bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mental health during the COVID-19 pandemic in two longitudinal UK population cohorts
Authors: Kwong Alex S. F. , Pearson Rebecca M. , Adams Mark J. , Northstone Kate , Tilling Kate , Smith Daniel , Fawns-Ritchie Chloe , Bould Helen , Warne Naomi , Zammit Stan , Gunnell David , Moran Paul , Micali Nadia , Reichenberg Abraham , Hickman Matthew , Rai Dheeraj , Haworth Simon , Campbell Archie , Altschul Drew , Flaig Robin , McIntosh Andrew M. , Lawlor Deborah A. , Porteous David , Timpson Nicholas J. 
Published: June 2020

SummaryBackgroundThe impact of COVID-19 on mental health is unclear. Evidence from longitudinal studies with pre pandemic data are needed to address (1) how mental health has changed from pre-pandemic levels to during the COVID-19 pandemic and (2), whether there are groups at greater risk of poorer mental health during the pandemic?MethodsWe used data from COVID-19 surveys (completed through April/May 2020), nested within two large longitudinal population cohorts with harmonised measures of mental health: two generations of the Avon Longitudinal Study of Parents and Children (ALPSAC): the index generation ALSPAC-G1 (n= 2850, mean age 28) and the parent’s generation ALSPAC-G0 (n= 3720, mean age = 59) and Generation Scotland: Scottish Family Health Study (GS, (n= 4233, mean age = 59), both with validated pre-pandemic measures of mental health and baseline factors. To answer question 1, we used ALSPAC-G1, which has identical mental health measures before and during the pandemic. Question 2 was addressed using both studies, using pre-pandemic and COVID-19 specific factors to explore associations with depression and anxiety in COVID-19.FindingsIn ALSPAC-G1 there was evidence that anxiety and lower wellbeing, but not depression, had increased in COVID-19 from pre-pandemic assessments. The percentage of individuals with probable anxiety disorder was almost double during COVID-19: 24% (95% CI 23%, 26%) compared to pre-pandemic levels (13%, 95% CI 12%, 14%), with clinically relevant effect sizes. In both ALSPAC and GS, depression and anxiety were greater in younger populations, women, those with pre-existing mental and physical health conditions, those living alone and in socio-economic adversity. We did not detect evidence for elevated risk in key workers or health care workers.InterpretationThese results suggest increases in anxiety and lower wellbeing that may be related to the COVID-19 pandemic and/or its management, particularly in young people. This research highlights that specific groups may be disproportionally at risk of elevated levels of depression and anxiety during COVID-19 and supports recent calls for increasing funds for mental health services.FundingThe UK Medical Research Council (MRC), the Wellcome Trust and University of Bristol.
Endometriosis And Chronic Pelvic Pain Have Similar Impact On Women, But Time To Diagnosis Is Decreasing: An Australian Survey
Authors: Armour Mike , Sinclair Justin , Ng Cecilia H M , Hyman Mikayla S , Lawson Kenny , Smith Caroline A , Abbott Jason 
Published: June 2020

AbstractChronic pelvic pain (CPP) affects a significant number of women worldwide. Internationally, people with endometriosis report significant negative impact across many areas of their life. We aimed to use an online survey using the EndoCost tool to determine if there was any difference in the impact of CPP in those with vs. those without a confirmed diagnosis of endometriosis, and if there was any change in diagnostic delay since the introduction of clinical guidelines in 2005. 409 responses were received; 340 with a diagnosis of endometriosis and 69 with no diagnosis. People with CPP, regardless of diagnosis, reported moderate to severe dysmenorrhea and non-cyclical pelvic pain. Dyspareunia was also common. Significant negative impact was reported for social, academic, and sexual/romantic relationships in both cohorts. In the endometriosis cohort there was a mean diagnostic delay of eight years, however there was a reduction in both the diagnostic delay (p<0.001) and number of doctors seen before diagnosis (p<0.001) in those presenting more recently. Both endometriosis and CPP have significant negative impact. Whilst there is a decrease in the time to diagnosis, there is an urgent need for improved treatment options and support for women with the disease once the diagnosis is made.
Exosomal microRNAs Drive Thrombosis in COVID-19
Authors: Gambardella Jessica , Sardu Celestino , Morelli Marco Bruno , Messina Vincenzo , Castellanos Vanessa , Marfella Raffaele , Maggi Paolo , Paolisso Giuseppe , Wang Xujun , Santulli Gaetano 
Published: June 2020

