bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peer Education Intervention Reduced Sexually Transmitted Infections Among Male Tajik Labor Migrants Who Inject Drugs: Results of a Cluster-randomized Controlled Trial
Authors: Mackesy-Amiti Mary Ellen , Levy Judith A. , Luc Casey M. , Jonbekov Jonbek 
Published: August 2024

AbstractBackgroundIn a cluster-randomized controlled trial, the “Migrants’ Approached Self-Learning Intervention in HIV/AIDS for Tajiks” (MASLIHAT) reduced intervention participants’ sexual risk behaviour including any condomless sex, condomless sex with female sex workers, and multiple sexual partners. This analysis investigates if observed changes in sexual risk behaviors translated into fewer reported STIs among participants over 12-month follow-up.MethodsThe MASLIHAT intervention was tested in a cluster-randomized controlled trial with sites assigned to either the MASLIHAT intervention or comparison health education training (TANSIHAT). Participants and network members (n=420) were interviewed at baseline and 3-month intervals for one year to assess HIV/STI sex and drug risk behaviour. We conducted mixed effects robust Poisson regression analyses to test for differences between conditions in self-reported STIs during 12 months of follow-up, and to test the contribution of sexual risk behaviours to STI acquisition. We then tested the mediating effects of sexual behaviours during the first six months following the intervention on STIs reported at the 9 and 12-month follow-up interviews.ResultsParticipants in the MASLIHAT condition were significantly less likely to report an STI during follow-up (IRR=0.27, 95% CI 0.13-0.58). Condomless sex with a non-main (casual or commercial) partner was significantly associated with STI acquisition (IRR=2.30, 95% CI 1.26-4.21). Adjusting for condomless sex with a non-main partner, the effect of MASLIHAT intervention participation was reduced (IRR=0.36, 95% CI 0.16-0.80), signalling possible mediation. Causal mediation analysis indicated that the intervention’s effect on reported STI was partially mediated by reductions among MASLIHAT participants in condomless sex with a non-main partner.ConclusionsThe MASLIHAT peer-education intervention reduced reported STIs among Tajik labour migrants partly through reduced condomless sex with casual and commercial partners.Clinical trial registrationClinicalTrials.gov, 2021-04-16,NCT04853394.
Implementation and adaptation of WASH FIT in healthcare facilities: A systematic scoping review
Authors: Kpodzro Sena , Cronk Ryan , Lineberger Hannah , Lansing Lauren , Anderson Darcy M. 
Published: August 2024

AbstractEnvironmental health services (e.g., water, sanitation, hygiene, energy) are important for patient safety and strong health systems, yet services in many low- and middle-income countries are poor. To address this, the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF) developed the Water and Sanitation for Health Facility Improvement Tool (WASH FIT) to drive improvements. While widely used, there is currently no systematic documentation of how WASH FIT has been adapted in different contexts and the implications of these adaptations. We conducted a systematic scoping review to assess WASH FIT adaptation and implementation, specifically evaluating context and implementing stakeholders, the WASH FIT process and adaptation, and good practices for implementation. Our search yielded 20 studies. Implementation was typically government-led or had a high level of government engagement. Few details on healthcare facility contexts were reported. Adaptation was widespread, with nearly all studies deviating from the five-step WASH FIT cycle as designed in the WHO/UNICEF manual. Notably, many studies conducted only one facility assessment and one or no rounds of improvement. However, reporting quality across studies was poor, and some steps may have been conducted but not reported. Despite substantial deviations, WASH FIT was favorably described by all studies. Good practices for implementation included adequate resourcing, government leadership, and providing WASH FIT teams with sufficient training and autonomy to implement improvements. Low-quality reporting and a high degree of adaptation make it challenging to determine how and why WASH FIT achieves change. We hypothesize that healthcare-facility level action by WASH FIT teams to assess conditions and implement improvements has some effect. However, advocacy that uses WASH FIT indicators to highlight deficiencies and promotion of WASH FIT by WHO and UNICEF to pressure governments to act may be equally or more powerful drivers of change. More rigorous evidence to understand how and why WASH FIT works is essential to improve its performance and inform scale-up.HighlightsAdaptation in WASH FIT programs is common but not always evidence-basedSome programs initiate WASH FIT assessments but never implement improvementsSome programs complete one round of improvements but never iterate the WASH FIT cycleLow-quality evidence impedes research to identify WASH FIT’s theory of changeWASH FIT may drive change through national advocacy and peer pressure to unlock funding
Chemotherapy causes a reversible decrease inVMP1/MIR21DNA methylation in granulocytes from breast cancer survivors
Authors: Abrahamsen Marie-Louise , Jachowicz Zuzanna , Buch-Larsen Kristian , Marina Djordje , Andersson Michael , Schwarz Peter , Dela Flemming , Gillberg Linn 
Published: August 2024

