bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of poly(A) tail length and non-A residues during the human oocyte-to-embryo transition
Authors: Liu Yusheng , Wu Keliang , Shao Fanghong , Nie Hu , Zhang Jingye , Li Cheng , Hou Zhenzhen , Wang Jiaqiang , Zhou Bing , Zhao Han , Lu Falong 
Published: August 2021

AbstractPoly(A) tail-mediated post-transcriptional regulation of maternal mRNA has been shown to be vital in the oocyte-to-embryo transition (OET) in flies, fish, frogs, and mice1–8. However, nothing is known about poly(A) tail dynamics for even a single gene during the human OET, because of the limited availability of human oocytes and embryos in combination with the low sensitivity of previous methods. Here, we systematically profiled the transcriptome-wide mRNA poly(A) tails in human oocytes at the germ-vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as pre-implantation embryos at the 1-cell (1C), 2-cell (2C), 4-cell (4C), 8-cell (8C), morula (MO), and blastocyst (BL) stages using single-oocyte/embryo PAIso-seq1 and PAIso-seq2 methods. We show that poly(A) tail length is highly dynamic during the OET, with BTG4 responsible for global deadenylation. Moreover, we reveal that non-A residues occur primarily in poly(A) tails of maternal RNA, which begin to increase at the MI stage, become highly abundant after fertilization (with U residues occurring in about two thirds, G residues in about one third, and C residues in about one fifth of mRNAs), and decline at the 8C stage. Importantly, we reveal that TUT4/7 can add U residues to deadenylated mRNA, which can then be re- polyadenylated to produce 5′-end and internal U residues. In addition, the re- polyadenylated mRNA can be stabilized through the addition of G residues by TENT4A/B. Finally, we demonstrate that U residues in poly(A) tails mark the maternal transcripts for quicker degradation in 8C human embryos compared to those without U residues. Together, our results not only reveal the dynamics of poly(A) tail length and non-A residues, but also provide mechanistic insights into the regulation of the length and the role of non-A residues during human OET. These findings further scientific understanding and open a new door for studying the human OET.
nf-core/mag: a best-practice pipeline for metagenome hybrid assembly and binning
Authors: Krakau Sabrina , Straub Daniel , Gourlé Hadrien , Gabernet Gisela , Nahnsen Sven 
Published: August 2021

ABSTRACTThe analysis of shotgun metagenomic data provides valuable insights into microbial communities, while allowing resolution at individual genome level. In absence of complete reference genomes, this requires the reconstruction of metagenome assembled genomes (MAGs) from sequencing reads. We present the nf-core/mag pipeline for metagenome assembly, binning and taxonomic classification. It can optionally combine short and long reads to increase assembly continuity and utilize sample-wise group-information for co-assembly and genome binning. The pipeline is easy to install - all dependencies are provided within containers -, portable and reproducible. It is written in Nextflow and developed as part of the nf-core initiative for best-practice pipeline development. All code is hosted on GitHub under the nf-core organization https://github.com/nf-core/mag and released under the MIT license.
Phylogenomics invokes the clade housing Cryptista, Archaeplastida, and Microheliella maris
Authors: Yazaki Euki , Yabuki Akinori , Imaizumi Ayaka , Kume Keitaro , Hashimoto Tetsuo , Inagaki Yuji 
Published: August 2021

