bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-silico studies on thermodynamics of ligand binding to Fluoride riboswitch aptamer
Authors: Das Soumi 
Published: June 2024

AbstractRiboswitch is a non-coding messenger RNA (m-RNA) whose aptamer domain binds cognate ligands and subsequently undergoes conformational changes in the expression platform leading to the regulation of gene expression. Fluoride riboswitch has immense pharmacological potential due to its presence in some human bacterial pathogens. Several experimental studies shed light on the bacterial defense mechanism of Fluoride riboswitch upon binding of F-cognate ligand in the presence of Mg2+. However, the structural and thermodynamic basis of ligand binding with Fluoride riboswitch aptamer is not well known. This fascinates us for investigating the conformational stability of (i) the holo form of T. Petrophila fluoride riboswitch aptamer (RNA+F-+Mg2++K+) with respect to (ii) the apo form of fluoride riboswitch (RNA in the absence of F-+Mg2++K+). Conformational thermodynamics results derived from molecular dynamics simulation reveal that the holo form of the Fluoride riboswitch aptamer is stabilized by ion recognition site, pseudoknot, and stem1. However, Stem2, Loop1, Loop2, and most of the unpaired bases show significant disorder and destabilization. Molecular docking study validates the thermodynamically destabilized and disordered residues from Loop1 and Stem2 of the Fluoride riboswitch aptamer to serve as putative binding sites for non-cognate ligands. The global health system in the current century faces a serious crisis to counteract bacterial infection due to the severe emergence of bacterial resistance to antibiotics. Consequently, a need for a new generation of antibiotics against resistant bacteria is critically acclaimed. Our work hopefully improves the design of new ligands and aptamers which may be helpful in nucleic acid-targeted therapeutics.Graphical AbstractHighlightsConformational stability of (i) the holo form of T. Petrophila fluoride riboswitch aptamer (RNA+F-+Mg2++K+) with respect to (ii) the apo form of fluoride riboswitch (RNA in the absence of F-+Mg2++K+) is studied.Holo Fluoride riboswitch aptamer gets energetically and entropically stable at Pseudoknot, Stem1, and Ion recognition sites whereas Stem2, Loop1, Loop2, and most of the unpaired bases show significant disorder and destabilization.The hydrogen bond network for Pseudoknot, Stem1, and Stem2 in apo Fluoride riboswitch is significantly weak.Molecular Docking study confirms that the thermodynamically destabilized and disordered residues from Stem2 and Loop1 of the holo Fluoride riboswitch aptamer serve as putative binding sites for non-cognate ligands.
Decoding a cell’s fate: How Notch and Receptor Tyrosine Kinase Signals Specify the Drosophila R7 Photoreceptor
Authors: Arias Ronald A. , Tomlinson Andrew 
Published: June 2024

AbstractThe Drosophila R7 photoreceptor is a classic model for understanding how integration of signaling information can provide precise fate directives. It entails extensive interactions between the RTK and Notch signaling pathways, with Notch providing three distinct functions: it both opposes and promotes the general photoreceptor fate, and it determines the specific photoreceptor type. The RTK pathway promotes transcription ofphyl- a gene expression critical for photoreceptor specification. We show that Notch activity induces transcription ofyanwhich encodes a transcriptional repressor ofphyl. This defines the antagonism between the two pathways, with RTK promoting and Notch opposingphyltranscription. We previously showed that Notch provides Sevenless to the cell to allow RTK pathway hyperactivation to overcome the Notch repression, and we now identify the regulation of Yan activity as the integration site of the RTK and Notch functions. Once the cell is specified as a photoreceptor, the third Notch function then preventsseven-up(svp) transcription. The Svp transcription factor directs the R1/6 photoreceptor fate, and the prevention of its expression ensures the default R7 specification.Summary StatementThis paper examines how the different signals received by the Drosophila R7 photoreceptor precursor are decoded and used to direct the cell’s appropriate differentiation pathway.
From many voices, one question: Community co-design of a population-based qualitative cancer research study
Authors: Ayre Susannah K. , Johnston Elizabeth A. , Bourdaniotis Xanthia E. , Zajdlewicz Leah , Beesley Vanessa L. , Pole Jason D. , Hansen Aaron , Gasper Harry , Cossio Danica , Lock Gemma , Goodwin Belinda C. 
Published: June 2024

