bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation Threats to Humans in Space and an alternative approach with Probiotics
Authors: Diken Dilara , Brodsky Elia , Kaur Harpreet , Mazumder Mohit 
Published: March 2021

ABSTRACTSpace type radiation is an important factor to consider for scientists on International Space Stations, especially high linear transfer energy (LET) since it has imminent effects on microorganisms. The abundances of bacteria are a good indicator of how radiation influences the gut microbiome. The current study is an attempt towards this; thus, we have employed a public dataset (Bioproject code PRJNA368790) of 80 mice samples treated with a range of doses from 0Gy to 1Gy and feces samples were collected at different time points of post radiation treatment. Metagenomic analysis was performed on this data to understand the effect of radiation doses on the abundance of microbial species or microbial diversity implementing the DADA2 and Phyloseq pipelines. Our analyses have shown that 0.1Gy high LET radiation had the significant effect on the species of bacteria. There is a significant decrease in four types of bacteria, i.e., Bifidobacterium longum, Bifidobacterium castoris, Lactobacillus gasseri and Lactobacillus johnsonii, with p-value of 7.05×10-5, 0.020, 0.057and 0.020, respectively. Additionally, pathway analysis indicates the protein coding products of these bacteria are involved in the GABAergic synaptic pathway. Further, our study has shown the significant difference between post radiation time points, i.e., 10 days vs.30 days and suggested the acclimatization period could be around 10 days for these bacteria.
A role for a micron-scale supramolecular myosin array in adherens junction cytoskeletal assembly
Authors: Yu-Kemp Hui-Chia , Szymanski Rachel A. , Gadda Nicole C. , Lillich Madeline L. , Peifer Mark 
Published: March 2021

AbstractEpithelial cells assemble specialized actomyosin structures at E-Cadherin-based cell-cell junctions, and the force exerted drives cell shape change during morphogenesis. The mechanisms used to build this supramolecular actomyosin structure remain unclear. We used ZO-knockdown MDCK cells, which assemble a robust, polarized and highly organized actomyosin cytoskeleton at the zonula adherens, and combined genetic and pharmacological approaches with super-resolution microscopy to define molecular machines required. To our surprise, inhibiting individual actin assembly pathways (Arp2/3, formins or Ena/VASP) did not prevent or delay assembly of this polarized actomyosin structure. Instead, as junctions matured, micrometer-scale supramolecular myosin arrays assembled, with aligned stacks of myosin filaments adjacent to the apical membrane, while associated actin filaments remained disorganized. This suggested these myosin arrays might bundle actin at mature junctions. Consistent with this, inhibiting ROCK or myosin ATPase disrupted myosin localization/organization, and prevented actin bundling and polarization. These results suggest a novel mechanism by which myosin self-assembly helps drive actin organization to facilitate cell shape change.SummaryWe explored mechanisms epithelial cells use to assemble supramolecular actomyosin structures at E-Cadherin-based cell-cell junctions. Our data suggest individual actin assembly pathways are not essential. Instead, microscopy and pharmacological inhibition suggest micrometer-scale supramolecular myosin arrays help bundle actin at mature junctions.
Injury caused by alcoholic cardiomyopathy in spontaneous ethanol drinking rats
Authors: Camargo Victória Mokarzel de Barros , Fioravante Vanessa Caroline , Pinheiro Patricia Fernanda Felipe , Martinez Francisco Eduardo 
Published: March 2021

ABSTRACTWhen speaking of pathologies caused or aggravated by the constant ingestion of ethanol, people with liver and central nervous system diseases soon come to mind, however, the acute intake of large amounts of ethanol and chronic abuse induce toxic effects in the majority of tissues. The heart is highlighted, since alcoholic cardiomyopathy (AC) has prevalence among alcoholics of 23 to 40% and occurs more frequently in men than in women. AC is characterized by dilation and poor contraction of one or both ventricles in the presence of increased ventricular wall thickness, along with a long history of ethanol abuse and no other cause identified. Our aim is to quantify the rate of cardiac tissue replacement, collagen fiber deposition and pro inflammatory cytokines in the left ventricle myocardium of volunteer ethanol drinking rats.
Thermal stimulation of pressure phosphenes
Authors: Kholmanskiy Alexander , Konyukhova Elena , Minakhin Andrey 
Published: March 2021