AbstractAs-yet-undescribed branches in the tree of eukaryotes are potentially represented by some of “orphan” protists (unicellular micro-eukaryotes), of which phylogenetic affiliations have not been clarified in previous studies. By clarifying the phylogenetic positions of orphan protists, we may fill the previous gaps in the diversity of eukaryotes and further uncover the novel affiliation between two (or more) major lineages in eukaryotes. Microheliella maris was originally described as a member of the phylum Heliozoa, but a pioneering large-scale phylogenetic analysis failed to place this organism within the previously described species/lineages with confidence. In this study, we analyzed a 319-gene alignment and demonstrated that M. maris represents a basal lineage of one of the major eukaryotic lineages, Cryptista. We here propose a new clade name “Pancryptista” for Cryptista plus M. maris. The 319-gene analyses also indicated that M. maris is a key taxon to recover the monophyly of Archaeplastida and the sister relationship between Archaeplastida and Pancryptista, which is collectively called as “CAM clade” here. Significantly, Cryptophyceae tend to be attracted to Rhodophyta depending on the taxon sampling (ex., in the absence of M. maris and Rhodelphidia) and the particular phylogenetic “signal” most likely hindered the stable recovery of the monophyly of Archaeplastida in previous studies. We hypothesize that many cryptophycean genes (including those in the 319-gene alignment) recombined partially with the homologous genes transferred from the red algal endosymbiont during secondary endosymbiosis and bear a faint phylogenetic affinity to the rhodophytan genes.
Discrepancies in the detection of SARS-CoV-2 by qRT-PCR are dependent on the target gene used for its amplification: Implications in the diagnosis of clinical infection
Authors: Campos-Pardos Elena , Calvet-Seral Juan , Aguilera Antonio , Milagro-Beamonte Ana , Martínez-Sapiña Ana , Barbeito Gema , del Molino María Luisa Pérez , Gonzalo-Asensio Jesús 
Published: August 2021

AbstractDiscrepancies exist in Cycle threshold (Ct) values during detection of SARS-CoV-2 by qRT-PCR. We demonstrate that Ct values depend on the position of the target gene in the viral genome. Simultaneous detection of five genes in positive samples revealed lower Ct values as we move further to the 3’ end (orf1AB/RdRp>E>M>orf7a>N). These findings were confirmed in a retrospective analysis with 363 positive clinical samples. Our findings have key implications in clinical diagnostics of SARS-CoV-2, patient management and public health interventions.
Racism as a Leading Cause of Death: Measuring Excess Deaths in the US
Authors: Massey Daisy S. , Faust Jeremy S. , Dorsey Karen B. , Lu Yuan , Krumholz Harlan M. 
Published: August 2021

AbstractBackgroundExcess death for Black people compared with White people is a measure of health equity. We sought to determine the excess deaths under the age of 65 (<65) for Black people in the United States (US) over the most recent 20-year period. We also compared the excess deaths for Black people with a cause of death that is traditionally reported.MethodsWe used the Center of Disease Control (CDC) WONDER’s Multiple Cause of Death 1999-2019 dataset to report age-adjusted mortality rates among non-Hispanic Black (Black) and non-Hispanic White (White) people and to calculate annual age-adjusted <65 excess deaths for Black people from 1999-2019. We measured the difference in mortality rates between Black and White people and the 20-year and 5-year trends using linear regression. We compared age-adjusted <65 excess deaths for Black people to the primary causes of death among <65 Black people in the US.ResultsFrom 1999 to 2019, the age-adjusted mortality rate for Black men was 1,186 per 100,000 and for White men was 921 per 100,000, for a difference of 265 per 100,000. The age-adjusted mortality rate for Black women was 802 per 100,000 and for White women was 664 per 100,000, for a difference of 138 per 100,000. While the gap for men and women is less than it was in 1999, it has been increasing among men since 2014. These differences have led to many Black people dying before age 65. In 1999, there were 22,945 age-adjusted excess deaths among Black women <65 and in 2019 there were 14,444—deaths that would not have occurred had their risks been the same as those of White women. Among Black men, 38,882 age-adjusted excess <65 deaths occurred in 1999 and 25,850 in 2019. When compared to the top 5 causes of deaths among <65 Black people, death related to disparities would be the highest mortality rate among both <65 Black men and women.CommentIn the US, over the recent 20-year period, disparities in mortality rates resulted in between 61,827 excess deaths in 1999 and 40,294 excess deaths in 2019 among <65 Black people. The race-based disparity in the US was the leading cause of death among <65 Black people. Societal commitment and investment in eliminating disparities should be on par with those focused on other leading causes of death such as heart disease and cancer.
The impact of pausing the Oxford-AstraZeneca COVID-19 vaccine on uptake in Europe: a difference-in-differences analysis
Authors: Jain Vageesh , Lorgelly Paula 
Published: August 2021

