bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ablation of three major phospho-sites in RyR2 preserves the global adrenergic response but creates an arrhythmogenic substrate
Authors: Zheng Jingjing , Dooge Holly C. , Valdivia Héctor H. , Alvarado Francisco J. 
Published: July 2024

ABSTRACTBackgroundRyanodine receptor 2 (RyR2) is one of the first substrates undergoing phosphorylation upon catecholaminergic stimulation. Yet, the role of RyR2 phosphorylation in the adrenergic response remains debated. To date, three residues in RyR2 are known to undergo phosphorylation upon adrenergic stimulation. We generated a model of RyR2 phospho-ablation of all three canonical phospho-sites (RyR2-S2031A/S2808A/S2814A, triple phospho-mutant, TPM) to elucidate the role of phosphorylation at these residues in the adrenergic response.MethodsCardiac structure and function, cellular Ca2+dynamics and electrophysiology, and RyR2 channel activity both under basal conditions and under isoproterenol (Iso) stimulation were systematically evaluated. We used echocardiography and electrocardiography in anesthetized mice, single-cell Ca2+imaging and whole-cell patch clamp in isolated adult cardiomyocytes, and biochemical assays.ResultsIso stimulation produced normal chronotropic and inotropic responses in TPM mice as well as an increase in the global Ca2+transients in isolated cardiomyocytes. Functional studies revealed fewer Ca2+sparks in permeabilized TPM myocytes, and reduced RyR2-mediated Ca2+leak in intact myocytes under Iso stimulation, suggesting that the canonical sites may regulate RyR2-mediated Ca2+leak. TPM mice also displayed increased propensity for arrhythmia. TPM myocytes were prone to develop early afterdepolarizations (EADs), which were abolished by chelating intracellular Ca2+with EGTA, indicating that EADs require SR Ca2+release. EADs were also blocked by a low concentration of tetrodotoxin, further suggesting reactivation of the sodium current (INa) as the underlying cause.ConclusionPhosphorylation of the three canonical residues on RyR2 may not be essential for the global adrenergic responses. However, these sites play a vital role in maintaining electrical stability during catecholamine stimulation by fine-tuning RyR2-mediated Ca2+leak. These findings underscore the importance of RyR2 phosphorylation and a finite diastolic Ca2+leak in maintaining electrical stability during catecholamine stimulation.
Proportional Mortality and Years of Potential Life Lost Due to Liver Diseases among Agricultural Workers, Brazil, 2017 to 2022
Authors: Silva Jailma dos Santos , Arruda Soraia , Nunes Thayane Silva , Dias Wiler de Paula , Awoniyi Adedayo Michael , Meyer Armando , Cremonese Cleber 
Published: July 2024

AbstractThe objective of the study was to describe the profile and calculate the Years of Potential Life Lost (YPLL) due to liver diseases in Brazilian agricultural workers, between 2017 and 2022. For this, we analyzed microdata available in the Mortality Information System (Sistema de Informação de Mortalidade - SIM), considering the outcome as the underlying cause of death with codes K70-K77 (ICD-10). Workers’ profile was characterized according to socio-demographic variables and the Brazilian regions, with a comparison group formed by all other Brazilian workers aged 18 to 69 who died in the same period and from the same underlying cause. Calculations of proportional mortality, YPLL rates, and YPLL rate ratios were applied. In the studied period, 15,362 deaths due to liver diseases were recorded among Brazilian agricultural workers, with an average age at death of 51.3 years (±10.7), concentrated in K70 - Alcoholic liver disease (53.8%). Higher proportional mortality was observed in men (86.2%), Brown race (61.1%), up to 49 years old (40.9%), with ≤7 years of education level (52.4%), and residents in Northeast (56.9%). The total sum of YPLL was 382,869 years among agricultural workers, with YPLL rate of 4,527 years per 100,000 workers and YPLL rate ratio 1.45 times higher than the national average. The concentration of deaths due to K70 raises concern for potential chronic exposure to alcoholic beverages. These results highlight the early causes of deaths resulting from liver diseases among agricultural workers, especially those in the Northeast region of Brazil and of Brown race.
What’s in a name? Protocol for a bibliometric and content analysis of rehabilitation, reablement, reactivation, and restorative health care services
Authors: MacEachern Evan , Wu Miranda C. , Cronin Shawna , Carroll Áine , Inzitari Marco , Perman Gaston , Prvu-Bettger Janet , Nelson Michelle L. A. 
Published: July 2024

