bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation
Authors: Slager Jelle , Simpson Hanna L. , Gacesa Ranko , Chen Lianmin , Tan Ineke L. , Gelderloos Jody , Maatman Astrid , Wijmenga Cisca , Zhernakova Alexandra , Fu Jingyuan , Weersma Rinse K. , Gonera Gieneke , Jonkers Iris H. , Withoff Sebo 
Published: March 2024

AbstractBackgroundCoeliac disease (CeD) is an immune-mediated disorder primarily affecting the small intestine, characterised by an inflammatory immune reaction to dietary gluten. CeD onset results from a multifaceted interplay of genetic and environmental factors. While recent data show that alterations in gut microbiome composition could play an important role, many current studies are constrained by small sample sizes and limited resolution.MethodsTo address these limitations, we analysed faecal gut microbiota from two Dutch cohorts, CeDNN (128 treated CeD patients (tCeD), 106 controls) and the Lifelines Dutch Microbiome Project (24 self-reported tCeD, 654 controls), using shotgun metagenomic sequencing. Self-reported IBS (570 cases, 1710 controls) and IBD (93 cases, 465 controls) were used as comparative conditions of the gastrointestinal tract. Interindividual variation within the case and control groups was calculated at whole microbiome and strain level. Finally, species-specific gene repertoires were analysed in tCeD patients and controls.ResultsWithin-individual microbiome diversity was decreased in patients with self-reported IBS and IBD but not in tCeD patients. Each condition displayed a unique microbial pattern and, in addition to confirming previously reported microbiome associations, we identify an increase in the levels ofClostridium sp. CAG:253,Roseburia hominis, andEggerthella lenta, amongst others. We further show that the observed changes can partially be explained by gluten-free diet adherence. We also observe increased interindividual variation of gut microbiome composition among tCeD patients and a higher bacterial mutation frequency in tCeD that contributes to higher interindividual variation at strain level. In addition, the immotile European subspecies ofEubacterium rectale, which has a distinct carbohydrate metabolism potential, was nearly absent in tCeD patients.ConclusionOur study sheds light on the complex interplay between the gut microbiome and CeD, revealing increased interindividual variation and strain-level variation in tCeD patients. These findings expand our understanding of the microbiome’s role in intestinal health and disease.HighlightsThis is the largest microbiome collection of coeliac disease (CeD) patients assembled to date, providing insights into gut microbiome composition down to strain level.Compared to controls, treated CeD (tCeD) patients adhering to a gluten-free diet show novel gut microbiome associations.tCeD patients also have a less uniform gut microbiome than controls.Bacteria display higher mutation frequency in tCeD compared to controls.Hallmarks of the European subspecies ofEubacterium rectaleare nearly absent in tCeD patients, implying selection at strain level.
Variant mutation in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation
Authors: Kubinski Hannah C. , Despres Hannah W. , Johnson Bryan A. , Schmidt Madaline M. , Jaffrani Sara A. , Mills Margaret G. , Lokugamage Kumari , Dumas Caroline M. , Shirley David J. , Estes Leah K. , Pekosz Andrew , Crothers Jessica W. , Roychoudhury Pavitra , Greninger Alexander L. , Jerome Keith R. , Di Genova Bruno Martorelli , Walker David H. , Ballif Bryan A. , Ladinsky Mark S. , Bjorkman Pamela J. , Menachery Vineet D. , Bruce Emily A. 
Published: March 2024

ABSTRACTThe evolution of SARS-CoV-2 variants and their respective phenotypes represents an important set of tools to understand basic coronavirus biology as well as the public health implications of individual mutations in variants of concern. While mutations outside of Spike are not well studied, the entire viral genome is undergoing evolutionary selection, particularly the central disordered linker region of the nucleocapsid (N) protein. Here, we identify a mutation (G215C), characteristic of the Delta variant, that introduces a novel cysteine into this linker domain, which results in the formation of a disulfide bond and a stable N-N dimer. Using reverse genetics, we determined that this cysteine residue is necessary and sufficient for stable dimer formation in a WA1 SARS-CoV-2 background, where it results in significantly increased viral growth bothin vitroandin vivo. Finally, we demonstrate that the N:G215C virus packages more nucleocapsid per virion and that individual virions are larger, with elongated morphologies.
Click-free imaging of carbohydrate trafficking in live cells using an azido photothermal probe
Authors: Xia Qing , Perera Harini A. , Bolarinho Rylie , Piskulich Zeke A. , Guo Zhongyue , Yin Jiaze , He Hongjian , Li Mingsheng , Ge Xiaowei , Cui Qiang , Ramström Olof , Yan Mingdi , Cheng Ji-Xin 
Published: March 2024

