bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA 21 induces carcinogenesis in hepatic cells by modulating mitochondrial metabolism
Authors: Maurya Ashutosh Kumar , Edatt Lincy , Kumar V.B. Sameer 
Published: April 2024

AbstractMitochondria plays crucial role in cell’s survivability and normal functioning. But in the case of cancer, the mitochondrial machinery (ETC) is altered and glycolytic pathway is activated as an alternate source of energy. The main reason behind the reprogramming of mitochondrial machinery could be mutations in mitochondrial genes or suppression of genes involved in normal functioning of the mitochondria. MicroRNAs could be a key player in modulating the mitochondrial metabolism, as they have targets on various important mitochondrial genes involved in the Electron Transport Chain of the mitochondria. Any alteration in the expression pattern of the mitochondrial genes would directly contribute to the modulation of normal functioning of the mitochondrial machinery. Micro RNA 21 is an oncomiR, located at q arm of the 17thchromosome. MiR 21 has been reported to be involved in many types of cancer. MiR 21 is reported to have targets on many important genes, crucial for cell survivability and proliferation, most of which falls in the category of tumor suppressor genes. With our bioinformatics analysis, we found that miR 21 has targets on important mitochondrial genes involved in the ETC. So, we tried to elucidate the role of miR 21 in modulation of the mitochondrial machinery and role of this alteration in the mitochondrial mechanism in carcinogenesis. Our results revealed that miR 21 have targets on the Cytochrome C Oxidase 1 (Cox1), which is directly involved in the Complex 4 of the electron transport chain. Next we checked the phenotypic effects of this down regulation of Cox1 by measuring the oxygen consumption by the mitochondria and found that O2 consumption goes significantly down in miR 21 over expressing cells. Along with this, we also checked if exosomes from miR 21 overexpressing cancer cells could induce the carcinogenesis in the normal hepatic cells and found that miR 21 accelerates the rate of cellular migration and enhances the colony formation. The results together suggest that miR 21 posses carcinogenic property, possibly by modulating mitochondrial machinery.
Redesigning theDrosophilahistone gene cluster: An improved genetic platform for spatiotemporal manipulation of histone function
Authors: Crain Aaron T. , Nevil Markus , Leatham-Jensen Mary P. , Reeves Katherine B. , Matera A. Gregory , McKay Daniel J. , Duronio Robert J. 
Published: April 2024

AbstractMutating replication-dependent (RD) histone genes is an important tool for understanding chromatin-based epigenetic regulation. Deploying this tool in metazoan models is particularly challenging because RD histones in these organisms are typically encoded by many genes, often located at multiple loci. Such RD histone gene arrangements make the ability to generate homogenous histone mutant genotypes by site-specific gene editing quite difficult.Drosophila melanogasterprovides a solution to this problem because the RD histone genes are organized into a single large tandem array that can be deleted and replaced with transgenes containing mutant histone genes. In the last ∼15 years several different RD histone gene replacement platforms have been developed using this simple strategy. However, each platform contains weaknesses that preclude full use of the powerful developmental genetic capabilities available toDrosophilaresearchers. Here we describe the development of a newly engineered platform that rectifies many of these weaknesses. We used CRISPR to precisely delete the RD histone gene array (HisC), replacing it with a multifunctional cassette that permits site-specific insertion of either one or two synthetic gene arrays using selectable markers. We designed this cassette with the ability to selectively delete each of the integrated gene arrays in specific tissues using site-specific recombinases. We also present a method for rapidly synthesizing histone gene arrays of any genotype using Golden Gate cloning technologies. These improvements facilitate generation of histone mutant cells in various tissues at different stages ofDrosophiladevelopment and provide an opportunity to apply forward genetic strategies to interrogate chromatin structure and gene regulation.
Equilibrium Tension and Compression Mechanical Properties of the Human Uterus
Authors: Fang Shuyang , Duarte-Cordon Camilo A. , Fodera Daniella M. , Shi Lei , Chen Xiaowei , Advincula Arnold , Vink Joy , Hendon Christine , Myers Kristin M. 
Published: April 2024