AbstractBackgroundDNA methylation alterations within theVMP1/MIR21gene region, a potential epigenetic biomarker of systemic inflammation, have been demonstrated in mononuclear blood cells from early breast cancer (BC) patients after chemotherapy. Whether these changes are present in granulocytes, persist in the years after treatment, and affectVMP1orMIR21gene expression, remains unknown.AimWe aimed to investigate whether adjuvant chemotherapy alters the DNA methylation and gene expression ofVMP1/MIR21in granulocytes from postmenopausal BC patients and, if so, whether these treatment-induced changes are reversible in the first two years after completed chemotherapy.MethodsWhole blood samples were obtained from 30 postmenopausal BC patients before chemotherapy and every six months for two years, and from 10 healthy age- and BMI-matched controls. DNA and RNA was extracted from isolated granulocytes, and DNA methylation of four CpG sites located in the gene body ofVMP1, which is situated in the promoter region ofMIR21, was assessed through bisulfite pyrosequencing. qPCR was used for assessment ofVMP1andMIR21expression.ResultsVMP1/MIR21was significantly demethylated in granulocytes from BC patients shortly after completed chemotherapy compared to before (10 percentage points decrease,p<0.0001). Six months thereafter, DNA methylation values were significantly increased (6 percentage points, p = 0.002), and they were further increased to pre-chemotherapy levels 12, 18 and 24 months post chemotherapy. Chemotherapy did not cause significant changes in the expression ofVMP1orMIR21.ConclusionThe unique follow-up samples in this study demonstrated that chemotherapy induced a transient reduction in DNA methylation of theVMP1/MIR21region in granulocytes from postmenopausal BC patients. Although transient, chemotherapy-induced epigenetic changes in blood cells may contribute to the increased risk of inflammatory-related comorbidities in BC survivors.
Cappable-Seq reveals the transcriptional landscape of stress responses in the bacterial endosymbiontWolbachia
Authors: Suliman Youseuf , Li Zhiru , Sinha Amit , Dyer Philip D. , Hartley Catherine S. , Darby Alistair C. , Carlow Clotilde K. , Makepeace Benjamin L. 
Published: August 2024

AbstractBacterial endosymbionts are highly prevalent among invertebrate animals, in which they can confer fitness benefits such as pathogen defence and/or act as reproductive manipulators, inducing phenotypes including cytoplasmic incompatibility (CI). For the alpha-proteobacteriumWolbachia, its wide distribution among macroparasites and disease-transmitting arthropods coupled with mutualistic roles, reduction of vector competence, and CI have found recent applications in the control of several vector-borne tropical diseases. However, in common with other bacterial endosymbionts, which often lose regulatory elements during genomic erosion, the degree to whichWolbachiacan respond to environmental or pharmacological stressors is poorly understood. Here, we apply Cappable-Seq methodology to achieve unprecedented depth and resolution of transcriptional start sites (TSS) in twoWolbachiastrains (wMelPop-CLA andwAlbB) that have been used to transinfect mosquitoes for arbovirus control. We exposedWolbachiain mosquito cell lines to temperature stress (both strains) or antibiotics (wAlbB only) and observed that all classes of TSS (including antisense) exhibited differential regulation, some of which were associated with mobile elements and may control ncRNA expression. Cappable-Seq also resolved the organisation of the bicistroniccifA/cifBoperon that is responsible for inducing CI inWolbachiahosts and shows great promise for revealing regulation of symbiont functions in whole invertebrates.
HSP90 interacts with VP37 to facilitate the cell-to-cell movement of broad bean wilt virus 2
Authors: Kim Myung-Hwi , Jang Seok-Yeong , Choi Ji-Soo , Kim Sora , Lee Yubin , Park Suejin , Kwon Sun-Jung , Seo Jang-Kyun 
Published: August 2024

