bluuebunny/crossref_metadata_2025_split huggingface dataset:
The histidine kinase NahK regulates denitrification and nitric oxide accumulation through RsmA in
Pseudomonas aeruginosa
Authors: Guercio Danielle , Boon Elizabeth 
Published: December 2024

ABSTRACT

Pseudomonas aeruginosa
have a versatile metabolism; they can adapt to many stressors, including limited oxygen and nutrient availability. This versatility is especially important within a biofilm where multiple microenvironments are present. As a facultative anaerobe,
P. aeruginosa
can survive under anaerobic conditions utilizing denitrification. This process produces nitric oxide (NO) which has been shown to result in cell elongation. However, the molecular mechanism underlying this phenotype is poorly understood. Our laboratory has previously shown that NosP is a NO-sensitive hemoprotein that works with the histidine kinase NahK to regulate biofilm formation in
P. aeruginosa
. In this study, we identify NahK as a novel regulator of denitrification under anaerobic conditions. Under anaerobic conditions, deletion of
nahK
leads to a reduction of growth coupled with reduced transcriptional expression and activity of the denitrification reductases. Furthermore, during stationary phase under anaerobic conditions, Δ
nahK
does not exhibit cell elongation, which is characteristic of
P. aeruginosa
. We determine the loss of cell elongation is due to changes in NO accumulation in Δ
nahK
. We further provide evidence that NahK may regulate denitrification through modification of RsmA levels.

IMPORTANCE

Pseudomonas aeruginosa
is an opportunistic multi-drug resistance pathogen that is associated with hospital-acquired infections.
P. aeruginosa
is highly virulent, in part due to its versatile metabolism and ability to form biofilms. Therefore, better understanding of the molecular mechanisms that regulate these processes should lead to new therapeutics to treat
P. aeruginosa
infections. The histidine kinase NahK has been previously shown to be involved in both nitric oxide (NO) signaling and quorum sensing through RsmA. The data presented here demonstrate that NahK is responsive to NO produced during denitrification to regulate cell morphology. Understanding the role of NahK in metabolism under anaerobic conditions has larger implications in determining its role in a heterogeneous metabolic environment such as a biofilm.
2-Thiouridine formation in
Escherichia coli
: a critical review
Authors: Leimkühler Silke 
Published: December 2024

ABSTRACT

Modifications of transfer RNA (tRNA) have been shown to play critical roles in the biogenesis, metabolism, structural stability, and function of RNA molecules, and the specific modifications of nucleobases with sulfur atoms in tRNA are present in prokaryotes and eukaryotes. The s
2
group of s
2
U34 stabilizes anticodon structure, confers ribosome-binding ability to tRNA, and improves reading frame maintenance. In particular, specific enzymes catalyze the biosynthesis of sulfur-containing nucleosides of s
2
U34, such as the L-cysteine desulfurase IscS and the tRNA thiouridylase MnmA in
Escherichia coli
. Until recently, the mechanism of sulfur transfer in
E. coli
was considered to involve persulfide chemistry; however, a newly proposed mechanism suggests the involvement of a [4Fe–4S] cluster bound to MnmA. This review provides a critical appraisal of recent evidence for [4Fe–4S]-dependent or [4Fe–4S]-independent tRNA thiolation in 2-thiouridine formation.
Underappreciated layers of antibody-mediated immune synapse architecture and dynamics
Authors: Goldberg Benjamin S. , Ackerman Margaret E. 
Published: December 2024

ABSTRACT

The biologic activities of antibody drugs are dictated by structure-function relationships—emerging from the kind, composition, and degree of interactions with a target antigen and with soluble and cellular antibody receptors of the innate immune system. These activities are canonically understood to be both modular: antigen recognition is driven by the heterodimeric antigen-binding fragment, and innate immune recruitment by the homodimeric constant/crystallizable fragment. The model that treats these domains with a high degree of independence has served the field well but is not without limitations. Here, we consider how new insights, particularly from structural studies, complicate the model of neat biophysical separation between these domains and shape our understanding of antibody effector functions. The emerging model endeavors to explain the phenotypic impact of both antibody intrinsic characteristics and extrinsic features—fitting them within a spatiotemporal paradigm that better accounts for observed antibody activities. In this review, we will use insights from recent models of classical complement complexes and T cell immune synapse formation to explore how structural differences in antibody-mediated immune synapses may relate to their functional diversity.
Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation
Authors: Innokentev Aleksei , Sanchez Ana M. , Monetti Mara , Schwer Beate , Shuman Stewart 
Published: December 2024