AbstractReal-time tracking of intracellular carbohydrates remains challenging. While click chemistry allows bio-orthogonal tagging with fluorescent probes, the reaction permanently alters the target molecule and only allows a single snapshot. Here, we demonstrate click-free mid-infrared photothermal (MIP) imaging of azide-tagged carbohydrates in live cells. Leveraging the micromolar detection sensitivity for 6-azido-trehalose (TreAz) and the 300-nm spatial resolution of MIP imaging, the trehalose recycling pathway in single mycobacteria, from cytoplasmic uptake to membrane localization, is directly visualized. A peak shift of azide in MIP spectrum further uncovers interactions between TreAz and intracellular protein. MIP mapping of unreacted azide after click reaction reveals click chemistry heterogeneity within a bacterium. Broader applications of azido photothermal probes to visualize the initial steps of the Leloir pathway in yeasts and the newly synthesized glycans in mammalian cells are demonstrated.
A consensus motif inASH1and further transcripts unifies several RNA motifs required for interaction with the She2p/She3p transport machinery and mRNA localization in yeast
Authors: Seiler Markus , Niedner Annika , Heber Simone , Feldbrügge Michael , Jansen Ralf-Peter , Niessing Dierk , Zarnack Kathi 
Published: March 2024

AbstractAsymmetric localization of theASH1transcript is a central step in the regulation of mating type switching inSaccharomyces cerevisaeand a paradigm for localized mRNAs specifically recognized by the She2p/3p transport machinery. Four RNA elements inASH1are known to mediate bud localization, but it remained unclear what a consensus motif of all four She2p/3p recognition sites (SRS) might look like. In this study, we derive the SRS consensus motif, which is characterized by an L-shaped, double-stranded RNA conformation with two cytosine-containing sequence motifs at conserved positions and a central asymmetric bulge. It is noteworthy that the spatial arrangement of these features can be retained, despite their altered order within the nucleotide sequence. We termed these variations “configurations” and confirmed in biochemical studies that SRS function inASH1elements is preserved when changing configurations. We tested other known and predicted SRS elements in target transcripts of She2p/3p by biochemical and biophysical studies and confirmed the conserved SRS function even in switched configuration. Consistently, we present theSRS instance collection, which includes further predictions of SRS instances of transcript targets of the She2p/3p translocation pathway.
Latent tuberculosis infection and incident cardiovascular and non-cardiovascular death
Authors: Magodoro Ita M , Wilkinson Katalina A , Claggett Brian L , Aluoch Aloice , Siedner Mark J , Ntsekhe Mpiko , Ntusi Ntobeko AB , Nyirenda John M , Wilkinson Robert J 
Published: March 2024

SummaryActive tuberculosis may heighten the risk of incident cardiovascular morbidity and premature mortality, whereas whether latent TB infection (LTBI) recapitulates these adverse outcomes is unclear. We evaluated the effect of LTBI on all-cause and cardiovascular-specific death among US adults who underwent tuberculin skin testing in 1999-2000 and were followed up to December 31st, 2019. We also examined the impact of co-occuring traditional risk factors on these outcomes. Adjustments were made for socio-economic and demographic factors. LTBI was defined as tuberculin skin induration ≥10mm, and cause of death as cardiovascular if from heart or cerebrovascular diseases, and non-cardiovascular if otherwise. LTBI was associated with increased of overall and non-cardiovascular specific death but not cardiovascular-specific death. Risk of death was highest when LTBI was comorbid LTBI with diabetes. LTBI may increase risk of death by mechanisms other than progression to active TB disease.
Novel Ser74 of NF-κB/CgIκBα Phosphorylated by MAPK/ERK Regulates Temperature Adaptation in Oysters
Authors: Wang Chaogang , Jiang Zhuxiang , Du Mingyang , Cong Rihao , Wang Wei , Zhang Taiping , Chen Jincheng , Zhang Guofan , Li Li 
Published: March 2024

