bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perinatal Oxycodone Exposure Causes Long Term Sex-Dependent Changes in Sensory and Reward Processing in Adult Mice
Authors: Minakova Elena , Mikati Marwa O. , Madasu Manish K. , Conway Sineadh M. , Baldwin Justin W. , Swift Raylynn G. , McCullough Katherine B. , Dougherty Joseph D. , Maloney Susan E. , Al-Hasani Ream 
Published: February 2022

ABSTRACTIn utero opioid exposure is associated with lower weight and a Neonatal Opioid Withdrawal Syndrome (NOWS) at birth, along with longer-term adverse neurodevelopmental outcomes and mood disorders. While NOWS is sometimes treated with continued opioids, clinical studies have not addressed if long-term neurobehavioral outcomes are worsened with continued postnatal exposure to opioids. In addition, pre-clinical studies comparing in utero only opioid exposure to continued post-natal opioid administration for withdrawal mitigation are lacking. Therefore, we implemented a rodent perinatal opioid exposure model of Oxycodone (Oxy) exposure for comparison of long-term consequences of Oxy exposure until birth (Short Oxy) to the impact of continued postnatal opioid exposure (Long Oxy) spanning gestation through birth and lactation. Short Oxy exposure was associated with a sex-specific increase in weight gain trajectory in adult male mice. Long Oxy exposure caused an increased weight gain trajectory in adult males, sex-dependent changes in morphine conditioned place preference, and alterations in nociceptive processing in females. Importantly, there was no evidence of long-term social behavioral deficits, anxiety, hyperactivity, or memory deficits following Short or Long Oxy exposure. Our findings suggest that offspring with prolonged opioid exposure experienced some long-term sequelae compared to pups with opioid cessation at birth. These results highlight the potential long-term consequences of opioid administration as a mitigation strategy for clinical NOWS symptomology and suggest alternatives should be explored.
A possible way to relate the effects of SARS-CoV-2 induced changes in transferrin to severe COVID-19 associated diseases
Authors: Telek Elek , Ujfalusi Zoltán , Kemenesi Gábor , Zana Brigitta , Jakab Ferenc , Lukács András , Hild Gábor 
Published: February 2022

AbstractThe potentially life-threatening Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is responsible for the coronavirus pandemic in 2019 (COVID-19). The transferrin as an essential component of iron-metabolism was suggested to be a link between iron transport associated diseases and COVID-19 infection.The effect of SARS-CoV-2 on human whole blood was studied by differential scanning calorimetry. The analysis and deconvolution of the thermal transition curves showed that the Tm of transferrin related second peak decreased by 5.16 °C (6.4%) in the presence of SARS-CoV-2 virus. The ratio of the under-curve area of the two main peaks was greatly affected while the total enthalpy of the heat denaturation was nearly unchanged in the presence of the virus.Based on the results it is possible to conclude that SARS-CoV-2 through binding to transferrin can influence it’s Fe3+ uptake by inducing thermodynamic changes. Transferrin may stay in iron-free apo-conformational state, which probably depends on the SARS-CoV-2 concentration.SARS-CoV-2 might induce disturbance in the erythropoiesis due to the free iron overload generated iron toxicity. As a late consequence iron toxicity related hepatocellular carcinoma can even develop.Our work can support the basic role of transferrin in COVID-19 related severe diseases.
Comparative sub-cellular proteome analyses reveals metabolic differentiation and production of effector-like molecules in the dieback phytopathogen Phytophthora cinnamomi
Authors: Andronis Christina E. , Jacques Silke , Lipscombe Richard , Tan Kar-Chun 
Published: February 2022