AbstractBackgroundSeveral countries paused their rollouts of the Oxford-AstraZeneca COVID-19 vaccine in mid-March 2021 due to concerns about vaccine-induced thrombosis and thrombocytopenia. Many warned that this risked damaging public confidence during a critical period of pandemic response. This study investigated whether the pause in the use of the Oxford-AstraZeneca vaccine had an impact on subsequent vaccine uptake in European countries.MethodsWe used a difference-in-differences approach capitalizing on the fact that some countries halted their rollouts whilst others did not. A longitudinal panel was constructed for European Economic Area countries spanning 15 weeks in early 2021. Media reports were used to identify countries that paused the Oxford-AstraZeneca vaccine and the timing of this. Data on vaccine uptake were available through the European Centre for Disease Control and Prevention COVID-19 Vaccine Tracker. Difference-in-differences linear regression models controlled for key confounders that could influence vaccine uptake, and country and week fixed effects. Further models and robustness checks were performed.ResultsThe panel included 28 countries, with 19 in the intervention group and 9 in the control group. Pausing the Oxford-AstraZeneca vaccine was associated with a 0.52% decrease in uptake for the first dose of a COVID-19 vaccine and a 1.49% decrease in the uptake for both doses, comparing countries that paused to those that did not. These estimates are not statistically significant (p=0.86 and 0.39 respectively). For the Oxford-AstraZeneca vaccine only, the pause was associated with a 0.56% increase in uptake for the first dose and a 0.07% decrease in uptake for both doses. These estimates are also not statistically significant (p= 0.56 and 0.51 respectively). All our findings are robust to sensitivity analyses.ConclusionAs new COVID-19 vaccines emerge, regulators should be cautious to deviate from usual protocols if further investigation on clinical or epidemiological grounds is warranted.
Genomic diversity and antimicrobial resistance of Prevotella spp. isolated from chronic lung disease airways
Authors: Webb Kasey A. , Olagoke Olusola , Baird Timothy , Neill Jane , Pham Amy , Wells Timothy J. , Ramsay Kay A. , Bell Scott C. , Sarovich Derek S. , Price Erin P. 
Published: August 2021

AbstractCystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are characterised by increasingly frequent acute pulmonary exacerbations that reduce life quality and length. Human airways are home to a rich polymicrobial environment, including members of the obligately anaerobic genus, Prevotella. Despite their commonness, surprisingly little is known about the prevalence, role, genomic diversity, and antimicrobial resistance (AMR) potential of Prevotella species/strains in healthy and diseased airways. Here, we used comparative genomics to develop a real-time PCR assay to permit rapid Prevotella spp. quantification from cultures and clinical specimens. Assay specificity was validated across a panel of Prevotella and non-Prevotella species, followed by PCR screening of CF and COPD respiratory-derived cultures. Next, 35 PCR-positive isolates were subjected to whole-genome sequencing. Of eight identified species, P. histicola, P. melaninogenica, P. nanceiensis, P. salivae and P. denticola overlapped between participant cohorts. Phylogenomic analysis revealed considerable interhost but limited intrahost diversity, suggesting patient-specific lineages in the lower airways, probably from oral cavity aspirations. Correlation of phenotypic AMR profiles with AMR gene presence identified excellent correlation between tetQ presence and decreased doxycycline susceptibility, and ermF presence and decreased azithromycin susceptibility and clindamycin resistance. AMR rates were higher in the CF isolates, reflecting greater antibiotic use in this cohort. All tested Prevotella isolates were tobramycin-resistant, providing a potential selection method to improve Prevotella culture retrieval rates. Our addition of 35 airway-derived Prevotella genomes to public databases will enhance ongoing efforts to unravel the role of this diverse and enigmatic genus in both chronic respiratory diseases and healthy lungs.Data summaryThirty-five Prevotella spp. genomes generated in this study are available in the Sequence Read Archive (SRA) and GenBank databases under BioProject accession PRJNA742126.
Microbiomes in drinking water treatment and distribution: a meta-analysis from source to tap
Authors: Thom Claire , Smith Cindy J , Moore Graeme , Weir Paul , Ijaz Umer Z 
Published: August 2021

