bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Insights into Immature Dengue Virus-Like Particles Revealed by Cryo-EM and Molecular Dynamics Simulations
Authors: Palur Venkata Raghuvamsi , Chen Guan-Wen , Chao Day-Yu , Wu Ya-Na , Galula Jedhan U. , Wang Chun-Hsiung , Bond Peter J. , Marzinek Jan K. , Wu Shang-Rung 
Published: January 2025

ABSTRACTThe lack of efficacious vaccines against dengue (DENV) infections imposes an enormous burden on global health and the economy. Virus-like particles (VLPs), such as mature DENV VLPs (mDVLPs), have been shown to induce broadly neutralizing antibodies, making them promising next-generation vaccine candidates. However, the limited structural details have restricted efforts to engineer VLPs to attain the desired biophysical and immunological properties. In the current work, we present the cryo-electron microscopy (cryo-EM) structure of immature dengue serotype 2 VLP (imD2VLPs), revealing an architecture composed of a glycoprotein layer with prominent spikes in a T=1 arrangement. These spikes, composed of envelope (E) and precursor membrane (prM) protein heterodimers capped by pr domains, closely resemble immature flavivirus particles. Complementing the static structural details, we performed multiscale molecular dynamics (MD) simulations to elucidate the functional dynamics of imD2VLPs in the context of different lipid envelope compositions. Additionally, MD simulations uncovered the transition pathway between our previously solved mature VLP structure and immature VLP from this work. Here we show that VLP maturation involves a simple sliding-rotating motion without any clashes between E proteins. Our results also indicated that lipid composition plays a critical role in VLP stability, with phospholipid-dominant environments providing greater stability than diacylglycerol-rich vesicles. In addition, we demonstrated enhanced production efficiency of VLPs by generating a stable mammalian cell line using CHO-K1 cells. These findings enabled us not only to predict and manipulate the immunogenic properties of dengue VLPs but also underscored the potential of VLPs as a simplified and manageable model for investigating the structural basis of the dengue virus more effectively.
Selection and transmission of the gut microbiome alone shifts mammalian behavior
Authors: Suzuki Taichi A. , Akbuğa-Schön Tanja , Waters Jillian L. , Jakob Dennis , Vu Dai Long , Ballinger Mallory A. , Di Rienzi Sara C. , Chang Hao , de Araujo Ivan E. , Tyakht Alexander V. , Ley Ruth E. 
Published: January 2025

AbstractNatural selection acts on phenotypic variation, which is influenced by genetic and environmental factors including the microbiome. Whether microbiome-mediated host phenotypes can be selected and transmitted remains untested in vertebrates. Here, we first identified locomotor activity as a trait transmissible through the gut microbiome in mice. We then performed a selection experiment, where we serially transferred microbiomes from low-activity mice to independently bred germ-free mice. Over four transfer rounds, microbiome transfer significantly reduced locomotor activity. Reduced locomotion was associated with increased Lactobacilli and their metabolite indolelactate. In a test of causality, independent administration to the mouse gut ofLactobacillus johnsoniior indolelactate reduced locomotion. These findings demonstrate that selection and transmission of microbes can modulate host traits independently of selection on the mammalian genome.One Sentence SummarySerial transfer of the gut microbiome of low-activity mice to germfree recipients reproducibly transferred activity levels, revealing the microbiome’s potential to impact the host’s response to selection without host genomic changes.
Molecular Mechanism and Structural Models of Protein-Mediated Copper Transfer to theArabidopsis thalianaEthylene Receptor ETR1 at the ER Membrane
Authors: Dluhosch Dominik , Kersten Lisa Sophie , Minges Alexander , Schott-Verdugo Stephan , Gohlke Holger , Groth Georg 
Published: January 2025

AbstractIn plants, the gaseous plant hormone ethylene regulates a wide range of developmental processes and stress responses. The small unsaturated hydrocarbon is detected by a family of receptors (ETRs) located in the membrane of the endoplasmic reticulum, which rely on a monovalent copper cofactor to detect this hydrocarbon. The copper-transporting P-type ATPase RAN1 (HMA7), located in the same membrane, is known to be essential for the biogenesis of ETRs. Still, the precise molecular mechanism by which the receptors acquire their copper cofactor remains unclear. A recent study by our laboratory demonstrated a direct interaction between RAN1 and soluble copper chaperones of the ATX1 family with the model ethylene receptor ETR1, providing initial insights into the mechanism by which copper is transferred from the cytosol to the membrane-bound receptors. In this study, we further investigated these interactions with respect to the function of individual domains in complex formation. To this end, we combined biochemical experiments and computational predictions and unraveled the processes and mechanisms by which copper is transferred to ETR1 at the molecular level.
Distinct memory CD4 subset tropism of two CCR5-tropic HIV-1 in a rapid progressor
Authors: Marichannegowda Manukumar Honnayakanahalli , Farah Yasmine , Bose Meera , Sanders-Buell Eric , King David , Francisco Leilani , Eller Leigh Anne , Tovanabutra Sodsai , Michael Nelson L. , Robb Merlin L. , Song Hongshuo 
Published: January 2025