AbstractThrombotic and thromboembolic complications have been shown to play a critical role in the clinical outcome of COVID-19. Emerging evidence has shown that exosomal miRNAs are functionally involved in a number of physiologic and pathologic processes. However, neither exosomes nor miRNAs have been hitherto investigated in COVID-19. To test the hypothesis that exosomal miRNAs are a key determinant of thrombosis in COVID-19, we enrolled patients positive for COVID-19. Circulating exosomes were isolated from equal amounts of serum and levels of exosomal miRNAs were quantified. We divided our population in two groups based on the serum level of D-dimer on admission. Strikingly, we found that exosomal miR-424 was significantly upregulated whereas exosomal miR-103a, miR-145, and miR-885 were significantly downregulated in patients in the high D-dimer group compared to patients in the low D-Dimer group (p<0.0001).
The effectiveness of interventions to reduce COVID-19 transmission in a large urban jail
Authors: Malloy Giovanni S. P. , Puglisi Lisa , Brandeau Margaret L. , Harvey Tyler D. , Wang Emily A. 
Published: June 2020

ABSTRACTObjectivesTo estimate the impact of various mitigation strategies on COVID-19 transmission in a U.S. jail beyond those offered in national guidelines.MethodsWe developed a stochastic dynamic transmission model of COVID-19 in one large urban U.S. jail among staff and incarcerated individuals. We divided the outbreak into four intervention phases: the start of the outbreak, depopulation of the jail, increased proportion of people in single cells, and asymptomatic testing. We used the next generation method to estimate the basic reproduction ratio, R0, in each phase. We estimated the fraction of new cases, hospitalizations, and deaths averted by these interventions along with the standard measures of sanitization, masking, and social distancing interventions.ResultsFor the first outbreak phase, the estimated R0 was 8.23 (95% CrI: 5.01-12.90), and for the subsequent phases, R0,phase 2 = 3.58 (95% CrI: 2.46-5.08), R0,phase 3 = 1.72 (95% CrI: 1.41-2.12), and R0,phase 4 = 0.45 (95% CrI: 0.32-0.59). In total, the jail’s interventions prevented approximately 83% of projected cases and hospitalizations and 89% of deaths over 83 days.ConclusionsDepopulation, single celling, and asymptomatic testing within jails can be effective strategies to mitigate COVID-19 transmission in addition to standard public health measures.Policy ImplicationsDecision-makers should prioritize reductions in the jail population, single celling, and testing asymptomatic populations, as additional measures to manage COVID-19 within correctional settings.
An evolutionary functional genomics approach identifies novel candidate regions involved in isoniazid resistance inMycobacterium tuberculosis
Authors: Furió Victoria , Moreno-Molina Miguel , Chiner-Oms Álvaro , Villamayor Luis M , Torres-Puente Manuela , Comas Iñaki 
Published: June 2020

AbstractEfforts to eradicate tuberculosis are hampered by the rise and spread of antibiotic resistance. Several large-scale projects have aimed to specifically link clinical mutations to resistance phenotypes, but they were limited in both their explanatory and predictive powers. Here, we combine functional genomics and phylogenetic associations using clinical strain genomes to decipher the architecture of isoniazid resistance and search for new resistance determinants. This approach has allowed us to confirm the main target route of the antibiotic, determine the clinical relevance of redox metabolism as an isoniazid resistance mechanism and identify novel candidate genes harboring resistance mutations in strains with previously unexplained isoniazid resistance. This approach can be useful for characterizing how the tuberculosis bacilli acquire resistance to new antibiotics and how to forestall them.
High-order mutants reveal an essential requirement for peroxidases but not laccases in Casparian strip lignification
Authors: Rojas-Murcia Nelson , Hématy Kian , Lee Yuree , Emonet Aurélia , Ursache Robertas , Fujita Satoshi , De Bellis Damien , Geldner Niko 
Published: June 2020

