bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lineage-specific genes are clustered with allorecognition loci and respond to G × E factors regulating the switch from asexual to sexual reproduction inNeurospora
Authors: Wang Zheng , Wang Yaning , Kasuga Takao , Wang Yen-Wen , Lopez-Giraldez Francesc , Zhang Yang , Zhang Zhang , Dong Caihong , Sil Anita , Trail Frances , Yarden Oded , Townsend Jeffrey P. 
Published: June 2022

AbstractLineage-specific genes (LSGs) have long been postulated to play roles in the establishment of genetic barriers to intercrossing and speciation. However, there is a lack of working hypotheses as to how they might play that role. In the genome ofNeurospora crassa, most of the 670NeurosporaLSGs that are aggregated adjacent to the telomeres are clustered with 61% of the HET-domain genes, which regulate self-recognition and define vegetative incompatibility groups. Among the 342 LSGs that are dynamically expressed during both asexual and sexual phases, 64% were detectable on unusual carbon sources such as furfural and HMF—wildfire-produced chemicals that are a strong inducer of sexual development. Expression of a significant portion of the LSGs was sensitive to light and temperature, factors that regulate the switch from asexual to sexual reproduction. Furthermore, expression of the LSGs was significantly affected in the knockouts ofadv-1andpp-1that regulate hyphal communication, and expression of more than one quarter of the LSGs was affected by perturbation of the mating locus. Accordingly, we propose a gene-by-environment interaction model encouraging further investigation of the roles of LSGs and HET-domain genes in speciation inNeurospora. This gene-by-environment interaction model emphasizes the roles of the LSGs in response to genetic and environmental factors, leading to the regulation of the switch from the asexual growth and fusion, such that vegetative incompatibility governed by allorecognition promotes allelic homogeneity, sexual reproduction, and outbreeding, whereas VI repression and meiotic recombination promotes allelic polymorphism.
Impaired Neutralization of SARS-CoV-2 Including Omicron Variants after COVID-19 mRNA Booster Immunization under Methotrexate Therapy
Authors: Habermann Elisa , Gieselmann Lutz , Tober-Lau Pinkus , Hagen Alexander ten , Albach Fredrik N , Zernicke Jan , Ahmadov Elvin , de Silva Amanthi Nadira Arumahandi , Frommert Leonie Maria , Klotsche Jens , Kurth Florian , Sander Leif Erik , Burmester Gerd , Klein Florian , Biesen Robert 
Published: June 2022

ABSTRACTObjectiveTo determine the immediate need for a fourth COVID-19 vaccination based on the neutralizing capacity in patients on methotrexate (MTX) therapy after mRNA booster immunization.MethodsIn this observational cohort study, neutralizing serum activity against SARS-CoV-2 wildtype (Wu01) and variant of concern (VOC) Omicron BA.1 and BA.2 were assessed by pseudovirus neutralization assay before, 4 and 12 weeks after mRNA booster immunization in 50 rheumatic patients on MTX, 26 of whom paused the medication. 44 non-immunosuppressed persons (NIP) served as control group.ResultsWhile the neutralizing serum activity against SARS-CoV-2 Wu01 and Omicron variants increased 67-to 73-fold in the NIP after booster vaccination, the serum activity in patients receiving MTX increased only 20-to 23-fold. As a result, significantly lower neutralizing capacities were measured in patients on MTX compared to the NIP at week 4. Patients who continued MTX treatment during vaccination had significantly lower neutralizing serum titres against all three virus strains at week 4 and 12 compared to patients who paused MTX and the control group, except for BA.2 at week 12. Patients who paused MTX reached comparably high neutralization titres as the NIP, except for Wu01 at week 12. Neutralization of omicron variants was significantly lower in comparison to wildtype in both groups.ConclusionPatients pausing MTX showed a similar vaccine response to NIP. Patients who continued MTX demonstrated an impaired booster response indicating a potential benefit of a second booster vaccination.
HEALTH ECONOMIC BURDEN ON HEPATITIS B IMMUNOGLOBULIN VACCINATION
Authors: Laurito Arbeen A. , Bett Lourdes L. 
Published: June 2022