ABSTRACT

The fission yeast
PHO
regulon genes
pho1
,
pho84
, and
tgp1
—encoding a cell surface-associated acid phosphatase (Pho1), a plasma membrane inorganic phosphate transporter (Pho84), and a plasma membrane glycerophosphocholine transporter (Tgp1)—are strongly upregulated in response to acute phosphate starvation, as are the
SPBPB2B2.06c
and
SPAC1039.02
genes that encode putative 5'-nucleotidase paralogs of the binuclear metallophosphoesterase enzyme superfamily. Via proteomic analysis of the medium harvested from phosphate-replete and phosphate-starved fission yeast, we define a starvation secretome that includes SPBPB2B2.06c (renamed Efn1, for
e
xtracellular
f
ive-prime
n
ucleotidase), SPAC1039.02 (henceforth Efn2), and Pho1 among the most abundant exported proteins elaborated by phosphate-starved cells. We demonstrate and characterize a 5'-nucleotidase activity secreted into the medium of phosphate-starved
efn1
+
efn2
+
cells, which is eliminated by simultaneous deletion of
efn1
and
efn2
. By singly deleting
efn1
and
efn2
, we find that Efn1 contributes the greater share of secreted 5'-nucleotidase activity. Efn1 and Efn2 catalyze the release of inorganic phosphate from all four standard ribonucleoside monophosphates, in order of preference: CMP > UMP > AMP > GMP. Whereas
efn1
+
efn2
+
cells can use extracellular CMP as a source of phosphate during phosphate starvation,
efn1
∆
efn2
∆ cells cannot. The secretion of 5'-nucleotidase enzymes during phosphate limitation is a newly appreciated facet of fission yeast phosphate homeostasis.

IMPORTANCE

Schizosaccharomyces pombe
adapts to phosphate starvation by upregulating the expression of a cell surface acid phosphatase that mobilizes inorganic phosphate from the extracellular milieu, as well as transmembrane transporters that take up inorganic phosphate and glycerophosphocholine. This study identifies two paralogous extracellular 5'-nucleotidase enzymes, Efn1 and Efn2, encoded by genes that are highly transcriptionally induced during acute phosphate starvation, as major proteins secreted into the medium by phosphate-starved fission yeast cells. Secreted Efn1 and Efn2 catalyze the release of inorganic phosphate from all ribonucleoside monophosphates, with a preference for CMP. Secretion of Efn1 and Efn2 enables phosphate-starved fission yeast to thrive by using extracellular CMP as a source of inorganic phosphate. The starvation-induced production of extracellular 5'-nucleotidases adds a new layer of pro-adaptive function during phosphate limitation.
What do women experiencing domestic violence expect from healthcare professionals? A qualitative study in Sri Lanka
Authors: Silva Tharuka , Rathnayake Abey , Evans Maggie , Knipe Duleeka , Rajapakse Thilini , Agampodi Thilini 
Published: December 2024

