bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acyl-AcpB, a FabT corepressor in
Streptococcus pyogenes
Authors: Lambert Clara , d'Orfani Alice , Gaillard Marine , Zhang Qiufen , Gloux Karine , Poyart Claire , Fouet Agnes 
Published: October 2023

ABSTRACT

Membranes are a universal barrier to all cells. Phospholipids, essential bacterial membrane components, are composed of a polar head and apolar fatty acid (FA) chains. Most bacterial FAs are synthesized by the Type II FA synthesis pathway (FASII). In Streptococcaceae, Enterococci, and
Lactococcus lactis
, a unique feedback mechanism controls the FASII gene expression. FabT, encoded in the FASII main locus, is the repressor, and it is activated by long-chain acyl-acyl carrier protein (acyl-ACP). Many Streptococci,
Enterococcus faecalis
, but not
L. lactis
, possess two ACPs. The AcpA-encoding gene is within the FASII locus and is coregulated with the FASII genes. Acyl-AcpA is the end product of FASII. The AcpB-encoding gene is in operon with
plsX
encoding an acyl-ACP:phosphate acyltransferase. The role of acyl-AcpB as FabT corepressor is controversial.
Streptococcus pyogenes
, which causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections, possesses AcpB. In this study, by comparing the expression of FabT-controlled genes in an
acpB
-deleted mutant with those in a wild-type and in a
fabT
mutant strain, grown in the presence or absence of exogenous FAs, we show that AcpB is the
S. pyogenes
FabT main corepressor. Its deletion impacts membrane FA composition and bacterial adhesion to eucaryotic cells, highlighting the importance of FASII control.

Importance

Membrane composition is crucial for bacterial growth or interaction with the environment. Bacteria synthesize fatty acids (FAs), membrane major constituents, via the Type II FAS (FASII) pathway. Streptococci control the expression of the FASII genes via a transcriptional repressor, FabT, with acyl-acyl carrier proteins (ACPs) as corepressor.
Streptococcus pyogenes
that causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections possesses two ACPs.
acpA
, but not
acpB
, is a FASII gene. In this study, we show that acyl-AcpBs are FabT main corepressors. Also, AcpB deletion has consequences on the membrane FA composition and bacterial adhesion to host cells. In addition to highlighting the importance of FASII control in the presence of exogeneous FAs for the adaptation of bacteria to their environment, our data indicate that FASII gene repression is mediated by a corepressor whose gene expression is not repressed in the presence of exogenous FAs.
SERPINB1 promotes Senecavirus A replication by degrading IKBKE and regulating the IFN pathway via autophagy
Authors: Yan Junfang , Gao Yanni , Bai Juan , Li Jian , Li Minjing , Liu Xing , Jiang Ping 
Published: October 2023

ABSTRACT
Innate immunity and autophagy play crucial roles in regulating Senecavirus A (SVA) replication. However, the reciprocal coordination between these systems during virus infection is not understood. Our results show that SERPINB1, a member of the SERPINB family, facilitates SVA replication. Mechanistically, ectopic expression of SERPINB1 increases the degradation of IκB kinase epsilon (IKBKE) through the ubiquitin-proteasome pathway. The removal of IKBKE antagonizes the IKBKE-mediated inhibition of proliferation that normally generates an interferon response via the AKT/mTOR/BECN1 axis. We conclude that SERPINB1 promotes SVA replication by eliciting autophagy-triggered innate inhibition, suggesting that SERPINB1 is a potential therapeutic target for the control of viral infection.

IMPORTANCE
Senecavirus A (SVA) is an emerging picornavirus associated with vesicular disease, which wide spreads around the world. It has evolved multiple strategies to evade host immune surveillance. The mechanism and pathogenesis of the virus infection remain unclear. In this study, we show that SERPINB1, a member of the SERPINB family, promotes SVA replication, and regulates both innate immunity and the autophagy pathway. SERPINB1 catalyzes K48-linked polyubiquitination of IκB kinase epsilon (IKBKE) and degrades IKBKE through the proteasome pathway. Inhibition of IKBKE expression by SERPINB1 induces autophagy to decrease type I interferon signaling, and ultimately promotes SVA proliferation. These results provide importantly the theoretical basis of SVA replication and pathogenesis. SERPINB1 could be a potential therapeutic target for the control of viral infection.
Major data analysis errors invalidate cancer microbiome findings
Authors: Gihawi Abraham , Ge Yuchen , Lu Jennifer , Puiu Daniela , Xu Amanda , Cooper Colin S. , Brewer Daniel S. , Pertea Mihaela , Salzberg Steven L. 
Published: October 2023

ABSTRACT
We re-analyzed the data from a recent large-scale study that reported strong correlations between DNA signatures of microbial organisms and 33 different cancer types and that created machine-learning predictors with near-perfect accuracy at distinguishing among cancers. We found at least two fundamental flaws in the reported data and in the methods: (i) errors in the genome database and the associated computational methods led to millions of false-positive findings of bacterial reads across all samples, largely because most of the sequences identified as bacteria were instead human; and (ii) errors in the transformation of the raw data created an artificial signature, even for microbes with no reads detected, tagging each tumor type with a distinct signal that the machine-learning programs then used to create an apparently accurate classifier. Each of these problems invalidates the results, leading to the conclusion that the microbiome-based classifiers for identifying cancer presented in the study are entirely wrong. These flaws have subsequently affected more than a dozen additional published studies that used the same data and whose results are likely invalid as well.