AbstractA meta-analysis of existing and available Illumina 16S rRNA datasets from drinking water source, treatment and drinking water distribution systems (DWDS) were collated to compare changes in abundance and diversity throughout. Samples from bulk water and biofilm were used to assess principles governing microbial community assembly and the value of amplicon sequencing to water utilities. Individual phyla relationships were explored to identify competitive or synergistic factors governing DWDS microbiomes. The relative importance of stochasticity in the assembly of the DWDS microbiome was considered to identify the significance of source and treatment in determining communities in DWDS. Treatment of water significantly reduces overall species abundance and richness, with chlorination of water providing the most impact to individual taxa relationships. The assembly of microbial communities in the bulk water of the source, primary treatment process and DWDS is governed by more stochastic processes, as is the DWDS biofilm. DWDS biofilm is significantly different from bulk water in terms of local contribution to beta diversity, type and abundance of taxa present. Water immediately post chlorination has a more deterministic microbial assembly, highlighting the significance of this process in changing the microbiome, although elevated levels of stochasticity in DWDS samples suggest that this may not be the case at customer taps. 16S rRNA sequencing is becoming more routine, and may have several uses for water utilities, including: detection and risk assessment of potential pathogens such as those within the genera ofLegionellaandMycobacterium;assessing the risk of nitrification in DWDS; providing improved indicators of process performance and monitoring for significant changes in the microbial community to detect contamination. Combining this with quantitative methods like flow cytometry will allow a greater depth of understanding of the DWDS microbiome.
Filling of a water-free void explains the allosteric regulation of the β1-adrenergic receptor by cholesterol
Authors: Abiko Layara Akemi , Teixeira Raphael Dias , Engilberge Sylvain , Grahl Anne , Grzesiek Stephan 
Published: August 2021

ABSTRACTProteins often contain cavities, which are usually assumed to be water-filled. Recent high-pressure NMR results indicate that the preactive conformation of the β1-adrenergic receptor (β1AR) contains completely empty cavities (dry voids) of about ∼100 Å3 volume, which disappear in the active conformation of the receptor. Here we have localized these cavities by X-ray crystallography on xenon-derivatized β1AR crystals. One of the cavities coincides with the binding pocket of cholesterol. Solution NMR data show that addition of the soluble cholesterol analog cholesteryl hemisuccinate (CHS) impedes the formation of the active conformation of the receptor by blocking conserved GPCR microswitches. This wedge-like action explains the function of the cellularly highly abundant cholesterol as a negative allosteric modulator of β1AR. The detailed understanding of GPCR regulation by cholesterol via filling of a dry void and the easy scouting for such voids by xenon may provide new routes for the development of allosteric drugs.
Strikingly different roles of SARS-CoV-2 fusion peptides uncovered by neutron scattering
Authors: Santamaria Andreas , Batchu Krishna C. , Matsarskaia Olga , Prévost Sylvain F. , Russo Daniela , Natali Francesca , Seydel Tilo , Hoffmann Ingo , Laux Valerie , Haertlein Michael , Darwish Tamim A. , Russell Robert A. , Corucci Giacomo , Fragneto Giovanna , Maestro Armando , Zaccai Nathan R. 
Published: August 2021