Abstract of the StudyBackgroundChronic Hepatitis B infection comprises the mortality among viral hepatitis despite primary hepatitis B vaccination was implemented in different states health programs. Different modalities of combining active and passive hepatitis B vaccination were conducted. Pregnant women hepatitis screening was not yet streamlined in the clinical management due to social and economic challenges. Fetal to maternal vertical transmission of hepatitis B virus is still a burden to our health system. It is the objective of the study to present the cost of incorporating hepatitis B immunoglobulin vaccine in the current vaccination program, as strengthen the preventive measures of hepatitis infection locally and nationally.MethodsSurvey questionnaires were utilized to gather demographic data among randomly selected pregnant women during their prenatal visits at the hospital. Hospital and city-based census were used for projecting cost and revenues of having hepatitis B immunoglobulin vaccination.ResultsA total of 74 respondents were identified. A financial 5-year was forecast would show a revenue of Php 1,494,500.00 ($28,869.5) on the 5th year and would spare the mothers from OOP expenses with a total amount of Php 945,500 ($18,264.40). Moreover, the monthly revenue of Hep B Ig vaccination (based on 2016 census) on a city-wide was forecasted. The difference of the total amount of PHIC reimbursement from the amount of vaccine purchasing would give the facility a projected revenue of Php 3,381,123.00 ($65,313.62) or a monthly average of Php (281,760.25). A total of 1,380 newborns would be at risk to hepatitis B-reactive mothers and would be protected by securing hepatitis B immunoglobulin and be made available in the hospital pharmacy. Furthermore, pregnant women are protected against financial risk of unnecessary out-of-pocket expenses.ConclusionThis study found that the pregnant women was aware of the economic burden of hepatitis B immunoglobulin vaccine and it would benefit the healthcare facility by strategically addressing the external factors for a sustained vaccination program.
Separation of transcriptional repressor and activator functions in HDAC3
Authors: Tang Min , Regadas Isabel , Belikov Sergey , Shilkova Olga , Xu Lei , Wernersson Erik , Liu Xuewen , Wu Hongmei , Bienko Magda , Mannervik Mattias 
Published: June 2022

AbstractThe histone deacetylase HDAC3 is associated with the NCoR/SMRT co-repressor complex and its canonical function is in transcriptional repression, but it can also activate transcription. Here we show that the repressor and activator functions of HDAC3 can be genetically separated in Drosophila. A lysine substitution in the N-terminus (K26A) disrupts its catalytic activity and activator function, whereas a combination of substitutions (HEBI) abrogating the interaction with SMRTER enhance repressor activity beyond wild-type in the early embryo. We conclude that the critical functions of HDAC3 in embryo development involve catalytic-dependent gene activation and non-enzymatic repression by several mechanisms, including tethering of loci to the nuclear periphery.
Structure of SARS-CoV-2 M protein in lipid nanodiscs
Authors: Dolan Kimberly A. , Dutta Mandira , Kern David M. , Kotecha Abhay , Voth Gregory A. , Brohawn Stephen G. 
Published: June 2022

AbstractSARS-CoV-2 encodes four structural proteins incorporated into virions, spike (S), envelope (E), nucleocapsid (N), and membrane (M). M plays an essential role in viral assembly by organizing other structural proteins through physical interactions and directing them to sites of viral budding. As the most abundant protein in the viral envelope and a target of patient antibodies, M is a compelling target for vaccines and therapeutics. Still, the structure of M and molecular basis for its role in virion formation are unknown. Here, we present the cryo-EM structure of SARS-CoV-2 M in lipid nanodiscs to 3.5 Å resolution. M forms a 50 kDa homodimer that is structurally related to the SARS-CoV-2 ORF3a viroporin, suggesting a shared ancestral origin. Structural comparisons reveal how intersubunit gaps create a small, enclosed pocket in M and large open cavity in ORF3a, consistent with a structural role and ion channel activity, respectively. M displays a strikingly electropositive cytosolic surface that may be important for interactions with N, S, and viral RNA. Molecular dynamics simulations show a high degree of structural rigidity and support a role for M homodimers in scaffolding viral assembly. Together, these results provide insight into roles for M in coronavirus assembly and structure.
The adipose-neural axis is critically involved in cardiac arrhythmias
Authors: Fan Yubao , Huang Shanshan , Li Suhua , Wu Bingyuan , Huang Li , Zhao Qi , Zheng Zhenda , Xie Xujing , Liu Jia , Huang Weijun , Sun Jiaqi , Zhu Xiulong , Wang Maosheng , Zhu Jieming , Xiang Andy Peng , Li Weiqiang 
Published: June 2022