AbstractCCR5 tropic HIV-1 mainly infect memory CD4+T cells. Memory CD4+T cells are heterogenous which comprise central memory (CM), transitional memory (TM) and effector memory (EM) subsets based on cell differentiation stages. Previous studies demonstrate that low viral burden in the CM subset correlates with long-term non-progressive HIV-1 infection (1, 2) and is a hallmark of non-pathogenetic SIV infection (3, 4). These findings indicate the importance of CD4 subset tropism of HIV/SIV in determining disease progression. However, an important, yet unanswered question is whether CCR5 HIV-1 variants have different memory CD4 subset preferences. Here, we demonstrate clear compartmentalization of two CCR5 HIV-1 in different memory CD4 subsetsin vivo.
Inhibition of SQSTM1/p62 oligomerization and Keap1 sequestration by the Cullin-3 adaptor SHKBP1
Authors: Luan Lin , Cao Xiaofu , Baskin Jeremy M. 
Published: January 2025

ABSTRACTSQSTM1/p62 is a master regulator of the autophagic and ubiquitination pathways of protein degradation and the antioxidant response. p62 functions in these pathways via reversible assembly and sequestration of additional factors into cytoplasmic phase-separated structures termed p62 bodies. The physiological roles of p62 in these various pathways depends on numerous mechanisms for regulating p62 body formation and dynamics that are incompletely understood. Here, we identify a new mechanism for regulation of p62 oligomerization and incorporation into p62 bodies by SHKBP1, a Cullin-3 E3 ubiquitin ligase adaptor, that is independent of its potential functions in ubiquitination. We map a SHKBP1–p62 protein-protein interaction outside of p62 bodies that limits p62 assembly into p62 bodies and affects the antioxidant response by preventing sequestration and degradation of Keap1. These studies provide a non-ubiquitination-based mechanism for an E3 ligase adaptor in regulating p62 phase separation and cellular responses to oxidative stress.
Development of an RT-RPA assay for La Crosse virus detection provides insights into age-dependent neuroinvasion in mice
Authors: Lumkong Lily , Alatrash Reem , Sridhar Sainetra , Herrera Bobby Brooke 
Published: January 2025

AbstractLa Crosse virus (LACV) is a mosquito-borne arbovirus that causes pediatric encephalitis in North America, primarily affecting children under the age of 16 years of age. Early and accurate diagnosis is crucial to reducing morbidity in this vulnerable population; however, existing molecular and serological methods face limitations in sensitivity, specificity, and accessibility. Here, we present the development of a reverse transcription recombinase polymerase amplification (RT-RPA) assay for LACV detection. Our assay detects LACV within 20 minutes with a limit of detection of 100-1000 viral copies, demonstrating high specificity without cross-reactivity against closely related or geographically relevant arboviruses. We further integrate the RT-RPA assay into a lateral flow format, potentially enabling simple and inexpensive point-of-care diagnosis. To complement our assay development, we investigated viral pathogenesis in a mouse model that recapitulates the age-dependent susceptibility observed in human populations. Using this RT-RPA assay, we reveal that LACV invades the brains of weanling mice as early as 4 days post-infection (dpi) and adult mice by 5 dpi. Surviving adult mice had no detectable virus within their brains by 20 dpi. These results underscore the utility of our RT-RPA-based platform for LACV diagnosis and offer novel insights into the age-dependent temporal dynamics of LACV neuroinvasion and viral clearance.
Supracellular contractility inXenopus laevisembryonic epithelia regulated by extracellular nucleotides and the purinergic G-protein coupled receptor P2Y2
Authors: Joshi Sagar D. , Jackson Timothy R. , Zhang Lin , Stuckenholz Carsen , Davidson Lance A. 
Published: January 2025