AbstractA successful pregnancy relies on the proper cellular, biochemical, and mechanical functions of the uterus. A comprehensive understanding of uterine mechanical properties during pregnancy is key to understanding different gynecological and obstetric disorders such as preterm birth, placenta accreta, leiomyoma, and endometriosis. This study sought to characterize the macro-scale equilibrium material behaviors of the human uterus in non-pregnancy and late pregnancy under both compressive and tensile loading. Fifty human uterine specimens from 16 patients (8 nonpregnant [NP] and 8 pregnant [PG]) were tested using spherical indentation and uniaxial tension coupled with digital image correlation (DIC). A three-level incremental load–hold protocol was applied to both tests. A microstructurally-inspired material model considering fiber architecture was applied to this dataset. Inverse finite element analysis (IFEA) was then performed to generate a single set of mechanical parameters to describe compressive and tensile behaviors. The freeze-thaw effect on uterine macro mechanical properties was also evaluated. PG tissue exhibits decreased overall stiffness and increased fiber network extensibility compared to NP uterine tissue. Under indentation, ground substance compressibility was similar between NP and PG uterine tissue. In tension, the fiber network of the PG uterus was found to be more extensible and dispersed than in nonpregnancy. Lastly, a single freeze-thaw cycle did not systematically alter the macro-scale material behavior of the human uterus.
Substrate-directed control of N-glycosylation in the endoplasmic reticulum calibrates signal reception at the cell-surface
Authors: Ma Mengxiao , Dubey Ramin , Jen Annie , Pusapati Ganesh V. , Shishkova Evgenia , Overmyer Katherine A. , Cormier-Daire Valérie , Aravind L. , Coon Joshua J. , Rohatgi Rajat 
Published: April 2024

ABSTRACTOne-fifth of human proteins are N-glycosylated in the endoplasmic reticulum (ER) by two oligosaccharyltransferases, OST-A and OST-B. Contrary to the prevailing view of N-glycosylation as a housekeeping function, we identified an ER pathway that modulates the activity of OST-A. Genetic analyses linked OST-A to HSP90B1, an ER chaperone for membrane receptors, and CCCD134, an ER protein we identify as the first specificity factor for N-glycosylation. During its translocation into the ER, a N-terminal peptide in HSP90B1 functions as a pseudosubstrate inhibitor of OST-A and templates the assembly of specialized ER translocon complexes containing CCDC134. Unexpectedly, OST-A functions as a scaffold rather than an enzyme in this context, stabilizing HSP90B1 by preventing its hyperglycosylation and degradation. Disruption of this pathway impairs WNT signaling at the cell surface and causes the bone developmental disorder Osteogenesis Imperfecta. Thus, N-glycosylation can be regulated by ER factors to control cell-surface receptor signaling and tissue development.One-Sentence SummaryN-glycosylation of asparagine residues on proteins can be regulated by specificity factors in the endoplasmic reticulum to control cell-surface signaling and tissue development.
Cell Simulation as Cell Segmentation
Authors: Jones Daniel C. , Elz Anna E. , Hadadianpour Azadeh , Ryu Heeju , Glass David R. , Newell Evan W. 
Published: April 2024

AbstractSingle-cell spatial transcriptomics promises a highly detailed view of a cell’s transcriptional state and microenvironment, yet inaccurate cell segmentation can render this data murky by misattributing large numbers of transcripts to nearby cells or conjuring nonexistent cells. We adopt methods from ab initio cell simulation to rapidly infer morphologically plausible cell boundaries that preserve cell type heterogeneity. Benchmarking applied to datasets generated by three commercial platforms show superior performance and computational efficiency of this approach compared with existing methods. We show that improved accuracy in cell segmentation aids greatly in detection of difficult to accurately segment tumor infiltrating immune cells such as neutrophils and T cells. Lastly, through improvements in our ability to delineate subsets of tumor infiltrating T cells, we show that CXCL13-expressing CD8+ T cells tend to be more closely associated with tumor cells than their CXCL13-negative counterparts in data generated from renal cell carcinoma patient samples.
An ingestible, battery-free, tissue-adhering robotic interface for non-invasive and chronic electrostimulation of the gut
Authors: Nan Kewang , Wong Kiwan , Li Dengfeng , Ying Binbin , McRae James C , Feig Vivian R , Wang Shubing , Yao Kuanming , Zhou Jingkun , Li Jian , Jenkins Joshua , Ishida Keiko , Kuosmanen Johannes , Madani Wiam Abdalla Mohammed , Hayward Alison , Ramadi Khalil , Yu Xinge , Traverso Giovanni 
Published: April 2024

AbstractIngestible electronics have the capacity to transform our ability to effectively diagnose and potentially treat a broad set of conditions. Current applications could be significantly enhanced by addressing poor electrode-tissue contact, lack of navigation, short dwell time, and limited battery life. Here we report the development of an ingestible, battery-free, and tissue-adhering robotic interface (IngRI) for non-invasive and chronic electrostimulation of the gut, which addresses challenges associated with contact, navigation, retention, and powering (C-N-R-P) faced by existing ingestibles. We show that near-field inductive coupling operating near 13.56 MHz was sufficient to power and modulate the IngRI to deliver therapeutically relevant electrostimulation, which can be further enhanced by a bio-inspired, hydrogel-enabled adhesive interface. In swine models, we demonstrated the electrical interaction of IngRI with the gastric mucosa by recording conductive signaling from the subcutaneous space. We further observed changes in plasma ghrelin levels, the “hunger hormone,” while IngRI was activatedin vivo, demonstrating its clinical potential in regulating appetite and treating other endocrine conditions. The results of this study suggest that concepts inspired by soft and wireless skin-interfacing electronic devices can be applied to ingestible electronics with potential clinical applications for evaluating and treating gastrointestinal conditions.
Effects of Age on Cross-Cultural Differences in the Neural Correlates of Memory Retrieval
Authors: Cho Isu , Leger Krystal R. , Valoumas Ioannis , Mair Ross W. , Goh Joshua Oon Soo , Gutchess Angela 
Published: April 2024