AbstractPurposeThis study formed the development stage of a population-based survey aiming to: (i) understand the needs and experiences of people affected by cancer in Queensland, Australia and (ii) recruit a pool of participants for ongoing cancer survivorship research. The current study aimed to co-design and test a single qualitative survey question and study invitation materials to maximise acceptability of, and participation in, the survey and future research.MethodsFifty-two community members participated across 15 co-design workshops and 20 pretest interviews. During workshops, participants generated and refined ideas for an open-ended survey question and provided feedback on a study invitation letter. The use of a single, open-ended question aims to minimise participant burden while collecting rich information about needs and experiences. The research team then shortlisted the question ideas and revised study invitation materials based on workshop feedback. Next, using interviews, community members were asked to respond to a shortlisted question to test its interpretability and relevance and to review revised invitation materials. Content analysis of participant feedback was used to identify principles for designing study materials.ResultsTen principles for designing qualitative survey questions were identified from participant feedback. Key principles included:define the question timeframe and scope; provide reassurance that responses are valid and valued;anduse simple wording. For the study invitation materials, 11 principles were identified, including these key principles:communicate empathy and sensitivity; facilitate reciprocal benefit;andinclude a ‘human element’.The qualitative survey question and study invitation materials created using these principles were considered relevant and acceptable for use in a population-based survey.ConclusionsThrough community consultation and co-design, this study identified principles for designing qualitative data collection and invitation materials for use in cancer survivorship research. These principles can be applied by other researchers to develop study materials that are sensitive to the needs and preferences of community members.
Abnormal Blood Pressure Among Individuals Evaluated for Latent Tuberculosis Infection in a U.S. Public Health Tuberculosis Clinic
Authors: Stantliff Trevor M. , Salindri Argita D. , Egoavil-Espejo Rocio , Hall Ashton D. , Medina-Rodriguez Laura , Patel Kavya , Magee Matthew J. , Urbina Elaine M. , Huaman Moises A. 
Published: June 2024

SummaryTuberculosis infection (LTBI) has been associated with increased cardiovascular risks. We aimed to characterize abnormal blood pressure (BP) readings in individuals with LTBI. We conducted a retrospective study of adults with LTBI presenting for their initial medical visit at a large midwestern US public health clinic between 2019-2020. Abnormal BP was defined as having a systolic BP≥ 130mmHg and/or a diastolic BP≥ 80mmHg. Of 310 individuals with LTBI, median age was 36 years (interquartile range 27 – 48), 34% were male, 64% non-US-born; 58 (18.7%) were previously diagnosed with hypertension. The prevalence of any hypertension (i.e., had a history of hypertension and/or an abnormal BP reading) was 64.2% (95% confidence interval 58.7 – 69.4). Any hypertension was independently associated with older age, male sex, higher body mass index, and Black race. In conclusion, any hypertension was present in over half of adults evaluated for LTBI in our clinic. Established hypertension risk factors were also common among this group, suggesting that individuals with LTBI could benefit from clinical and public health interventions aiming to reduce the risk of future cardiovascular events.
Clinical Utility of the Molecular Microscope Diagnostic System in a Real-World Transplant Cohort: Moving Towards a New Paradigm
Authors: Fernandez Valledor Andrea , Moeller Cathrine M. , Rubinstein Gal , Rahman Salwa , Oren Daniel , Baranowska Julia , Lee Changhee , Salazar Ruben , Hennecken Carolyn , Rahman Afsana , Elad Boaz , Lotan Dor , DeFilippis Ersilia M. , Yunis Adil , Fried Justin , Raihkelkar Jayant , Oh Kyung T. , Bae David , Lin Edward , Lee Sun Hi. , Regan Matthew , Yuzelpolskaya Melana , Colombo Paolo , Majure David T. , Latif Farhana , Clerkin Kevin D. , Sayer Gabriel T. , Uriel Nir 
Published: June 2024