AbstractExtracellular signals regulate epithelial homeostasis, cell fate and pattern cell behaviors during embryogenesis, wound healing, regeneration, and disease progression. Previous studies in our group found cell lysate from intentionally wounded embryos triggers a strong but transient contraction in neighboring epithelia, whether contiguous to the wound site or in non-wounded embryos. We previously identified extracellular ATP (eATP) as a possible candidate. Here we test additional candidates and find several nucleotides including ADP, UTP, and UDP also trigger contractility. Through a temporal and spatial screen of lysate activity, an inhibitor screen, and morpholino knock-down of candidate receptors, we find contractility is mediated by a G-protein coupled purinergic receptor P2Y2 (P2RY2). Activated P2RY2 triggers F-actin assembly and myosin II contractility. Knockdown of P2RY2 or overexpression of mutant G-protein effectors abrogate epithelial contractility when epithelia are exposed to eATP or lysate. We demonstrate that the major contributors to epithelial contractility in lysate are extracellular nucleotide triphosphates ATP and UTP, which are sensed by P2RY2 and transduced through G-proteins to contract the epithelium.Summary StatementContractility of theXenopusembryonic epithelium can be driven by extracellular nucleotides ATP or UTP and actuated by the G-protein coupled purinergic receptor P2Y2 (P2RY2).HighlightsExtracellular nucleotides ATP and UTP can trigger epithelial contractility.Epithelia contract in response to (ATP ∼ UTP) > (ADP ∼ UDP) > ADO (adenosine).The purinergic G-protein coupled receptor P2Y2 is responsible for this contractile response by indirectly modulating actomyosin contractility.
Using Mobile Phone Infrastructure Provides Evidence of a Reduction in Diagnostic Turnaround Times and Improved HIV Viral Load Monitoring in Malawi
Authors: Haggard Rachel , Mwase Christopher , Klyn Brandon , Metz Lynn , Smith Tyler , Cooper Hannah , Chiwandira Brown , Chewere Linley , Green Dylan 
Published: January 2025

AbstractBackgroundMalawi has 991,600 people living with HIV and has expanded access to annual HIV viral load (VL) testing to enhance care quality for clients. However, significant delays persist in returning VL results from laboratories to facilities and from sample collection to client receipt. To address this, we implemented a digital viral load results return (VLRR) application, using existing mobile phone platforms (SMS/USSD), to expedite results return to clients and healthcare providers (HCPs).MethodsVLRR is a digital SMS/USSD platform leveraging mobile phones to reduce turnaround time (TAT) and improve access to VL results. To evaluate the VLRR intervention, we: (1) estimated the TAT for digital results return and compared it to the paper-based process, (2) calculated open rates for digital results, (3) conducted a qualitative evaluation with VLRR users, and (4) estimated the potential cost savings from avoiding unnecessary sample redraws.ResultsFrom April 2022 to June 2024, HCPs registered 4,067 clients. Before VLRR implementation, the average TAT for clients to receive VL results was 128 days. After VLRR enrollment, it was 48.5 days (a 62.4% improvement) using electronic medical record data. By Q2 2023, VLRR clients and HCPs received results in an average of 30 and 38 days.The overall open rate for digital results (opened by either a client or HCP) was 72%. Of the clients interviewed, 98% expressed a desire to continue using VLRR, and 100% of HCPs recommended expanding the platform to other HCPs.ConclusionVLRR is effective in reducing TAT and improving access to VL results for both clients and HCPs. To enhance uptake and achieve national scale, VLRR can be integrated into Malawi’s existing EMR systems, further reducing TAT and enabling HCPs to deliver higher quality care and improve long-term clinical outcomes.
Sex Differences in the Risk of Bronchopulmonary Dysplasia and Pulmonary Hypertension: A Bayesian Meta-Analysis
Authors: van Westering-Kroon Elke , Hundscheid Tamara M. , Van Mechelen Karen , Bartoš František , Abman Steven H. , Villamor Eduardo 
Published: January 2025

