bluuebunny/crossref_metadata_2025_split huggingface dataset:
The alternative sigma factor SigN of
Bacillus subtilis
is intrinsically toxic
Authors: Burton Aisha T. , Pospíšilová Debora , Sudzinova Petra , Snider Elizabeth V. , Burrage Andrew M. , Krásný Libor , Kearns Daniel B. 
Published: September 2023

ABSTRACT

Sigma factors bind and direct the RNA polymerase core to specific promoter sequences, and alternative sigma factors direct transcription of different regulons of genes. Here, we study the pBS32 plasmid-encoded sigma factor SigN of
Bacillus subtilis
to determine how it contributes to DNA damage-induced cell death. We find that SigN causes cell death when expressed at high levels and does so in the absence of its regulon suggesting it is intrinsically toxic. One way toxicity was relieved was by curing the pBS32 plasmid, which eliminated a positive feedback loop that led to SigN hyper-accumulation. Another way toxicity was relieved was through mutating the chromosomally encoded transcriptional repressor protein AbrB, thereby derepressing a potent antisense transcript that antagonized SigN expression. SigN efficiently competed with the vegetative sigma factor SigA
in vitro
, and SigN accumulation in the absence of positive feedback reduced SigA-dependent transcription suggesting that toxicity may be due to competitive inhibition of one or more essential transcripts. Why
B. subtilis
encodes a toxic sigma factor is unclear but SigN may function in host-inhibition during lytic conversion, as phage lysogen genes are also encoded on pBS32.

IMPORTANCE

Alternative sigma factors activate entire regulons of genes to improve viability in response to environmental stimuli. The pBS32 plasmid-encoded alternative sigma factor SigN of
Bacillus subtilis
however
,
is activated by the DNA damage response and leads to cellular demise. Here we find that SigN impairs viability by hyper-accumulating and outcompeting the vegetative sigma factor for the RNA polymerase core. Why
B. subtilis
retains a plasmid with a deleterious alternative sigma factor is unknown.
Expanding our grasp of two-component signaling in
Clostridioides difficile
Authors: Berumen Alvarez Orlando , Purcell Erin B. 
Published: September 2023

ABSTRACT

The intestinal pathogen
Clostridioides difficile
encodes roughly 50 TCS, but very few have been characterized in terms of their activating signals or their regulatory roles. A. G. Pannullo, B. R. Zbylicki, and C. D. Ellermeier (J Bacteriol 205:e00164-23, 2023,
https://doi.org/10.1128/jb.00164-23
) have identified both for the novel
C. difficile
TCD DraRS. DraRS responds to antibiotics that target lipid-II molecules in the bacterial cell envelope, and regulates the production of a novel glycolipid necessary for bacitracin and daptomycin resistance in
C. difficile
.
Multi-site performance evaluation of the Alinity m Molecular assay for quantifying Epstein-Barr virus DNA in plasma samples
Authors: Wessels Els , Albert Eliseo , Vreeswijk Tom , Claas Eric C. J. , Giménez Estela , Reinhardt Birgit , Sasaki Mark M. , Navarro David 
Published: September 2023

ABSTRACT

Detection and monitoring of acute infection or reactivation of Epstein-Barr virus (EBV) are critical for treatment decision-making and to reduce the risk of EBV-related malignancies and other associated diseases in immunocompromised individuals. The analytical and clinical performance of the Alinity m EBV assay was evaluated at two independent study sites; analytical performance was assessed by evaluating precision with a commercially available 5-member EBV verification panel, while the clinical performance of the Alinity m EBV assay was compared to the RealTi
me
EBV assay and a laboratory-developed test (LDT) as the routine test of record (TOR). Analytical analysis demonstrated standard deviation (SD) between 0.08 and 0.13 Log IU/mL. A total of 300 remnant plasma specimens were retested with the Alinity m EBV assay, and results were compared to those of the TOR at the respective study sites (
n
= 148 with the RealTi
m
e EBV assay and
n
= 152 with the LDT EBV assay). Agreement between Alinity m EBV and RealTi
m
e EBV or LDT EBV assays had kappa values of 0.88 and 0.84, respectively, with correlation coefficients
r
of 0.956 and 0.912, while the corresponding observed mean bias was −0.02 and −0.19 Log IU/mL. The Alinity m EBV assay had a short median onboard turnaround time of 2:40 h. Thus, the Alinity m system can shorten the time to results and, therefore, to therapy.
Functional comparisons of the virus sensor RIG-I from humans, the microbat
Myotis daubentonii
, and the megabat
Rousettus aegyptiacus
, and their response to SARS-CoV-2 infection
Authors: Schoen Andreas , Hölzer Martin , Müller Marcel A. , Wallerang Kai B. , Drosten Christian , Marz Manja , Lamp Benjamin , Weber Friedemann 
Published: September 2023

