bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nationwide Epidemiological Analysis of Surgically Treated Upper Limb Vascular Trauma Over 16 Years in Brazil
Authors: Ceratti Marcella Moura , Sorbello Carolina Carvalho Jansen , da Silva Marcelo Fiorelli Alexandrino , Teivelis Marcelo Passos , Wolosker Nelson 
Published: August 2024

ABSTRACTBackgroundUpper limb vascular trauma (ULVT) is a prevalent injury associated with significant morbidity and mortality. Despite its clinical importance, epidemiological studies on ULVT are scarce, particularly in developing countries where the incidence may be heightened by factors such as traffic accidents and violence.ObjectiveTo analyze the epidemiology of ULVT across Brazil, a developing country, evaluating incidence rates, demographic characteristics, mortality rates, days of hospitalization, and related healthcare costs.MethodsA cross-sectional, retrospective analysis using data from the Brazilian public health system (SUS) over a sixteen-year period (2008-2023). The automated data extraction utilized Python-based tools to gather information on vascular trauma procedures identified by ICD-10 codes. Statistical analyses were performed to assess variations in incidence, mortality, and treatment costs across Brazilian regions.ResultsA total of 25,573 cases of ULVT were recorded, representing approximately 0.02% of the studied population. The majority of cases occurred in males (79.8%) with a mean age of 34.71 years, with a peak incidence in the 20-24 age group. The region in Brazil with the highest incidence of ULVT was the North (16.6 cases per 100,000 inhabitants) and the region with the lowest was the Southeast (10.7 cases per 100,000 inhabitants). The average hospital stay was 4.39 days and 92,8% of patients did not need to be admitted to an intensive care unit (ICU). Of the patients admitted to the ICU, the average length of stay was 4.52 days. Overall lethality (deaths per cases of ULVT) was 2.37%, with higher lethality observed in bilateral ULVT cases (3.81%).ConclusionsULVT is more prevalent in Brazil than in developed countries, even when adjusted for population size. However, mortality rates and hospitalization durations do not appear to differ significantly from those in developed countries.
NF-κB Mediated Thyroid Inflammation and Its Implications for the Risk of Follicular Thyroid Carcinoma: a systematic review
Authors: Shafi Ovais , Raveena  , Arshad Fatima , Kanwal Finza , Khan Osama Jawed , Ashar Muhammad , Jabbar Abdul , Kumar Haresh , Rajpar Rahimeen , Sohail Khizer , Madhwani Manwar , Waqas Muhammad 
Published: August 2024

AbstractObjectiveThe objective of this study is to determine how NF-κB-mediated inflammation disrupts thyroid specific genes/TFs/signaling pathways and the resultant increase in the risk of Follicular Thyroid Carcinoma.BackgroundThyroid follicular carcinoma (FTC) is linked to chronic inflammation and NF-κB activation, which disrupts key thyroid-specific genes/transcription factors and signaling pathways. This dysregulation leads to impaired differentiation and increased proliferation, fostering oncogenesis. The interplay between NF-κB and thyroid components is critical for developing possible targeted therapies. This study aims to focus on these mechanisms, with the future potential of possibly improving diagnostic, prognostic, and therapeutic strategies for FTC.MethodsDatabases, including PubMed, MEDLINE, Google Scholar, and open access/ subscription-based journals were searched for published articles without any date restrictions, to investigate how NF-κB-mediated inflammation disrupts thyroid specific genes/TFs/signaling pathways and the resultant increase in the risk of Follicular Thyroid Carcinoma. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate the research question. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).ResultsNF-κB activation disrupts key thyroid transcription factors and signaling pathways, leading to increased risk of thyroid follicular carcinoma. Dysregulation of NKX2-1, PAX8, FOXE1, and HHEX impairs thyroid development and differentiation. NF-κB alters TSH signaling and disrupts RET/PTC, leading to aberrant cell proliferation. It further impacts the MAPK/ERK, PI3K/AKT, and Wnt/β- catenin pathways, driving oncogenic transformations. Additionally, NF-κB-induced changes in FGF, Shh, BMP, Notch, and TGF beta pathways exacerbate tumorigenesis by promoting abnormal cell growth and survival, collectively increasing follicular carcinoma risk.ConclusionChronic inflammation and NF-κB activation disrupt key transcription factors (NKX2-1, PAX8, FOXE1, HHEX) and signaling pathways (TSH, RET/PTC, MAPK/ERK, PI3K/AKT, Wnt/β-catenin, FGF, Shh, BMP, Notch, TGF-β) essential for thyroid development and function. This dysregulation leads to impaired differentiation, increased proliferation, and enhanced survival of thyroid follicular cells, fostering genomic instability and oncogenic transformation. These findings highlight the role of NF-κB in promoting follicular thyroid carcinoma (FTC) and points towards the need for targeted therapies to restore normal signaling and prevent malignancy in thyroid diseases.
Stable isotope analysis (δ13C,δ15N,δ34S) reveal divers manuring practices of rye (Secale cereale) in northern Europe since 1500 years
Authors: Schlütz Frank , Bittmann Felix , Jahns Susanne , König Sonja , Shumilovskikh Lyudmila , Baumecker Michael , Kirleis Wiebke 
Published: August 2024