IMPORTANCE
Recent reports showing that human cancers have a distinctive microbiome have led to a flurry of papers describing microbial signatures of different cancer types. Many of these reports are based on flawed data that, upon re-analysis, completely overturns the original findings. The re-analysis conducted here shows that most of the microbes originally reported as associated with cancer were not present at all in the samples. The original report of a cancer microbiome and more than a dozen follow-up studies are, therefore, likely to be invalid.
M13KO7 bacteriophage enables Potato Virus Y detection
Authors: Seo Haneul , Cho Sang-Ho , Vo Thuy T. B. , Lee Ahlim , Cho Sungrae , Kang Sol , Kil Eui-Joon , Byun Hee-Seong , Lee Mi-Gi , Kwon Myung-Hee , Chung Woo-Jae , Lee Young-Gyu , Lee Sukchan 
Published: October 2023

ABSTRACT

Potato virus Y
(PVY) is one of the foremost plant viruses affecting potato plants and production. Many diagnostic and detection techniques are available to detect and prevent the spread of this virus. Serological analyses, such as enzyme-linked immunosorbent assay (ELISA), are widely used in laboratories as well as in the field. In addition, recently, serological methods using whole or recombinant antibodies have been developed. However, these antibodies are unstable under certain chemical conditions and can be easily degraded by exposure to enzymes. M13KO7, a derivative of bacteriophage M13, with a filamentous structure similar to PVY, was used for antibody screening. We found that PVY and “bald” M13KO7 had binding activity similar to that of antigen-antibody in ELISA analyses. The binding interactions between PVY and M13KO7 were highly specific. A new method for detecting PVY using ELISA analysis with M13KO7 was developed in this study. These results provide new insights into two virus-binding interactions and novel systems for the detection of plant viruses.

IMPORTANCE

In this study, we confirmed the binding of M13KO7 to
Potato virus Y
(PVY) using enzyme-linked immunosorbent assay. M13KO7 is a “bald” bacteriophage in which no recombinant antibody is displayed. M13KO7 is easy to propagate by using
Escherichia coli
, making this method more reasonable in economic perspective. Based on this study, we suggest that M13KO7 detection system has applicability as a novel biological tool for the detection of PVY
Risk factors and biomarkers for post-tuberculosis lung damage in a Chinese cohort of male smokers and non-smokers: protocol for a prospective observational study
Authors: Gai Xiaoyan , Cao Wenli , Rao Yafei , Zeng Lin , Xu Wei , Wu Haifeng , Li Gen , Sun Yongchang 
Published: October 2023

IntroductionPost-tuberculosis lung damage (PTLD) refers to the residual pulmonary impairment following the completion of antituberculosis (TB) therapy, characterised by persistent respiratory symptoms and abnormal pulmonary function. The risk factors and biomarkers for PTLD have been scarcely investigated. More importantly, whether and to what extent cigarette smoking is involved in PTLD remain to be known.Methods and analysisThis prospective observational study will enrol 400 male smoking or non-smoking patients aged 25–65 years, with newly confirmed active TB between 2022 and 2024, from the Department of Respiratory and Critical Care Medicine at Peking University Third Hospital and the Tuberculosis Department at Beijing Geriatric Hospital. Because females rarely smoke in China, we will enrol only males in this study. Demographic data, smoking history and amount, clinical symptoms, lung function, and chest CT findings will be prospectively collected. Respiratory questionnaires, lung function measurements and chest CT examinations will be performed immediately after, and 1 year, 2 years and 3 years after the completion of TB treatment. Peripheral blood samples will be obtained at baseline and at the end of anti-TB therapy, and a Luminex xMAP-based multiplex immunoassay will be used to measure inflammatory mediators and cytokines in serum. The collected data will be analysed to determine the incidence and factors/biomarkers of PTLD according to smoking status.Ethics and disseminationThe study was approved by the Ethics Committee of Peking University Third Hospital (approval number: (2022)271-03; approval date: 8 June 2022). The research results will be disseminated through scientific and medical conferences and will be published in an academic journal.Trial registration numberNCT04966052.
Did the UK’s COVID-19 restrictions during 2020 have a differential impact on the well-being of the LGBQ+ population: a mixed methods study
Authors: Hope Vivian D , Timpson Hannah , Porcellato Lorna , Brett Caroline E , Harrison Rebecca , Hunt Anna , Bigland Charlotte , Leavey Conan , Hay Gordon , Saini Pooja 
Published: October 2023

