bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic insights into adaptations of TMA-utilizing methanogens to diverse habitats including the human gut
Authors: de la Cuesta-Zuluaga Jacobo , Spector Timothy D. , Youngblut Nicholas D. , Ley Ruth E. 
Published: September 2020

AbstractArchaea of the orderMethanomassiliicoccalesuse methylated-amines such as trimethylamine as a substrate for methane production. They form two large phylogenetic clades and reside in diverse environments, from soil to the human gut. Two genera, one from each clade, inhabit the human gut:Methanomassiliicoccus, which has one cultured representative, and “candidatusMethanomethylophilus”, which has none. Questions remain regarding their distribution across different biomes and human populations, their association with other taxa in the human gut, and whether host genetics correlate with their abundance. To gain insight into theMethanomassiliicoccales, and the human-associated members in particular, we performed a genomic comparison of 72Methanomassiliicoccalesgenomes and assessed their presence in metagenomes derived from the human gut (n=4472 representing 25 populations), nonhuman animal gut (n=145) and nonhost environments (n=160). Our analyses showed that all taxa are generalists: they were detected in animal gut and environmental samples. We confirmed two large clades, one enriched in the gut, the other enriched in the environment, with notable exceptions. Genomic adaptations to the gut include genome reduction, a set of adhesion factors distinct from that of environmental taxa, and genes involved in the shikimate pathway and bile resistance. Genomic adaptations differed by clade, not habitat preference, indicating convergent evolution between the clades. In the human gut, the relative abundance ofMethanomassiliicoccalescorrelated with trimethylamine-producing bacteria and was unrelated to host genotype. Our results shed light on the microbial ecology of this group may help guideMethanomassiliicoccales-basedstrategies for trimethylamine mitigation in cardiovascular disease.ImportanceMethanomassiliicoccalesare a lesser known component of the human gut microbiota. This archaeal order is composed of methane producers that use methylated amines, such as trimethylamine, in methane production. This group has only one cultured representative; how they adapted to inhabit the mammalian gut and how they interact with other microbes is largely unknown. Using bioinformatics methods applied to DNA from a wide range of samples, we profiled the relative abundances of these archaea in environmental and host-associated microbial communities. We observed two groups ofMethanomassiliicoccales, one largely host-associated and one largely found in environmental samples, with some exceptions. When host-associated, these archaea have a distinct set of genes related to adhesion and possess genes related to bile resistance. We did not detectMethanomassiliicoccalesin all human populations tested but when present, they are correlated withBacteriaknown to produce trimethylamine. Since trimethylamine is linked to cardiovascular disease risk, these intriguing Archaea may also be involved.
Histidine-rich Ca2+-binding protein stimulates the transport cycle of SERCA through a conformation-dependent fuzzy complex
Authors: Ayeotan Temitope I. , Hansen Line Cecilie , Boesen Thomas , Olesen Claus , Møller Jesper V. , Nissen Poul , Kjaergaard Magnus 
Published: September 2020

AbstractThe histidine-rich Ca2+-binding protein (HRC) stimulates the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) to increase Ca2+-uptake into the lumen. HRC also binds the triadin scaffold in a Ca2+-dependent manner, and HRC tunes both the uptake and release of Ca2+depending on the concentration in the intracellular Ca2+-stores. We investigated how HRC stimulates SERCA pumping using biochemical and biophysical assays, and show that HRC is an intrinsically disordered protein that binds directly to SERCA via electrostatic interactions. The affinity of the interaction depends on the conformation of SERCA, and HRC binds most tightly in the calcium-released E2P state. This state marks the end of the rate-limiting [Ca2]E1P to E2P transition of SERCA, and suggests that HRC stimulates SERCA by preferentially stabilizing the end point of this transition. HRC remains disordered in the bound state and thus binds in a dynamic, fuzzy complex. The binding of HRC to SERCA shows that fuzzy complexes formed by disordered proteins may be conformation-specific, and use this specificity to modulate the functional cycle of complex molecular machines such as a P-type ATPase.
Metabolic stress and disease-stage specific basigin expression of peripheral blood immune cell subsets in COVID-19 patients
Authors: Siska Peter J. , Singer Katrin , Klitzke Jana , Kauer Nathalie , Decking Sonja-Maria , Bruss Christina , Matos Carina , Kolodova Kristina , Peuker Alice , Schönhammer Gabriele , Raithel Johanna , Lunz Dirk , Graf Bernhard , Geismann Florian , Lubnow Matthias , Mack Matthias , Hau Peter , Bohr Christopher , Burkhardt Ralph , Gessner Andre , Salzberger Bernd , Hanses Frank , Hitzenbichler Florian , Heudobler Daniel , Lüke Florian , Pukrop Tobias , Herr Wolfgang , Wolff Daniel , Poeck Hendrik , Brochhausen Christoph , Hoffmann Petra , Rehli Michael , Kreutz Marina , Renner Kathrin 
Published: September 2020

