bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased interhemispheric asymmetry of cerebral blood flow in comatose adult patients on extracorporeal membrane oxygenation
Authors: Johnson Thomas W. , Dar Irfaan , Donohue Kelly , Xu Yama Y. , Santiago Esmeralda , Selioutski Olga , Marinescu Mark A. , Maddox Ross K. , Wu Tong Tong , Schifitto Giovanni , Gosev Igor , Choe Regine , Khan Imad 
Published: October 2021

AbstractExtracorporeal membrane oxygenation (ECMO) is a mechanical circulatory support method that is associated with a high burden of neurologic injury, but neurologic examination and imaging of this population presents prohibitive medical and logistical challenges. Diffuse correlation spectroscopy (DCS) can measure relative cerebral blood flow (rBF) non-invasively at the bedside. In this study we observed interhemispheric differences in rBF in response to mean arterial pressure (MAP) changes in adult ECMO recipients. Thirteen patients were recruited (ages 21-78, 7 with cardiac arrest, 4 with acute heart failure, 2 with acute respiratory distress syndrome). They were dichotomized via Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; n=4) and non-comatose (GCS-M > 4; n=9) groups. Comatose patients had more interhemispheric rBF asymmetry (ASYMrBF) vs. non-comatose patients over a range of MAP values (29% [IQR 23-34%] vs. 11% [IQR 8-13%], p=0.009). ASYMrBFin comatose patients resolved near a MAP range of 70-80 mm Hg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Associations between post-oxygenator pCO2or pH vs. ASYMrBFindividually did not meet significance, though the linear model slopes were different between comatose and non-comatose subgroups. Here we have demonstrated asymmetric cerebral autoregulation in comatose ECMO patients.
Cost-effective epigenetic age profiling in shallow methylation sequencing data
Authors: Trapp Alexandre , Gladyshev Vadim N. 
Published: October 2021

AbstractThere is a critical need for robust, high-throughput assays of biological aging trajectories. Among various approaches, epigenetic aging clocks emerged as reliable molecular trackers of the aging process. However, current methods for epigenetic age profiling are inherently costly and lack throughput. Here, we leverage the scAge framework for accurate prediction of biological age from very few bisulfite sequencing reads in bulk samples, thereby enabling drastic (100-1,000-fold) reduction in sequencing costs per sample. Our approach permits age assessment based on distinct assortments of CpG sites in different samples, without the need for targeted site enrichment or specialized reagents. We demonstrate the efficacy of this method to quantify the age of mouse blood samples across independent cohorts, identify the effect of calorie restriction as an attenuator of the aging process, and discern rejuvenation upon cellular reprogramming. We propose that this framework may be used for epigenetic age prediction in extremely high-throughput applications, enabling robust, large-scale and inexpensive interventions testing and age profiling.
Detection of SARS-CoV-2 RNA Throughout Wastewater Treatment Plants and A Modeling Approach to Understand COVID-19 Infection Dynamics in Winnipeg, Canada
Authors: Yanaç Kadir , Adegoke Adeola , Wang Liqun , Yuan Qiuyan , Uyaguari Miguel 
Published: October 2021

ABSTRACTAlthough numerous studies have detected SARS-CoV-2 in wastewater and attempted to find correlations between the concentration of SARS-CoV-2 and the number of cases, no consensus has been reached on sample collection and processing, and data analysis. Moreover, the fate of SARS-CoV-2 in wastewater treatment plants is another issue, specifically regarding the discharge of the virus into environmental settings and the water cycle. The current study monitored SARS-CoV-2 in influent and effluent wastewater samples with three different concentration methods and sludge samples over six months (July to December 2020) to compare different virus concentration methods, assess the fate of SARS-CoV-2 in wastewater treatment plants, and describe the potential relationship between SARS-CoV-2 concentrations in influent and infection dynamics. Skimmed milk flocculation (SMF) resulted in higher recoveries (15.27% ± 3.32%) of an internal positive control, Armored RNA, and higher positivity rate of SARS-CoV-2 in samples compared to ultrafiltration methods employing a prefiltration step to eliminate solids. Our results suggested that SARS-CoV-2 may predominate in solids and therefore, concentration methods focusing on both supernatant and solid fractions may result in better recovery. SARS-CoV-2 was detected in influent and primary sludge samples but not in secondary and final effluent samples, indicating a significant reduction during primary and secondary treatments. SARS-CoV-2 was first detected in influent on September 30th, 2020. A decay-rate formula was applied to estimate initial concentrations of late-processed samples with SMF. A model based on shedding rate and new cases was applied to estimate SARS-CoV-2 concentrations and the number of active shedders. Inferred sensitivity of observed and modeled concentrations to the fluctuations in new cases and test-positivity rates indicated a potential contribution of newly infected individuals to SARS-CoV-2 loads in wastewater.
Single-cell profiling of transcriptome and histone modifications with EpiDamID
Authors: Rang Franka J. , de Luca Kim L. , de Vries Sandra S. , Valdes-Quezada Christian , Boele Ellen , Nguyen Phong D. , Guerreiro Isabel , Sato Yuko , Kimura Hiroshi , Bakkers Jeroen , Kind Jop 
Published: October 2021