AbstractTo investigate effect on the intensity of pressure phosphenes (PP) of various methods of heating hands, as well as manual influence on cervical spine. This study included subjective assessments of the PP intensity in 10 healthy men, and chronometry of bioelectrical activity of brain and heart using electroencephalography (EEG) and electrocardiography (ECG). EEG and ECG frequency spectra respond synchronously to pressure, heat and light. The time of excitation of potential oscillations in the visual area of the cortex of both hemispheres is consistent with the delay in the onset of PP flaring. The effect of PP stimulation is enhanced when the hands and body are heated in a humid environment and at temperatures above 42 °C. Stimulation of PP by heating indicates the convergence of impulses from neurons of the lateral geniculate body (LGB) and nuclei of the thalamus, which are responsible for thermoreceptors in the skin of the palms and fingers. The thermal stimulation effect of PP is enhanced at temperatures above 42 °C due to the fact that thermoreceptors work as pain receptors. The mechanism of PP generation is dominated by the processes of redistribution and recombination of charges in the layers of the retina and LGB.
The dynamic effect of regulatory genetic variation on thein vivoER stress transcriptional response
Authors: Russell Nikki D. , Chow Clement Y. 
Published: March 2021

AbstractGenotype x Environment (GxE) interactions occur when environmental conditions drastically change the effect of a genetic variant. In order to truly understand the effect of genetic variation, we need to incorporate multiple environments into our analyses. Many variants, under steady state conditions, may be silent or even have the opposite effect under stress conditions. This study uses anin vivomouse model to investigate how the effect of genetic variation changes with tissue type and cellular stress. Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. This triggers the unfolded protein response (UPR), a large transcriptional response which attempts to return the cell to homeostasis. This transcriptional response, despite being a well conserved, basic cellular process, is highly variable across different genetic backgrounds, making it an ideal system to study GxE effects. In this study, we sought to better understand how genetic variation alters expression across tissues, in the presence and absence of ER stress. The use of different mouse strains and their F1s allow us to also identify context specificcis- andtrans-regulatory mechanisms underlying variable transcriptional responses. We found hundreds of genes that respond to ER stress in a tissue- and/or genotype-dependent manner. Genotype-dependent ER stress-responsive genes are enriched for processes such as protein folding, apoptosis, and protein transport, indicating that some of the variability occurs in canonical ER stress factors. The majority of regulatory mechanisms underlying these variable transcriptional responses derive fromcis-regulatory variation and are unique to a given tissue or ER stress state. This study demonstrates the need for incorporating multiple environments in future studies to better elucidate the effect of any particular genetic factor in basic biological pathways, like the ER stress response.Author SummaryThe effect of genetic variation is dependent on environmental context. Here we use genetically diverse mouse strains to understand how genetic variation interacts with stress state to produce variable transcriptional profiles. In this study, we take advantage of the endoplasmic reticulum (ER) stress response which is a large transcriptional response to misfolded proteins. Using this system, we uncovered tissue- and ER stress-specific effects of genetic variation on gene expression. Genes with genotype-dependent variable expression levels in response to ER stress were enriched for canonical ER stress functions, such as protein folding and transport. These variable effects of genetic variation are driven by unique sets of regulatory variation that are only active under context-specific circumstances. The results of this study highlight the importance of including multiple environments and genetic backgrounds when studying the ER stress response and other cellular pathways.
Context-dependent miR-21 regulation of TLR7-mediated autoimmune and foreign antigen driven antibody-forming cell and germinal center responses
Authors: Schell Stephanie L. , Bricker Kristen N. , Fike Adam J. , Chodisetti Sathi Babu , Domeier Phillip P. , Choi Nicholas M. , Fasnacht Melinda J. , Luckenbill Sara A. , Ziegler Steven F. , Rahman Ziaur S.M. 
Published: March 2021