AbstractBackground:Various terms are used interchangeably to describe health care services that focus on supporting functional recovery after experiencing a health event. Previous literature has identified these terms as the 4R’s: rehabilitation, reablement, reactivation, and restorative health care services. However, there lacks a clear understanding and delineation between these concepts, making it difficult to measure the efficacy of each program type. This study protocol proposes a bibliometric and content analysis to map the current scientific literature within each 4R term.Methods:Using a predefined search strategy, we will identify and retrieve publications from databases Scopus and PubMed between the years 1924-2024 for each 4R concept. Two independent researchers will screen articles for eligibility. Bibliometric analyses will be conducted using RStudio software and Bibliometrix and Biblioshiny extensions. Bibliometric analyses will each include a performance analysis, citation analysis, co-citation analysis, bibliographic coupling, and co-word analysis to identify key research connections and emerging trends temporally and geographically. Bibliometric indicators of interest will include total publications, yearly output, author names, and countries, among others. In addition, we will also perform a qualitative content analysis to provide a more in-depth examination of the characteristics of each program type.Implications:Our line of inquiry intends to clarify the similarities and differences among the 4R terms to conceptualize each definition. Findings from this study have several implications for research, practice, and policy within the 4Rs, and can overall help to delineate these concepts and facilitate decision-making and resource allocation for these health care services. This study will reveal citation patterns, research connections, and foundation themes that can inform the suitability of practice transfer and resource allocation within and between rehabilitation fields. A methodological understanding of the 4R service types can inform decision-making on the patient, healthcare professional, and system level for each service.
Infantile Colic in Karachi: Exploring Maternal Awareness, Attitude and Management Approaches
Authors: Ali Syed Rohan , Raqib Moosa Abdur , Mehtab Kiran , Nafees Munir , Tafheem Malik Hamdan 
Published: July 2024

AbstractInfantile colic, characterized by severe abdominal pain and excessive crying, significantly impacts both infants and their parents. This study examined maternal awareness, knowledge, and attitudes towards colic, with a focus on socio-demographic factors. Conducted over eight months with a sample of 400 infants in Karachi, the research employed structured questionnaires and clinical evaluations. Statistical analysis revealed significant variations in colic occurrence based on age (p < 0.001), maternal age (p = 0.005), and educational background (p = 0.001). Gender differences in digestive issues (p = 0.02) and responses to crying based on gestational age were also notable. Additionally, educational status significantly affected perceptions of colic severity (p = 0.000) and its impact on parental mental health (p = 0.03). These findings highlight the necessity for tailored healthcare strategies that consider familial contexts and educational interventions to enhance understanding and management of infantile colic. Future research should explore the influence of gut microbiota and probiotics, aiming to develop empathetic and evidence-based approaches to improve outcomes for affected families.ObjectiveThis study aimed to provide updated insights into the epidemiology of infantile colic in Karachi, contributing to targeted healthcare interventions and policies aimed at alleviating colic-related distress among infants and their families in urban settings
Cerebrospinal fluid levels of NfM in relation to NfL and pNfH as prognostic markers in amyotrophic lateral sclerosis
Authors: Olofsson Jennie , Bergström Sofia , Mravinacová Sára , Kläppe Ulf , Öijerstedt Linn , Zetterberg Henrik , Blennow Kaj , Ingre Caroline , Nilsson Peter , Månberg Anna 
Published: July 2024