ABSTRACTThe systemic spread of viruses in plants requires successful viral cell-to-cell movement through plasmodesmata (PD). Viral movement proteins (MPs) interact with cellular proteins to modify and utilize host transport routes. Broad bean wilt virus 2 (BBWV2), a widespread plant RNA virus, moves from cell to cell as a virion through the PD gated by VP37, the MP of BBWV2. However, the host proteins that function in the cell-to-cell movement of BBWV2 remain unclear. In this study, we identified cellular heat shock protein 90 (HSP90) as an interacting partner of VP37. The interaction between HSP90 and VP37 was assessed using the yeast two-hybrid assay, co-immunoprecipitation, and bimolecular fluorescence complementation. Tobacco rattle virus-based virus-induced gene silencing analysis revealed thatHSP90silencing significantly inhibited the systemic spread of BBWV2 inN. benthamianaplants. Furthermore,in plantatreatment with geldanamycin (GDA), an inhibitor of the chaperone function of HSP90, demonstrated the necessity of HSP90 in successful cell-to-cell movement and systemic infection of BBWV2. Interestingly, GDA treatment inhibited the HSP90-VP37 interaction at the PD, resulting in the inhibition of VP37-derived tubule formation through the PD. Our results suggest that the HSP90-VP37 interaction regulates VP37-derived tubule formation through the PD, thereby facilitating the cell-to-cell movement of BBWV2.IMPORTANCEThis study highlights the regulatory role of heat shock protein 90 (HSP90) in facilitating the cell-to-cell movement of broad bean wilt virus 2 (BBWV2). HSP90 interacted with VP37, the movement protein of BBWV2, specifically at plasmodesmata (PD). This study demonstrated that the HSP90-VP37 interaction is crucial for viral cell-to-cell movement and the formation of VP37-derived tubules, which are essential structures for virus transport through the PD. The ATP-dependent chaperone activity of HSP90 is integral to this interaction, as demonstrated by the inhibition of virus movement upon treatment with geldanamycin (GDA), which disrupts the function of HSP90. These findings elucidate the molecular mechanisms underlying the cell-to-cell movement of plant viruses, and highlight the role of HSP90 in viral infection. This study suggests that the chaperone activity of HSP90 may function in changing the conformational structure of VP37, thereby facilitating the assembly and function of virus-induced structures required for viral cell-to-cell movement.
Serum Amyloid P Secreted by Bone Marrow Adipocytes Drives Skeletal Amyloidosis
Authors: Kumar Surendra , Song Kangping , Wang Jiekang , Baghel Meghraj Singh , Wong Philip , Cao Xu , Wan Mei 
Published: August 2024

SUMMARYThe accumulation of amyloid fibrils has been identified in tissues outside the brain, yet little is understood about the formation of extracerebral amyloidosis and its impact on the aging process of these organs. Here, we demonstrate that both transgenic mice modeling Alzheimer’s disease (AD) and naturally aging mice exhibit accumulated senescent bone marrow adipocytes (BMAds), accompanied by amyloid deposits surrounding the BMAds. Senescent BMAds acquire a secretory phenotype, resulting in a marked increase in the secretion of serum amyloid P component (SAP), also known as pentraxin 2 (PTX2). SAP/PTX2 colocalizes with amyloid deposits around senescent BMAdsin vivoand is sufficient to promote the formation of insoluble amyloid deposits from soluble Aβ peptides inin vitroandex vivo3D BMAd-based culture experiments. Additionally, Combined treatment with SAP/PTX2 and Aβ peptides promotes osteoclastogenesis but inhibits osteoblastogenesis of the precursor cells. Transplantation of senescent BMAds into the bone marrow cavity of healthy young mice is sufficient to induce bone loss. Finally, pharmacological depletion of SAP/PTX2 from aged mice abolishes bone marrow amyloid deposition and effectively rescues the low bone mass phenotype. Thus, senescent BMAds, through the secretion of SAP/PTX2, contribute to the age-associated development of skeletal amyloidosis and resultant bone deficits.
Membrane tension regulation is required for wound repair
Authors: Raj Nikita , Weiss Martin , Vos Bart E. , Weischer Sarah , Brinkmann Frauke , Betz Timo , Trappmann Britta , Gerke Volker 
Published: August 2024