ObjectiveThe social distancing measures governments implemented in response to the COVID-19 pandemic have had substantial impacts. For some communities, these impacts will be disproportionate, with those communities experiencing inequalities, marginalisation or discrimination facing specific challenges. Lesbian, gay, bisexual, queer and allied (LGBQ+) communities experience a range of well-being inequalities that may have been impacted by the pandemic. The study aimed to assess the comparative impact of the UK’s response to COVID-19 on LGBQ+ communities.DesignA mixed-method explanatory sequential study of the general population using a cross-sectional online survey and semistructured interviews.SettingCommunity, North West of England.ParticipantsAdults aged 18 years and over; 1540 participated in the survey (192, 12%, LGBQ+) with 49 undergoing semistructured interviews (15 LGBQ+) during spring and summer of 2020.ResultsSurvey findings indicated that LGBQ+ people experienced similar positive and negative impacts to the rest of the population, but some negative impacts were more marked among the LGBQ+ community. LGBQ+ participants were more likely to disagree that ‘the government considered the impact on people like you’ when preparing guidance. They were significantly more likely to report being unable to access sufficient food and required medication, eating less healthily, exercising less regularly, experiencing poorer quality sleep and taking more pain medicine than usual. Interview data supported these differences; isolation, being unable to access social networks and concerns about health were commonly discussed by the LGBQ+ participants. Positive impacts, including better work–life balance, were similar across both groups.ConclusionsThe findings indicate LGBQ+ communities’ wellbeing inequalities have been compounded by the social distancing restrictions, for example, by impacts on social networks increasing loneliness. Preparedness planning for future pandemics should include equality impact assessments for potential interventions.
Prevalence of non-communicable diseases and risk factors of pre-eclampsia/eclampsia in four local government areas in Nigeria: a cross-sectional study
Authors: Ogboye Ayoposi , Akpakli Jonas Kofi , Iwuala Amira , Etuk Imo , Njoku Kendra , Jackson Stodia , Okoli Ugo , Hill Kathleen , Omoera Victoria , Oludara Folashade , Ekong Iniobong , Mobisson Nneka 
Published: October 2023

ObjectivesTo assess the prevalence of non-communicable diseases (NCDs) and risk factors associated with pre-eclampsia and eclampsia (PE/E) in women of reproductive age (WRA) in Nigeria.DesignA cross-sectional survey was administered to the entire study population. In the point-of-care testing, physical and biochemical measurements were taken in a subset of the participants.SettingThe study was conducted in the Ikorodu and Alimosho local government areas (LGAs) in Lagos and the Abuja Municipal Area Council and Bwari LGAs in the Federal Capital Territory.ParticipantsSystematic random sampling was used to randomly select and recruit 639 WRA (aged 18–49 years) between May 2019 and June 2019.Outcome measuresPrevalence of select NCDs (hypertension or raised blood pressure, diabetes or raised blood sugar levels, anaemia, truncal obesity and overweight/obesity) and risk factors associated with PE/E (physical activity, fruit and vegetable consumption, alcohol consumption and smoking).ResultsThe prevalence of raised blood pressure measured among the WRA was 36.0% (95% CI 31.3% to 40.9%). Approximately 10% (95% CI 7.2% to 13.4%) of participants had raised blood sugar levels. About 19.0% (95% CI 15.3% to 23.2%) of the women had moderate or severe anaemia. Excluding WRA who were pregnant, 51.9% (95% CI 45.7% to 58.0%) of the women were either overweight or obese based on their body mass index. Approximately 58.8% (95% CI 53.8% to 63.6%) of WRA surveyed reported three to five risk factors for developing NCDs and PE/E in future pregnancies.ConclusionsThe study identified a high prevalence of NCDs and associated PE/E risk factors in surveyed women, signifying the importance of early detection and intervention for modifiable NCD and associated PE/E risk factors in WRA. Further research is necessary to assess the national prevalence of NCDs.
Longitudinal assessment of bacterial vaginosis prior to and during incident pregnancy: an observational study in Kenyan adolescent girls and young women
Authors: Oluoch Lynda , Tapia Kenneth , Kiptinness Catherine , Casmir Edinah , Maina Stephen Gakuo , Makena L , Selke Stacy , Wang Melody , Chohan Bhavna , Sycuro Laura , Wald Anna , Ngure Kenneth , Mugo Nelly , Roxby Alison 
Published: October 2023