AbstractRecent advances in single-cell sequencing technologies have enabled simultaneous measurement of multiple cellular modalities, including various combinations of transcriptome, genome and epigenome. However, comprehensive profiling of the histone post-translational modifications that influence gene expression at single-cell resolution has remained limited. Here, we introduce EpiDamID, an experimental approach to target a diverse set of chromatin types by leveraging the binding specificities of genetically engineered proteins. By fusing Dam to single-chain variable fragment antibodies, engineered chromatin reader domains, or endogenous chromatin-binding proteins, we render the DamID technology and all its implementations compatible with the genome-wide identification of histone post-translational modifications. Importantly, this enables the joint analysis of chromatin marks and transcriptome in a variety of biological systems at the single-cell level. In this study, we use EpiDamID to profile single-cell Polycomb occupancy in mouse embryoid bodies and provide evidence for hierarchical gene regulatory networks. We further demonstrate the applicability of this method to in vivo systems by mapping H3K9me3 in early zebrafish embryogenesis, and detect striking heterochromatic regions specifically in the notochord. Overall, EpiDamID is a new addition to a vast existing toolbox for obtaining systematic insights into the role of chromatin states during dynamic cellular processes.
Increased alcohol self-administration following repeated Toll-like receptor 3 agonist treatment in male and female rats
Authors: Lovelock Dennis F. , Randall Patrick A. , Van Voorhies Kalynn , Vetreno Ryan P. , Crews Fulton T. , Besheer J. 
Published: October 2021

AbstractToll-like receptor (TLR) signaling may play an important role in the neuroimmune system’s involvement in the development and maintenance of alcohol use disorder. In the present study we administered TLR3 agonist poly(I:C) in male and female Long-Evans rats to determine whether TLR3 agonism can increase alcohol consumption in a daily 15% alcohol operant self-administration paradigm. We found few effects when poly(I:C) was given every-other-day at 0.3 or 1.0 mg/kg, however when instead 1.0 mg/kg was given on consecutive days alcohol intake increased in the days following injections specifically in females. Furthermore, in a second experiment we found that this effect only emerged when rats had a history of multiple poly(I:C) injections. In the final experiment the dose was increased to 3.0 mg/kg on consecutive days which resulted in significant reductions on injection days in females that were not accompanied by subsequent increases. The dose was increased to 9 mg/kg for one final pair of injections which led to reductions in intake in both males and females but only increased subsequent alcohol consumption in males. Overall, poly(I:C) was able to increase subsequent alcohol consumption in both sexes, with females being sensitive to lower doses than males both in terms of changes in alcohol consumption and general locomotor reduction. These findings show that TLR3 agonism may be involved in driving increased alcohol consumption and add to the body of work identifying the neuroimmune system as a potential therapeutic target for AUD.
On stability of the Darwinian dynamics
Authors: Satouri Mohammadreza , Rezaei Jafar , Staňková Kateřina 
Published: October 2021

