bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resting-State Network Analysis of Suicide Attempt History in the UK Biobank
Authors: Thompson Matthew F. , Ghahramanlou-Holloway Marjan , Murphy Mikela A. , Perera Kanchana U. , Benca-Bachman Chelsie , Palmer Rohan H. C. , Gray Joshua C. 
Published: January 2022

AbstractBackgroundPrior research has identified altered brain structure and function in individuals at risk for self-directed violence thoughts and behaviors. However, these studies have largely utilized healthy controls and findings have been inconsistent. Thus, this study examined differences in resting-state functional network connectivity among individuals with lifetime suicide attempt(s) versus lifetime self-directed violence thoughts alone.MethodsUsing data from the UK Biobank, this study utilized a series of linear regressions to compare individuals with lifetime suicide attempt(s) (n= 566) versus lifetime self-directed violence thoughts alone (n= 3,447) on within- and between-network resting-state functional connectivity subnetworks.ResultsThere were no significant between-group differences for between-network, within-network, or whole-brain functional connectivity after adjusting for age, sex, ethnicity, and body mass index and performing statistical corrections for multiple comparisons.ConclusionsResting-state network measures may not differentiate between individuals with lifetime suicide attempt(s) and lifetime self-directed violence thoughts alone. Null findings diverge from results reported in smaller neuroimaging studies of suicide risk, but are consistent with null findings in other large-scale studies and meta-analyses. Strengths of the study include its large sample size and stringent control group. Future research on a wider array of imaging, genetic, and psychosocial risk factors can clarify relative contributions of individual and combined variables to suicide risk and inform scientific understanding of ideation-to-action framework.
Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in In Vitro, In Vivo and Ex Vivo Models of Pulmonary Fibrosis
Authors: Ahangari Farida , Becker Christine , Foster Daniel G. , Chioccioli Maurizio , Nelson Meghan , Beke Keriann , Wang Xing , Readhead Benjamin , Meador Carly , Correll Kelly , Lili Loukia , Roybal Helen M. , Rose Kadi-Ann , Ding Shuizi , Barnthaler Thomas , Briones Natalie , Deluliis Giuseppe , Schupp Jonas C. , Li Qin , Omote Norihito , Aschner Yael , Kopf Katrina W. , Magnusson Björn , Hicks Ryan , Backmark Anna , Cousens Leslie P. , Dudley Joel T. , Kaminski Naftali , Downey Gregory P. 
Published: January 2022

AbstractIdiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Two FDA approved anti-fibrotic drugs, nintedanib and pirfenidone, slow the rate of decline in lung function, but responses are variable and side effects are common. Using an in-silico data-driven approach, we identified a robust connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor, originally developed for oncological indications. Based on these observations, we hypothesized that saracatinib would be effective at attenuating pulmonary fibrosis. We investigated the anti-fibrotic efficacy of saracatinib relative to nintedanib and pirfenidone in three preclinical models: (i) in vitro in normal human lung fibroblasts (NHLFs); (ii) in vivo in bleomycin and recombinant adenovirus transforming growth factor-beta (Ad-TGF-β) murine models of pulmonary fibrosis; and (iii) ex vivo in precision cut lung slices from these mouse models. In each model, the effectiveness of saracatinib in blocking fibrogenic responses was equal or superior to nintedanib and pirfenidone.
Recurrent co-option and recombination of cytokine and three finger proteins in multiple reproductive tissues throughout salamander evolution
Authors: Wilburn Damien B. , Kunkel Christy L. , Feldhoff Richard C. , Feldhoff Pamela W. , Searle Brian C. 
Published: January 2022