ABSTRACTThe invention of lignin has been at the heart of plants’ capacity to colonize land, allowing them to grow tall, transport water within their bodies and protect themselves against various stresses. Consequently, this polyphenolic polymer, that impregnates the cellulosic plant cell walls, now represents the second most abundant polymer on Earth, after cellulose itself. Yet, despite its great physiological, ecological and economical importance, our knowledge of lignin biosynthesisin vivo, especially the crucial last steps of polymerization within the cell wall, remains vague. Specifically, the respective roles and importance of the two main polymerizing enzymes classes, laccases and peroxidases have remained obscure. One reason for this lies in the very high numbers of laccases and peroxidases encoded by 17 and 73 homologous genes, respectively, in the Arabidopsis genome. Here, we have focused on a specific lignin structure, the ring-like Casparian strips (CS) within the endodermis of Arabidopsis roots. By reducing the number of possible candidate genes using cellular resolution expression and localization data and by boosting the levels of mutants that can be stacked using CRISPR/Cas9, we were able to knock-out more than half of all laccases in the Arabidopsis genome in a nonuple mutant – abolishing the vast majority of laccases with detectable endodermal-expression. Yet, we were unable to detect even slight defects in CS formation. By contrast, we were able to induce a complete absence of CS formation in a quintuple peroxidase mutant. Our findings are in stark contrast to the strong requirement of xylem vessels for laccase action and indicate that lignin in different cell types can be polymerized in very distinct ways. We speculate that cells lignify differently depending on whether they deposit lignin in a localized or ubiquitous fashion, whether they stay alive during and after lignification as well as the composition of the cell wall.
Pervasive RNA secondary structure in the genomes of SARS-CoV-2 and other coronaviruses – an endeavour to understand its biological purpose
Authors: Simmonds P. 
Published: June 2020

ABSTRACTThe ultimate outcome of the COVID-19 pandemic is unknown and is dependent on a complex interplay of its pathogenicity, transmissibility and population immunity. In the current study, SARS coronavirus 2 (SARS-CoV-2) was investigated for the presence of large scale internal RNA base pairing in its genome. This property, termed genome scale ordered RNA structure (GORS) has been previously associated with host persistence in other positive-strand RNA viruses, potentially through its shielding effect on viral RNA recognition in the cell. Genomes of SARS-CoV-2 were remarkably structured, with minimum folding energy differences (MFEDs) of 15%, substantially greater than previously examined viruses such as HCV (MFED 7-9%). High MFED values were shared with all coronavirus genomes analysed created by several hundred consecutive energetically favoured stem-loops throughout the genome. In contrast to replication-association RNA structure, GORS was poorly conserved in the positions and identities of base pairing with other sarbecoviruses – even similarly positioned stem-loops in SARS-CoV-2 and SARS-CoV rarely shared homologous pairings, indicative of more rapid evolutionary change in RNA structure than in the underlying coding sequences. Sites predicted to be base-paired in SARS-CoV-2 showed substantially less sequence diversity than unpaired sites, suggesting that disruption of RNA structure by mutation imposes a fitness cost on the virus which is potentially restrictive to its longer evolution. Although functionally uncharacterised, GORS in SARS-CoV-2 and other coronaviruses represent important elements in their cellular interactions that may contribute to their persistence and transmissibility.
BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance
Authors: Donoghue Lauren J. , Markovetz Matthew R. , Morrison Cameron B. , McFadden Kathryn M. , Rogers Troy D. , Button Brian , Ehre Camille , Hill David B. , Grubb Barbara R. , Kelada Samir N. P. 
Published: June 2020

ABSTRACTAirway mucociliary clearance (MCC) is required for host defense and often diminished in chronic lung diseases. Effective clearance depends upon coordinated actions of the airway epithelium and a mobile mucus layer. Dysregulation of the primary secreted airway mucin proteins, MUC5B and MUC5AC, is associated with a reduction in the rate of MCC; however, how other secreted proteins impact the integrity of the mucus layer and MCC remains unclear. We previously identified the geneBpifb1/Lplunc1as a regulator of airway MUC5B levels using genetic approaches. Here, we show that BPIFB1 is required for normal mucociliary clearancein vivousingBpifb1knockout (KO) mice. Reduced MCC inBpifb1KO mice occurred in the absence of defects in sodium or chloride ion transport or reduced ciliary beat frequency. BPIFB1 loss resulted in airway mucus flakes with significantly increased complex viscosity, a key biophysical property of mucus known to impact MCC. Finally, we detected colocalization of BPIFB1 and MUC5B in secretory granules in mice and in the protein mesh of secreted mucus in human airway cultures. Collectively, our findings demonstrate that BPIFB1 is an important component of the mucociliary apparatus in mice and a key component of the mucus protein network.
The genetic basis of adaptation in phenology in an introduced population of Black Cottonwood (Populus trichocarpa, Torr. & Gray)
Authors: Apuli Rami-Petteri , Richards Thomas , Rendon Martha , Karacic Almir , Wästljung Ann-Christin Rönnberg , Ingvarsson Pär K. 
Published: June 2020