AbstractPhytopathogenic oomycetes pose a significant threat to global biodiversity and food security. The proteomes of these oomycetes likely contain important factors that contribute to their pathogenic success, making their discovery crucial for elucidating pathogenicity. Oomycetes secrete effector proteins that overcome or elicit a defence response in susceptible hosts. Phytophthora cinnamomi is a root pathogen that causes dieback in a wide variety of crops and a range of native vegetation world-wide. Virulence proteins produced by P. cinnamomi are not well defined and a large-scale approach to understand the biochemistry of this pathogen has not been documented. Here, soluble mycelial, zoospore and secreted proteomes were obtained and label-free quantitative proteomics was used to compare the composition of protein content of the three sub-proteomes by matching the MS/MS data to a sequenced P. cinnamomi genome. Mass spectra matched to a total of 4635 proteins, validating 17.7% of the predicted gene set of the P. cinnamomi genome. The mycelia were abundant in transporters for nutrient acquisition, metabolism and cellular proliferation. The zoospores had less metabolic related ontologies than the mycelia but were abundant in energy generating, motility and signalling associated proteins. Virulence-associated proteins were identified in the secretome such as candidate effector and effector-like proteins, which interfere with the host immune system. These include hydrolases, cell wall degrading enzymes, putative necrosis-inducing proteins and elicitins. The secretome elicited a hypersensitive response on the roots of a model host and thus suggests evidence of effector activity.SignificancePhytophthora cinnamomi is a phytopathogenic oomycete that causes dieback disease in native vegetation and several horticultural crops such as avocado, pineapple and macadamia. Whilst this pathogen has significance world-wide, its pathogenicity and virulence have not been described in depth. We carried out comparative label-free proteomics of the mycelia, zoospores and secretome of P. cinnamomi. This study highlights the differential metabolism and cellular processes between the sub-proteomes. Proteins associated with metabolism, nutrient transport and cellular proliferation were over represented in the mycelia. The zoospores have a specialised proteome showing increased energy generation geared towards motility. Candidate effectors and effector-like secreted proteins were also identified, which can be exploited for genetic resistance. This demonstrates a better understanding of the biology and pathogenicity of P. cinnamomi infection that can subsequently be used to develop effective methods of disease management
Discovery of Novel Trans-Ancestry and Ancestry-Specific Gene Loci for Total Testosterone in a Multi-Ancestral Analysis of Men in the Million Veteran Program
Authors: Pagadala Meghana S. , Jasuja Guneet K. , Palnati Madhuri , Lynch Julie , Anglin Tori , Chang Nelson , Deka Rishi , Lee Kyung Min , Agiri Fatai Y. , Seibert Tyler M. , Rose Brent S. , Carter Hannah , Panizzon Matthew S. , Hauger Richard L. 
Published: February 2022

AbstractUtilizing data from the Million Veteran Program (MVP), we investigated the genetic determinants underlying total testosterone levels via a multi-ancestral analysis of 124,593 individuals of European (n=88,385), African (n=25,235) and Hispanic (n=10,973) ancestry. We identified 46 trans-ancestry variants and 17 ancestry-specific variants, of which 14 trans-ancestry variants and 15 ancestry-specific variants are novel associations with testosterone. Results implicate genes regulating testosterone shared across ancestral groups, which include SHBG, JMJD1C, FXR2, SENP3, TNFSF12-TNFSF13 while implicating genes such as MSN, DMD, VSIG4, CHEK2, TKTL1 that may underlie ancestry-group differences in testosterone regulation. We also linked testosterone variants on the X chromosome with differential risk of chronic kidney disease and hereditary hemolytic anemias in African and Hispanic ancestry groups, respectively. Lastly, we constructed a polygenic score from our 46 trans-ancestry variants and associated it with testicular dysfunction, hyperlipidemia, gout and prostate cancer with stronger prostate cancer associations in Hispanic and African ancestry groups compared to the European ancestry group. These findings provide insight into ancestry-specific androgen regulation and identify novel variants for disease risk stratification in patients.
The public health impact of poor sleep on severe COVID-19, influenza and upper respiratory infections
Authors: Jones Samuel E. , Maisha Fahrisa I. , Strausz Satu J. , Cade Brian E. , Tervi Anniina M. , Helaakoski Viola , Broberg Martin E. , Lammi Vilma ,   FinnGen, Lane Jacqueline M. , Redline Susan , Saxena Richa , Ollila Hanna M. 
Published: February 2022