AbstractObjectiveTo evaluate the prognostic potential of neurofilament medium chain (NfM) in CSF from patients with ALS and explore its relationship with the extensively studied neurofilament light chain (NfL) and phosphorylated heavy chain (pNfH).MethodCSF levels of NfL, NfM, and pNfH were analysed in 235 samples from patients with ALS, ALS mimics, and healthy controls in a well-characterized cohort from Karolinska ALS Clinical Research Centre in Stockholm, Sweden. NfM levels were analysed using an antibody-based suspension bead-array and NfL and pNfH levels were measured using standard ELISA. Clinical data, including ALS Revised Functional Rating Scale (ALSFRS-R), and survival outcomes were utilized for disease progression estimations.ResultIncreased NfM levels were observed in patients with ALS compared with mimics and healthy controls, consistent with the results observed for NfL and pNfH. Similar to NfL and pNfH, significant associations of NfM levels with disease progression were found, with higher levels in fast progressors compared with slow progressors, both in total progression and the ALSFRS-R subscores. For all neurofilaments, higher survival probability was observed for patients with low CSF levels. Additionally, all three proteins showed similar predictive performance for disease progression rates (AUC 0.85-0.86). Although there was no statistical difference between the curves, combining them slightly improved the performance (AUC 0.86-0.87).ConclusionBased on this cross-sectional study, the prognostic value provided by NfM aligns with the more established markers, NfL and pNfH. However, additional investigations with independent cohorts and longitudinal studies are needed to further explore the potential added value of NfM.
The relationship between anxiety and levels of Alzheimer’s disease plasma biomarkers
Authors: Bernard Mark A. , Boutajangout Allal , Debure Ludovic , Ahmed Wajiha , Briggs Anthony Q. , Boza-Calvo Carolina , Vedvyas Alok , Marsh Karyn , Bubu Omonigho M. , Osorio Ricardo S. , Wisniewski Thomas , Masurkar Arjun V. 
Published: July 2024

ABSTRACTAnxiety is highly prevalent in Alzheimer’s disease (AD), correlating with CSF/PET biomarkers and disease progression. Relationships to plasma biomarkers are unclear. Herein, we compare levels of plasma biomarkers in research participants with and without anxiety at cognitively normal, mild cognitive impairment, and AD dementia stages. We observed significantly higher plasma tau/Aβ42 ratio in AD participants with anxiety versus those without, but did not observe differences at other stages or plasma biomarkers. No such relationships were evident with depression. These results support a unique pathophysiological relationship between anxiety and AD that can be reflected in plasma biomarkers, suggestive of heightened neurodegeneration.
Epigenetic Alteration of Smooth Muscle Cells Regulates Endothelin-Dependent Blood Pressure and Hypertensive Arterial Remodeling
Authors: Mangum Kevin D. , Li Qinmengge , Bauer Tyler M. , Wolf Sonya J. , Shadiow James , Moon Jadie Y. , Barrett Emily C. , Joshi Amrita D. , Ahmed Zara , Wasikowski Rachael , Boyer Kylie , Obi Andrea T. , Davis Frank M. , Chang Lin , Tsoi Lam C. , Gudjonsson Johann , Gallagher Katherine A. 
Published: July 2024

AbstractLong-standing hypertension (HTN) affects multiple organ systems and leads to pathologic arterial remodeling, which is driven largely by smooth muscle cell (SMC) plasticity. Although genome wide association studies (GWAS) have identified numerous variants associated with changes in blood pressure in humans, only a small percentage of these variants actually cause HTN. In order to identify relevant genes important in SMC function in HTN, we screened three separate human GWAS and Mendelian randomization studies to identify SNPs located within non-coding gene regions, focusing on genes encoding epigenetic enzymes, as these have been recently identified to control SMC fate in cardiovascular disease. We identified SNPs rs62059712 and rs74480102 in the promoter of the humanJMJD3gene and show that the minor C allele increasesJMJD3transcription in SMCs via increased SP1 binding to theJMJD3promoter. Using our novel SMC-specific Jmjd3-deficient murine model (Jmjd3flox/floxMyh11CreERT), we show that loss ofJmjd3in SMCs results in HTN, mechanistically, due to decreasedEDNRBexpression and a compensatory increase inEDNRAexpression. As a translational corollary, through single cell RNA-sequencing (scRNA-seq) of human arteries, we found strong correlation betweenJMJD3andEDNRBexpression in SMCs. Further, we identified that JMJD3 is required for SMC-specific gene expression, and loss of JMJD3 in SMCs in the setting of HTN results in increased arterial remodeling by promoting the SMC synthetic phenotype. Our findings link a HTN-associated human DNA variant with regulation of SMC plasticity, revealing therapeutic targets that may be used in the screening and/or personalized treatment of HTN.Graphical Abstract
MELD-XI Predicts Severe Right Ventricular Failure after HeartMate 3 Implantation in a Contemporary Cohort
Authors: Lambert David S. , Picó Ana María , Vincent Justin D. , Deych Elena , Coglianese Erin , Schilling Joel D. , Vader Justin M. , Yang Bin Q. 
Published: July 2024