ABSTRACT

Bats (order
Chiroptera
) are a major reservoir for emerging and re-emerging zoonotic viruses. Their tolerance toward highly pathogenic human viruses led to the hypothesis that bats may possess an especially active antiviral interferon (IFN) system. Here, we cloned and functionally characterized the virus RNA sensor, retinoic acid-inducible gene-I (RIG-I), from the “microbat”
Myotis daubentonii
(suborder
Yangochiroptera
) and the “megabat”
Rousettus aegyptiacus
(suborder Yinpterochiroptera) and compared them to the human ortholog. Our data show that the overall sequence and domain organization are highly conserved and that all three RIG-I orthologs can mediate a similar IFN induction in response to viral RNA at 37° and 39°C but not at 30°C. Like human RIG-I, bat RIG-Is were optimally activated by double stranded RNA containing a 5’-triphosphate end and required mitochondrial antiviral-signaling protein (MAVS) for antiviral signaling. Moreover, the RIG-I orthologs of humans and of
R. aegyptiacus
, but not of
M. daubentonii
, enable innate immune sensing of SARS-CoV-2 infection. Our results thus show that microbats and megabats express a RIG-I that is not substantially different from the human counterpart with respect to function, temperature dependency, antiviral signaling, and RNA ligand properties, and that human and megabat RIG-I are able to sense SARS-CoV-2 infection.

IMPORTANCE

A common hypothesis holds that bats (order
Chiroptera
) are outstanding reservoirs for zoonotic viruses because of a special antiviral interferon (IFN) system. However, functional studies about key components of the bat IFN system are rare. RIG-I is a cellular sensor for viral RNA signatures that activates the antiviral signaling chain to induce IFN. We cloned and functionally characterized RIG-I genes from two species of the suborders
Yangochiroptera
and
Yinpterochiroptera
. The bat RIG-Is were conserved in their sequence and domain organization, and similar to human RIG-I in (i) mediating virus- and IFN-activated gene expression, (ii) antiviral signaling, (iii) temperature dependence, and (iv) recognition of RNA ligands. Moreover, RIG-I of
Rousettus aegyptiacus
(suborder
Yinpterochiroptera
) and of humans were found to recognize SARS-CoV-2 infection. Thus, members of both bat suborders encode RIG-Is that are comparable to their human counterpart. The ability of bats to harbor zoonotic viruses therefore seems due to other features.
Microbial activity contributes to spatial heterogeneity of wetland methane fluxes
Authors: Arnold Wyatt , Taylor Meghan , Bradford Mark , Raymond Peter , Peccia Jordan 
Published: September 2023

ABSTRACT

The emission of methane from wetlands is spatially heterogeneous, as concurrently measured surface fluxes can vary by orders of magnitude within the span of a few meters. Despite extensive study and the climatic significance of these emissions, it remains unclear what drives large, within-site variations. While geophysical factors (e.g., soil temperature) are known to correlate with methane (CH
4
) flux, measurable variance in these parameters often declines as spatial and temporal scales become finer. As methane emitted from wetlands is the direct, net product of microbial metabolisms which both produce and degrade CH
4
, it stands to reason that characterizing the spatial variability of microbial communities within a wetland—both horizontally and vertically—may help explain observed variances in flux. To that end, we surveyed microbial communities to a depth of 1 m across an ombrotrophic peat bog in Maine, USA using amplicon sequencing and gene expression techniques. Surface methane fluxes and geophysical factors were concurrently measured. Across the first meter of peat at the site, we observed significant changes in the abundance and composition of methanogenic taxa at every depth sampled, with variance in methanogen abundance explaining 70% of flux heterogeneity at a subset of plots. Among measured environmental factors, only peat depth emerged as correlated with flux, and had significant impact on the abundance and composition of methane-cycling communities. These conclusions suggest that a heightened awareness of how microbial communities are structured and spatially distributed within wetlands could offer improved insights into predicting CH
4
flux dynamics.