AbstractHere we analyze Darwinian dynamics of cancer introduced in [1], extended by including a competition matrix, and evaluate (i) when the eco-evolutionary equilibrium is positive and (ii) when the eco-evolutionary equilibrium is asymptotically stable.
Effects of Superhydrophobic Sand Mulching on Evapotranspiration and Phenotypic Responses in Tomatoes (Solanum lycopersicum) under Normal and Reduced Irrigation
Authors: Odokonyero Kennedy , Gallo Adair , Santos Vinicius Dos , Mishra Himanshu 
Published: October 2021

AbstractIrrigated agriculture in arid and semi-arid regions is a vital contributor to the global food supply; however, these regions endure massive evaporative losses that are compensated by unsustainable freshwater withdrawals. Plastic mulches have been used to curtail evaporation, improve water-use efficiency, and ensure food–water security, but they are non-biodegradable and their disposal is unsustainable. We recently developed superhydrophobic sand (SHS), which comprises sand grains with a nanoscale wax coating that could offer a more sustainable mulching solution. Here, the effects of adding a 1.0 cm-thick layer of SHS mulch on the evapotranspiration and phenotypic responses of tomato (Solanum lycopersicum) plants are studied under normal and reduced irrigation. Under both irrigation regimes, SHS mulching suppressed evaporation and enhanced transpiration by 78% and 17%, respectively relative to the bare soil. Overall, SHS mulching enhanced root xylem vessel diameter, stomatal aperture, stomatal conductance, and chlorophyll content index by 21%, 25%, 28%, and 23%, respectively. Total fruit yields, total dry mass, and harvest index increased in SHS-mulched plants by 33%, 20%, and 16%, respectively than in bare soil. These findings demonstrate the potential of SHS to boost irrigation efficiency in water-limited environments and provide mechanistic insights behind yield enhancement by SHS mulching.
Upregulated PD-1 Signaling is an Important Antagonist to Glomerular Health in Aged Kidneys
Authors: Pippin Jeffrey W. , Kaverina Natalya , Wang Yuliang , Eng Diana G. , Zeng Yuting , Tran Uyen , Loretz Carol J. , Chang Anthony , O’Connor Christopher , Bitzer Markus , Wessely Oliver , Shankland Stuart J. 
Published: October 2021

ABSTRACTKidney aging and its contribution to disease and its underlying mechanisms are not well understood. With an aging population, kidney health becomes an important medical and socioeconomic factor. We previously showed that podocytes isolated from aged mice exhibit increased expression of Programed Cell Death Protein 1 (PD-1) surface receptor and its two ligands (PD-L1, PD-L2).PDCD1transcript increases with age in micro-dissected human glomeruli, which correlates with lower eGFR, and higher segmental glomerulosclerosis and vascular arterial intima to lumen ratio.In vitrostudies in podocytes demonstrate a critical role for PD-1 signaling in cell survival and induction of a Senescence-Associated Secretory Phenotype (SASP). To prove PD-1 signaling is critical to podocyte aging, aged mice were injected with anti-PD-1 antibody (aPD-1ab). Treatment significantly improved the aging phenotype in both kidney and liver. In the glomerulus, it increased the life-span of podocytes, but not parietal epithelial, mesangial or endothelial cells. Transcriptomic and immunohistochemistry studies demonstrate that anti-PD-1 treatment improved the health-span of podocytes. It restored the expression of canonical podocyte genes, transcription factors and gene regulatory networks, increased cellular metabolism signatures and lessened SASPs. These results suggest a critical contribution for increased PD-1 signaling towards both kidney and liver aging.
seqr : a web-based analysis and collaboration tool for rare disease genomics
Authors: Pais Lynn S. , Snow Hana , Weisburd Ben , Zhang Shifa , Baxter Samantha , DiTroia Stephanie , O’Heir Emily , England Eleina , Chao Katherine , Lemire Gabrielle , Osei-Owusu Ikeoluwa , VanNoy Grace E. , Wilson Michael , Nguyen Kevin , Arachchi Harindra , Phu William , Solomonson Matthew , Mano Stacy , O’Leary Melanie , Lovgren Alysia , Babb Lawrence , Austin-Tse Christina , Rehm Heidi L. , MacArthur Daniel G. , O’Donnell-Luria Anne 
Published: October 2021