AbstractCulture can shape memory, but little research investigates age effects. The present study examines the neural correlates of memory retrieval for old, new, and similar lures in younger and older Americans and Taiwanese. Results show that age and culture impact discrimination of old from new items. Taiwanese performed worse than Americans, with age effects more pronounced for Taiwanese. Americans activated the hippocampus for new more than old items, but pattern of activity for the conditions did not differ for Taiwanese, nor did it interact with age. The engagement of left inferior frontal gyrus (LIFG) differed across cultures. Patterns of greater activity for old (for Americans) or new (for Taiwanese) items were eliminated with age, particularly for older Americans. The results are interpreted as reflecting cultural differences in orientation to novelty vs. familiarity for younger, but not older, adults, with the LIFG supporting interference resolution at retrieval. Support is not as strong for cultural differences in pattern separation processes. Although Americans had higher levels of memory discrimination than Taiwanese and engaged the LIFG for correct rejections more than false alarms, the patterns of behavior and neural activity did not interact with culture and age. Neither culture nor age impacted hippocampal activity, which is surprising given the region’s role in pattern separation. The findings suggest ways in which cultural life experiences and concomitant information processing strategies can contribute to consistent effects of age across cultures or contribute to different trajectories with age in terms of memory.
FIGL1 attenuates meiotic interhomolog repair and is counteracted by RAD51 paralog XRCC2 and chromosome axis protein ASY1 during meiosis
Authors: Emmenecker Côme , Pakzad Simine , Ture Fatou , Guerin Julie , Hurel Aurelie , Chambon Aurelie , Girard Chloe , Mercier Raphael , Kumar Rajeev 
Published: April 2024

AbstractTwo recombinases, RAD51 and DMC1, catalyze meiotic break repair to ensure crossovers (COs) between homologous chromosomes (interhomolog) rather than between sisters (intersister). FIDGETIN-LIKE-1 (FIGL1) downregulates both recombinases. However, the understanding of FIGL1 functions in meiotic repair remains limited. Here, we discover new genetic interactions ofArabidopsis thaliana FIGL1that are importantin vivodeterminants of meiotic repair outcome. Infigl1, compromising the RAD51-dependent repair by either losing RAD51 paralogs (RAD51B or XRCC2) or RAD54 or inhibiting RAD51’s catalytic activity results in either unrepaired breaks or meiotic CO defects. Further, XRCC2 physically interacts with FIGL1 and partially counteracts FIGL1 for RAD51 focus formation. Our data support that RAD51-mediated repair mechanisms compensate for the FIGL1 dysfunction. FIGL1 is dispensable for intersister repair indmc1but is essential for meiotic repair completion in mutants with impaired DMC1 functions and interhomolog bias such asasy1. We show that FIGL1 attenuates interhomolog repair, and ASY1 counteracts FIGL1 to promote interhomolog recombination.
Spatial distribution of Tree-related Microhabitats in a primeval mountain forest: from natural patterns to landscape planning and forest management recommendations
Authors: Przepióra Fabian , Lewandowski Paweł , Ciach Michał 
Published: April 2024