ABSTRACTObjectivesTo evaluate the clinical implications of adjunctive molecular gene expression analysis (MMDx)of biopsy specimens in heart transplant (HT)recipients with suspected rejection.IntroductionHistopathological evaluation remains the standard method for rejection diagnosis in HT. However, the wide interobserver variability combined with a relatively common incidence of “biopsy-negative” rejection has raised concerns about the likelihood of false-negative results. MMDx, which uses gene expression to detect early signs of rejection, is a promising test to further refine the assessment of HT rejection.MethodsSingle-center prospective study of 418 consecutivefor-causeendomyocardial biopsies performed between November 2022 and May 2024. Each biopsy was graded based on histology and assessed for rejection patterns using MMDx. MMDx results were deemed positive if borderline or definitive rejection was present. The impact of MMDx results on clinical management was evaluated. Primary outcomes were 1-year survival and graft dysfunction following MMDx-guided clinical management. Secondary outcomes included changes in donor-specific antibodies, MMDx gene transcripts, and donor-derived cell-free DNA (dd-cfDNA) levels.ResultsWe analyzed 418 molecular samples from 237 unique patients. Histology identified rejection in 32 cases (7.7%), while MMDx identified rejection in 95 cases (22.7%). Notably, in 79 of the 95 cases where MMDx identified rejection, histology results were negative, with the majority of these cases being antibody-mediated rejection (62.1%). Samples with rejection on MMDx were more likely to show a combined elevation of dd-cfDNA and peripheral blood gene expression profiling than those with borderline or negative MMDx results (36.7% vs 28.0% vs 10.3%; p<0.001). MMDx results led to the implementation of specific antirejection protocols or changes in immunosuppression in 20.4% of cases, and in 73.4% of cases where histology was negative and MMDx showed rejection. 1-year survival was better in the positive MMDx group where clinical management was guided by MMDx results (87.0% vs 78.6%; log rank p=0.0017).ConclusionsIn our cohort, MMDx results more frequently indicated rejection than histology, often leading to the initiation of antirejection treatment. Intervention guided by positive MMDx results was associated with improved outcomes.Graphical abstract
Social Determinants of Cardiovascular Disease in US Women with and without Breast Cancer
Authors: Wadden Elena , Yogeswaran Vidhushei , Ray Roberta M , Vasbinder Alexi , Shadyab Aladdin H , Xiao Qian , Richey Phyllis A , Saquib Nazmus , Sun Yangbo , Jung Su Yon , Pichardo Margaret S. , Manson JoAnn E , Anderson Garnet , Simon Michael , Stefanick Marcia , Reding Kerryn , Barac Ana , Cheng Richard K 
Published: June 2024

AbstractBackgroundSocial determinants of health (SDOH) may be related to CV risk in women with and without breast cancer (BC).MethodsIn 153,401 women without prevalent CV disease in the Women’s Health Initiative (WHI), SDOH factors included geographic region, rurality, insurance status, and household income. Cox proportional hazard models were used to assess associations between SDOH factors and a composite CV outcome (myocardial infarction, stroke, hospitalization for heart failure, or CV death). Effect modification by BC was assessed between BC status and SDOH.ResultsThe final cohort included 10,954 (mean age 62±7 years) women who subsequently developed BC and 142,144 (mean age 63 ± 7) women without BC. During a median follow-up of 13 years, 18,148 women had an incident composite CV outcome. Rurality, low household income, and non-private insurance were associated with an increased risk of composite CV outcome and mortality in both women with and without BC. There was no effect modification by BC status for associations with rurality, insurance, or household income. By geographic region, there was no difference in composite CV outcome in women without BC. However, there was a significant interaction by BC status for geographic region and the composite endpoint (p=0.009). Women with BC in the South had a lower risk of the composite outcome (HR 0.68, 95% CI 0.54-0.87).ConclusionsSDOH are associated with an increased risk of CV events and mortality among women. There were no differential associations based on BC status, suggesting that women with BC face similar vulnerabilities related to SDOH.
CD11c-expressing microglia are transient, driven by interactions with apoptotic cells
Authors: Ghena Nathaniel , Anderson Sarah R , Roberts Jacqueline M , Irvin Emmalyn , Schwakopf Joon , Bosco Alejandra , Vetter Monica L 
Published: June 2024