AbstractExome and genome sequencing have become the tools of choice for rare disease diagnosis, leading to large amounts of data available for analyses. To identify causal variants in these datasets, powerful filtering and decision support tools that can be efficiently used by clinicians and researchers are required. To address this need, we developed seqr - an open source, web-based tool for family-based monogenic disease analysis that allows researchers to work collaboratively to search and annotate genomic callsets. To date, seqr is being used in several research pipelines and one clinical diagnostic lab. In our own experience through the Broad Institute Center for Mendelian Genomics, seqr has enabled analyses of over 10,000 families, supporting the diagnosis of more than 3,800 individuals with rare disease and discovery of over 300 novel disease genes. Here we describe a framework for genomic analysis in rare disease that leverages seqr’s capabilities for variant filtration, annotation, and causal variant identification, as well as support for research collaboration and data sharing. The seqr platform is available as open source software, allowing low-cost participation in rare disease research, and a community effort to support diagnosis and gene discovery in rare disease.
The association between lymphocyte mitochondrial DNA abundance and Stroke: a combination of multivariable-adjusted survival and mendelian randomization analyses
Authors: Martens Leon G , Luo Jiao , Wermer Marieke J H , van Dijk Ko Willems , Hägg Sara , Grassmann Felix , Noordam Raymond , van Heemst Diana 
Published: October 2021

AbstractBackground and PurposeMitochondrial dysfunction is associated with increased Reactive Oxygen Species that are thought to drive risk of disease, including stroke. We investigated the association between mtDNA abundance, as a proxy for mitochondrial function, and incident stroke using multivariable-adjusted survival and Mendelian Randomization (MR) analyses.MethodsCox-proportional hazard model analyses were conducted to assess the association between lymphocyte mtDNA abundance, and incident ischemic and hemorrhagic stroke over a maximum of 14-years follow-up in unrelated European-ancestry participants from UK Biobank. MR was conducted using independent (R2<0.001) lead variants for lymphocyte mtDNA abundance (p < 5×10-8) as instrumental variables. Single-Nucleotide Polymorphism (SNP)- ischemic stroke associations were derived from three published open source European-ancestry results databases (cases/controls): MEGASTROKE (60,341/454,450), UK Biobank (2,404/368,771) and FinnGen (10,551/202,223). MR was performed per study, and results were subsequently meta-analyzed.ResultsA total of 288,572 unrelated participants (46% men) with mean (SD) age of 57 (8) years were included in the cox-proportional hazard analyses. After correction for considered confounders (BMI, hypertension, cholesterol, T2D), no association was found between mtDNA abundance and ischemic or hemorrhagic stroke (lowest 20% versus highest 20%: ischemic stroke, hazard ratio, 1.06 [95% confidence interval 0.95, 1.18]; hemorrhagic stroke, hazard ratio 0.97 [95% confidence interval, 0.82, 1.15]). In line, in the MR analyses, we found no evidence for an association between genetically-influenced mtDNA abundance and ischemic stroke (odds ratio, 1.04; confidence interval, 0.95, 1.15).ConclusionsFrom the multivariable-adjusted survival analyses and the MR analyses, we did not find support for low lymphocyte mtDNA abundance as a causal risk factor in the development of stroke.
Boosting of Cross-Reactive Antibodies to Endemic Coronaviruses by SARS-CoV-2 Infection but not Vaccination with Stabilized Spike
Authors: Crowley Andrew R. , Natarajan Harini , Hederman Andrew P. , Bobak Carly A. , Weiner Joshua A. , Wieland-Alter Wendy , Lee Jiwon , Bloch Evan M. , Tobian Aaron A.R. , Redd Andrew D. , Blankson Joel N. , Wolf Dana , Goetghebuer Tessa , Marchant Arnaud , Connor Ruth I. , Wright Peter F. , Ackerman Margaret E. 
Published: October 2021