SummaryEntering and exiting winter dormancy presents important trade-offs between growth and survival at northern latitudes and many forest trees display local adaptation across latitude. Transfers of a species outside its native range introduce the species to novel combinations of environmental conditions potentially requiring different combinations of alleles to optimize growth.We performed genome wide association analyses and a selection scan in aP. trichocarpamapping population derived from crossings between clones collected across the native range and introduced into Sweden. GWAS analyses were performed using phenotypic data collected across two field seasons and in a controlled phytotron experiment.We uncovered 629 putative candidate genes associated with spring and autumn phenology traits as well as with growth. Many regions harboring variation significantly associated with the initiation of leaf shed and leaf autumn coloring appeared to have been evolving under positive selection in the native environments ofP. trichocarpa.A comparison between the candidate genes identified with results from earlier GWAS analyses performed in the native environment found a smaller overlap for spring phenology traits than for autumn phenology traits, aligning well with earlier observations that spring phenology transitions have a more complex genetic basis that autumn phenology transitions.
SMC and the bactofilin/PadC scaffold have distinct yet redundant functions in chromosome segregation and organization inMyxococcus xanthus
Authors: Anand Deepak , Schumacher Dominik , Søgaard-Andersen Lotte 
Published: June 2020

AbstractIn bacteria, ParABSsystems and structural maintenance of chromosome (SMC) condensin-like complexes are important for chromosome segregation and organization. The rod-shapedMyxococcus xanthuscells have a unique chromosome arrangement in which a scaffold composed of three bactofilins (BacNOP) and PadC positions the essential ParB·parSsegregation complexes and the DNA segregation ATPase ParA in the subpolar regions. Here, we identify the Smc and ScpAB subunits of the SMC complex inM. xanthusand demonstrate that SMC is conditionally essential with mutants containingsmcorscpABdeletions being temperature sensitive. Lack of SMC caused defects in chromosome segregation and organization. Lack of the BacNOP/PadC scaffold caused chromosome segregation defects but was not essential. Inactivation of SMC was synthetic lethal with lack of the BacNOP/PadC scaffold. Lack of SMC interfered with formation of the BacNOP/PadC scaffold while lack of this scaffold did not interfere with chromosome association by SMC. Altogether, our data support that three systems cooperate to enable chromosome segregation inM. xanthus, whereby ParABSconstitutes the basic machinery and SMC and the BacNOP/PadC scaffold have distinct yet redundant roles in this process with SMC supporting individualization of daughter chromosomes and BacNOP/PadC making the ParABS system operate more robustly
Inchworm stepping of Myc-Max heterodimer protein diffusion along DNA
Authors: Dai Liqiang , Yu Jin 
Published: June 2020