AbstractFirst analysis of stable isotopes in rye from northern and eastern Germany provides insights into the early history of rye cultivation from the migration to the late medieval period. A comparison of theδ15N with modern experiments reveals that already the early cultivation involved the practice of intensive manuring. The intensity of manuring does not demonstrate a discernible trend over time but high variability. In some instances, it is likely that rye was cultivated as part of a rotation cultivation system including manuring. Through itsδ34S values some rye turned out to be manured with marine peats. Rye, reputed to be a frugal crop, was cultivated on poor sandy soils to a limited extent only. Statistically significant correlation between the13C content and yields demonstrates that the highest yield success on dwelling mounds was achieved, while the majority of fields on dry sandy soils yielded in relation only 40 to 70 %. Manured rye facilitated the emergence of multi-headed village communities and towns and stabilized the political power systems. The cultivation on mounds flooded by winter storm surges emphasises that summer rye was initially cultivated, before winter-rye became the dominating crop in Germany until the mid-20th century.
DNA methylation associates with sex-specific effects of experimentally increased yolk testosterone in wild nestlings
Authors: Sepers Bernice , Ruuskanen Suvi , van Mastrigt Tjomme , Mateman A. Christa , van Oers Kees 
Published: August 2024

AbstractMaternal hormones can profoundly impact offspring physiology and behaviour in sex-dependent ways. Yet little is known on the molecular mechanisms linking these maternal effects to offspring phenotypes. DNA methylation, an epigenetic mechanism, is suggested to facilitate maternal androgens’ effects. To assess whether phenotypic changes induced by maternal androgens associate with DNA methylation changes, we experimentally manipulated yolk testosterone levels in wild great tit eggs (Parus major) and quantified phenotypic and DNA methylation changes in the hatched offspring. Increased yolk testosterone levels decreased the begging probability, emphasised sex-differences in fledging mass and affected methylation at 763 CpG sites, but always in a sex-specific way. These sites associated with genes involved in growth, oxidative stress and reproduction, suggesting sex-specific trade-offs to balance the costs and benefits of exposure to high yolk testosterone levels. Future studies should assess if these effects extend beyond the nestling stage and impact fitness.
The microbiome of Total Suspended Particles (TSP) and its influence on the respiratory microbiome of healthy office workers
Authors: Solazzo Giulia , Rovelli Sabrina , Iodice Simona , Chung Matthew , Frimpong Michael , Bollati Valentina , Ferrari Luca , Ghedin Elodie 
Published: August 2024