SummaryCoronavirus disease 2019 (COVID-19) is driven by dysregulated immune responses yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 47 patients with confirmed SARS-CoV-2 infection and 16 uninfected controls, we found an immunometabolic dysregulation specific for patients with progressed disease that was reversible in the recovery phase. Specifically, T cells and monocytes exhibited increased mitochondrial mass, accumulated intracellular ROS and these changes were accompanied by disrupted mitochondrial architecture. Basigin (CD147), but not established markers of T cell activation, was up-regulated on T cells from progressed COVID-19 patients and correlated with ROS accumulation, reflected in the transcriptome. During recovery, basigin and ROS decreased to match the uninfected controls.In vitroanalyses confirmed the correlation and showed a down-regulation of ROS by dexamethasone treatment. Our findings provide evidence of a basigin-related and reversible immunometabolic dysregulation in COVID-19.
Mental health in higher-education students and non-students: evidence from a nationally representative panel study
Authors: Tabor Evangeline , Patalay Praveetha , Bann David 
Published: September 2020

SummaryDespite increasing policy focus on mental health provision for higher education students, it is unclear whether they have worse mental health outcomes than their non-student peers. In a nationally-representative UK study spanning 2010-2019 (N=11,519), 17-24 year olds who attended higher education had lower average psychological distress (GHQ score difference=–0.37, 95%CI: −0.60, −0.08) and lower odds of case-level distress than those who did not (OR=0.91, 95%CI: 0.81, 1.02). Increases in distress between 2010 and 2019 were similar in both groups. Accessible mental health support outside higher education settings is necessary to prevent further widening of socioeconomic inequalities in mental health.
Relationships between demographic, geographic, and environmental statistics and the spread of novel coronavirus disease (COVID-19) in Italy
Authors: Rovetta Alessandro , Castaldo Lucia 
Published: September 2020

AbstractBackgroundSince January 2020, the COVID-19 pandemic has raged around the world, causing nearly a million deaths and hundreds of severe economic crises. In this scenario, Italy has been one of the most affected countries.ObjectiveThis study investigated significant correlations between COVID-19 cases and demographic, geographical, and environmental statistics of each Italian region from February 26 to August 12, 2020. We further investigated the link between the spread of SARS-CoV-2 and particulate matter (PM) 2.5 and 10 concentrations before the lockdown in Lombardy.MethodsAll demographic data were obtained from the AdminStat Italia website, and geographic data were from the Il Meteo website. The collection frequency was one week. Data on PM2.5 and PM10 average daily concentrations were collected from previously published articles. We used Pearson’s coefficients to correlate the quantities that followed a normal distribution, and Spearman’s coefficient to correlate quantities that did not follow a normal distribution.ResultsWe found significant strong correlations between COVID-19 cases and population number in 60.0% of the regions. We also found a significant strong correlation between the spread of SARS-CoV-2 in the various regions and their latitude, and with the historical averages (last 30 years) of their minimum temperatures. We identified a significant strong correlation between the number of COVID-19 cases until August 12 and the average daily concentrations of PM2.5 in Lombardy until February 29, 2020. No significant correlation with PM10 was found in the same periods. However, we found that 40 μg/m3 for PM2.5 and 50 μg/m3 PM10 are plausible thresholds beyond which particulate pollution clearly favors the spread of SARS-CoV-2.ConclusionSince SARS-CoV-2 is correlated with historical minimum temperatures and PM10 and 2.5, health authorities are urged to monitor pollution levels and to invest in precautions for the arrival of autumn. Furthermore, we suggest creating awareness campaigns for the recirculation of air in enclosed places and to avoid exposure to the cold.
Symptoms of pediatric feeding disorders among individuals with 3q29 deletion syndrome
Authors: Wawrzonek Addam J. , Burrell T. Lindsey , Sharp William , Gillespie Scott E. , Pollak Rebecca M ,   The Emory 3q29 Project, Murphy Melissa , Mulle Jennifer Gladys 
Published: September 2020