AbstractBackgroundRight ventricular failure (RVF) after left ventricular assist devices (LVAD) is associated with significant morbidity and mortality and identifying patients at risk for severe RVF is an important clinical goal. Current risk prediction models were not developed in contemporary LVAD populations and have limited clinical applicability.ObjectivesTo evaluate whether the Model for End Stage Liver Disease – eXcluding INR (MELD-XI) can predict severe RVF after HeartMate 3 (HM3) implantation.MethodsWe retrospectively analyzed all adult patients who received HM3 LVAD as initial implantation at two academic medical centers. We assessed whether MELD-XI is an independent risk factor for severe RVF in multivariate analysis and compared the predictive accuracy of MELD-XI with previously published risk scores. We also investigated the relationship between MELD-XI and markers of right ventricular function and whether MELD-XI was associated with death or pump exchange at 1-year follow-up.ResultsOur study included a total of 246 patients, of which 74 (30%) experienced severe RVF. After adjusting for relevant covariables, MELD-XI was independently associated with severe RVF (OR 1.18, CI 1.09-1.29, p<0.001) and performed similarly to the EUROMACS and Michigan RVF risk scores. In addition, MELD-XI was not reflective of traditional echocardiographic or hemodynamic measures of right ventricular function. Finally, MELD-XI ≥ 14 predicted worse in-hospital mortality.ConclusionsAmong patients undergoing HM3 implantation, MELD-XI is independently associated with an increased risk of RVF and in-hospital mortality.
Microbial Hauberks: Composition and Function of Surface Layer Proteins in Gammaproteobacterial Methanotrophs
Authors: Hamilton Richard , Gebbie William , Bowman Chynna , Mantanona Alex , Kalyuzhnaya Marina G. 
Published: July 2024

ABSTRACTMany species of proteobacterial methane-consuming bacteria (methanotrophs) form a hauberk-like envelope represented by a surface (S-) layer protein matrix. While several proteins were predicted to be associated with the cell surface, the composition and function of the hauberk matrix remained elusive. Here we report the identification of the genes encoding the hauberk-forming protein in two gamma-proteobacterial (Type I) methanotrophs,Methylotuvimicrobium buryatense5GB1 (EQU24_15540) andMethylotuvimicrobium alcaliphilum20ZR(MEALZ_0971 and MEALZ_0972). The proteins share 40% AA identity with each other and are distantly related to the RsaA proteins fromCaulobacter crescentus(20% AA identity).Deletion of these genes resulted in loss of the characteristic hauberk pattern on the cell surface. A set of transcriptional fusions between the MEALZ_0971 and a superfolder green fluorescent protein (sfGFP) further confirmed its surface localization. The functional roles of the hauberk and cell-surface associated proteins, including MEALZ_0971, MEALZ_0972, EQU24_15540, and a copper-induced CorA protein, were further investigated via gene expression studies and phenotypic tests. The hauberk core protein shows constitutive expression across 18 growth conditions. TheM. alcaliphilum20ZRΔ0971 showed reduced growth at high salinity, high methanol and metal-limited conditions, suggesting a role in cell-envelope stability and metal scavenging.Overall, understanding the genetics, composition and cellular functions of the S-layers contributes to our knowledge of methanotroph adaptation to environmental perturbations and opens a promising prospect for (nano)biotechnology applications.
The RRM domain-containing protein Rbp3 interacts with ribosomes and the 3′ ends of mRNAs encoding photosynthesis proteins
Authors: Hemm Luisa , Lichtenberg Elisabeth , Tholen Stefan , Reimann Viktoria , Kakazu Kenta , Machida Sotaro , Mahbub Moontaha , Schilling Oliver , Wilde Annegret , Watanabe Satoru , Mullineaux Conrad W. , Hess Wolfgang R. 
Published: July 2024