AbstractThe proteomic composition of amphibian gametes is largely a molecular mystery, particularly for Urodeles (salamanders and newts) which have few genomic-scale resources. Lungless salamanders (family Plethodontidae) include approximately two thirds of all extant salamander species and are classic models of vertebrate mating behavior. As part of an extended, multi-stage courtship ritual, male plethodontid salamanders deliver rapidly evolving protein pheromones that modify female behavior and improve male reproductive success. Despite great interest in this set of pre-mating reproductive barriers, limited characterization of plethodontid gametes has prohibited investigation of post-mating pre-zygotic barriers such as sperm-egg recognition. In this study, we performed transcriptomic analyses of testis and ovary using long-read PacBio sequencing and proteomic analyses of sperm using mass spectrometry for two evolutionary divergent plethodontid species, Plethodon shermani and Desmognathus ocoee. In both species, many of the most abundant sperm proteins were paralogs of the courtship pheromones Plethodontid Receptivity Factor (PRF), Plethodontid Modulating Factor (PMF), and Sodefrin Precursor-like Factor (SPF). Sperm-specific paralogs of PMF and SPF are likely the most abundant secreted proteins in P. shermani and D. ocoee, respectively. In contrast, sperm PRF lacks a signal peptide and may be expressed in cytoplasm. PRF pheromone genes evolved independently multiple times through repeated gene duplication of sperm PRF genes and signal peptides recovered by recombination with PMF genes. Phylogenetic analysis of courtship pheromones and their sperm paralogs support that each protein family evolved for these two reproductive contexts at distinct evolutionary time points between 17 and 360 million years ago. As the first molecular characterization of salamander gametes, this study expands our knowledge of amphibian fertilization beyond frogs and provides novel insight into the evolutionary processes by which new, rapidly evolving reproductive proteins may evolve.
Towards transboundary networks of climate-smart marine reserves in the Southern California Bight
Authors: Arafeh-Dalmau Nur , Munguia-Vega Adrian , Micheli Fiorenza , Vilalta-Navas Ainoa , Villasenor-Derbez Juan Carlos , Précoma-de la Mora Magdalena , Schoeman David S. , Medellín-Ortíz Alfonso , Cavanaugh Kyle C. , Sosa-Nishizaki Oscar , Burnham Theresa L.U. , Knight Christopher J. , Woodson C. Brock , Abas Marina , Abadía-Cardoso Alicia , Aburto-Oropeza Octavio , Esgro Michael W. , Espinosa-Andrade Noemi , Beas-Luna Rodrigo , Cardenas Nirari , Carr Mark H. , Dale Katherine E. , Cisneros-Soberanis Frida , Flores-Morales Ana Laura , Fulton Stuart , García-Rodríguez Emiliano , Giron-Nava Alfredo , Gleason Mary G. , Green Alison L. , Hernández-Velasco Arturo , Ibarra-Macías Beatriz , Johnson Andrew F. , Lorda Julio , Malpica-Cruz Luis , Montaño-Moctezuma Gabriela , Olguín-Jacobson Carolina , Parés-Sierra Alejandro , Raimondi Peter T. , Ramírez-Ortiz Georgina , Ramirez-Valdez Arturo , Reyes-Bonilla Héctor , Saarman Emily , Saldaña-Ruiz Luz Erandi , Smith Alexandra , Soldatini Cecilia , Suárez Alvin , Torres-Moye Guillermo , Walther Mariana , Watson Elizabeth Burke , Worden Sara , Possingham Hugh P. 
Published: January 2022

AbstractClimate-smart conservation addresses the vulnerability of biodiversity to climate change impacts but may require transboundary considerations. Here, we adapt and refine 16 biophysical guidelines for climate-smart marine reserves for the transboundary California Bight ecoregion. We link several climate-adaptation strategies (e.g., maintaining connectivity, representing climate refugia, and forecasting effectiveness of protection) by focusing on kelp forests and associated species. We quantify transboundary larval connectivity along ∼800 km of coast and find that the number of connections and the average density of larvae dispersing through the network under future climate scenarios could decrease by ∼50%, highlighting the need to protect critical steppingstone nodes. We also find that although focal species will generally recover with 30% protection, marine heatwaves could hinder subsequent recovery in the following 50 years, suggesting that protecting climate refugia and expanding the coverage of marine reserves is a priority. Together, these findings provide a first comprehensive framework for integrating climate resilience for networks of marine reserves and highlight the need for a coordinated approach in the California Bight ecoregion.
Herpes simplex virus 1 expressing GFP-tagged virion host shutoff (vhs) protein uncouples the activities of degradation and nuclear retention of the infected cell transcriptome
Authors: Wise Emma L , Samolej Jerzy , Elliott Gillian 
Published: January 2022