AbstractDysfunction of the sympathetic nervous system and increase of epicardial adipose tissue (EAT) have been independently associated with the occurrence of cardiac arrhythmia. However, their exact roles in triggering arrhythmia remain elusive due to a lack of appropriate human disease models. Here, using the in vitro co-culture system with sympathetic neurons, cardiomyocytes, and adipocytes, we show that adipocyte-derived leptin could activate sympathetic neurons and increase the release of NPY, which in turn trigger arrhythmia of cardiomyocytes by interaction with NPY1R and subsequently enhancing the activity of NCX and CaMKII. The arrhythmic phenotype could be partially blocked by leptin neutralizing antibody, or an inhibitor of NPY1R, NCX or CaMKII. More importantly, increased EAT thickness accompanied with higher leptin/NPY blood levels was detected in atrial fibrillation patients compared to control group. Our study provides the first evidence that adipose-neural axis would contribute to arrhythmogenesis and represent a potential therapeutic target for arrhythmia.
Glaucoma cases reported post-COVID-19 vaccination : A VAERS database analysis
Authors: Singh Rohan Bir , Parmar Uday Pratap Singh , Ichhpujani Parul 
Published: June 2022

ABSTRACTObjectiveTo evaluate glaucoma cases reported post-COVID-19 vaccination and describe the clinical presentations in these cases.DesignAn analysis of the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS) databaseParticipantsThe study includes 161 individuals who were reported for glaucoma after administration of COVID-19 vaccines [BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna) and Ad26.COV2.S (Janssen)] between December 2020 and April 2022.Main Outcome MeasuresEstimated crude reporting rate of glaucoma, clinical presentations, onset duration and associated risk factors.ResultsA total of 2,061,557,270 doses of COVID-19 vaccines were administered during the study timeframe. During this period, 161 glaucoma cases were reported with an estimated crude reporting rate (per million doses) of 0.09, 0.06 and 0.07 for BNT162b2, mRNA-1273 and Ad26.COV2.S, respectively. The majority of patients (n=130, 80.7%) received BNT162b2, vaccine, while 27 patients (16.8%) received mRNA-1273 and four patients (2.5%) received rAd26.COV2.S vaccines. The mean age of patients in the cohort was 60.41±17.56 years and 67.7% (n=109) were women. More than half (56.6%) were reported within the first week after vaccination. The glaucoma onset interval was significantly shorter in patients who received BNT162b2 and rAd26.COV2.S vaccines compared to mRNA-1273 (p=0.013). A higher risk of glaucoma incidence was observed in the short term in patients who received BNT162b2 vaccines compared to mRNA-1273 (p=0.05). In patients vaccinated with mRNA-1273, a significantly higher frequency of glaucoma cases was reported in older patients (p=0.047) compared to younger age groups.ConclusionsThe CDC-VAERS data suggest an extremely low safety concern for glaucoma on receiving BNT162b2, mRNA-1273, or Ad26.COV2.S vaccines. The onset interval of adverse events was shorter in patients who received BNT162b2 and rAd26.COV2.S vaccines compared to mRNA-1273. The glaucoma cases after mRNA-1273 vaccination were more commonly reported in older patients. These findings are subject to the limitations of passive reporting systems, under reporting and presumptive case definition, and should be considered preliminary without the medical record analysis for establishing a definitive diagnosis.
Atlas of plasma nuclear magnetic resonance biomarkers for health and disease in 118,461 individuals from the UK Biobank
Authors: Julkunen Heli , Cichońska Anna , Tiainen Mika , Koskela Harri , Nybo Kristian , Mäkelä Valtteri , Nokso-Koivisto Jussi , Kristiansson Kati , Perola Markus , Salomaa Veikko , Jousilahti Pekka , Lundqvist Annamari , Kangas Antti J. , Soininen Pasi , Barrett Jeffrey C. , Würtz Peter 
Published: June 2022

AbstractBlood lipids and metabolites are both markers of current health and indicators of risk for future disease. Here, we describe plasma nuclear magnetic resonance (NMR) biomarker data for 118,461 participants in the UK Biobank, an open resource for public health research with extensive clinical and genomic data. The biomarkers cover 249 measures of lipoprotein lipids, fatty acids, and small molecules such as amino acids, ketones, and glycolysis metabolites. We provide a systematic atlas of associations of these biomarkers to prevalence, incidence, and mortality of over 700 common diseases (biomarker-atlas.nightingale.cloud/). The results reveal a plethora of biomarker associations, including susceptibility to infectious diseases and risk for onset of various cancers, joint disorders, and mental health outcomes, indicating that abundant circulating lipids and metabolites are risk markers well beyond cardiometabolic diseases. Clustering analyses indicate similar biomarker association patterns across different types of diseases, such as liver diseases and polyneuropathies, suggesting latent systemic connectivity in the susceptibility to a diverse set of diseases. The release of NMR biomarker data at scale in the UK Biobank highlights the promise of metabolic profiling in large cohorts for public health research and translation.
Predictive value of automated coronary calcium scoring in lung cancer screening with low dose computed tomography
Authors: Sabia Federica , Balbi Maurizio , Ledda Roberta E. , Milanese Gianluca , Ruggirello Margherita , Valsecchi Camilla , Marchianò Alfonso , Sverzellati Nicola , Pastorino Ugo 
Published: June 2022