ObjectiveTo determine bacterial vaginosis (BV) status at multiple time points among adolescent girls and young women (AGYW) and assess the impact of pregnancy on their BV status.DesignLongitudinal cohort study.SettingThika, Kenya.ParticipantsAGYW aged 16–20 years enrolled prior to first sex or reporting only a single lifetime partner.Main outcome measuresThe primary outcome was relative risk (RR) of BV during pregnancy compared with before pregnancy by analysing longitudinal trends in BV over time. BV risk was estimated using Poisson regression models.ResultsA total of 121 AGYW became pregnant in the parent cohort and had BV results before, during or after pregnancy. Point prevalence of BV was 11.0% at visits >12 months pre-pregnancy, 13.0% at 3–12 months pre-pregnancy, 22.1% at <3 months pre-pregnancy and 13.4% during pregnancy. Compared with visits during pregnancy, RR of BV was 1.65 (95% CI: 1.00 to 2.71; p=0.05) at visits <3 months pre-pregnancy, 0.97 (95% CI: 0.62 to 1.52; p=0.90) at visits 3–12 months pre-pregnancy and 0.82 (95% CI: 0.44 to 1.53; p=0.53) at visits 12 months pre-pregnancy. An adjusted analysis including age, income, residence, date of first sex, recent sexual activity and positive sexually transmitted infection test resulted in small changes in risk estimates, with adjusted RR of BV of 1.66 (95% CI: 1.04 to 2.67; p=0.04) at visits <3 months pre-pregnancy compared with visits during pregnancy.ConclusionsBV risk during pregnancy was lower than during the immediate pre-pregnancy period. Hormonal changes in pregnancy may reduce BV.
Promoting Empathy and Affiliation in Relationships (PEAR) study: protocol for a longitudinal study investigating the development of early childhood callous-unemotional traits
Authors: Wagner Nicholas , Perkins Emily , Rodriguez Yuheiry , Ordway Cora , Flum Michaela , Hernandez-Pena Lucia , Perelstein Polina , Sem Kathy , Paz Yael , Plate Rista , Popoola Ayomide , Lynch Sarah , Astone Kristina , Goldstein Ethan , Njoroge Wanjikũ F M , Raine Adriane , Pincus Donna , Pérez-Edgar Koraly , Waller Rebecca 
Published: October 2023

IntroductionChildren with callous-unemotional (CU) traits are at high lifetime risk of antisocial behaviour. Low affiliation (ie, social bonding difficulties) and fearlessness (ie, low threat sensitivity) are proposed risk factors for CU traits. Parenting practices (eg, harshness and low warmth) also predict risk for CU traits. However, few studies in early childhood have identified attentional or physiological markers of low affiliation and fearlessness. Moreover, no studies have tested whether parenting practices are underpinned by low affiliation or fearlessness shared by parents, which could further shape parent–child interactions and exacerbate risk for CU traits. Addressing these questions will inform knowledge of how CU traits develop and isolate novel parent and child targets for future specialised treatments for CU traits.Methods and analysisThe Promoting Empathy and Affiliation in Relationships (PEAR) study aims to establish risk factors for CU traits in children aged 3–6 years. The PEAR study will recruit 500 parent–child dyads from two metropolitan areas of the USA. Parents and children will complete questionnaires, computer tasks and observational assessments, alongside collection of eye-tracking and physiological data, when children are aged 3–4 (time 1) and 5–6 (time 2) years. The moderating roles of child sex, race and ethnicity, family and neighbourhood disadvantage, and parental psychopathology will also be assessed. Study aims will be addressed using structural equation modelling, which will allow for flexible characterisation of low affiliation, fearlessness and parenting practices as risk factors for CU traits across multiple domains.Ethics and disseminationEthical approval was granted by Boston University (#6158E) and the University of Pennsylvania (#850638). Results will be disseminated through conferences and open-access publications. All study and task materials will be made freely available on lab websites and through the Open Science Framework (OSF).
Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol
Authors: Subramanian Anuradhaa , Lee Siang Ing , Hemali Sudasinghe Sudasing Pathirannehelage Buddhika , Wambua Steven , Phillips Katherine , Singh Megha , Azcoaga-Lorenzo Amaya , Cockburn Neil , Wang Jingya , Fagbamigbe Adeniyi , Usman Muhammad , Damase-Michel Christine , Yau Christopher , Kent Lisa , McCowan Colin , OReilly Dermot , Santorelli Gillian , Hope Holly , Kennedy Jonathan , Mhereeg Mohamed , Abel Kathryn Mary , Eastwood Kelly-Ann , Black Mairead , Loane Maria , Moss Ngawai , Brophy Sinead , Brocklehurst Peter , Dolk Helen , Nelson-Piercy Catherine , Nirantharakumar Krishnarajah 
Published: October 2023

IntroductionConsidering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk–benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.Methods and analysisUsing a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure–outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.Ethics and disseminationEthical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.