ABSTRACTAir particulate matter (PM) is widely recognized for its potential to negatively affect human health, including changes in the upper respiratory microbiome. However, research on PM-associated microbiota remains limited and mostly focused on PM (e.g., PM2.5and PM10). This study aims to characterize for the first time the microbiome of Total Suspended Particles (TSP) and investigate the correlations of indoor TSP with the human upper respiratory microbiome. Biological and environmental samples were collected over three collection periods lasting three weeks each, between May and July 2022 at the University of Milan and the University of Insubria Como. TSP were sampled using a filter-based technique, while respiratory samples from both anterior nares (AN) and the nasopharynx (NP) were collected using swabs. Microbiome analysis of both human (N = 145) and TSP (N = 51) samples was conducted on metagenomic sequencing data. A comparison of indoor and outdoor TSP microbiomes revealed differences in microbial diversity and taxonomic composition. The indoor samples had higher relative abundance of environmental bacteria often associated with opportunistic infections likeParacoccussp., as well as respiratory bacteria such asStaphylococcus aureusandKlebsiella pneumoniae. Additionally, both indoor and outdoor TSP samples contained broad spectrum antibiotic resistance genes. Indoor TSP exposure was negatively associated with commensal bacteria and positively associated withStaphylococcus aureusrelative abundance. Finally, a correlation between the relative abundance of respiratory bacteria identified in the indoor TSP and the upper respiratory microbiome was found, suggesting a potential interaction between TSP and the upper airways.
Dynamics of duplicated gene regulatory networks governing cotton fiber development following polyploidy
Authors: Xiong Xianpeng , Zhu De , Grover Corrinne E. , Wendel Jonathan F. , Ma Xiongfeng , Hu Guanjing 
Published: August 2024

AbstractCotton fiber development entails complex genome-wide gene regulatory networks (GRN) that remain mostly unexplored. Here we present integrative analyses of fiber GRNs using public RNA-seq datasets, integrated with multi-omics genomic, transcriptomic, and cistromic data. We detail the fiber co-expression dynamics and regulatory connections, validating findings with external datasets and transcription factor (TF) binding site data. We elucidate previously uncharacterized TFs that regulate genes involved in fiber-related functions and cellulose synthesis, and identify the regulatory role of two homoeologous G2-like transcription factors on fiber length. Analysis of duplicated gene expression and network relationships in allopolyploid cotton, which has two co-resident genomes (A, D), revealed novel aspects of asymmetric subgenomic developmental contributions. Whereas D-based homoeolog pairs drive higher overall gene expression from the D subgenome, TFs from the A subgenome play a preferential regulatory role in the fiber gene regulatory network. Following allopolyploid formation, it appears that the trans-regulatory roles of TFs diversified more rapidly between homoeologs than did the cis-regulatory elements of their target genes. Our approach underscores the utility of network analysis for detection of master regulators and provides fresh perspectives on fiber development and polyploid functional genomics, through the lens of co-expression and GRN dynamics.
Discovery of a single-subunit oligosaccharyltransferase that enables glycosylation of full-length IgG antibodies inEscherichia coli
Authors: Sotomayor Belen , Donahue Thomas C. , Mahajan Sai Pooja , Taw May N. , Hulbert Sophia W. , Bidstrup Erik J. , Owitipana D. Natasha , Pang Alexandra , Yang Xu , Ghosal Souvik , Alabi Christopher A. , Azadi Parastoo , Gray Jeffrey J. , Jewett Michael C. , Wang Lai-Xi , DeLisa Matthew P. 
Published: August 2024