AbstractCoronary artery calcium (CAC) is a known risk factor for cardiovascular events, but not yet routinely evaluated in Low Dose Computed Tomography (LDCT) screening. The present analysis compared the accuracy of a new automated CAC quantification versus prior manual quantification on baseline LDCT screening images as predictors of all-cause mortality at 12 years.The study included 1129 volunteers of the Multicentric Italian Lung Detection (MILD) trial who underwent a baseline LDCT scan from September 2005 to September 2006, already analyzed in a previous paper on CAC scoring. The initial manual CAC (mCAC) had been scored by one operator using a dedicated software, while the new automated CAC (aCAC) score was measured by a fully automated artificial intelligence software. All CAC scores were stratified in four categories: 0, 0.1- 19.9, 20-399, and ≥ 400.The study showed a high correlation between aCAC and mCAC scores, with an Intraclass Correlation Coefficient of 0.887. Of 613 negative mCAC score, 87.6% had aCAC score >0, and 14.0% >20. A CAC score >20 revealed a higher risk of 12-year all-cause mortality both with mCAC and aCAC. Focusing on the 535 individuals with false negative mCAC score, aCAC identified a subset of volunteers with a significantly poorer survival of 86% (aCAC 20-399, p=0.0007).CAC quantification could be accurately and safely performed with a fully automated software on baseline LDCT screening images to predict all-cause mortality risk.
Interferon Beta-1α ring prophylaxis to reduce household transmission of SARS-CoV-2: the Containing Coronavirus Disease-19 randomized clinical trial
Authors: Castro-Rodriguez José A. , Fish Eleanor N. , Kollmann Tobi , Iturriaga Carolina , Karpievitch Yuliya , Shannon Casey , Chen Virginia , Balshaw Robert , Montgomery Samuel T. , Ho Joseph , Othman Rym Ben , Aniba Radhouana , Gidi-Yunge Francisca , Hartnell Lucy , Pérez-Mateluna Guillermo , Urzúa Marcela , Tebbutt Scott , García-Huidobro Diego , Perret Cecilia , Borzutzky Arturo , Stick Stephen M. 
Published: June 2022

AbstractImportanceEvidence suggests that early, robust type 1 interferon responses to SARS-CoV-2 are critical determinants for COVID-19 disease outcomes, accelerating viral clearance and limiting viral shedding.ObjectiveWe undertook a ring prophylaxis study to determine whether pegylated IFNβ-1α could reduce SARS-CoV-2 household transmission.DesignA cluster randomized clinical trial of pegylated IFNβ-1α conducted in Santiago, Chile. Recruitment was conducted between December 4th2020, and 31stMay 2021, with the last follow-up completed June 29th2021.SettingThe study was conducted across 341 households in the metropolitan area of Santiago, Chile.ParticipantsIndex cases were identified from databases of those with confirmed SARS-CoV-2 from COVID-19 clinics and emergency room visits in Santiago, Chile. 5,154 index cases were assessed for eligibility, 1,372 index cases were invited to participate, and 341 index cases and their household contacts (n = 831) were enrolled in the study.InterventionHouseholds were cluster randomized to receive 125µg subcutaneous pegylated IFNβ-1α (n = 172 households, 607 participants), or standard care (n = 169 households, 565 participants).Main Outcome(s) and Measure(s)Frequentist and Bayesian analyses were undertaken to determine the effects of treatment on (i) reducing viral shedding in index cases and (ii) reducing viral transmission to treatment-eligible household contacts. Four secondary outcomes were assessed including duration of viral shedding, effects on viral transmission and seroconversion, incidence of hospitalization, and incidence and severity of reported adverse events. A post-hoc ‘at risk population’ was defined as households where the index case was positive at the start of the study and there was at least one treatment eligible contact in a household who tested negative for SARS-CoV-2.ResultsIn total, 1172 participants in 341 households underwent randomization, with 607 assigned to receive IFNβ-1α and 565 to standard care. Based on intention to treat and per protocol analyses, IFNβ-1α treatment was ineffective. However, in the ‘at risk’ population, the relative risk of infection was reduced by 23% in treated individuals and that there was a 95% probability that IFNβ-1α reduced household transmissionConclusions and RelevanceRing prophylaxis with IFNβ-1α reduces the probability of SARS-CoV-2 transmission within a household.Trial RegistrationClinicaltrials.govidentifier:NCT04552379
A general, highly efficient and facile synthesis of biocompatible rhodamine dyes and probes for live-cell multicolor nanoscopy
Authors: Bucevičius Jonas , Gerasimaitė Rūta , Kiszka Kamila A. , Pradhan Shalini , Kostiuk Georgij , Koenen Tanja , Lukinavičius Gražvydas 
Published: June 2022