AbstractBackgroundBronchopulmonary dysplasia (BPD) is generally considered to be more frequent in males than in females. We conducted a Bayesian model-averaged (BMA) meta-analysis of studies addressing sex differences in the risk of developing different severities of BPD and BPD-associated pulmonary hypertension (BPD-PH).MethodsWe used BMA to calculate Bayes factors (BFs). The BF10is the ratio of the probability of the data under the alternative hypothesis (presence of sex differences) over the probability of the data under the null hypothesis (absence of sex differences). BPD was classified as BPD28 (supplemental oxygen at or during 28 days), BPD36 (oxygen at 36 weeks postmenstrual age), mild, moderate, and severe BPD.ResultsWe included 222 studies (541,826 infants). The BMA analysis showed extreme evidence in favor of a male disadvantage in BPD28 (BF10>105), BPD36 (BF10>1021), and severe BPD (BF10=87.55), but not in mild BPD (BF10=0.28), or BPD-PH (BF10=0.54). The evidence for a male disadvantage in BPD decreased as the gestational age of the cohort decreased.ConclusionsWe confirmed the presence of a male disadvantage in moderate-to-severe BPD, but not in less severe forms of BPD or in BPD-PH. The male disadvantage in BPD is much less apparent in the more immature infants.ImpactThis Bayesian meta-analysis confirms that the risk of developing moderate to severe bronchopulmonary dysplasia (BPD) is approximately 20% higher in males than in females.Sex differences in BPD decrease with decreasing gestational age, are heterogeneous across geographic and sociodemographic settings, and have remained persistently stable over time.There is no evidence supporting sex differences in pulmonary hypertension associated with BPD.An important step in the process of individualizing the approach to BPD may be to consider the sex of the infant, as this information can be used to personalize care and potentially improve outcomes.
Multiomic profiling of metastatic potential in estrogen receptor-positive human epidermal growth factor-negative breast cancer
Authors: Mosquim Sergio , Zamore Måns , Vallon-Christersson Johan , Rydén Lisa , Levander Fredrik 
Published: January 2025

AbstractMetastatic disease is the main cause of breast cancer-related deaths. Given advances in the molecular profiling of tumors, we here aimed at integrating proteome, phosphoproteome and transcriptome data for the profiling of primary tumors to allow for discovery of new subtypes and features predicting lymph node and distant metastases in breast cancer (BC). We analyzed a total of 182 estrogen-receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative BC samples using label-free Data Independent Acquisition (DIA) liquid chromatography tandem mass spectrometry (LC-MS/MS), quantifying a total of 13571 protein groups, 7107 phosphopeptides and 13085 expressed genes in at least 70% of the samples. Unsupervised consensus cluster analyses permitted the identification of potential subtypes with differential immune infiltration pattern and survival. Immune deconvolution data was combined with multiomics factor analysis, providing unique insight into different markers for lymph node and distant metastases. In summary, we further developed a protocol for parallel acquisition of matched proteomics, phosphoproteomics and transcriptomics data, resulting in the most comprehensive dataset of its kind and allowing for unique insights into metastatic processes in ER-positive/HER2-negative BC.
Disparities in US public historic cancer mortality data: Advocacy for gastrointestinal cancers, tailored prevention measures, and the inclusion of oversea deaths. -Under-reporting of cancer deaths as sign of health disparity
Authors: Zhang Tingting , Valle Juan , Patel Ashokkumar A. , Lindsey Stacie , Smith Aki , Hung Tony Kin Wai 
Published: January 2025

ABSTRACTHistorically, data from US death certificates, available through the CDC’s WONDER database, have been used to highlight health disparities. The 5 year (2018-2022) underlying-cause-of-death data were analyzed for different race/ethnicity groups. Gastrointestinal (GI) cancers of the colon/rectum, pancreas, liver/bile duct, and stomach contributed to more than a quarter of cancer deaths in the US, calling for focused advocacy. Known disparities for Black non-Hispanic Americans were verified in cancers of the colon/rectum, and pancreas. However, mortality data for “More than one race” non-Hispanic group or non-White Hispanic group appeared unreliable, suggesting that under-reporting is also a sign of health disparity. Age-specific death rates (ASDRs) were calculated to view health disparities in various age groups. Cancers of the colon/rectum, liver, and stomach cause significant mortality in the under-50 population. And minority groups are more likely to die from cancers in the liver or the stomach compared to the White non-Hispanics. Liver cancer crude death rate was lower than expect in Asian Non-Hipanics when compared with the high mortalities of IARC’s GLOBOCAN estimates for Asian countries. Census data were then used to calculate Asian sub-groups’ ASDRs. Significantly higher risks were seen in gastric cancer for Korean Americans and liver cancer for Vietnamese Americans. The Asian Indian group had the lowest death rates across several GI cancers, even in gallbladder cancer. Some immigrants go back to their birth countries at end of life and these deaths are not reflected in WONDER because consulate reports of American citizens’ deaths abroad do not include race/ethnicity data.SIGNIFICANCEGastrointestinal cancers should be advocacy focuses to promote cancer equity. Under-reporting of deaths for minority groups is a sign of health disparity. ASDRs (Age Specific Death Rates) provide bases for tailored screening and prevention. Exclusion of American citizen’s deaths abroad in U.S. public health datasets may mask care access issues faced by immigrant cancer patients who may die overseas. Updating how these deaths are reported will help address this issue.
Meta-analysis of studies on the association between physician characteristics and patient outcomes
Authors: Haslam Alyson , Miller Sarah L. , Prasad Vinay 
Published: January 2025