IMPORTANCE

Globally, wetlands are one of the largest sources of methane (CH
4
), a greenhouse gas with a warming impact significantly greater than CO
2
. Methane produced in wetlands is the byproduct of a group of microorganisms which convert organic carbon into CH
4
. Despite our knowledge of how this process works, it is still unclear what drives dramatic, localized (<10 m) variance in emission rates from the surface of wetlands. While environmental conditions, like soil temperature or water table depth, correlate with methane flux when variance in these factors is large (e.g., spring vs fall), the explanatory power of these variables decline when spatial and temporal scales become smaller. As methane fluxes are the direct product of microbial activity, we profiled how the microbial community varied, both horizontally and vertically, across a peat bog in Maine, USA, finding that variance in microbial communities was likely contributing to much of the observed variance in flux.
Sulfasalazine as a cause of false-positive elevation of urinary normetanephrine in patients with adrenal mass and suspected phaeochromocytoma: a diagnostic challenge
Authors: Zuling Eunice Ter , Debono Miguel , Rab Edmund , Balasubramanian Sabapathy 
Published: September 2023

In patients with suspected phaeochromocytoma, biochemical screening of urine or blood for excess secretion catecholamines and/or their metabolites is performed. Elevated levels of catecholamines and metanephrines help in establishing the diagnosis of phaeochromocytoma. In two patients with adrenal lesions who were subjected to biochemical testing significantly elevated urinary normetanephrines appeared to establish the diagnosis of phaeochromocytoma. However, on subsequent investigations, this was demonstrated to be a ‘false positive’ finding. Both these patients were on sulfasalazine, an anti-inflammatory drug used in inflammatory bowel disease, rheumatoid arthritis and ankylosing spondylitis. Sulfasalazine can cause analytical interference in some assays for urinary normetanephrine and result in spuriously elevated levels, leading to misdiagnosis of phaeochromocytoma. In this report, one patient underwent adrenalectomy and another had conservative management.Although this has been previously reported, increased awareness of the possibility of false-positive results on urinary metanephrines testing is important to reduce the potential for misdiagnosis and unnecessary treatment.
Exploring the association between household access to water, sanitation and hygiene (WASH) services and common childhood diseases using data from the 2017–2018 Demographic and Health Survey in Benin: focus on diarrhoea and acute respiratory infection
Authors: Gaffan Nicolas , Degbey Cyriaque , Kpozehouen Alphonse , Ahanhanzo Yolaine Glele , Paraïso Moussiliou Noël 
Published: September 2023

ObjectiveThe paper aimed to study the association between household access to water, sanitation and hygiene (WASH) services and the occurrence of diarrhoea and acute respiratory infection among children under 5 years in Benin.DesignWe performed secondary analyses using Benin’s Fifth Demographic and Health Survey datasets. The dependent variables were diarrhoea and acute respiratory infection (yes=1, no=0). Among the independent variables were the household access to individual WASH services, grouped as follows: ‘basic’, ‘limited’, ‘unimproved’ and ‘no service’. Multivariate logistic regression was used to determine the association between household access to WASH services and the occurrence of diarrhoea and acute respiratory infection. Results from the multivariate logistic regression were presented using adjusted Odds Ratios (aORs) with 95% Confidence Intervals (95% CIs).SettingBenin.ParticipantsChildren under 5 years successfully surveyed during Benin’s Fifth Demographic and Health Survey.Outcome measuresDiarrhoea and acute respiratory infection.ResultsIn the current study, 12 034 children under 5 years met the selection criteria and were included in the analyses. The prevalence of diarrhoea and acute respiratory infection was 10.5% (95% CI=9.8% to 11.3%) and 2.9% (95% CI=2.5% to 3.4%), respectively. Children living in households without sanitation service, that is, practising open defecation (aOR=1.9, 95% CI=1.4 to 2.6), and with unimproved (aOR=1.9, 95% CI=1.3 to 2.7) and limited (aOR=1.5, 95% CI=1.1 to 2.2) services were more likely to have diarrhoea compared with children with basic sanitation services. Household access to WASH services was not associated with acute respiratory infection.ConclusionWe suggest reinforcing household access to basic sanitation services to combat diarrhoea in children under 5 years. Further research is needed on the effects of WASH interventions on diarrhoea and acute respiratory infection in children under 5 years.
Impact of Long Covid on the school experiences of children and young people: a qualitative study
Authors: MacLean Alice , Wild Cervantee , Hunt Kate , Nettleton Sarah , Skea Zoë C , Ziebland Sue 
Published: September 2023