SummaryVirion host shutoff (vhs) protein is an endoribonuclease encoded by herpes simplex virus 1 (HSV1). Vhs causes a number of changes to the infected cell environment that favour translation of late (L) virus proteins: cellular mRNAs are degraded, immediate-early (IE) and early (E) viral transcripts are sequestered in the nucleus with polyA binding protein (PABPC1), and dsRNA is degraded to help dampen the PKR-dependent stress response. To further our understanding of the cell biology of vhs, we constructed a virus expressing vhs tagged at its C-terminus with GFP. When first expressed, vhs-GFP localised to juxtanuclear clusters, and later it colocalised and interacted with its binding partner VP16, and was packaged into virions. Despite vhs-GFP maintaining activity when expressed in isolation, it failed to degrade mRNA or relocalise PABPC1 during infection, while viral transcript levels were similar to those seen for a vhs knockout virus. PKR phosphorylation was also enhanced in vhs-GFP infected cells, in line with a failure to degrade dsRNA. Nonetheless, mRNA FISH revealed that as in Wt but not Δvhs infection, IE and E, but not L transcripts were retained in the nucleus of vhs-GFP infected cells at late times. Moreover, a representative cellular transcript which is ordinarily highly susceptible to vhs degradation, was also retained in the nucleus. These results reveal that the vhs-induced nuclear retention of the infected cell transcriptome is dependent on vhs expression but not on its endoribonuclease activity, uncoupling these two functions of vhs.ImportanceLike many viruses, herpes simplex virus 1 (HSV1) expresses an endoribonuclease, the virion host shutoff (vhs) protein, which regulates the RNA environment of the infected cell and facilitates the classical cascade of virus protein translation. It does this by causing the degradation of some mRNA molecules and the nuclear retention of others. Here we describe a virus expressing vhs tagged at its C-terminus with green fluorescent protein (GFP) and show that the vhs-GFP fusion protein retains the physical properties of native vhs, but does not induce the degradation of mRNA. Nonetheless, vhs-GFP maintains the ability to trap the infected cell transcriptome in the nucleus, proving for the first time that mRNA degradation is not a prerequisite for vhs effects on the nuclear transcriptome. This virus has therefore uncoupled the nuclear retention and degradation activities of vhs, providing new understanding of vhs during infection.
Lineage replacement and evolution captured by three years of the United Kingdom Covid Infection Survey
Authors: Lythgoe Katrina , Golubchik Tanya , Hall Matthew , House Thomas , Cahuantzi Roberto , MacIntyre-Cockett George , Fryer Helen , Thomson Laura , Nurtay Anel , Ghafani Mahan , Buck David , Green Angie , Trebes Amy , Piazza Paolo , Lonie Lorne J , Studley Ruth , Rourke Emma , Smith Darren , Bashton Matthew , Nelson Andrew , Crown Matthew , McCann Clare , Young Gregory R , Santos Rui Andre Nunes dos , Richards Zack , Tariq Adnan ,   Wellcome Sanger Institute COVID-19 Surveillance Team,   COVID-19 Infection Survey Group,   The COVID-19 Genomics UK (COG-UK) Consortium, Fraser Christophe , Diamond Ian , Barrett Jeff , Walker Ann Sarah , Bonsall David 
Published: January 2022

AbstractThe Office for National Statistics COVID-19 Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non- SGTF over time. Evolution was characterised by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens, particularly in the current phase of the pandemic with routine RT-PCR testing now ended in the community.
Durability of protection post-primary COVID-19 vaccination in the US: matched case-control study
Authors: Zheutlin Amanda , Ott Miles , Sun Ran , Zemlianskaia Natalia , Rubel Meagan , Hayden Jennifer , Neri Breno , Kamath Tripthi , Khan Najat , Schneeweiss Sebastian , Sarsour Khaled 
Published: January 2022