ObjectivesFor healthcare professionals (HCPs) to provide optimal support for women experiencing domestic violence (DV), it is important to understand what type of support women expect from HCPs. The objective of this study was to explore what kind of support women who experienced DV in Sri Lanka expect from HCPs.DesignA qualitative descriptive design was used.SettingThis study was conducted in two gender-based violence centres (Mithuru Piyasa centres) and a toxicology unit, situated in hospitals in the Central Province of Sri Lanka.ParticipantsTwenty women who had experienced DV and presented to health services were purposefully recruited using the maximum variation sampling technique, ensuring diversity of age and socio-economic variables. In-depth interviews were conducted with women who consented.ResultsWomen who have experienced DV expect varying assistance from HCPs, including changing their abusive partner’s behaviour, resolving their issues or restoring family and marital harmony. Women expect HCPs to intervene in different ways, such as by conversing with both parties or offering support to help the abusive partner overcome alcohol or drug addiction. Women also recommend community-based programmes that concentrate on enhancing marital and family cohesion. Financial and instrumental social support also emerged as key expectations. They anticipate emotional support from HCPs, whom they expect to maintain confidentiality, exhibit empathy, listen attentively and give more importance to DV disclosures. A few women requested referrals to other support services.ConclusionsA multisectoral approach including a proper referral system and social support between health and other social services is a timely recommendation, given the women’s requests for financial and instrumental social support, which go beyond the health sector. The women’s requests for HCPs to talk with both women and their partners to resolve their issues is a more complex and new finding, which warrants further exploration.
Socioeconomic inequality in cervical cancer screening uptake among women in sub-Saharan Africa: a decomposition analysis of Demographic and Health Survey data
Authors: Asgedom Yordanos Sisay , Kassie Gizachew Ambaw , Habte Aklilu , Ketema Daniel Bekele , Aragaw Fantu Mamo 
Published: December 2024

ObjectiveTo examine socioeconomic inequalities in the use of cervical cancer screening among women in sub-Saharan Africa.DesignSecondary data from the Demographic and Health Survey data in sub-Saharan Africa.SettingSub-Saharan Africa.ParticipantsWomen aged 15–64 years.Outcome measuresSocioeconomic inequalities in cervical cancer screening uptake and the pooled prevalence of cervical cancer screening.ResultsThe pooled prevalence of cervical cancer screening among women in sub-Saharan African countries was 10.51% (95% CI: 7.54% to 13.48%). Cervical cancer screening uptake showed a significant pro-rich distribution of wealth-related inequalities, with a weighted Erreygers normalised concentration index of 0.084 and an SE of 0.003 (p value <0.0001). This finding suggests that disparities in cervical cancer screening uptake among women are related to wealth. Decomposition analysis revealed that the wealth index, educational status, place of residence and media exposure were the most important factors contributing to this pro-rich socioeconomic inequality in cervical cancer screening.ConclusionThis study emphasises the importance of addressing modifiable factors such as improving educational opportunities, increasing media exposure accessibility in households and improving the country’s economy to reduce wealth disparities and improve cervical cancer screening uptake among women.
Environmental multiple sclerosis (MS) risk factors, genetic MS risk, and brain development in a general paediatric population
Authors: de Mol Casper Louk , Lamballais Sander , Muetzel Ryan , Duijts Liesbeth , Smolders Joost , White Tonya , Neuteboom Rinze Frederik 
Published: December 2024

BackgroundNeuroaxonal loss occurs in the early stages of multiple sclerosis (MS), but whether it results from early inflammatory brain damage or an ongoing neurodegenerative process remains unclear. We hypothesise that genetic and childhood environmental risk factors for MS may already have an impact on neurodevelopment before the typical age of onset for MS in the general population.MethodsWe examined associations and interactions of genetic and environmental risk factors for MS with brain MRI outcomes, including volumetric (n=5350) and diffusion data (n=5649), at ages 9 and 13 years in a large, population-based childhood cohort without MS diagnoses. Polygenic risk scores (PRSs) were used to assess genetic burden, with rs10191329 as a marker of MS severity. Environmental factors at age 5 included Epstein-Barr virus (EBV) serology, vitamin D status, body mass index, duration of outdoor activities, and household parental smoking.ResultsGenetic data were available for 2817 and 2970 participants with volumetric and diffusion data, respectively. The MS-PRS was positively associated with EBV viral capsid antigen titres among EBV-positive children (β=0.15, p=2.98×10−6). A negative association was observed between the MS-PRS and subcortical grey matter volume (β=−0.03, p=0.014). Interaction between the MS-PRS and household parental smoking was negatively linked to total brain (β=−0.21, p=0.025) and thalamic volumes (β=−0.22, p=0.003), where a higher MS-PRS and household smoking were associated with lower volumes. No associations were observed for rs10191329 with brain outcomes.ConclusionsGenetic and environmental risk factors for MS interact to influence brain volumes in childhood, suggesting a potential window for preventing MS in genetically susceptible individuals by reducing exposure to household smoking.
Effets de la concentration en nutriments des feuilles et de la fertilisation azotée et phosphatée sur la culture du bleuet nain sauvage
Authors: Lafond Jean 
Published: December 2024