AbstractMicroglia, the parenchymal macrophage of the central nervous system serve crucial remodeling functions throughout development. Microglia are transcriptionally heterogenous, suggesting that distinct microglial states confer discrete roles. Currently, little is known about how dynamic these states are, the cues that promote them, or how they impact microglial function. In the developing retina, we previously found a significant proportion of microglia express CD11c (Integrin αX, complement receptor 4,Itgax) which has also been reported in other developmental and disease contexts. Here, we sought to understand the regulation and function of CD11c+ microglia. We found that CD11c+ microglia track with prominent waves of neuronal apoptosis in postnatal retina. Using genetic fate mapping, we provide evidence that microglia transition out of the CD11c state to return to homeostasis. We show that CD11c+ microglia have elevated lysosomal content and contribute to the clearance of apoptotic neurons, and found that acquisition of CD11c expression is, in part, dependent upon the TAM receptor Axl. Using selective ablation, we found CD11c+ microglia are not uniquely critical for phagocytic clearance of apoptotic cells. Together, our data suggest CD11c+ microglia are a transient state induced by developmental apoptosis rather than a specialized subset mediating phagocytic elimination.
Developmental and age-related synapse elimination is mediated by glial Croquemort
Authors: Jay Taylor R , Kang Yunsik , Ouellet-Massicotte Victor , Micael Mariel Kristine B , Kacouros-Perkins Victoria L , Chen Jiakun , Sheehan Amy , Freeman Marc R 
Published: June 2024

SummaryNeurons and glia work together to dynamically regulate neural circuit assembly and maintenance. In this study, we showDrosophilaexhibit large-scale synapse formation and elimination as part of normal CNS circuit maturation, and that glia use conserved molecules to regulate these processes. Using a high throughput ELISA-basedin vivoscreening assay, we identify new glial genes that regulate synapse numbers inDrosophila in vivo,including the scavenger receptor ortholog Croquemort (Crq). Crq acts as an essential regulator of glial-dependent synapse elimination during development, with glial Crq loss leading to excess CNS synapses and progressive seizure susceptibility in adults. Loss of Crq in glia also prevents age-related synaptic loss in the adult brain. This work provides new insights into the cellular and molecular mechanisms that underlie synapse development and maintenance across the lifespan, and identifies glial Crq as a key regulator of these processes.
DeePosit: an AI-based tool for detecting mouse urine and fecal depositions from thermal video clips of behavioral experiments
Authors: Peles David , Netser Shai , Ray Natalie , Suliman Taghreed , Wagner Shlomo 
Published: June 2024

AbstractIn many mammals, including rodents, social interactions are often accompanied by active urination (micturition), which is considered a mechanism for spatial scent marking. Urine and fecal deposits contain a variety of chemosensory signals that convey information about the individual’s identity, genetic strain, social rank, and physiological or hormonal state. Furthermore, scent marking has been shown to be influenced by the social context and by the individual’s internal state and experience. Therefore, analyzing scent-marking behavior during social interactions can provide valuable insight into the structure of mammalian social interactions in health and disease. However, conducting such analyses has been hindered by several technical challenges. For example, the widely used void spot assay lacks temporal resolution and is prone to artifacts, such as urine smearing. To solve these issues, recent studies employed thermal imaging for the spatio-temporal analysis of urination activity. However, this method involved manual analysis, which is time-consuming and susceptible to observer bias. Moreover, defecation activity was hardly analyzed by previous studies. In the present study, we integrate thermal imaging with an open-source algorithm based on a transformer-based video classifier for automatic detection and classification of urine and fecal deposits made by male and female mice during various social behavior assays. Our results reveal distinct dynamics of urination and defecation in a test-, strain- and sex-dependent manner, indicating two separate processes of scent marking in mice. We validate this algorithm, termed by us DeePosit, and show that its accuracy is comparable to that of a human annotator and that it is efficient in various setups and conditions. Thus, the method and tools introduced here enable efficient and unbiased automatic spatio-temporal analysis of scent marking behavior in the context of behavioral experiments in small rodents.
SubtiToolKit - a bioengineering kit forBacillus subtilisand Gram-positive bacteria
Authors: Caro-Astorga Joaquin , Rogan Matt , Malci Koray , Ming Hia , Debenedictis Erika , James Paul , Ellis Tom 
Published: June 2024