AbstractMicroRNAs (miRNAs) are involved in healthy B cell responses and the loss of tolerance in systemic lupus erythematosus (SLE), though the role of many miRNAs remains poorly understood. Dampening miR-21 activity was previously shown to reduce splenomegaly and blood urea nitrogen levels in SLE-prone mice, but the detailed cellular responses and mechanism of action remains unexplored. Herein, using the TLR7 agonist imiquimod-induced SLE model, we observed that loss of miR-21 inSle1bmice prevented the formation of plasma cells and autoantibody forming cells (AFC), without a significant effect on the magnitude of the germinal center (GC) response. We further observed reduced dendritic cell and monocyte numbers in the spleens of miR-21 deficientSle1b(Sle1b.miR-21KO) mice that were associated with reduced interferon, proinflammatory cytokines, and effector CD4+T cell responses. RNAseq analysis on B cells fromSle1b.miR-21KO mice revealed reduced activation and response to interferon and cytokine and target array analysis revealed modulation of numerous miR-21 target genes in response to TLR7 activation and type I interferon stimulation. Our findings in the B6.Sle1b.Yaa spontaneous model recapitulated the miR-21 role in TLR7-induced responses with an additional role in autoimmune GC and Tfh responses. Finally, immunization with T-dependent antigen revealed a role for miR-21 in foreign antigen driven GC and Ab, but not AFC responses. Our data suggest a potential multifaceted, context-dependent role for miR-21 in autoimmune and foreign antigen driven AFC and GC responses. Further study is warranted to delineate the cell-intrinsic requirements and mechanisms of miR-21 during infection and SLE development.Key PointsmiR-21 has context dependent effects on AFC and GC responsesmiR-21 promotes TLR7-driven autoimmunity with activation of multiple B cell pathwaysmiR-21 is required for optimal B cell responses to T-dependent foreign antigen
A natural mutator allele shapes mutation spectrum variation in mice
Authors: Sasani Thomas A. , Ashbrook David G. , Beichman Annabel C. , Lu Lu , Palmer Abraham A. , Williams Robert W. , Pritchard Jonathan K. , Harris Kelley 
Published: March 2021

Summary ParagraphAlthough germline mutation rates and spectra can vary within and between species, genetic modifiers of these traits have long eluded detection. In this study, we searched for loci that influence germline mutagenesis using a uniquely powerful resource: a panel of recombinant inbred mouse lines known as theBXD, descended from the laboratory mouse strains C57BL/6J (B) and DBA/2J (D). Each BXD lineage has been maintained by brother-sister mating in the near absence of natural selection, accumulatingde novomutations for up to 50 years on a known genetic background that is a unique linear mosaic ofBandDhaplotypes. We show that mice inheritingDhaplotypes at a quantitative trait locus (QTL) on chromosome 4 accumulate C>A germline mutations at a 50% higher rate than those inheritingBhaplotypes, primarily due to the activity of a C>A-dominated mutational signature known as SBS18. TheBandDQTL haplotypes encode different alleles of the DNA repair geneMutyh, which underlies the heritable colorectal cancer syndrome in which SBS18 was first identified. TheBandD Mutyhalleles are present in wild populations ofMus musculus domesticus, providing evidence that common genetic variation modulates germline mutagenesis in a model mammalian species.
Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance
Authors: Tsai Kaitlyn , Stojković Vanja , Noda-Garcia Lianet , Young Iris D. , Myasnikov Alexander G. , Kleinman Jordan , Palla Ali , Floor Stephen N. , Frost Adam , Fraser James S. , Tawfik Dan S. , Fujimori Danica Galonić 
Published: March 2021

ABSTRACTAlteration of antibiotic binding sites through modification of ribosomal RNA (rRNA) is a common form of resistance to ribosome-targeting antibiotics. The rRNA-modifying enzyme Cfr methylates an adenosine nucleotide within the peptidyl transferase center, resulting in the C-8 methylation of A2503 (m8A2503). Acquisition ofcfrresults in resistance to eight classes of ribosome-targeting antibiotics. Despite the prevalence of this resistance mechanism, it is poorly understood whether and how bacteria modulate Cfr methylation to adapt to antibiotic pressure. Moreover, direct evidence for how m8A2503 alters antibiotic binding sites within the ribosome is lacking. In this study, we performed directed evolution of Cfr under antibiotic selection to generate Cfr variants that confer increased resistance by enhancing methylation of A2503 in cells. Increased rRNA methylation is achieved by improved expression and stability of Cfr through transcriptional and post-transcriptional mechanisms, which may be exploited by pathogens under antibiotic stress as suggested by natural isolates. Using a variant which achieves near-stoichiometric methylation of rRNA, we determined a 2.2 Å cryo-EM structure of the Cfr-modified ribosome. Our structure reveals the molecular basis for broad resistance to antibiotics and will inform the design of new antibiotics that overcome resistance mediated by Cfr.
MicroMator: Open and Flexible Software for Reactive Microscopy
Authors: Fox Zachary R , Fletcher Steven , Fraisse Achille , Aditya Chetan , Sosa-Carrillo Sebastián , Gilles Sébastien , Bertaux François , Ruess Jakob , Batt Gregory 
Published: March 2021