Les rendements en fruits du bleuet nain sauvage ( Vaccinium angustifolium Ait.) varient d'un champ à l'autre malgré une fertilisation minérale équivalente. Il serait plausible que le statut nutritif de la plante défini par les concentrations foliaires en éléments nutritifs des feuilles soit responsable de ces variations. L'objectif a été d’évaluer la réponse de la culture à la fertilisation azotée et phosphatée selon les concentrations en azote (N) et phosphore (P) des feuilles prélevées lors de l'année de végétation. Pour évaluer cette réponse, quatre doses de N (0 à 90 kg N ha−1) et trois doses de P (0, 10 et 20 kg P2O5 ha−1) ont été appliquées au printemps de l'année de végétation. Le dispositif expérimental, établi sur 34 sites au Saguenay-Lac-St-Jean, était un factoriel en blocs complets aléatoires. Les rendements en fruits ont augmenté de 25 % avec la fertilisation en N comparativement aux parcelles non fertilisées alors que la fertilisation en P n'a eu aucun effet. Les concentrations en N et P des feuilles ont augmenté significativement avec la fertilisation et étaient significativement corrélées aux rendements. L'accroissement de la productivité par kg de N ajouté a été plus élevé lorsque les concentrations en N et P des feuilles étaient faibles. Ainsi, la concentration en N et P des feuilles a expliqué en partie les variations des rendements mesurées aux différents sites. La fertilisation azotée et phosphatée pourrait donc être ajustée en fonction des concentrations en N et P des feuilles et être diminuée lorsque les concentrations sont optimales.
Quasinormal modes of three $$(2+1)$$-dimensional black holes in string theory, conformal gravity, and Hu–Sawicki F(R) theory via the Heun function
Authors: Naderi F. , Rezaei-Aghdam A. 
Published: December 2024

Abstract
We study the propagation of massless fermionic fields, implementing a family of special functions: Heun functions, in solving the wave equation in three three-dimensional backgrounds, including the BTZ black hole in string theory and Lifshitz black hole solutions in conformal gravity and Hu–Sawicki F(R) theory. The main properties of the selected black hole solutions is that their line elements are Weyl related to that of a homogeneous spacetime, whose spatial part possesses Lie symmetry, described by Lobachevsky-type geometry with arbitrary negative Gaussian curvature. Using the Weyl symmetry of massless Dirac action, we consider the perturbation equations of fermionic fields in relation to those of the homogeneous background, which having definite singularities, are transformed into Heun’s equation. We point out the existence of quasinormal modes labeled by the accessory parameter of the Heun function. The distribution of the quasinormal modes has been clarified to satisfy the boundary conditions that require ingoing and decaying waves at the event horizon and conformal infinity, respectively. It turned out that the procedure based on the Heun function, beside reproducing the previously known results obtained via hypergeometric function for the BTZ and Lifshitz black hole solution in conformal gravity, brings up new families of quasinormal frequencies, which can also contain purely imaginary modes. Also, the analysis of the quasinormal modes shows that with the negative imaginary part of complex frequencies

$$\omega =\omega _{Re}+i\omega _{Im}$$

ω
=

ω

Re

+
i

ω

Im

, the fermionic perturbations are stable in this background.
Collider imprint of vector-like leptons in light of anomalous magnetic moment and neutrino data
Authors: Dehghani Parham , Frank Mariana , Fuks Benjamin 
Published: December 2024