SummaryBuilding DNA constructs of increasing complexity is key to synthetic biology. Golden Gate methods led to the creation of cloning toolkits - collections of modular standardized DNA parts hosted on hierarchic plasmids, developed for yeast, plants, Gram-negative bacteria, and human cells. However, Gram-positive bacteria have been neglected.Bacillus subtilisis a Gram-positive model organism and a workhorse in the bioindustry. Here, we present the SubtiToolKit, a high- efficiency cloning toolkit forB. subtilisand Gram-positive bacteria. Its design permits DNA constructs for transcriptional units, operons, knock-in and knock-out applications. It contains libraries of promoters, RBSs, fluorescent proteins, protein tags, terminators, genome integration parts, a no-leakage genetic device to control the expression of toxic products duringE. coliassembly, and a toolbox for industrially relevant strains ofGeobacillusandParageobacillusas an example of SubtiToolKit versatility for other Gram-positive bacteria and its future perspective as a reference toolkit.
Beyond Volume: Unraveling the Genetics of Human Brain Geometry
Authors: Primus Sabrina A. , Hoffstaedter Felix , Raimondo Federico , Eickhoff Simon B. , Winkelmann Juliane , Oexle Konrad , Patil Kaustubh R. 
Published: June 2024

AbstractBrain geometry impacts brain function. A quantitative encoding of form is provided by the Laplace-Beltrami operator’s spectrum of eigenvalues (LBS). We examined LBS genetics of 22 subcortical brain structures including cerebellum in 19,862 healthy White-British UK Biobank participants by multivariate GWAS (MOSTest) on the first 49 eigenvalues each. Controlling for surface and volume, we identified 80 unique variants (p<1/22*5E-8) influencing the shapes of one or several structures, with the highest yield (37 variants) for brain stem. The previously known influence of several of these loci on basic morphology, such as volume, is thus shown to also influence complex shape. Known associations of observed loci with blood pressure, neurodegeneration, alcohol consumption, and mental disorders hint at preclinical stages of these conditions potentially mediating the genetic effect on brain morphology. Significant correlations between LBS of several brain structures and the polygenic risks of hypertension, ischemic stroke and schizophrenia evince brain shapes as early biomarkers.
Antibiotic-free vaginal microbiota transplantation (VMT) changes vaginal microbiota and immune profile in women with asymptomatic dysbiosis – reporting of a randomized, placebo-controlled trial
Authors: Bosma Elleke F. , Mortensen Brynjulf , DeLong Kevin , Røpke Mads A. , Juel Helene Baek , Rich Randi , Axelsen Amalie M. , Scheeper Marouschka J. , Marvig Rasmus L. , Rasmussen Thomas Gundelund , Acosta Colleen , Binné Ulrich K. , Thomsen Anne Bloch , Ingerslev Hans-Christian , Zulfiqar Fareeha , Wrønding Tine , Cotter Paul D. , O’Brien Marcus , Patel Shriram , Dam Sarita A. , Nicholson Julia Albert , Nielsen Henriette Svarre , Dinan Timothy G. , McCarthy Fergus P. , van Hylckama Vlieg Johan E.T. , Ensign Laura M. 
Published: June 2024

AbstractHere, we describe the first placebo-controlled trial of vaginal microbiota transplantation (VMT) in women with asymptomatic dysbiosis without the use of antibiotic pretreatment. Importantly, we also describe the implementation of a donor program and banking of donor cervicovaginal secretions (CVS) while retaining sample viability, which is crucial to allow for scale-up and confirmatory quality testing. By metagenome sequencing, we demonstrate that VMT provided a significant increase in combinedLactobacillusspecies in the active arm and strain-level genetic analysis confirmedLactobacillusengraftment. Moreover, VMT was well tolerated and showed a good safety profile. Furthermore, a shift toward increasedLactobacilluswas associated with a change in the expression profile of genes in the complement pathway to a more anti-inflammatory profile. Vaginal microbial and immune profile restoration using VMT may have a positive impact on a wide range of conditions in women’s health.