AbstractBackgroundIntrinsic durability of immune responses elicited by COVID-19 vaccines will drive vaccine effectiveness long-term across settings and may differ by vaccine type. We aimed here to determine durability of protection of three COVID-19 vaccines BNT162b2, mRNA-1273 and Ad26.COV2.S following primary vaccination against breakthrough infections, hospitalisations, and intensive care unit (ICU) admissions in the United States (US).MethodsUsing national claims and laboratory data covering 168 million lives, we conducted a matched case-control study with fully vaccinated individuals between January 1 and September 7, 2021. Odds ratios (OR) for developing outcomes in months two through six following primary vaccination were estimated relative to the first month after primary vaccination for each vaccine separately. Results compare each vaccine to itself and are not directly comparative. Odds ratios were translated into vaccine effectiveness (VE) using assumptions about event rates in an unvaccinated cohort.FindingsRelative to its baseline, stable protection was observed for the single-shot Ad26.COV2.S against infections and severe disease. Relative to their baseline protection waned overtime against infections for BNT162b2 and mRNA-1273 and against hospitalisations for BNT162b2. No waning of baseline protection was observed at any time for ICU admissions for all three vaccines. Calculated baseline VE was consistent with the published literature.InterpretationWhile the starting protection level provided by the primary series may differ by vaccine type and mechanism of action, this study demonstrated by comparing each vaccine to its own baseline protection that the three vaccines in three separate populations may have different durability profiles. Further investigation is required to fully characterize the durability profile of the three vaccines. Moreover, as the COVID-19 pandemic continues, and as more countries and populations implement a standard of care consisting of three doses of the mRNA vaccines or two doses of Ad26.COV2.S, further investigation is critical to understand the level of protection and the durability of response over longer periods, novel variants and in response to homologous and heterologous boosting.
Protection afforded by prior infection against SARS-CoV-2 reinfection with the Omicron variant
Authors: Altarawneh Heba , Chemaitelly Hiam , Tang Patrick , Hasan Mohammad R. , Qassim Suelen , Ayoub Houssein H. , AlMukdad Sawsan , Yassine Hadi M. , Benslimane Fatiha M. , Khatib Hebah A. Al , Coyle Peter , Kanaani Zaina Al , Kuwari Einas Al , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul Rahim Hanan F. , Nasrallah Gheyath K. , Al Kuwari Mohamed Ghaith , Butt Adeel A. , Al Romaihi Hamad Eid , Al-Thani Mohamed H. , Khal Abdullatif Al , Bertollini Roberto , Abu-Raddad Laith J. 
Published: January 2022

AbstractBACKGROUNDNatural SARS-CoV-2 infection elicits strong protection against reinfection with the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants. However, the Omicron (B.1.1.529) variant harbors multiple mutations that can mediate immune evasion. We estimated effectiveness of prior infection in preventing reinfection (PES) with Omicron and other SARS-CoV-2 variants in Qatar.METHODSPES was estimated using the test-negative, case-control study design, employing a methodology that was recently investigated and validated for derivation of robust estimates for PES. Cases (PCR-positive persons with a variant infection) and controls (PCR-negative persons) were exact-matched by sex, 10-year age group, nationality, and calendar time of PCR test, to control for known differences in the risk of exposure to SARS-CoV-2 infection in Qatar.RESULTSPES against symptomatic reinfection was estimated at 90.2% (95% CI: 60.2-97.6) for Alpha, 84.8% (95% CI: 74.5-91.0) for Beta, 92.0% (95% CI: 87.9-94.7) for Delta, and 56.0% (95% CI: 50.6-60.9) for Omicron. Only 1 Alpha, 2 Beta, 0 Delta, and 2 Omicron reinfections progressed to severe COVID-19. None progressed to critical or fatal COVID-19. PES against hospitalization or death due to reinfection was estimated at 69.4% (95% CI: −143.6-96.2) for Alpha, 88.0% (95% CI: 50.7-97.1) for Beta, 100% (95% CI: 43.3-99.8) for Delta, and 87.8% (95% CI: 47.5-97.1) for Omicron.CONCLUSIONSProtection afforded by prior infection in preventing symptomatic reinfection with Alpha, Beta, or Delta is robust, at about 90%. While such protection against reinfection with Omicron is lower, it is still considerable at nearly 60%. Prior-infection protection against hospitalization or death at reinfection appears robust, regardless of variant.
Association between vaccination status and reported incidence of post-acute COVID-19 symptoms in Israel: a cross-sectional study of patients tested between March 2020 and November 2021
Authors: Kuodi Paul , Gorelik Yanay , Zayyad Hiba , Wertheim Ofir , Wiegler Karine Beiruti , Jabal Kamal Abu , Dror Amiel A. , Nazzal Saleh , Glikman Daniel , Edelstein Michael 
Published: January 2022