ObjectivesTo explore the impact of Long Covid (LC) on the school experiences of children and young people (CYP).DesignQualitative study using narrative interviews.Participants22 CYP (aged 10–18 years, 15 female) with LC and 15 parents/caregivers (13 female) of CYP (aged 5–18 years) with LC.SettingInterviews were conducted between October 2021 and July 2022 via online video call or telephone. Recruitment routes included social media, LC support groups, clinicians, community groups and snowballing.ResultsThree key findings were identified. Finding 1: Going to school is a valued part of CYP’s lives and participants viewed educational attainment as important for their future trajectories. Returning to school full time was highlighted as a key part of regaining ‘normal life’. Finding 2: Attending school (in-person or online) with LC is extremely difficult; even a gradual return required CYP to balance the impact of being at and engaging with school, with the need to manage symptoms to prevent relapse. Often this meant prioritising school and rest over other aspects of their lives. Finding 3: School responses to CYP with LC were reported to be mixed and hampered by difficulties communicating with healthcare professionals during the pandemic and a lack of awareness of LC among healthcare and education professionals. Participants viewed supportive school responses as staff believing, understanding and taking them seriously, alongside schools offering tailored and flexible adaptations which allowed engagement with school while limiting any deterioration of symptoms.ConclusionsThis study describes how LC affects the school experiences of CYP and generates recommendations for supportive school responses alongside supportive healthcare professionals. Further research could explore the approaches that facilitate a successful return to school for CYP with LC and investigate education professionals’ perspectives on support they require to positively engage with returning pupils.
Immune monitoring of prevalent kidney transplant recipients using Torque Teno Virus: Protocol for a single-centre prospective cohort study
Authors: Ho Quan Yao , Lai Chooi Mun Deborah , Liew Ian Tatt , Oon Lynette Lin Ean , Lim Kun Lee , Chung Shimin Jasmine , Thangaraju Sobhana , Tien Shan-Yeu Carolyn , Tan Chieh Suai , Kee Terence 
Published: September 2023

IntroductionKidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression, but are also at risk of graft loss from rejection with underimmunosuppression. Biomarkers that predict both iRAEs and rejection while allowing individualisation of immunosuppression exposure are lacking. Although plasma viral DNA levels of torque teno virus (TTV), a widely prevalent, non-pathogenic virus, have been shown to predict both iRAE and rejection in newly transplanted KTRs within the first year after transplant, its role for prevalent KTRs on stable immunosuppression is less clear.This study aims to determine the prognostic value of TTV levels for severe infections (defined as infections requiring hospitalisation) in prevalent KTRs on stable immunosuppression for at least 3 months and compare it against that of other commonly available biomarkers. The study also aims to explore the relationship between TTV levels and factors affecting the ‘net state of immunosuppression’ as well as other clinical outcomes.Methods and analysisThis is a single-centre, prospective, observational cohort study of 172 KTRs on stable immunosuppression for more than 3 months. TTV levels will be measured using the TTV R-GENE kit upon recruitment when study subjects are admitted and when kidney allograft biopsies are performed. Subjects will be monitored for iRAEs and rejection for at least 12 months. The relationship between TTV load and clinical outcomes such as severe infections will be analysed and compared against that from other common biomarkers and previously published predictive scores.Ethics and disseminationThe study was approved by the SingHealth Centralised Institutional Review Board (2023/2170). The results will be presented at conferences and submitted for publication in peer-reviewed journals.Trial registration numberNCT05836636.
Time-course transcriptome analysis of a double challenge bleomycin-induced lung fibrosis rat model uncovers ECM homoeostasis-related translationally relevant genes
Authors: Bonatti Martina , Pitozzi Vanessa , Caruso Paola , Pontis Silvia , Pittelli Maria Gloria , Frati Caterina , Mangiaracina Chiara , Lagrasta Costanza Anna Maria , Quaini Federico , Cantarella Simona , Ottonello Simone , Villetti Gino , Civelli Maurizio , Montanini Barbara , Trevisani Marcello 
Published: September 2023