AbstractBackgroundPoor sleep is associated with an increased risk of infections and all-cause mortality, and acute sleep loss and disruption have been linked with inflammation and poorer immune control. Previous studies, however, have been unable to evidence causality between the chronic effects of poor sleep and respiratory infection risk. In light of the ongoing COVID-19 pandemic and potential future disease outbreaks, understanding the risk factors for these infections is of great importance.AimOur goal was to understand if chronic poor sleep could be identified as a causal risk factor for respiratory infections including influenza, upper respiratory infections and COVID-19.MethodsWe used population cohorts from the UK Biobank (N ≈ 231,000) and FinnGen (N ≈ 327,000) with ICD-10 based electronic health records and obtained diagnoses of insomnia, influenza and upper respiratory infections (URIs) from primary care and hospital settings. We computed logistic regression to assess association between poor sleep and infections, disease free survival hazard ratios, and used summary statistics from genome-wide association studies of insomnia, influenza, URI and COVID-19 to perform Mendelian randomization analyses and assess causality.FindingsUtilizing 23 years of registry data and follow-up, we saw that insomnia diagnosis associated with increased risk for infections in FinnGen and in UK Biobank (FinnGen influenza HR = 5.32 [4.09, 6.92], P = 1.02×10−35, UK Biobank influenza HR = 1.54 [1.37, 1.73], P = 2.49×10−13). Mendelian randomization indicated that insomnia causally predisposed to influenza (OR = 1.59, P = 6.23×10−4), upper respiratory infections (OR = 1.71, P = 7.60×10−13), COVID-19 infection (OR = 1.08, P = 0.037) and risk of hospitalization from COVID-19 (OR = 1.47, P = 4.96×10−5).ConclusionsOur findings indicate that chronic poor sleep is a causal risk factor for contracting respiratory infections, and in addition contributes to the severity of respiratory infections. These findings highlight the role of sleep in maintaining sufficient immune response against pathogens as suggested by earlier work. As the current COVID-19 pandemic has increased the number of people suffering from poor sleep, safe interventions such as sleep management and treating individuals with insomnia could be promoted to reduce infections and save lives.
Association between sexual and reproductive health knowledge and protective sexual behaviors among young women in Nigeria
Authors: Okunola David Aduragbemi , Alawode Oluwatobi Abel , Ajayi Anthony Idowu 
Published: February 2022

AbstractBackgroundWhile the literature is replete with studies on young people’s risky sexual behaviors and their effects on HIV and STI acquisition, unintended pregnancy, and unsafe abortion, few studies have explored the practice of protective sexual behaviors and its association with sexual and reproductive health knowledge. We examined the association between sexual and reproductive health knowledge and protective sexual behaviors using data of young women in Nigeria.MethodsData of 8,995 young women (aged 15-24) who were neither married nor living with a partner were obtained from the 2018 Nigeria Demographic and Health Survey (NDHS) and analyzed in this study. Protective sexual behaviors were measured using questions exploring sexual fidelity, condom use, having multiple partners, and abstinence, while sexual and reproductive health knowledge was measured with questions on fertility, fecundity, contraceptives, and HIV prevention. We fitted multinomial logistic regression to examine the association between sexual and reproductive health knowledge and protective sexual behaviors.ResultsThe median score on sexual and reproductive health knowledge was five. The majority of the sample (71.5%) had no sexual experience, 6.6% abstained from sex in the past year, 7.2% used condoms and practiced sexual fidelity, 1.0% used condoms but did not practice sexual fidelity, 12.7% did not practice sexual fidelity but used condoms while 0.8% neither used condom nor practiced sexual fidelity. After controlling for important covariates, sexual and reproductive health knowledge was positively associated with “condom use and sexual fidelity” (uRRR = 1.28; CI = 1.04-1.60) relative to “not using condoms nor practicing sexual fidelity.” However, the association between sexual and reproductive health knowledge and other categories of protective sexual behaviors, such as no sexual experience, abstinence in the past year, and sexual fidelity but no condom use, did not reach a significant level.ConclusionWe found a high prevalence of protective sexual behavior among young women in Nigeria. Our study provides evidence in support of the association between sexual and reproductive health knowledge and a higher likelihood of practicing protective sexual behaviors. Intervention efforts can focus on providing sexual and reproductive health education to young people to equip them with information to safeguard their sexual health.
A novel SEIR-e model for disease transmission and pathogen exposure
Authors: Tambyah Tamara A. , Testolin Matthew J. , Hill Alexander M. 
Published: February 2022