AbstractPhosphorylation of IκBα at Ser32 and Ser36 by IKKs during biotic stress triggers its ubiquitin-proteasome degradation, causing to the nuclear translocation of REL, representing a key cascade mechanism in metazoans conserved and immune core signaling pathway, NF-κB. However, studies on its response to abiotic stress and signal transduction by phosphorylation in mollusks are lacking. Here, we firstly report a novel heat-induced phosphorylation site (Ser74) at the major NF-κB/CgIκBα of oysters, phosphorylated by MAPK/CgERK1/2, which independently mediated the subsequent ubiquitin-proteasome degradation without phosphorylation at Ser32 and Ser36 and decreased thermal stability. The degradation ofCgIκBα promotedCgREL nuclear translocation, which stimulated cell survival related gene expression to defend against thermal stress. The MAPK and NF-κB pathways exhibited stronger activation patterns in higher environmental temperature and in the warm-adaptedCrassostrea angulatathan those in the cold-adaptedC. gigas-two allopatric congeneric oyster species with differential habitat temperatures. These findings unveil the complex and unique phosphorylation-mediated signal transduction mechanisms in marine invertebrates, and further expand our understanding of the evolution and function of established classical pathway crosstalk mechanisms.
Pre-trained molecular representations enable antimicrobial discovery
Authors: Olayo-Alarcon Roberto , Amstalden Martin K. , Zannoni Annamaria , Bajramovic Medina , Sharma Cynthia M. , Brochado Ana Rita , Rezaei Mina , Müller Christian L. 
Published: March 2024

AbstractThe rise in antimicrobial resistance poses a worldwide threat, reducing the efficacy of common antibiotics. Determining the antimicrobial activity of new chemical compounds through experimental methods is still a time-consuming and costly endeavor. Compound-centric deep learning models hold the promise to speed up this search and prioritization process. Here, we introduce a lightweight computational strategy for antimicrobial discovery that builds onMolE(Molecular representation through redundancy reducedEmbedding), a deep learning framework that leverages unlabeled chemical structures to learn task-independent molecular representations. By combiningMolErepresentation learning with experimentally validated compound-bacteria activity data, we design a general predictive model that enables assessing compounds with respect to their antimicrobial potential. The model correctly identified recent growth-inhibitory compounds that are structurally distinct from current antibiotics and discoveredde novothree human-targeted drugs asStaphylococcus aureusgrowth inhibitors which we experimentally confirmed. Our framework offers a viable cost-effective strategy to accelerate antibiotics discovery.
Estradiol and Flutamide Effects on the Song System of Developing Male Zebra Finches
Authors: Grisham William , McCormick Mary Ellen 
Published: March 2024

AbstractEstradiol (E2) masculinizes the developing song system of female zebra finches (Taeniopygia castanotis) if it is administered in early life, but the effects of E2on the developing song system in males have not been thoroughly explored. Also, reports of early antiandrogen administration in developing male zebra finches differ in their findings. Therefore. this study was conducted to further explore the effects of administering E2alone, flutamide (Flut) alone, or the two in combination during early development. Brains and testes were examined after day 100. The results showed definite demasculinizing effects of early E2on the song nucleus HVC (proper name)—its volume and neuron number were markedly reduced. Nonetheless, early E2hypermasculinized HVC neuronal size. Flut slightly hypermasculinized RA volume (Robust nucleus of the Arcopallium), which replicates a previous study, but the absence of any additional effects is at odds with other studies. Arguments are put forward suggesting that early E2action on HVC development could be a consequence of differential steroid action on the male versus female genotype and/or a disruption of the temporal sequence of gene regulation in developing males. Early E2resulted in markedly reducing testes size, which is likely to be a consequence of hijacking endogenous endocrine feedback mechanisms. The reduction in testes size suggests low steroid secretion, which also could contribute to the demasculinization of HVC.
Enhanced tameness byLimosilactobacillus reuterifrom gut microbiota of selectively bred mice
Authors: Biswa Bhim B. , Mori Hiroshi , Toyoda Atsushi , Kurokawa Ken , Koide Tsuyoshi 
Published: March 2024