AbstractObjectiveTo evaluate symptoms of pediatric feeding disorders in a sample of individuals with 3q29 Deletion Syndrome. Previous research has found that individuals with 3q29 deletion syndrome (3q29Del) may experience elevated feeding concerns in early childhood; however, the specificity of these feeding concerns in this pediatric population is not well understood.MethodsWe compared individuals with 3q29Del (n = 60) to matched controls (n = 59) using an 11-item survey that assessed commonly reported symptoms associated with pediatric feeding disorders. An exploratory analysis also examined individuals with 3q29Del with and without a comorbid autism spectrum disorder (ASD) diagnosis.ResultsCaregivers of 3q29Del cases reported higher incidences of feeding concerns on all 11 items included in the survey. This included statistically significant differences in food refusal behaviors, rejection of one or more food group, and a history of failure to thrive. Parents of children with comorbid autism were more likely to report concerns regarding rejection of one or more food group compared to children with 3q29Del without autism.ConclusionsResults suggest individuals with 3q29Del experience increased symptoms of pediatric feeding disorders. Future research should include a more thorough multidisciplinary evaluation to further document the severity and identify optimal remediation strategies.
In the long shadow of our best intentions: model-based assessment of the consequences of school reopening during the COVID-19 pandemic
Authors: Johnson Kaitlyn E. , Stoddard Madison , Nolan Ryan P. , White Douglas E. , Hochberg Natasha S. , Chakravarty Arijit 
Published: September 2020

AbstractAs the United States grapples with the ongoing COVID-19 pandemic, a particularly thorny set of questions surrounds the reopening of K-12 schools and universities. The benefits of in-person learning are numerous, in terms of education quality, mental health, emotional well-being, equity and access to food and shelter. Early reports suggested that children might have reduced susceptibility to COVID-19, and children have been shown to experience fewer complications than older adults. Over the past few months, our understanding of COVID-19 has been further shaped by emerging data, and it looks increasingly likely that children are as susceptible to infection as adults and have a similar viral load during infection. While the higher prevalence of asymptomatic disease among children makes symptom-based isolation strategies ineffective, asymptomatic patients do not in fact carry a reduced viral load. Using assumptions consistent with the emerging understanding of the disease, we conducted epidemiological modeling to explore the feasibility and consequences of school reopening in the face of differing rates of COVID-19 prevalence and transmission. Our findings indicate that, regardless of the initial prevalence of the disease, and in the absence of systematic surveillance testing, most schools in the United States can expect 20-60 days without a major cluster emerging. Without testing or contact tracing, the true extent of these disease clusters may not be apparent, and our research suggests that the case count will underestimate the true size of the clusters by a large margin. These disease clusters, in turn, can be expected to propagate silently through the community, with potentially hundreds to thousands of additional cases resulting from each individual school cluster. Thus, our findings suggest that the debate between the risks to student safety and benefits of in-person learning frames a false dual choice. Given the current circumstances in the United States, the most likely outcome in the late fall is that students will be deprived of the benefits of in-person learning while having incurred a significant risk to themselves and their communities.
Mutations on a novel brain-specific isoform of PGC1α leads to extensive upregulation of neurotransmitter-related genes and sexually dimorphic motor deficits in mice
Authors: Lozoya Oswaldo A. , Xu Fuhua , Grenet Dagoberto , Wang Tianyuan , Stevanovic Korey D. , Cushman Jesse D. , Jensen Patricia , Hernandez Bairon , Riadi Gonzalo , Moy Sheryl S. , Santos Janine H. , Woychik Richard P. 
Published: September 2020