AbstractOncogenic protein Myc serves as a transcription factor to control cell metabolisms. Myc dimerizes via leucine zipper with its associated partner protein Max to form a heterodimer structure, which then binds target DNA sequences to regulate gene transcription. The regulation depends on by Myc-Max binding to DNA and searching for target sequences via diffusional motions along DNA. Here, we conduct structure-based molecular dynamics (MD) simulations to investigate the diffusion dynamics of the Myc-Max heterodimer along DNA. We found that the heterodimer protein slides on the DNA in a rotation-uncoupled manner in coarse-grained simulations, as its two helical DNA binding basic regions (BRs) alternate between open and closed conformations via inchworm stepping motions. In such motions, the two BRs of the heterodimer step across the DNA strand one by one, with step sizes up about half of a DNA helical pitch length. Atomic MD simulations of the Myc-Max heterodimer in complex with DNA have also been conducted. Hydrogen bond interactions reveal between the two BRs and two complementary DNA strands, respectively. In the non-specific DNA binding, the BR shows an onset of stepping on one association DNA strand and dissociating from the complementary strand. Overall, our simulation studies suggest that the inchworm stepping motions of the Myc-Max heterodimer can be achieved during the protein diffusion along DNA.
Adaptive mechanoproperties characterize glioblastoma fitness for invasion
Authors: Monzo Pascale , Crestani Michele , Chong Yuk Kien , Hennig Katharina , Ghisleni Andrea , Li Qingsen , Richichi Cristina , Maiuri Paolo , Balland Martial , Sheetz Michael P. , Pelicci Giuliana , Ang Beng Ti , Tang Carol , Gauthier Nils C. 
Published: June 2020

AbstractGlioblastoma are heterogeneous tumors composed of highly invasive and highly proliferative clones. Heterogeneity in invasiveness could emerge from discrete biophysical properties linked to specific molecular expression. We identified clones of patient-derived glioma propagating cells that were either highly proliferative or highly invasive and compared their cellular architecture, migratory and biophysical properties. We discovered that invasiveness was linked to cellular fitness. The most invasive cells were stiffer, developed higher mechanical forces on the substrate and moved stochastically. The mechanochemical-induced expression of the formin FMN1 conferred invasive strength that was confirmed in patient samples. Moreover, FMN1 ectopic expression in less invasive clones increased fitness parameters. Mechanistically, FMN1 acts from the microtubule lattice, counteracting microtubule bundling and promoting a robust cell-body cohesion leading to highly invasive hurdling motility.One Sentence SummaryFMN1 increases cell mechanics and invasiveness.
Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV
Authors: Stukalov Alexey , Girault Virginie , Grass Vincent , Karayel Ozge , Bergant Valter , Urban Christian , Haas Darya A. , Huang Yiqi , Oubraham Lila , Wang Anqi , Hamad M. Sabri , Piras Antonio , Hansen Fynn M. , Tanzer Maria C. , Paron Igor , Zinzula Luca , Enghleitner Thomas , Reinecke Maria , Lavacca Teresa M. , Ehmann Rosina , Wölfel Roman , Jores Jörg , Kuster Bernhard , Protzer Ulrike , Rad Roland , Ziebuhr John , Thiel Volker , Scaturro Pietro , Mann Matthias , Pichlmair Andreas 
Published: June 2020

SummaryThe global emergence of SARS-CoV-2 urgently requires an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1–10. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. We therefore conducted a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactome of both viruses, as well as their influence on transcriptome, proteome, ubiquitinome and phosphoproteome in a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon SARS-CoV-2 and SARS-CoV infections at different layers and identified unique and common molecular mechanisms of these closely related coronaviruses. The TGF-β pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy by SARS-CoV-2 ORF3. The extensive dataset (available athttps://covinet.innatelab.org) highlights many hotspots that can be targeted by existing drugs and it can guide rational design of virus- and host-directed therapies, which we exemplify by identifying kinase and MMPs inhibitors with potent antiviral effects against SARS-CoV-2.
Is YouTube® promoting the exotic pet trade? Analysis of the global public perception of popular YouTube® videos featuring threatened exotic animals
Authors: Moloney Georgia , Tuke Jonathan , Dal Grande Eleonora , Nielsen Torben , Chaber Anne-Lise 
Published: June 2020

AbstractThe exploitation of threatened exotic species via social media challenges efforts to regulate the exotic pet trade and consequently threatens species conservation. To investigate how such content is perceived by the global community, sentiment analysis techniques were employed to explore variations in attitudes expressed through text and emoji usage in public comments associated with 346 popular YouTube® videos starring exotic wild cats or primates in captive or domestic situations. Although a negative trend in mean text sentiment was observed in 2015 for primates, an otherwise consistent positive mean sentiment text and emoji score through time was revealed in response to both exotic wild cat and primate videos, implying the societal normalisation and acceptance of exotic pets. These findings highlight the urgency for effective YouTube® policy changes and content management to promote public education and conservation awareness, whilst extinguishing false legitimisation and potential demand for the exotic pet trade.