AbstractObjectivePhysicians have a large role in patient outcomes, and some have questioned whether some physician characteristics lead to better outcomes for the patient. Multiple studies have been conducted on the topic, leading to a variety of conclusions. To determine how frequently studies find favorable patient outcomes, by physician characteristics and the pooled estimated effect.MethodsBy searching PubMed, Web of Science, and Google Scholar, we identified studies that reported the association between physician characteristics (age, experience, sex/gender, race/ethnicity, nationality, and patient/physician characteristic concordance) and patient outcomes (patient outcomes, such as survival/mortality, hospitalization, readmissions, length of stay, and morbidity). We calculated the frequency of studies reporting on each type of physician characteristics and each type of patient outcome, risk of bias in included studies, and pooled estimates of association between physician characteristics and patient outcomes.ResultsOf the 32 included studies, the most common outcome was mortality. There were no differences in outcomes for physicians with more experience, compared with less experience (pooled odds ratio [OR]: 0.99; 95% confidence interval: 0.98 to 1.01; I2: 56.5%), between older and younger physicians (pooled OR: 1.01; 95% confidence interval: 0.97 to 1.05; I2: 68.1%), but there were significantly better outcomes for patients with a female physician, compared to patients with a male physician, although this difference was small and biased (pooled OR: 0.97; 95% confidence interval: 0.96 to 0.98;I2: 35.5%). Selection bias, unaccounted measurement in physician and patient characteristics, and not accounting for unintended exposures limit the findings of these types of studies.ConclusionStrategies to improve patient outcomes should focus on other factors. Moreover, when seeking care, patients should be more concerned about physician track record than non-modifiable characteristics.
ACMG Secondary Findings in the Brazilian Rare Genomes Project: Insights from 5,402 genome sequencing
Authors: Perrone Eduardo , Virmond Luiza , Campos Coelho Antonio Victor , De França Marina , Moreno Carolina Araújo , Prota Joana Rosa Marques , Espolaor Jessica Grasiela de Araujo , Migliavacca Michele , Tonholo Silva Thiago Yoshinaga , Quaio Caio Robledo D’Angioli Costa , Ceroni José Ricardo Magliocco , Chen Kelin , Minillo Renata Moldenhauer , Teixeira Anne Caroline Barbosa , Yamada Renata Yoshiko , Cintra Vivian Pedigone , de Santana Lucas Santos , Campilongo Gabriela Pereira , Ribeiro da Silva Renata Martins , Pelegrino Karla de Oliveira , Filho João Bosco de Oliveira , de Almeida Tatiana Ferreira 
Published: January 2025

AbstractPurposeSecondary findings (SF) are pathogenic or likely pathogenic variants in genes unrelated to the primary purpose of genetic testing. The American College of Medical Genetics (ACMG) provides guidelines on which SF should be reported, involving 81 genes linked to different conditions. With the increasing use of genome sequencing (GS), SF are more frequently detected, presenting challenges for healthcare systems. The Brazilian population is often underrepresented in genomic studies, which limits population-specific knowledge.ObjectiveThis study aimed to outline the profile of SF in the Brazilian Rare Genomes Project (BRGP).MethodsWe analyzed retrospectively SF (ACMG) data from GS of 5,402 BRGP individuals.ResultsOf the 5,316 cases who consented to receive SF, 3.6% (191 cases) had at least one SF. The most common genes identified wereTTR, TTN,andBRCA2. SF were mainly related to cardiovascular conditions (40.2%) and cancer predisposition (37.6%). Some variants, such asTTR:c.424G>A; p. (Val142Ile) andTP53:c.1010G>A; p. (Arg337His), were recurrent, reflecting population-specific traits and founder effects. Novel variants were 10.6% of SF.ConclusionSF rate varies across studies and populations. While SF can aid early diagnosis, their relevance is debated due to potential psychological and healthcare burdens. Effective genetic counseling and public health policies are essential.