AbstractDomestication alters animal behaviour, primarily their tameness. In this study, we examine the effect of gut bacteria on mouse tameness. We previously conducted selective breeding for active tameness, defined as the motivation to approach a human hand, using genetically heterogeneous mice derived from eight wild inbred strains. We examined gut microbiota in the selectively bred mice by analysing faecal samples from 80 mice through shotgun metagenomic analysis. In the current study, we found that the selectively bred mice exhibit higher levels of active tameness as well as higher levels of blood oxytocin, which plays a key role in social behaviours. Selection for tameness did not substantially alter the taxonomic or functional diversity of the gut microbiota. However, we observed an increased abundance ofLimosilactobacillus reuteriin the selected groups and higher pyruvate levels in their plasma. We isolatedL. reuteristrains secreting extracellular pyruvate from mice faeces and administrated the cultured bacteria through drinking water. Mice treated withL. reuterishowed higher colonization of the bacteria in the gut, as well as higher levels of active tameness behaviour and blood oxytocin. Additionally, we generated 374 high-quality metagenome-assembled genomes (MAGs) of bacteria across 11 phyla. This collection includes 27 novel species level bacterial MAGs not previously known to exist in the mouse gut. This study elucidates the potential role ofL. reuteriin the animal domestication process and explores the underlying mechanisms that may influence this process.
Rem2 interacts with CaMKII at synapses and restricts long-term potentiation in hippocampus
Authors: Anjum Rabia , Clarke Vernon R J , Nagasawa Yutaro , Murakoshi Hideji , Paradis Suzanne 
Published: March 2024

AbstractSynaptic plasticity, the process whereby neuronal connections are either strengthened or weakened in response to stereotyped forms of stimulation, is widely believed to represent the molecular mechanism that underlies learning and memory. The holoenzyme CaMKII plays a well-established and critical role in the induction of a variety of forms of synaptic plasticity such as long-term potentiation (LTP), long-term depression (LTD) and depotentiation. Previously, we identified the GTPase Rem2 as a potent, endogenous inhibitor of CaMKII. Here, we report that knock out ofRem2enhances LTP at the Schaffer collateral to CA1 synapse in hippocampus, consistent with an inhibitory action of Rem2 on CaMKII in vivo. Further, re-expression of WT Rem2 rescues the enhanced LTP observed in slices obtained fromRem2conditional knock out (cKO) mice, while expression of a mutant Rem2 construct that is unable to inhibit CaMKII in vitro fails to rescue increased LTP. In addition, we demonstrate that CaMKII and Rem2 interact in dendritic spines using a 2pFLIM-FRET approach. Taken together, our data lead us to propose that Rem2 serves as a brake on runaway synaptic potentiation via inhibition of CaMKII activity. Further, the enhanced LTP phenotype we observe inRem2cKO slices reveals a previously unknown role for Rem2 in the negative regulation of CaMKII function.
Inhibition ofStreptococcus pyogenesbiofilm byLactiplantibacillus plantarumandLacticaseibacillus rhamnosus
Authors: Gómez-Mejia Alejandro , Orlietti Mariano , Tarnutzer Andrea , Shambat Srikanth Mairpady , Zinkernagel Annelies S. 
Published: March 2024

AbstractThe human pathobiontStreptococcus pyogenesforms biofilms and causes invasive infections, such as pharyngotonsillitis and necrotizing fasciitis. Bacterial biofilms are more resilient to antibiotic treatment and new therapeutic strategies are needed to control biofilm-associated infections, such as recurrent pharyngotonsillitis.Lactiplantibacillus plantarumandLacticaseibacillus rhamnosusare two bacterial commensals used for their probiotic properties. This study aimed to elucidate the anti-biofilm properties ofL. plantarumandL. rhamnosuscell-free supernatants (LPSN and LRSN, respectively) onS. pyogenesbiofilms grownin vitroin supplemented minimal medium. When planktonic or biofilmS. pyogeneswere exposed to LPSN or LRSN,S. pyogenessurvival was reduced significantly in a concentration-dependent manner and the effect was more pronounced on preformed biofilms. Enzymatic digestion of LPSN and LRSN suggested that glycolipid compounds might cause the antimicrobial effect. In conclusion, this study indicates thatL. plantarumandL. rhamnosusproduce glycolipid bioactive compounds that reduceS. pyogenesviability in planktonic and biofilm cultures.
We can be heroes at work: the relationship between psychological capital, motivation and well-being during the great resignation
Authors: Plessis Cédric , Altintas Emin 
Published: March 2024