AbstractDisruptions of the eukaryotic plasma membrane due to chemical and mechanical challenges are frequent and detrimental, and thus need to be repaired to maintain proper cell function and avoid cell death. However, the cellular mechanisms involved in wound resealing and restoration of homeostasis are diverse and contended. Here, we show that clathrin-mediated endocytosis is induced at later stages of plasma membrane wound repair following the actual resealing of the wound. This compensatory endocytosis occurs near the wound, predominantly at sites of previous early endosome exocytosis which is required in the initial stage of membrane resealing, suggesting a spatio-temporal co-ordination of exo- and endocytosis during wound repair. Using cytoskeletal alterations and modulation of membrane tension and membrane area, we identify membrane tension as a major regulator of the wounding-associated exo- and endocytic events that mediate efficient wound repair. Thus, membrane tension changes are a universal trigger for plasma membrane wound repair modulating the exocytosis of early endosomes required for resealing and subsequent clathrin-mediated endocytosis acting at later stages to restore cell homeostasis and function.
A widespread hydrogenase drives fermentative growth of gut bacteria in healthy people
Authors: Welsh Caitlin , Cabotaje Princess R. , Marcelino Vanessa R. , Watts Thomas D. , Kountz Duncan J. , Gould Jodee A. , Doan Nhu Quynh , Lingford James P. , Solari Jessica , D’Adamo Gemma L. , Huang Ping , Bong Natasha , Gulliver Emily L. , Young Remy B. , Walter Kaija , Wolf Patricia G. , Ridlon Jason M. , Gaskins H. Rex , Giles Edward M. , Lyras Dena , Lappan Rachael , Berggren Gustav , Forster Samuel C. , Greening Chris 
Published: August 2024

AbstractMolecular hydrogen (H2) is among the most central, but least understood, metabolites in the human gastrointestinal tract (gut). H2gas is produced in large quantities during bacterial fermentation and consumed as an energy source by bacteria and archaea. Disruption of H2cycling is linked to gastrointestinal disorders, infections, and cancers, with H2used as an indicator of gut dysfunction through breath tests. Despite this, the microorganisms, pathways, and enzymes mediating H2production remain unresolved. Here we show that a previously uncharacterised enzyme, the group B [FeFe]-hydrogenase, drives most fermentative H2production in the human gut. Analysis of stool, biopsy, and isolate (meta)genomes and (meta)transcriptomes show this hydrogenase is encoded by most gut bacteria and is highly expressed. Through analysis of 19 taxonomically diverse gut isolates, the group B [FeFe]-hydrogenase produces large amounts of H2gas and supports fermentative growth of both Bacteroidetes and Firmicutes.Bacteroidesparticularly dominate H2production. Biochemical and spectroscopic characterisation shows purified group B [FeFe]-hydrogenases are catalytically active and bind a di-iron active site. These hydrogenases are highly enriched in the guts of healthy individuals, but significantly depleted in favour of other fermentative hydrogenases in Crohn’s disease. Furthermore, we show that metabolically flexible respiratory bacteria are the most abundant H2oxidizers in the gut, not sulfate reducers, methanogens, and acetogens as previously thought. This combination of enzymatic, cellular, and ecosystem-level analysis provides the first detailed understanding of H2cycling in the human gut and reveals new links between microbiota function and gastrointestinal health.
Viral and bacterial plant pathogens suppress antiviral defense against flaviviruses in their insect vectors
Authors: Larrea-Sarmiento Adriana , Olmedo-Velarde Alejandro , West-Ortiz Michael , Stuehler Douglas , Hosseinzadeh Saeed , Coleman Aminah , Preising Stephanie , Parker Glenn , Fei Zhangjun , Heck Michelle 
Published: August 2024