AbstractIn this study, we couple compartment models for indoor air quality and disease transmission to develop a novel SEIR-e model for disease transmission and pathogen exposure. In doing so, we gain insight into the contribution of people–people and people–pathogen interactions to the spread of transmissible diseases. A general modelling framework is used to assess the risk of infection in indoor environments due to people–pathogen interactions via inhalation of viral airborne aerosols, and contact with contaminated surfaces. We couple the indoor environment model with a standard disease transmission model to investigate how both people–people and people–pathogen interactions result in disease transmission. The coupled model is referred to as the SEIR-e model. To demonstrate the applicability of the SEIR-e model and the novel insights it can provide into different exposure pathways, parameter values which describe exposure due to people–people and people–pathogen interactions are inferred using Bayesian techniques and case data relating to the 2020 outbreak of COVID-19 in Victoria (Australia).
Analytical Sensitivity of the SalivaDirect™ Assay on the Liberty16 for detecting SARS-CoV-2 B.1.1.529 (“Omicron”)
Authors: Tan Yen Pei , Al-Halbouni Mila , Chen Ching-Huan , Hirst David B. , Pickering Paul J. 
Published: February 2022

AbstractThe newly emerged Omicron variant of SARS-CoV-2 has numerous mutations that are not found in other variants of concern (VOCs). Despite acquiring extended functions in adapting to the host-cell environment, the viral genetic variation exerts a potential negative impact on a molecular test, which in turn, compromises public health and safety. The Liberty16 has been clinically validated as a flexible and accessible device system for running the affordable SalivaDirect™ real time PCR detection assay for SARS-CoV-2 especially in low resource settings. Preliminary, based on in-silico sequence analysis, we found that Omicron’s mutation at position 28,311 overlaps with the CDC 2019-nCoV_N1 probe binding region. In order to verify the performance of CDC 2019-nCoV-N1 primers-probe set in detecting the Omicron variant of SARS-CoV-2, plasmids containing Wuhan/WH01/2019 (wild-type) and B.1.1.529 (Omicron) sequences were serially diluted and subsequently directed for SalivaDirect™ RT-qPCR detection on Liberty16 using commercially procured reagents. Our findings provide analytical support for reports that the mutations in the Omicron variant have little or no impact on SalivaDirect™ assay in terms of amplification efficiency and detection sensitivity using either standard and the recently reported fast Liberty16 SalivaDirect™ thermal cycling protocols.
Decision formation in parietal cortex transcends a fixed frame of reference
Authors: So NaYoung , Shadlen Michael N 
Published: February 2022

AbstractNeurons in the lateral intraparietal cortex (area LIP) represent the formation of a decision when it is linked to a specific action, such as an eye movement to a choice target. However, these neurons should be unable to represent a decision that transpires across actions that would disrupt this linkage. We investigated this limitation by recording simultaneously from many neurons. While intervening actions disrupt the representation by single neurons, the ensemble achieves continuity of the decision process by passing information from currently active neurons to neurons that will become active after the action. In this way, the representation of an evolving decision can be generalized across actions and transcends the frame of reference that specifies the neural response fields. The finding extends previous observations of receptive field remapping, thought to support the stability of perception across eye movements, to the continuity of a thought process, such as a decision.
TraDIS-validate: a method for curating ordered gene-replacement libraries
Authors: Goodall Emily C. A. , Morris Faye C. , McKeand Samantha A. , Sullivan Rudi , Warner Isabel A. , Sheehan Emma , Boelter Gabriela , Icke Christopher , Cunningham Adam F. , Cole Jeffrey A. , Banzhaf Manuel , Bryant Jack A. , Henderson Ian R. 
Published: February 2022