Abstract
We investigate the impact of incorporating vector-like leptons into the Standard Model, aiming to address longstanding puzzles related to the anomalous magnetic moments of the muon and electron while maintaining consistency with neutrino masses and mixings. We find that among the various representations of vector-like leptons permitted by the Standard Model gauge symmetry, only weak doublets and singlets offer satisfactory solutions, all associated with a significantly constrained parameter space. Our analysis delves into the associated parameter space, identifying representative benchmark scenarios suitable for collider studies. These setups yield a distinctive six-lepton signature whose associated signals can easily be distinguished from the Standard Model background, providing a clear signal indicative of new physics models featuring vector-like leptons. Our work hence sheds light on the potential implications of vector-like leptons in resolving discrepancies inherent to the Standard Model, while also offering insights into experimental avenues for further exploration.
BEEx Is an Open-Source Tool That Evaluates Batch Effects in Medical Images to Enable Multicenter Studies
Authors: Wu Yuxin , Xu Xiongjun , Cheng Yuan , Zhang Xiuming , Liu Fanxi , Li Zhenhui , Hu Lei , Madabhushi Anant , Gao Peng , Liu Zaiyi , Lu Cheng 
Published: December 2024

Abstract
The batch effect is a nonbiological variation that arises from technical differences across different batches of data during the data generation process for acquisition-related reasons, such as collection of images at different sites or using different scanners. This phenomenon can affect the robustness and generalizability of computational pathology- or radiology-based cancer diagnostic models, especially in multicenter studies. To address this issue, we developed an open-source platform, Batch Effect Explorer (BEEx), that is designed to qualitatively and quantitatively determine whether batch effects exist among medical image datasets from different sites. A suite of tools was incorporated into BEEx that provide visualization and quantitative metrics based on intensity, gradient, and texture features to allow users to determine whether there are any image variables or combinations of variables that can distinguish datasets from different sites in an unsupervised manner. BEEx was designed to support various medical imaging techniques, including microscopy and radiology. Four use cases clearly demonstrated the ability of BEEx to identify batch effects and validated the effectiveness of rectification methods for batch effect reduction. Overall, BEEx is a scalable and versatile framework designed to read, process, and analyze a wide range of medical images to facilitate the identification and mitigation of batch effects, which can enhance the reliability and validity of image-based studies.
Significance: BEEx is a prescreening tool for image-based analyses that allows researchers to evaluate batch effects in multicenter studies and determine their origin and magnitude to facilitate development of accurate AI–based cancer models.
LSD flattens the hierarchy of directed information flow in fast whole-brain dynamics
Authors: Shinozuka Kenneth , Tewarie Prejaas K.B. , Luppi Andrea , Lynn Christopher , Roseman Leor , Muthukumaraswamy Suresh , Nutt David J. , Carhart-Harris Robin , Deco Gustavo , Kringelbach Morten L. 
Published: December 2024

Abstract
Psychedelics are serotonergic drugs that profoundly alter consciousness, yet their neural mechanisms are not fully understood. A popular theory, RElaxed Beliefs Under pSychedelics (REBUS), posits that psychedelics flatten the hierarchy of information flow in the brain. Here, we investigate hierarchy based on the imbalance between sending and receiving brain signals, as determined by directed functional connectivity. We measure properties of directed functional hierarchy in a magnetoencephalography (MEG) dataset of 16 healthy human participants who were administered a psychedelic dose (75 micrograms, intravenous) of lysergic acid diethylamide (LSD) under four different conditions: eyes-closed with or without music and eyes-open with or without a video stimulus. Across the whole brain, LSD diminishes the asymmetry of directed connectivity when averaged across time. Additionally, we demonstrate that machine learning classifiers distinguish between LSD and placebo more accurately when trained on one of our hierarchy metrics than when trained on traditional measures of functional connectivity. Taken together, these results indicate that LSD weakens the hierarchy of directed connectivity in the brain by increasing the balance between senders and receivers of neural signals.