AbstractHuman immunoglobulin G (IgG) antibodies are one of the most important classes of biotherapeutic agents and undergo glycosylation at the conserved N297 site in the CH2 domain, which is critical for IgG Fc effector functions and anti-inflammatory activity. Hence, technologies for producing authentically glycosylated IgGs are in high demand. While attempts to engineerEscherichia colifor this purpose have been described, they have met limited success due in part to the lack of available oligosaccharyltransferase (OST) enzymes that can installN-linked glycans within the QYNST sequon of the IgG CH2 domain. Here, we identified a previously uncharacterized single-subunit OST (ssOST) from the bacteriumDesulfovibrio marinusthat exhibited greatly relaxed substrate specificity and, as a result, was able to catalyze glycosylation of native CH2 domains in the context of both a hinge-Fc fragment and a full-length IgG. Although the attached glycans were bacterial in origin, conversion to a homogeneous, asialo complex-type G2N-glycan at the QYNST sequon of theE. coli-derived hinge-Fc was achieved via chemoenzymatic glycan remodeling. Importantly, the resulting G2-hinge-Fc exhibited strong binding to human FcγRIIIa (CD16a), one of the most potent receptors for eliciting antibody-dependent cellular cytotoxicity (ADCC). Taken together, the discovery of a unique ssOST fromD. marinusprovides previously unavailable biocatalytic capabilities to the bacterial glycoprotein engineering toolbox and opens the door to usingE. colifor the production and glycoengineering of human IgGs and fragments derived thereof.
Development of a highly efficient base editing system forLactobacillito improve probiotics and dissect essential functions
Authors: Mitsunobu Hitoshi , Kita Yudai , Nambu-Nishida Yumiko , Miyazaki Shoko , Nakajima Kensuke , Taoka Ken-ichiro , Kondo Akihiko , Nishida Keiji 
Published: August 2024

AbstractLactobacilliplay essential roles in the food industry and are increasingly explored for their potential as probiotics and therapeutic agents. Beneficial strains are primarily isolated from various natural sources including healthy human bodies, and undergo rigorous characterization and safety evaluations. Genomic and genetic information has increasingly accumulated and been linked to their various functions, to which transgenic approaches are being performed to verify crucial genes. In order to reasonably develop more useful strains, beneficial traits need to be introduced into any given strains and enhanced or combined. However, for practical use as probiotics or foods, organisms with transgene are hardly acceptable. Here, we have introduced the base editing Target-AID system specifically forLactobacilli, enabling precise installation of point mutations without donor DNA and at multiple genomic loci simultaneously.Lactiplantibacillus plantarumhas been successfully engineered to reduce production of imidazole propionate, which has been reported to be associated with type 2 diabetes. Additionally, this system enabled transient knock-out of an essential gene, such as one involved in cell division showing severe filamentous cell phenotype, providing a unique approach for dissecting essential gene function.ImportanceThis work provides highly efficient and multiplexable base editing system that installs precise point mutations in the genomes of the two majorLactobacillistrains. As the advanced CRISPR technology so-called non-cleaving genome editing, base editing is less toxic and does not integrate any foreign DNA into the genomes. Our approaches pave the way for dissecting and improving probiotics and food-grade microbes, ultimately creating better human health.
The Epithelial-to-Mesenchymal Transition Supports HCMV Infection and Biosynthesis in Mammary Epithelial Cells Through Two Distinct Mechanisms
Authors: Golconda Preethi , Andrade-Medina Mariana , Matrenec Rachel , McLachlan Alan , Oberstein Adam 
Published: August 2024

AbstractHuman cytomegalovirus (HCMV) infects a wide range of cell types in the body, including a variety of epithelial cell types. Despite the significance of epithelial cells during infection, HCMV has been difficult to study in epithelial cells. In this study, we examined HCMV infection in mammary and prostate epithelial cell lines, finding that the virus establishes a semi-permissive, biosynthetically abortive state. Building on previous work, we hypothesized that shifting epithelial cells to a mesenchymal cell state would restore HCMV biosynthesis and progeny production. To test this hypothesis, we induced epithelial-to-mesenchymal transition (EMT) using TGF-β and the EMT-transcription factor (EMT-TF) SNAIL. We found that shifting strongly epithelial cell lines to a mesenchymal cell state shifted HCMV infection from a semi-permissive to fully permissive state. This effect appeared to involve two distinct mechanisms: EMT-sensitive enhancement of viral entry and EMT-sensitive enhancement of viral mRNA translation. Although the precise mechanisms remain elusive, our findings identify the epithelial-mesenchymal cell state axis as an important regulator of HCMV infection and provide new insights into how cellular differentiation states influence viral replication. They also raise the possibility that the EMT pathway, a fundamental pathway involved in development and cancer metastasis, could regulate HCMV infectionin-vivo, potentially contributing to viral persistence or pathogenesis in epithelial tissues.
Interplay between the cyclophilin homology domain of RANBP2 and MX2 regulates HIV-1 capsid dependencies on nucleoporins
Authors: Flick Haley , Venbakkam Ananya , Singh Parmit K. , Layish Bailey , Huang Szu-Wei , Radhakrishnan Rajalingam , Kvaratskhelia Mamuka , Engelman Alan N. , Kane Melissa 
Published: August 2024