AbstractIn recent years the availability of genome sequence information has grown logarithmically resulting in the identification of a plethora of uncharacterised genes. To address this gap in functional annotation, many high-throughput screens have been devised with the goal of uncovering novel gene functions. Gene-replacement libraries are one such tool that can be screened in a high-throughput way to link genotype and phenotype and are key community resources. However, for a phenotype to be attributed to a specific gene, there needs to be confidence in the genotype. Construction of large libraries can be laborious and occasionally errors will arise. Here, we present a rapid and accurate method for the validation of any ordered gene-replacement library. We applied our method (TraDIS-Validate) to the well-known Keio library of Escherichia coli gene-deletion mutants. Our method identified 3,718 constructed mutants out of a total of 3,728 confirmed isolates. TraDIS-validate therefore had a success rate of 99.7% for identifying the correct kanamycin cassette position. This dataset provides a benchmark for the purity of the Keio mutants and a screening method for mapping the position of an antibiotic resistance cassette in any ordered library.
HIV-1 preintegration complex preferentially integrates the viral DNA into nucleosomes containing trimethylated histone 3-lysine 36 modification
Authors: Sapp Nicklas , Burge Nathaniel , Cox Khan , Thapa Santosh , Prakash Prem , Balasubramaniam Muthukumar , Christenson Devin , Li Min , Linderberger Jared , Kvaratskhelia Mamuka , Pandhare Jui , Craigie Robert , Sundquist Wesley , Poirier Michael G , Dash Chandravanu 
Published: February 2022

AbstractHIV-1 DNA integration into the host chromosomes is carried out by the preintegration complex (PIC). The PIC contains the viral DNA, virally encoded integrase enzyme and other critical viral/host factors. The PIC-associated viral DNA is preferentially integrated into gene bodies of actively transcribing genes. Here, we identify a biochemical mechanism underlying the preference of PIC-mediated viral DNA integration (PIC-VDI). Specifically, we observed that the PIC-VDI into human chromatin is preferred over the genomic DNA. Surprisingly, nucleosome core particles without any histone modifications were not preferred for PIC-VDI when compared to the analogous naked DNA. However, PIC-VDI was markedly enhanced with nucleosomes containing the trimethylated histone 3 lysine 36 (H3K36me3), an epigenetic mark linked to HIV-1 DNA integration preference. Interestingly, we observed that nucleosomes with flanking linker DNA promoted PIC-VDI in the presence of LEDGF/p75. We also discovered that nucleosomes with linker DNA and H3K36me3 served as the optimal substrate for PIC-VDI. Mapping of the integration sites within these substrates identified preference of specific regions of the nucleosome core DNA for integration. Finally, we provide biochemical and genetic evidence that histone H1 protein, that condenses the chromatin, negatively regulates HIV-1 DNA integration, consistent with the integration preference for open chromatin structure. Collectively, these results identify the role of specific chromatin marks that drive HIV-1 integration preference and define the optimal substrate requirement for efficient DNA integration by the PIC.
Autophagy promotes organelle clearance and organized cell separation of living root cap cells in Arabidopsis thaliana
Authors: Goh Tatsuaki , Sakamoto Kaoru , Wang Pengfei , Kozono Saki , Ueno Koki , Miyashima Shunsuke , Toyokura Koichi , Fukaki Hidehiro , Kang Byung-Ho , Nakajima Keiji 
Published: February 2022

AbstractThe root cap is a multi-layered tissue covering the tip of a plant root that directs root growth through its unique functions such as gravity-sensing and rhizosphere interaction. To prevent damages from the soil environment, cells in the root cap continuously turn over through balanced cell division and cell detachment at the inner and the outer cell layers, respectively. Upon displacement toward the outermost layer, columella cells at the central root cap domain functionally transition from gravity-sensing cells to secretory cells, but the mechanisms underlying this drastic cell fate transition are largely unknown. By using live-cell tracking microscopy, we here show that organelles in the outermost cell layer undergo dramatic rearrangements, and at least a part of this rearrangement depends on spatiotemporally regulated activation of autophagy. Notably, this root cap autophagy does not lead to immediate cell death, but rather is necessary for organized separation of living root cap cells, highlighting a previously undescribed role of developmentally regulated autophagy in plants.Summary statementTime-lapse microscope imaging revealed spatiotemporal dynamics of intracellular reorganization associated with functional transition and cell separation in the Arabidopsis root cap and the roles of autophagy in this process.