ABSTRACTA positive, single-stranded RNA virus member within theFlavivirusgenus was identified and characterized infectingMyzus persicae. This new insect-specific virus (ISV), Myzus persicae flavivirus (MpFV), is 23,236 nucleotides in length and encodes a large polyprotein from a single open reading frame. Analysis of conserved domains showed that helicases, NS3-proteases, Fts-J methyltransferase, and an RNA-dependent RNA polymerase are present in the coded polyprotein. Aphid-infecting ISVs have been reported to interact with plant viruses within the vector, modulating its titer and manipulating aphid behavior and morphology. Small RNA (sRNA) profile analysis of theM. persicaesRNA profile demonstrated that the circulative plant virus, potato leafroll virus (PLRV), modified the aphid antiviral immunity against MpFV. Abundant sRNA reads matching MpFV were detected when aphids were fed on healthy plants, sucrose diet, and potato virus Y-infected plants. In contrast, no MpFV reads were detected in aphids that had acquired PLRV from infected plants or artificial diet sachets containing purified virions. While the titer ofM. persicae densovirus(MpDNV) was previously reported to be regulated by expression of the PLRV silencing suppressor protein P0, P0 had no effect on MpFV titer in the aphid. MpFV was transmitted 100% vertically to the offspring, and exhibited tissue tropisms for the body rather than the head. By artificial diet assays, other aphid species, includingAphis gossypii(cotton aphid),Schizaphis graminum(greenbug aphid),Rhopalosiphumpadi (bird cherry-oat aphid), andR. maidis(corn leaf aphid), acquired the MpFV. These findings further support the idea that PLRV suppresses aphid immunity against ISVs, suggest the existence of at least two distinct pathways for PLRV-induced aphid immune system modulation. To test whether other circulative plant pathogens suppress insect anti-viral immunity against insect-specific flaviviruses, we quantified the small RNA response ofDiaphorina citri, vector of “CandidatusLiberibacter asiaticus” (CLas) associated with citrus greening disease and showed thatCLas also suppressesD. citrianti-viral immunity againstD. citri-like flavivirus(DcLFV). These data reveal an evolutionary conserved, unexpected role for diverse circulative plant pathogens in modulating anti-viral immunity in hemipteran vectors.
Microglia morphology in the developing primate amygdala and effects of early life stress
Authors: King Dennisha P. , Abdalaziz Miral , Majewska Ania K. , Cameron Judy L. , Fudge Julie L. 
Published: August 2024

AbstractA unique pool of immature glutamatergic neurons in the primate amygdala, known as the paralaminar nucleus (PL), are maturing between infancy and adolescence. The PL is a potential substrate for the steep growth curve of amygdala volume during this developmental period. A microglial component is also embedded among the PL neurons, and likely supports local neuronal maturation and emerging synaptogenesis. Microglia may alter neuronal growth following environmental perturbations such as stress. Using multiple measures, we first found that microglia in the infant primate PL had relatively large somas, and a small arbor size. In contrast, microglia in the adolescent PL had a smaller soma, and a larger dendritic arbor. We then examined microglial morphology in the PL after a novel maternal separation protocol, to examine the effects of early life stress. After maternal separation, the microglia had increased soma size, arbor size and complexity. Surprisingly, strong effects were seen not only in the infant PL, but also in the adolescent PL from subjects who had experienced the separation many years earlier. We conclude that under maternal-rearing conditions, PL microglia morphology tracks PL neuronal growth, progressing to a more ‘mature’ phenotype by adolescence. Maternal separation has long-lasting effects on microglia, altering their normal developmental trajectory, and resulting in a ‘hyper-ramified’ phenotype that persists for years. We speculate that these changes have consequences for neuronal development in young primates.Significance StatementThe paralaminar (PL) nucleus of the amygdala is an important source of plasticity, due to its unique repository of immature glutamatergic neurons. PL immature neurons mature between birth and adolescence. This process is likely supported by synaptogenesis, which requires microglia. Between infancy and adolescence in macaques, PL microglia became more dense, and shifted to a ‘ramified’ phenotype, consistent with increased synaptic pruning functions. Early life stress in the form of maternal separation, however, blunted this normal trajectory, leading to persistent ‘parainflammatory’ microglial morphologies. We speculate that early life stress may alter PL neuronal maturation and synapse formation through microglia.