AbstractInterlinked interactions between the viral capsid (CA), nucleoporins (Nups), the antiviral protein myxovirus resistance 2 (MX2/MXB) influence HIV-1 nuclear entry and the outcome of infection. Although RANBP2/NUP358 has been repeatedly identified as a critical player in HIV-1 nuclear import and MX2 activity, the mechanism by which RANBP2 facilitates HIV-1 infection is not well understood. To explore the interactions between MX2, the viral CA, and RANBP2, we utilized CRISPR-Cas9 to generate cell lines expressing RANBP2 from its endogenous locus but lacking the C-terminal cyclophilin (Cyp) homology domain, and found that both HIV-1 and HIV-2 infection were reduced significantly in RANBP2ΔCypcells. Importantly, although MX2 still localized to the nuclear pore complex in RANBP2ΔCypcells, antiviral activity against HIV-1 was decreased. By generating cells expressing specific point mutations in the RANBP2-Cyp domain we determined that the effect of the RANBP2-Cyp domain on MX2 anti-HIV-1 activity is due to direct interactions between RANBP2 and CA. We further determined that CypA and RANBP2-Cyp have similar effects on HIV-1 integration targeting. Finally, we found that the Nup requirements for HIV infection and MX2 activity were altered in cells lacking the RANBP2-Cyp domain. These findings demonstrate that the RANBP2-Cyp domain affects viral infection and MX2 sensitivity by altering CA-specific interactions with cellular factors that affect nuclear import and integration targeting.Significance StatementHIV-1 entry into the nucleus is an essential step in viral replication that involves complex interactions between the viral capsid and multiple cellular proteins, including nucleoporins such as RANBP2. Nups also mediate the function of the antiviral protein MX2, however determining the precise role of Nups in HIV infection has proved challenging due to the complex nature of the nuclear pore and significant pleiotropic effects elicited by Nup depletion. We have used precise gene editing to assess the role of the Cyp domain of RANBP2 in HIV-1 infection and MX2 activity. We find that this domain affects viral infection, nucleoporin requirements, MX2 sensitivity, and integration targeting in a CA-specific manner, providing detailed insights into how RANBP2 contributes to HIV-1 infection.
Vesiculation pathways in clathrin-mediated endocytosis
Authors: Wang Xinran , Berro Julien , Ma Rui 
Published: August 2024

AbstractDuring clathrin-mediated endocytosis, a patch of flat plasma membrane is internalized to form a vesicle. In mammalian cells, how the clathrin coat deforms the membrane into a vesicle remains unclear and two main hypotheses have been debated. The “constant area” hypothesis assumes that clathrin molecules initially form a flat lattice on the membrane and deform the membrane by changing its intrinsic curvature while keeping the coating area constant. The alternative “constant curvature” hypothesis assumes that the intrinsic curvature of the clathrin lattice remains constant during the formation of a vesicle while the surface area it covers increases. Previous experimental studies were unable to unambiguously determine which hypothesis is correct. In this paper, we show that these two hypotheses are only two extreme cases of a continuum of vesiculation pathways if we account for the free energies associated with clathrin assembly and curvature generation. By tracing the negative gradient of the free energy, we define vesiculation pathways in the phase space of the coating area and the intrinsic curvature of clathrin coat. Our results show that, overall, the differences in measurable membrane morphology between the different models are not as big as expected, and the main differences are most salient at the early stage of endocytosis. Furthermore, the best fitting pathway to experimental data is not compatible with the constant-curvature model and resembles a constant-area-like pathway where the coating area initially expands with minor changes in the intrinsic curvature, later followed by a dramatic increase in the intrinsic curvature and minor change in the coating area. Our results also suggest that experimental measurement of the tip radius and the projected area of the clathrin coat will be the key to distinguish between models.