PurposeThe Great Resignation has led to a significant increase in the number of people quitting their jobs due to reasons such as stagnant wages, rising cost of living, job dissatisfaction and safety concerns. Therefore, the aim of this study is that it is important to help people develop better cognitive resources to face adversity.Design/methodology/approachThe Great Resignation has led to a significant increase in the number of people quitting their jobs due to reasons such as stagnant wages, rising cost of living, job dissatisfaction and safety concerns. Therefore, it is important to help people develop better cognitive resources to face adversity. In this study, we administered a questionnaire to 250 employees to determine the variables that could help them build cognitive resources. These variables included the satisfaction of basic psychological needs (autonomy, competence and affiliation), psychological capital, motivation regulation (within the self-determination theory) and well-being (assessed by self-esteem, positive emotions, positive automatic thoughts and vitality). The results revealed that satisfaction of basic needs is associated with better psychological capital and more self-autonomous behavior, which leads to higher psychological well-being. These findings are discussed in the paper, emphasizing the importance of management and work context that satisfy the basic needs and help to build resources with psychological capital.FindingsThe results revealed that satisfaction of basic needs is associated with better psychological capital and more self-autonomous behavior, which leads to higher psychological well-being. These findings are discussed in the paper, emphasizing the importance of management and work context that satisfy the basic needs and help to build resources with psychological capital.Originality/valueHighlight the importance of consequences of the Great Resignation and the need to internationalize this concept.
The role of lived experience eye care champions in improving awareness and access to eye care services for people with learning disabilities and/or autism
Authors: Karas Marek , O'Brien Donna , Campbell Lance , Lunness Rebecca , Kennedy Joanne , McGill Grace , Kill Stephen , Donaldson Lisa 
Published: March 2024

AbstractBackgroundDocumented inequalities in access to eye care for people with learning disabilities and/or autism are caused by poor uptake of primary eye care services, poor identification of eye problems, lack of signposting and reasonable adjustments of existing services, concerns about costs of care and the low priority historically given to these issues in eye care policy at a regional and national level. In 2019, the charity SeeAbility employed four eye care champions (ECCs) with lived experience of learning disability and/or autism to work in local communities in London and the Northwest of England. They provided peer‐to‐peer support on understanding the need for good eye health and engaged with policy makers, and learning disability, autism and eye care professionals at the local, regional and national levels to influence both the clinical practice of individual practitioners (within existing service/pathway models) and more widely to influence the commissioning of the Easy Eye Care pathway. This study explores the experiences of these ECCs.MethodsThe study was conducted in April and May 2023. A case study approach was used to describe the experiences of the ECCs from March 2019 to March 2023. Data from structured interviews with the four ECCs and workload analysis were triangulated to provide a multifaceted understanding of this novel health promotion project.FindingsThe ECCs found the role useful and reported that confidence in their practice and impact grew with time but they required ongoing support in the role. A good understanding of the promotional messages was reported. Developing a good network of contacts at an early stage, both people with learning disabilities and healthcare professionals, was key. Relationships with professionals were supportive and positive and a positive emotive response to their lived experience was reported in these interactions.ConclusionsFrom the perspective of the ECCs, the role is useful and beneficial. The work suggests some key recommendations for future development which include planning to build networks, support in presentation and communications skills and defining key messages and knowledge. Confidence of the ECCs builds with time in the role but also needs support the emotive impact of their lived experiences on audiences is highlighted. There is a need to evaluate how the programme is perceived by those who interact with it and how it changes behaviours which leads to better health outcomes.