AbstractRNA recognition motif (RRM) domain proteins are crucial RNA-binding proteins (RBPs) across all domains of life. In cyanobacteria, single RRM domain proteins are involved in mRNA targeting to the thylakoid membrane and acclimation to certain stress conditions, but many details of their physiological functions and molecular targets have remained unknown. The model cyanobacteriumSynechocystissp. PCC 6803 has a family of three genes encoding the RRM domain-containing proteins Rbp1, Rbp2 and Rbp3. Here, we verified the RNA-binding activity of Rbp3in vivoand show that cells of a Δrbp3deletion strain had a lower PSI:PSII ratio and pigment content and were significantly smaller than wild-type cells. To identify the set of interacting molecules, co-immunoprecipitation experiments were performed with a strain expressing a C-terminally FLAG-tagged Rbp3. Mass spectrometry of the elution fraction suggested physical proximity between Rbp3, ribosomes, and a very small number of other proteins. The most highly enriched transcript in the co-eluting RNA fraction was thepsaABmRNA. This was corroborated by fluorescentin situhybridization (FISH) analyses showing decreasedpsaAmRNA signals and colocalization with Rbp3-GFP signals and ribosomes. Other enriched mRNAs encode thylakoid, plasma membrane and carboxysome proteins. The Rbp3-mRNA interactions occurred preferentially towards the end of coding regions or the 3′UTRs, although some were also mapped to other regions. Binding assays using Bio-layer Interferometry validated the Rbp3-psaABmRNA interaction, indicating a preference for folded RNA segments near or overlapping the respective stop codons.Significance statementThe mechanisms by which proteins are produced at specific sites and inserted into the intricate membrane systems of photosynthetic cyanobacteria are only partially understood. While RRM domain proteins are well-studied RNA-binding proteins in eukaryotes, their functions in bacteria remain underexplored. This study reveals that the RRM domain protein Rbp3 in the cyanobacteriumSynechocystissp. PCC 6803 binds mRNAs encoding photosynthetic proteins, plasma membrane proteins and carboxysome proteins and localizes near ribosomes. The bound RNA segments are typically near the ends of coding regions, or in 5′ untranslated regions. These findings suggest that Rbp3 is involved in targeting mRNAs to specific intracellular locations by interacting with structural elements within these mRNA molecules.
SARS-CoV-2 shedding dynamics in human respiratory tract
Authors: Jin Xiangxing , Ren Lili , Ren Xianwen , Wang Jianwei 
Published: July 2024

AbstractIt is crucial to understand how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) sheds in human respiratory tract, but this question is still elusive to understand due to technical limitations. Here we integrated published human metagenomic data of SARS-CoV-2 and developed a novel algorithm named as RedeCoronaVS to systematically dissect SARS-CoV-2 shedding modes with single-cell data as reference. We identify that SARS-CoV-2 particles are the dominant mode of viral shedding in the very early infection phase (≤24 hours after hospitalization). Within the first week after hospitalization, SARS-CoV-2 replicons within host cells dominate SARS-CoV-2 shedding together with viral particles. One week later, viral fragments become the dominant mode in patients with mild or moderate symptoms, but viral replicons still dominate in some patients with severe symptoms. In addition to epithelial cells, SARS-CoV-2 replicons in neutrophils, macrophages, and plasma cells also show important roles and are associate with sampling time and disease severity.
Deletion of HindIIR and HindIIIR improves DNA transfer via electroporation toHaemophilus influenzaeRd
Authors: Hamadache Samir , Huang Yu Kang , Shedeed Adam , Syed Aqil , Karas Bogumil J. 
Published: July 2024

ABSTRACTHaemophilus influenzaeis a bacterial species of interest for its medical relevance and utility as a model system. Despite its role in several landmark molecular and synthetic biology studies,H. influenzaeremains underexplored as a potential chassis organism. The limited availability of reliable and convenient transformation methods and genetic tools forH. influenzaeare obstacles to this end. However, a strain ofH. influenzaeRd KW20 lacking the type II restriction endonucleases HindII and HindIII has previously been developed. Here, we show that this strain is more readily transformable by electroporation than wild-type Rd KW20. We also developed a series of multi-host plasmids carrying antibiotic selection and fluorescent visual markers based on the pSU20 vector. The availability ofH. influenzaeΔHindII/III, paired with the electroporation method and plasmids presented here, will promote the exploration ofH. influenzaeas a host organism for synthetic biology applications.