AbstractMicroscopy image analysis has recently made enormous progress both in terms of accuracy and speed thanks to machine learning methods. This greatly facilitates the online adaptation of microscopy experimental plans using real-time information of the observed systems and their environments. Here we report MicroMator, an open and flexible software for defining and driving reactive microscopy experiments, and present applications to single-cell control and single-cell recombination.
Theory of Mind and Moral Decision-Making in the Context of Autism Spectrum Disorder
Authors: Ringshaw Jessica Ellen , Hamilton Katie , Malcolm-Smith Susan 
Published: March 2021

AbstractSocial impairment in Autism Spectrum Disorder (ASD) has been linked to Theory of Mind (ToM) deficits. However, little research has investigated the relationship between ToM and moral decision-making in children with ASD. This study compared moral decision-making and ToM between aggregate-matched ASD and neurotypical boys (n=38 per group; aged 6-12). In a third-party resource allocation task manipulating recipient merit, wealth and health, neurotypical children allocated significantly more resources to the morally deserving recipient, suggesting equitable allocation. A comparatively larger portion of the ASD group allocated equally. ToM emerged as a predictor of moral decision-making. We suggest that ToM (cognitive empathy) deficits may underly atypical moral decision-making in ASD by limiting the integration of empathic arousal (affective empathy) with moral information.
Standard care vs. awake prone position in adult non-intubated patients with acute hypoxaemic respiratory failure secondary to COVID-19 infection – A multi-centre feasibility randomized controlled trial
Authors: Jayakumar Devachandran , Ramachandran Pratheema , Rabindrarajan Ebenezer , Tirupakuzhi Vijayaraghavan Bharath Kumar , Ramakrishnan Nagarajan , Venkataraman Ramesh 
Published: March 2021

AbstractBackgroundThe primary manifestation of Corona Virus Disease −2019 (COVID-19) is acute hypoxic respiratory failure secondary to pneumonia and/or acute respiratory distress syndrome. Prone position has been shown to improve outcomes in ventilated patients with moderate to severe acute respiratory distress syndrome. The feasibility and safety of awake prone positioning and its impact on outcomes if any, in non-intubated patients with mild to moderate acute respiratory distress syndrome secondary to COVID-19 is unknown. Results of the observational studies published thus far in this pandemic have been conflicting. In this context, we conducted a multi-centre, parallel group, randomised controlled feasibility study on awake prone positioning in non-intubated patients with COVID-19 pneumonia requiring supplemental oxygen.Methods60 patients diagnosed with acute hypoxic respiratory failure secondary to COVID −19 pneumonia requiring 4 or more litres of oxygen to maintain a saturation of ≥ 92% were recruited in this study. Thirty patients each were randomised to either standard care or awake prone group. Patients randomised to the standard care were allowed to change their position as per comfort and patients randomized to the prone group were encouraged to self-prone for at least 6 hours a day. The primary outcome was the proportion of patients adhering to the protocol in each group. Secondary outcomes include failure of therapy leading to escalation of respiratory support, number of hours prone, maximum hours of continuous prone positioning in a day, length of stay in ICU, ICU mortality, total number of patients needing intubation and adverse events.ResultsIn the prone group, 43% (13 out of 30) of patients were able to self-prone for 6 or more hours a day. The median maximum prone duration per session was 2 hours. In the supine group, 47% (14 out of 30) were completely supine and 53% spent some hours in the prone position, but none exceeded 6 hours. There was no significant difference in any of the secondary outcomes between the two groups and there were no adverse events.InterpretationAwake proning in non-intubated patients with acute hypoxic respiratory failure is feasible and safe under clinical trial conditions. The results of our feasibility study will potentially help in the design of larger definitive trials to address this key knowledge gap.
Engagement with daily testing instead of self-isolating in contacts of confirmed cases of SARS-CoV-2
Authors: Martin Alex F , Denford Sarah , Love Nicola , Ready Derren , Oliver Isabel , Amlôt Richard , Rubin G. James , Yardley Lucy 
Published: March 2021