ABSTRACTCoronavirus disease-2019 (COVID-19), a lethal respiratory illness caused by the coronavirus SARS-CoV-2, emerged in the end of 2019 and has since spread aggressively across the globe. A thorough understanding of the molecular mechanisms of cellular infection by coronaviruses is therefore of utmost importance. A critical stage in infection is the fusion between viral and host membranes. Here, we present a detailed investigation of the role of the SARS-CoV-2 Spike protein, and the influence of calcium and cholesterol, in this fusion process. Structural information from specular neutron reflectometry and small angle neutron scattering, complemented by dynamics information from quasi-elastic and spin-echo neutron spectroscopy, revealed strikingly different functions encoded in the Spike fusion domain. Calcium drives the N-terminal of the Spike fusion domain to fully cross the host plasma membrane. Removing calcium however re-orients the protein to the lipid leaflet in contact with the virus, leading to significant changes in lipid fluidity and rigidity. In conjunction with other regions of the fusion domain which are also positioned to bridge and dehydrate viral and host membranes, the molecular events leading to cell entry by SARS-CoV-2 are proposed.SIGNIFICANCEWe have recreated here important elements of the critical membrane fusion mechanism of the SARS-CoV-2 coronavirus by simplifying the system down to its core elements, amenable to experimental analysis by neutron scattering. Neutrons are well suited for the study of protein – membrane interactions under physiological conditions, since they allow structural and dynamics characterization at room temperature. Our results revealed strikingly different functions encoded in the viral Spike fusion domain and thereby provide a potential calcium-dependent cell entry mechanism for SARS-CoV-2. In particular, calcium drives the protein’s N-terminal to harpoon through the host membrane, while removing calcium re-orients the protein so that it is able to bridge and dehydrate lipid membranes, facilitating their fusion.
Physiological basis underlying antidepressant-induced activation of TrkB receptors
Authors: Alitalo Okko , Kohtala Samuel , Rosenholm Marko , Kohtala Piia , Saarreharju Roosa , Matsui Nobuaki , Hernandez Gemma Gonzalez , Müller Heidi Kaastrup , Theilmann Wiebke , Sarparanta Mirkka , Klein Anders , Kärkkäinen Olli , Rozov Stanislav , Rantamäki Tomi 
Published: August 2021

SummaryWe show that both pharmacological and non-pharmacological treatments of depression activate TrkB receptors—a well-established target of antidepressants—by inducing a physiological response coupled to sedation. Several rapid-acting antidepressants trigger TrkB signaling by evoking a state associated with electroencephalographic slow-wave activity, behavioral immobility, reduced cerebral glucose utilization, and lowered body temperature. Remarkably, antidepressant-induced TrkB signaling was not compromised in animals exhibiting reduced activity-dependent release of BDNF but was diminished by maintaining animals in warm ambient temperature. Most importantly, prevention of the hypothermic response attenuated the behavioral effects produced by rapid-acting antidepressant nitrous oxide. Our results suggest that the phenomenon underlying TrkB transactivation—changes in energy expenditure and thermoregulation—is essential, but not sufficient, for antidepressant responses. Indeed, regardless of differential clinical and pharmacodynamic properties, all drugs that disrupt energy metabolism and induce hypothermia activated TrkB. This study challenges pharmacology-centric hypotheses regarding antidepressant effects and highlight the role of complex changes in bioenergetics and thermoregulation.HighlightsRapid-acting antidepressants evoke homeostatic emergence of slow-wave sleep during which TrkB signaling becomes regulated.Non-antidepressant metabolic inhibitors and diverse sedatives activate TrkB signaling.Reduction in body temperature determined the ability of antidepressants to transactivate TrkB.Drug-induced TrkB signaling was blunted by maintenance of normothermic body temperature.Warm ambient temperature after nitrous oxide exposure blocked the antidepressant-like effects.Graphical abstract
Modelling the future distribution of rare bryophytes in Scotland: is inclusion of habitat loss important?
Authors: Ferretto Anna , Smith Pete , Genney David , Matthews Robin , Brooker Rob 
Published: August 2021

AbstractSpecies distribution models (SDMs) have been widely used to predict species ranges and their future distribution under climate change scenarios. In this study we applied Maxent, one of the most used SDMs, to project the distribution of some rare bryophyte species in Scotland in the 2050s. Most of these species are strongly linked to the blanket bog habitat, which is threatened by climate change in the near future. To assess the extent to which changes in habitat distribution leads to a different modelled distribution of the selected bryophytes, blanket bog distribution was included in the model as one of the explanatory variables for some species, and Maxent was run for three 2050s scenarios: once with the current blanket bog distribution and two other runs using the blanket bog distribution derived from two bioclimatic models (Lindsay modified and Blanket Bog Tree model) under the same climate change scenario. For seven out of nine of our studied bryophyte species, the modelled distribution in Scotland was predicted to decline, with some species retreating towards the north-west and other species almost disappearing. When the change in blanket bog distribution was also accounted for, further areas in the north/centre east of Scotland and in the south were predicted to be unfavourable for many of the species considered. Our findings suggest that when modelling species distributions, habitat distribution also needs to be considered, especially when there is a strong relationship between the species and a particular habitat.