOF and favorable clinical outcomes on ICB in specific ccRCC clinical contexts. However, we again strongly caution against interpreting that this PBRM1 biological association, likely one of many modest mediators of tumor-immune-stromal interactions, achieves broadly generalizable predictive biomarker status for ICB in diverse clinical contexts. The PBRM1 LOF biological association has only been shown to be modestly predictive in the post-VEGF TKI ICB-monotherapy ccRCC patient population. Given emerging data about the biological role of PBRM1 in contributing to interwoven immune and angiogenesis programs (among many others), and the rapidly shifting therapeutic combination strategies invoking these processes in ccRCC, focused biological and predictive biomarker analyses in specific clinical settings using appropriately annotated clinical trial cohorts are necessary.
Extremely Preterm Children Demonstrate Interhemispheric Hyperconnectivity During Verb Generation: a Multimodal Approach
Authors: Barnes-Davis Maria E. , Merhar Stephanie L. , Holland Scott K. , Parikh Nehal A. , Kadis Darren S. 
Published: November 2020

ABSTRACTChildren born extremely preterm (EPT, <28 weeks gestation) are at risk for delays in development, including language. We use fMRI-constrained magnetoencephalography (MEG) during a verb generation task to assess the extent and functional connectivity (phase locking value, or PLV) of language networks in a large cohort of EPT children and their term comparisons (TC). 73 participants, aged 4 to 6 years, were enrolled (42 TC, 31 EPT). There were no significant group differences in age, sex, race, ethnicity, parental education, or family income. There were significant group differences in expressive language scores (p<0.05). Language representation was not significantly different between groups on fMRI, with task-specific activation involving bilateral temporal and left inferior frontal cortex. There were group differences in functional connectivity seen in MEG. To identify a possible subnetwork contributing to focal spectral differences in connectivity, we ran Network Based Statistics analyses. For both beta (20-25 Hz) and gamma (61-70 Hz) bands, we observed a subnetwork showing hyperconnectivity in the EPT group (p<0.05). Network strength was computed for the beta and gamma subnetworks and assessed for correlation with language performance. For the EPT group, exclusively, strength of the subnetwork identified in the gamma frequency band was positively correlated with expressive language scores (r=0.318, p<0.05). Thus, interhemispheric hyperconnectivity is positively related to language for EPT children and might represent a marker for resiliency in this population.
Rapid classification and prediction of COVID-19 severity by MALDI-TOF mass spectrometry analysis of serum peptidome
Authors: Gomila Rosa M. , Martorell Gabriel , Fraile-Ribot Pablo A. , Doménech-Sánchez Antonio , Oliver Antonio , García-Gasalla Mercedes , Albertí Sebastián 
Published: November 2020

ABSTRACTClassification and early detection of severe COVID-19 patients is urgently required to establish an effective treatment. Here, we tested the utility of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to classify and predict the severity of COVID-19 in a clinical setting. We used this technology to analyse the mass spectra profiles of the sera from 80 COVID-19 patients, clinically classified as mild (33), severe (26) and critical (21), and 20 healthy controls. We found a clear variability of the serum peptidome profile depending on COVID-19 severity. Seventy-eight peaks were significantly different and 12 at least four fold more intense in the set of critical patients than in the mild ones. Analysis of the resulting matrix of peak intensities by machine learning approaches classified severe (severe and critical) and non-severe (mild) patients with a 90% of accuracy. Furthermore, machine learning predicted correctly the favourable outcome of the severe patients in 85% of the cases and the unfavourable in 38% of the cases. Finally, liquid chromatography mass spectrometry analysis of sera identified five proteins that were significantly upregulated in the critical patients. They included serum amyloid proteins A1 and A2, which probably yielded the most intense peaks with m/z 11,530 and 11,686 detected by MALDI-TOF MS.In summary, we demonstrated the potential of the MALDI-TOF MS as a bench to bedside technology to aid clinicians in their decisions to classify COVID-19 patients and predict their evolution.
High prevalence of SARS-CoV-2 swab positivity and increasing R number in England during October 2020: REACT-1 round 6 interim report
Authors: Riley Steven , Ainslie Kylie E. C. , Eales Oliver , Walters Caroline E. , Wang Haowei , Atchison Christina , Fronterre Claudio , Diggle Peter J. , Ashby Deborah , Donnelly Christl A. , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Elliott Paul 
Published: November 2020

AbstractBackgroundREACT-1 measures prevalence of SARS-CoV-2 infection in representative samples of the population in England using PCR testing from self-administered nose and throat swabs. Here we report interim results for round 6 of observations for swabs collected from the 16th to 25th October 2020 inclusive.MethodsREACT-1 round 6 aims to collect data and swab results from 160,000 people aged 5 and above. Here we report results from the first 86,000 individuals. We estimate prevalence of PCR-confirmed SARS-CoV-2 infection, reproduction numbers (R) and temporal trends using exponential growth or decay models. Prevalence estimates are presented both unweighted and weighted to be representative of the population of England, accounting for response rate, region, deprivation and ethnicity. We compare these interim results with data from round 5, based on swabs collected from 18th September to 5th October 2020 inclusive.ResultsOverall prevalence of infection in the community in England was 1.28% or 128 people per 10,000, up from 60 per 10,000 in the previous round. Infections were doubling every 9.0 (6.1, 18) days with a national reproduction number (R) estimated at 1.56 (1.27, 1.88) compared to 1.16 (1.05, 1.27) in the previous round. Prevalence of infection was highest in Yorkshire and The Humber at 2.72% (2.12%, 3.50%), up from 0.84% (0.60%, 1.17%), and the North West at 2.27% (1.90%, 2.72%), up from 1.21% (1.01%, 1.46%), and lowest in South East at 0.55% (0.45%, 0.68%), up from 0.29% (0.23%, 0.37%). Clustering of cases was more prevalent in Lancashire, Manchester, Liverpool and West Yorkshire, West Midlands and East Midlands. Interim estimates of R were above 2 in the South East, East of England, London and South West, but with wide confidence intervals. Nationally, prevalence increased across all age groups with the greatest increase in those aged 55-64 at 1.20% (0.99%, 1.46%), up 3-fold from 0.37% (0.30%, 0.46%). In those aged over 65, prevalence was 0.81% (0.58%, 0.96%) up 2-fold from 0.35% (0.28%, 0.43%). Prevalence remained highest in 18 to 24-year olds at 2.25% (1.47%, 3.42%).ConclusionThe co-occurrence of high prevalence and rapid growth means that the second wave of the epidemic in England has now reached a critical stage. Whether via regional or national measures, it is now time-critical to control the virus and turn R below one if further hospital admissions and deaths from COVID-19 are to be avoided.