AbstractBackgroundLong COVID is a post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection syndrome characterised by not recovering for several weeks or months following the acute episode. The effectiveness of COVID-19 vaccines against long-term symptoms of COVID-19 is not well understood. We determined whether vaccination was associated with the incidence of reporting long-term symptoms post-SARS-CoV-2 infectionMethodsWe invited individuals who were PCR tested for SARS-CoV-2 infection at participating hospitals between March 2020-November 2021 to fill an online questionnaire that included baseline demographics, details of their acute episode and information about symptoms they were currently experiencing. Using binomial regression, we compared vaccinated individuals with those unvaccinated and those uninfected in terms of self-reported symptoms post-acute infection.ResultsWe included 951 infected and 2437 uninfected individuals. Of the infected, 637(67%) were vaccinated. The most commonly reported symptoms were; fatigue (22%), headache (20%), weakness (13%), and persistent muscle pain (10%). After adjusting for follow-up time and baseline symptoms, those who received two doses less likely than unvaccinated individuals to report any of these symptoms by 64%, 54%, 57%, and 68% respectively, (Risk ratios 0.36, 0.46, 0.43, 0.32, p<0.04 in the listed sequence). Those who received two doses were no more likely to report any of these symptoms than individuals reporting no previous SARS-CoV-2 infection.ConclusionsVaccination with at least two doses of COVID-19 vaccine was associated with a substantial decrease in reporting the most common post-acute COVID-19 symptoms, bringing it back to baseline. Our results suggest that, in addition to reducing the risk of acute illness, COVID-19 vaccination may have a protective effect against long COVID.
In vitrocharacterization of the full-length human dynein-1 cargo adaptor BicD2
Authors: Fagiewicz Robert , Crucifix Corinne , Klos Torben , Deville Célia , Kieffer Bruno , Nominé Yves , Busselez Johan , Rossolillo Paola , Schmidt Helgo 
Published: January 2022

SUMMARYCargo adaptors are crucial in coupling motor proteins with their respective cargos and regulatory proteins. BicD2 is a prominent example within the cargo adaptor family. BicD2 is able to recruit the microtubule motor dynein to RNA, viral particles and nuclei. The BicD2-mediated interaction between the nucleus and dynein is implicated in mitosis, interkinetic nuclear migration (INM) in radial glial progenitor cells, and neuron precursor migration during embryonic neocortex development.In vitrostudies involving full-length cargo adaptors are difficult to perform due to the hydrophobic character, low-expression levels, and intrinsic flexibility of cargo adaptors. Here we report the recombinant production of full-length human BicD2 and confirm its biochemical activity by interaction studies with RanBP2. We also describe pH-dependent conformational changes of BicD2 using cryoEM, template-free structure predictions, and biophysical tools. Our results will help define the biochemical parameters for thein vitroreconstitution of higher order BicD2 protein complexes.