BackgroundIdiopathic pulmonary fibrosis (IPF) is an irreversible disorder with a poor prognosis. The incomplete understanding of IPF pathogenesis and the lack of accurate animal models is limiting the development of effective treatments. Thus, the selection of clinically relevant animal models endowed with similarities with the human disease in terms of lung anatomy, cell biology, pathways involved and genetics is essential. The bleomycin (BLM) intratracheal murine model is the most commonly used preclinical assay to evaluate new potential therapies for IPF. Here, we present the findings derived from an integrated histomorphometric and transcriptomic analysis to investigate the development of lung fibrosis in a time-course study in a BLM rat model and to evaluate its translational value in relation to IPF.MethodsRats were intratracheally injected with a double dose of BLM (days 0–4) and sacrificed at days 7, 14, 21, 28 and 56. Histomorphometric analysis of lung fibrosis was performed on left lung sections. Transcriptome profiling by RNAseq was performed on the right lung lobes and results were compared with nine independent human gene-expression IPF studies.ResultsThe histomorphometric and transcriptomic analyses provided a detailed overview in terms of temporal gene-expression regulation during the establishment and repair of the fibrotic lesions. Moreover, the transcriptomic analysis identified three clusters of differentially coregulated genes whose expression was modulated in a time-dependent manner in response to BLM. One of these clusters, centred on extracellular matrix (ECM)-related process, was significantly correlated with histological parameters and gene sets derived from human IPF studies.ConclusionsThe model of lung fibrosis presented in this study lends itself as a valuable tool for preclinical efficacy evaluation of new potential drug candidates. The main finding was the identification of a group of persistently dysregulated genes, mostly related to ECM homoeostasis, which are shared with human IPF.
Responses of patients with cancer to mRNA vaccines depend on the time interval between vaccination and last treatment
Authors: Donhauser Lara Victoria , Veloso de Oliveira Julia , Schick Cordula , Manlik Wenzel , Styblova Sabrina , Lutzenberger Sarah , Aigner Michael , Philipp Patrick , Robert Sebastian , Gandorfer Beate , Hempel Dirk , Hempel Louisa , Zehn Dietmar 
Published: September 2023

BackgroundPersonalized mRNA vaccines are promising new therapeutic options for patients with cancer. Because mRNA vaccines are not yet approved for first-line therapy, the vaccines are presently applied to individuals that received prior therapies that can have immunocompromising effects. There is a need to address how prior treatments impact mRNA vaccine outcomes.MethodTherefore, we analyzed the response to BioNTech/Pfizer’s anti-SARS-CoV-2 mRNA vaccine in 237 oncology outpatients, which cover a broad spectrum of hematologic malignancies and solid tumors and a variety of treatments. Patients were stratified by the time interval between the last treatment and first vaccination and by the presence or absence of florid tumors and IgG titers and T cell responses were analyzed 14 days after the second vaccination.ResultsRegardless of the last treatment time point, our data indicate that vaccination responses in patients with checkpoint inhibition were comparable to healthy controls. In contrast, patients after chemotherapy or cortisone therapy did not develop an immune response until 6 months after the last systemic therapy and patients after Cht-immune checkpoint inhibitor and tyrosine kinase inhibitor therapy only after 12 months.ConclusionAccordingly, our data support that timing of mRNA-based therapy is critical and we suggest that at least a 6-months or 12-months waiting interval should be observed before mRNA vaccination in systemically treated patients.
Isotropic  Durgapal IV fluid sphere in bigravity
Authors: Rej Pramit 
Published: September 2023

We analyze an isotropic uncharged fluid sphere model within bigravity considering the Durgapal IV metric (M.C. Durgapal, J. Phys. A: Math. Gen. 15, 2637 (1982)). In this work, we investigate the effects of the scale parameter k on the local matter distribution. Here, we have chosen the compact star candidate SMC X-1 with observed values of mass = (1.29 ± 0.05) M⊙ and radius [Formula: see text] km, respectively, to analyze our results analytically as well as graphically. For smaller values of k, we get the stiff (or hard) equation of state (EoS). Here, we solve the modified Einstein field equations in the presence of the background metric γμν. Due to this constant curvature background, the density and pressure terms are modified by adding an extra term, which affects the EoS. For r ≪ k, the background de Sitter space–time reduces into Minkowski form, and the coupling vanishes. We discuss certain physical quantities of our obtained solution, such as density, isotropic pressure, sound speed, pressure-density gradients, compactness, and surface redshift, to claim the physical viability of our model. It is found that our model clearly satisfies all the energy conditions, the causality condition, and the dynamical equilibrium via a modified Tolman–Oppenheimer–Volkov equation. Finally, we can conclude that our proposed model is physically realistic and well behaved.