AbstractPre-existing antibodies to endemic coronaviruses (CoV) that cross-react with SARS-CoV-2 have the potential to influence the antibody response to COVID-19 vaccination and infection for better or worse. In this observational study of mucosal and systemic humoral immunity in acutely infected, convalescent, and vaccinated subjects, we tested for cross reactivity against endemic CoV spike (S) protein at subdomain resolution. Elevated responses, particularly to the β-CoV OC43, were observed in all natural infection cohorts tested and were correlated with the response to SARS-CoV-2. The kinetics of this response and isotypes involved suggest that infection boosts preexisting antibody lineages raised against prior endemic CoV exposure that cross react. While further research is needed to discern whether this recalled response is desirable or detrimental, the boosted antibodies principally targeted the better conserved S2 subdomain of the viral spike and were not associated with neutralization activity. In contrast, vaccination with a stabilized spike mRNA vaccine did not robustly boost cross-reactive antibodies, suggesting differing antigenicity and immunogenicity. In sum, this study provides evidence that antibodies targeting endemic CoV are robustly boosted in response to SARS-CoV-2 infection but not to vaccination with stabilized S, and that depending on conformation or other factors, the S2 subdomain of the spike protein triggers a rapidly recalled, IgG-dominated response that lacks neutralization activity.Graphical AbstractGraphical AbstractAntibody responses to SARS-CoV-2 and endemic CoV spike proteins were measured in diverse cohorts. While antibodies to SARS-CoV-2 were induced across all isotypes, only IgA and IgG responses to endemic CoV were robustly boosted, and only among naturally-infected but not vaccinated individuals. These recalled, cross-reactive responses to endemic CoV primarily recognized the better conserved S2 domain and were non-neutralizing. While other antiviral activities of broadly cross-reactive S2-specifc antibodies are not known, the differing antigenicity of natural infection and vaccination with stabilized pre-fusion spike has potential implications for the breadth and level of protection afforded by each.
Chlamydomonas State Transition Is Quiet Around Pyrenoid and Independent from Thylakoid Deformation
Authors: Zhang XianJun , Fujita Yuki , Kaneda Naoya , Tokutsu Ryutaro , Ye Shen , Minagawa Jun , Shibata Yutaka 
Published: October 2021

AbstractPhotosynthetic organisms have developed a rapid regulation mechanism called state transition (ST) to rapidly adjust the excitation balance between two photosystems by light-harvesting complex II (LHCII) movement. Though many researchers have assumed coupling of the ultrastructural dynamics of the thylakoid membrane to the ST mechanism, how ST is related to the ultrastructural dynamic of the thylakoid in Chlamydomonas remains elusive. To clarify the above-mentioned relation, here we used two specialized microscope techniques, observation via the excitation-spectral microscope (ESM) developed recently by us and the super-resolution imaging based on structured illumination microscopy (SIM). The ESM observation revealed a highly reversible rearrangement of LHCII-related fluorescence. More importantly, it clarified lower ST activity in the region surrounding the pyrenoid, which is the specific subcellular compartment associated with the carbon-fixation reaction. On the other hand, the SIM observation resolved partially irreversible fine thylakoid transformations induced by the ST-inducing illumination. Fine irreversible thylakoid transformation was also observed for the Stt7-kinase-lacking mutant. This result, together with the nearly equal structural changes in the less active ST regions around the pyrenoid, suggested the independence of the observed fine structural changes from the LHCII phosphorylation.
Universal features shaping organelle gene retention
Authors: Giannakis Konstantinos , Arrowsmith Samuel J. , Richards Luke , Gasparini Sara , Chustecki Joanna M. , Røyrvik Ellen C. , Johnston Iain G. 
Published: October 2021

AbstractMitochondria and plastids power complex life, and retain their own organelle DNA (oDNA) genomes, with highly reduced gene contents compared to their endosymbiont ancestors. Why some protein-coding genes are retained in oDNA and some lost remains a debated question. Here we harness over 15k oDNA sequences and over 300 whole genome sequences with tools from structural biology, bioinformatics, machine learning, and Bayesian model selection to reveal the properties of genes, and associated underlying mechanisms, that shape oDNA evolution. Striking symmetry exists between the two organelle types: gene retention patterns in both are predicted by the hydrophobicity of a protein product and its energetic centrality within its protein complex, with additional influences of nucleic acid and amino acid biochemistry. Remarkably, retention principles from one organelle type successfully and quantitatively predict retention in the other, supporting this universality; these principles also distinguish gene profiles in independent endosymbiotic relationships. The identification of these features shaping organelle gene retention both provides quantitative support for several existing evolutionary hypotheses, and suggests new biochemical and biophysical mechanisms influencing organelle genome evolution.