ABSTRACTThe development of live-cell fluorescence nanoscopy is powered by the availability of suitable fluorescent probes. Rhodamines are among the best fluorophores for labeling intracellular structures. Isomeric tuning is a powerful method for optimizing biocompatibility of the rhodamine-containing probes without affecting their spectral properties. However, the efficient synthesis pathway for rhodamine 4-isomers is still lacking. Herein, we present a facile protecting-group-free 4-carboxyrhodamines’ synthesis based on nucleophilic addition of lithium dicarboxybenzenide to the corresponding xanthone. This approach drastically reduces the number of synthesis steps and expands the achievable structural diversity, increases overall yields and permits a cheap gram-scale synthesis of the dyes. We prepared a wide range of symmetric and asymmetric 4-carboxyrhodamines covering the whole visible spectrum and targeted them to multiple structures in living cells – microtubules, DNA, actin, mitochondria, lysosomes, Halo-tagged and SNAP-tagged proteins. The enhanced permeability fluorescent probes operate at submicromolar concentrations allowing high contrast STED and confocal microscopy of living cells and tissues.
The soybean rust pathogen Phakopsora pachyrhizi displays transposable element proliferation that correlates with broad host-range adaptation on legumes
Authors: Gupta Yogesh K. , Marcelino-Guimarães Francismar C. , Lorrain Cécile , Farmer Andrew , Haridas Sajeet , Ferreira Everton Geraldo Capote , Lopes-Caitar Valéria S. , Oliveira Liliane Santana , Morin Emmanuelle , Widdison Stephanie , Cameron Connor , Inoue Yoshihiro , Thor Kathrin , Robinson Kelly , Drula Elodie , Henrissat Bernard , LaButti Kurt , Bini Aline Mara Rudsit , Paget Eric , Singan Vasanth , Daum Christopher , Dorme Cécile , van Hoek Milan , Janssen Antoine , Chandat Lucie , Tarriotte Yannick , Richardson Jake , do Vale Araújo Melo Bernardo , Wittenberg Alexander , Schneiders Harrie , Peyrard Stephane , Zanardo Larissa Goulart , Holtman Valéria Cristina , Coulombier-Chauvel Flavie , Link Tobias I. , Balmer Dirk , Müller André N. , Kind Sabine , Bohnert Stefan , Wirtz Louisa , Chen Cindy , Yan Mi , Ng Vivian , Gautier Pierrick , Meyer Maurício Conrado , Voegele Ralf Thomas , Liu Qingli , Grigoriev Igor V. , Conrath Uwe , Brommonschenkel Sérgio H. , Loehrer Marco , Schaffrath Ulrich , Sirven Catherine , Scalliet Gabriel , Duplessis Sébastien , van Esse H. Peter 
Published: June 2022

ABSTRACTAsian soybean rust, caused by Phakopsora pachyrhizi, is one of the world’s most economically damaging agricultural diseases. Despite P. pachyrhizi’s impact, the exceptional size and complexity of its genome prevented generation of an accurate genome assembly. We simultaneously sequenced three P. pachyrhizi genomes uncovering a genome up to 1.25 Gb comprising two haplotypes with a transposable element (TE) content of ~93%. The proliferation of TEs within the genome occurred in several bursts and correlates with the radiation and speciation of the legumes. We present data of clear de-repression of TEs that mirrors expression of virulence-related candidate effectors. We can see a unique expansion in amino acid metabolism for this fungus. Our data shows that TEs play a dominant role in P. pachyrhizi’s genome and have a key impact on various processes such as host range adaptation, stress responses and genetic plasticity of the genome.