AbstractThe peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1α) is known as a transcriptional co-activator in peripheral tissues but its function in the brain remains poorly understood. Various brain-specificPgc1αisoforms have been reported in mice and humans, including transcripts derived from a novel promoter about ∼580 Kb upstream from the reference gene. These isoforms incorporate repetitive sequences from the simple sequence repeat (SSR) and short interspersed nuclear element (SINE) classes and are predicted to give rise to proteins with distinct amino-termini. In this study, we show that a SINE-containing isoform is the predominant form ofPgc1αexpressed in neurons. We then generated a mouse carrying a mutation within the SINE to study its functional role in the brain. By combining genomics, biochemical and behavioural approaches, we show that this mutation leads to impaired motor coordination in females, but not male mice, associated with the upregulation of hundreds of cerebellar genes. Moreover, our analysis suggests that known nuclear receptors interact with this isoform of PGC1α in the brain to carry out the female transcriptional program. These data expand our knowledge on the role ofPgc1αin the brain and help explain its conflicting roles in neurological disease and behavioural outcomes.
A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent in vitro
Authors: Xiao Tianshu , Lu Jianming , Zhang Jun , Johnson Rebecca I. , McKay Lindsay G.A. , Storm Nadia , Lavine Christy L. , Peng Hanqin , Cai Yongfei , Rits-Volloch Sophia , Lu Shen , Quinlan Brian D. , Farzan Michael , Seaman Michael S. , Griffiths Anthony , Chen Bing 
Published: September 2020

AbstractEffective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the cellular receptor for SARS-CoV-2. It is also a key negative regulator of the renin-angiotensin system (RAS), conserved in mammals, which modulates vascular functions. We report here the properties of a trimeric ACE2 variant, created by a structure-based approach, with binding affinity of ~60 pM for the spike (S) protein of SARS-CoV-2, while preserving the wildtype peptidase activity as well as the ability to block activation of angiotensin II receptor type 1 in the RAS. Moreover, the engineered ACE2 potently inhibits infection of SARS-CoV-2 in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.
Loss of CIB2 causes non-canonical autophagy deficits and visual impairment
Authors: Sethna Saumil , Scott Patrick A. , Giese Arnaud P.J. , Duncan Todd , Redmond T. Michael , Riazuddin Saima , Ahmed Zubair M. 
Published: September 2020

SUMMARYNon-canonical autophagy or LC3-associated phagocytosis (LAP) is essential for the maintenance and functioning of the retinal pigment epithelium (RPE) and photoreceptors. Although molecular mechanisms still remain elusive, deficits in LAP have been found to be associated with age-related retinal pathology in both mice and humans. In this study, we found that calcium and integrin-binding protein 2 (CIB2) regulates LAP in the RPE. Mice lacking CIB2, both globally and specifically within RPE, have an impaired ability to process the engulfed photoreceptor outer segments due to reduced lysosomal capacity, which leads to marked accumulation of improperly digested remnants, lipid droplets, fused phago-melanosomes in RPE, and impaired visual function. In aged mice, we also found marked accumulation of drusen markers APOE, C3, and Aβ, along with esterified cholesterol. Intriguingly, we were able to transiently rescue the photoreceptor function inCib2mutant mice by exogenous retinoid delivery. Our study links LAP and phagocytic clearance with CIB2, and their relevance to the sense of sight.
Piperacillin/tazobactam resistant, cephalosporin susceptibleEscherichia colibloodstream infections are driven by multiple acquisition of resistance across diverse sequence types
Authors: Edwards Thomas , Heinz Eva , van Aartsen Jon , Howard Alex , Roberts Paul , Corless Caroline , Fraser Alice J. , Williams Christopher T. , Bulgasim Issra , Cuevas Luis E. , Parry Christopher M. , Roberts Adam P. , Adams Emily R. , Mason Jenifer , Hubbard Alasdair T. M. 
Published: September 2020