AbstractBackgroundIn December 2020, Public Health England with NHS Test and Trace initiated a pilot study in which close contacts of people with confirmed COVID-19 were given the option to carryout lateral flow device antigen tests at home, as an alternative to self-isolation for 10-14 days. In this study, we evaluated acceptability of and engagement with daily testing, and assessed levels of adherence to the rules relating to behaviour following positive or negative test results.MethodsWe conducted a service evaluation of a pilot study, involving an online cross-sectional survey offered to adult (> 18 years) contacts of confirmed COVID-19 cases who were invited to participate in seven days of daily testing instead of isolation. We used a comparison group of contacts who were not offered testing and performed self-isolation. Herein, we examine survey responses from a subset of those who took part in the pilot study and who responded to the evaluation questionnaire.ResultsAcceptability of daily testing was lower among survey respondents who were not offered the option of having it and among people from ethnic minority groups. Overall, 52% of respondents reported being more likely to share details of people that they had been in contact with following a positive test result, if they knew that their contacts would be offered the option of daily testing. Only 2% reported that they would be less likely to provide details of their contacts. On the days that they were trying to self-isolate, 19% of participants reported that they left the house, with no significant demographic group differences. Following a negative test, 13% of respondents reported that they increased their contacts, but most (58%) reported having fewer risky contacts.ConclusionsOur data suggest that daily testing is potentially acceptable, and may facilitate sharing contact details of close contacts among those who test positive for COVID-19, and promote adherence to self-isolation. A better understanding is needed of how to make this option more acceptable for all households. The impact of receiving a negative test on behaviour remains a risk that needs to be monitored and mitigated by appropriate messaging. Future research should examine attitudes and behaviour in a context where infection levels are lower, testing is more familiar, much of the population has been vaccinated and restrictions on activity have been reduced.
Independent, Diplotype and Haplotype Association Analyses of the Selected MTHFR SNPs with the Risk of Breast Cancers in a South-Asian Population
Authors: Ajaz Sadia , Zaidi Sani-e-Zehra , Mehboob Ali Saleema , Siddiqa Aisha , Memon Muhammad Ali , Abid Aiysha , Khaliq Shagufta 
Published: March 2021

AbstractPURPOSEMTHFR is a pivotal enzyme in the folic acid cycle. In specific populations, two functional SNPs in the encoding gene, i.e. rs1801133 (677C/T) and rs1801131 (1298A/C), have shown associations with different diseases including cancers. In the present study, the role of these SNPs was analyzed in breast cancer cases from Pakistani population.PARTICIPANTS AND METHODSThe pilot study includes 187 participants with 124 breast cancer patients and 63 matched individuals as controls. PCR-RFLP methods validated by Sanger sequencing were used for the polymorphic investigations. Hardy-Weinberg Equilibrium was tested by chi-squared goodness-of-fit test. Independent and combined associations were evaluated by Cochran-Armitage trend-test. Semi-parameteric haplotype analysis was carried out and odds ratios with 95% confidence interval were tabulated. Linkage disequilibrium between two loci was calculated. p-values <0.05 were significant.RESULTSBoth MTHFR 677C/T and MTHFR 1298A/C SNPs were in Hardy-Weinberg Disequilibium. Cochran-Armitage trend test showed lack of independent associations of these SNPs with the risk for breast cancers. The diplotype analysis revealed that 677CC+1298AC increased the risk of breast cancers significantly [OR: 2.553 (95% CI: 1.177-5.541)], while 677CT+1298AA had a protective effect [OR: 0.537 (95% CI: 0.404-0.713)]. Haplotype analysis did not show any significant association. Interestingly, despite the proximity, these loci were not linked (r2 = 0.042 and 0.046 in cases and controls, respectively).CONCLUSIONHere, we report association analysis of two putative candidate SNP markers in the MTHFR gene with breast cancers in a South-Asian population. To the best of our knowledge, two diplotype combinations show unique associations with breast cancer susceptibility in this population, which have not been reported earlier. The study implies translational potentials of these polymorphisms for breast cancer management.