AbstractResistance to piperacillin/tazobactam (TZP) inEscherichia colihas predominantly been associated with mechanisms that confer resistance to third generation cephalosporins. Recent reports have identifiedE. colistrains with phenotypic resistance to piperacillin/tazobactam but susceptibility to third generation cephalosporins (TZP-R/3GC-S). In this study we sought to determine the genetic diversity of this phenotype inE. coli(n= 58) isolated between 2014-2017 at a single tertiary hospital in Liverpool, UK, as well as the associated resistance mechanisms. We compare our findings to a UK-wide collection of invasiveE. coliisolates(n= 1509) with publicly available phenotypic and genotypic data. These data sets included the TZP-R/3GC-S phenotype(n= 68), a piperacillin/tazobactam and third generation cephalosporin-susceptible (TZP-S/3GC-S,n= 1271) phenotypes. The TZP-R/3GC-S phenotype was displayed in a broad range of sequence types which was mirrored in the same phenotype from the UK-wide collection, and the overall diversity of invasiveE. coliisolates. The TZP-R/3GC-S isolates contained a diverse range of plasmids, indicating multiple acquisition events of TZP resistance mechanisms rather than clonal expansion of a particular plasmid or sequence type. The putative resistance mechanisms were equally diverse, including hyperproduction of TEM-1, either via strong promoters or gene amplification, carriage of inhibitor resistant β-lactamases, and an S133Gb/aCTX-M-15mutation detected for the first time in clinical isolates. Several of these mechanisms were present at a lower abundance in the TZP-S/3GC-S isolates from the UK-wide collection, but without the associated phenotypic resistance to TZP. Our findings highlight the complexity of this cryptic phenotype and the need for continued phenotypic monitoring, as well as further investigation to improve detection and prediction of the TZP-R/3GC-S phenotype from genomic data.
A meta-analysis and experiment assessing phage-based FMDV vaccine
Authors: Wu Peng , Yang Ningning , Wang Yueli , Xu Mingguo , Zhang Yunfeng , Chen Chuangfu 
Published: September 2020

AbstractFoot-and-mouth disease (FMD) is a pathological disease caused by the foot- and-mouth disease virus (FMDV), which mainly affects cloven-hoofed animals. This study was conducted to a meta-analysis and experiment on the effect of bacteriophages used in the development of FMDV vaccines. A systematic search was conducted for the collection of the protection effect for the phage-based FMDV vaccine using sensitive search strategies. The extracted data were analyzed using Rev-Man 5.4 software. This experiment used the T7 phage to express the capsid protein VP1 of the OHM-02 strain, and the recombinant VP1 phage was termed OHM-T7. Antibodies and cytokines levels were assessed after immunizing BALB/C mice with OHM-T7. The results showed that a total of 115 articles were retrieved, and 4 of them met the inclusion criteria. There was no heterogeneity with I2= 0%, 20% or 43%. We used a fixed-effect model for meta-analysis, and the results showed a protective effect on FMDV between the phage group and control group (P<0.01) and between FMDV group and control group (P<0.01). Furthermore, when the phage group was compared to the FMDV group, there was also no significant difference (P>0.05). After successfully obtained the ohm-t7 strain and immunized the mice, it could induce high levels of IFN-γ levels in mice with little effect on IL-4 levels. OHM-T7 could be used to detect antibodies produced by mice immunized with different FMDV antigens and produce high levels of anti-FMD antibodies. In summary, these results showed the potential of phage-based FMDV vaccines in FMDV prevention.