AbstractTree-related Microhabitats (TreMs) are essential for sustaining forest biodiversity. Although TreMs represent ephemeral resources that are spread across the landscape, their spatial distribution within temperate forests remains poorly understood. To address this knowledge gap, we conducted a study on 90 sample plots (0.05 ha each) located in a primeval mountain European beechFagus sylvatica-dominated forest (Bieszczady Mountains, Carpathians). We explored the TreM profile with its link to habitat characteristics and described the spatial distribution of TreM indices. We identified 61 TreM types, with a mean richness of 19.7 ±4.9 SD TreM types per plot, a mean density of 740.7 ±292.5 SD TreM-bearing trees ha-1and a mean TreM diversity of 1.2 ±0.1 SD. The diameter and living status of trees (livingvsdead standing tree) were correlated with TreM richness on an individual tree. The stand structure, i.e. density and/or basal area of living and/or dead standing trees, and topographic conditions, i.e. slope exposure, were correlated with the TreM richness, density and diversity recorded on a study plot. We found no relationship between TreM richness, density and diversity and the presence of canopy gaps, which indicates that the influence of small-scale disturbances on the TreM profile is limited. However, our analysis revealed a clustered spatial pattern of TreM indices, with TreM-rich habitat patches (hot-spots) covering ∼20% of the forest. A moderate TreM richness, density and diversity dominated ∼60% of the forest, while TreM-poor habitat patches (cold-spots) covered ∼20%. Based on our findings, we advise the transfer of knowledge on the spatial distribution of TreMs from primeval to managed forests and advocate the ‘2:6:2’ triad rule: to allocate 20% of forests as strictly protected areas, to dedicate 60% to low-intensity forest management with the retention of large living trees and all dead standing trees, and to use the remaining 20% for intensive timber production. To ensure the continuance of the majority of TreM types, ≥ 55 living trees ha-1> 60 cm in diameter should be retained. Such an approach will maintain a rich and diverse TreM assemblage across a broad spatial scale, which in turn will support biodiversity conservation and ecosystem restoration in secondary or managed forests.HighlightsPrimeval mountain beech forest hosts rich and abundant TreM assemblageStand structure, slope exposure, but not canopy gaps mould TreM profilesHabitat patches with high/low TreM indices are spatially clusteredHot- and cold-spots each make up 20% of TreM richness, density and diversity2:6:2 - the protected: managed forest ratio for maintaining the TreM assemblage
Descriptive Epidemiology of Kyasanur Forest Disease in Thirthahalli Taluk, Shivamogga, 2018-2022
Authors: Srividya KV , Bhavesh LR , Choudhary Sushma , Shewale Ajit , Pallavi DM , Padma MR , Tiwari Simmi 
Published: April 2024

AbstractBackgroundKyasanur Forest Disease (KFD) is a zoonotic viral disease caused by the Kyasanur Forest Disease Virus (KFDV), belongs to the family Flaviviridae, and is transmitted to humans through the bites of infected ticks, primarily in forested regions. Thirthahalli taluk from Shivamogga district of Karnataka has been reporting consistently high burden of KFD. We describe the epidemiology of KFD cases in Thirthahalli taluk including their temporal and spatial distribution, correlate KFD hot-spots with the number of cases and identify high-risk groups.MethodsWe conducted a retrospective analysis of KFD surveillance data obtained from district surveillance unit, Shivamogga, on human, tick and monkey data, of Thirthahalli taluk from November 2017 to May 2022, described epidemiology, calculated the annual and seasonal time-trend of cases and correlated number of cases with number of tick pools and/ or monkey carcass positive for KFDV. We report Pearson’s correlation coefficient. We performed spatial analysis to identify clustering patterns and describe the PHC-wise disease burden.ResultsThirthahalli taluk reported 326 cases, all were lab-confirmed using either RT-PCR (93%) or IgM-ELISA (7%); with an annual incidence rate of 45.9 per 100,000 population, 58% in males and median age 40 (IQR 28-51) years. Most (71,5%) cases occurred from February to April, case fatality rate was 1.8%. The maximum number of cases occurred in the years 2019 (38%) and 2020 (44%) crossing the outbreak threshold. The populations coming under six Primary Health Centre (PHCs) reported 84% of all cases and reported all deaths. There was correlation between number of human cases in a PHC and tick pool positivity (r=0.62); and positive tick pools and positive monkey carcasses (r=0.71). Age groups with the highest average annual incidence were 45 to 49 years (8.4 per 100,000 population) and 50-54 years (8.1 per 100,000 population).ConclusionThirthahalli taluk had an ongoing endemic transmission of KFD during the study period including two outbreaks in consecutive years. All deaths occurred in PHCs with a high case burden; occurrence of human cases per year was moderately correlated with tick pool positivity. Age groups most at risk for both the occurrence of the disease and mortality were middle-aged adult males. We recommend continued tick surveillance and monkey carcass testing to map disease hot-spots; and targeted interventions in high-burden PHCs and at-risk age groups for effective disease control.
Latent Tuberculosis Diagnostics: A Systematic Review What is the past, present, and future in the diagnosis of latent tuberculosis?
Authors: Kostoudi Sofia , Hammond Robert J H 
Published: April 2024

ABSTRACTBackgroundTuberculosis (TB) is the second leading infectious killer after COVID-19 and the 13thleading cause of death worldwide. Latent tuberculosis (LTBI) has become a major pool of potential active tuberculosis cases and is propelling the TB global health burden further.ObjectiveThe creation and application of a diagnostic to effectively identify LTBI is vital. This systematic review aims to examine and analyze the present and proposed future diagnostics in the identification of latent tuberculosis.DesignSystematic ReviewMethodsPubMed and Scopus were scanned as primary databases during May 2022. Exclusion criteria for the papers scanned included patients with immunosuppression (due to HIV or treatment), pediatric TB, cancer and dialysis patients, pregnancy, IV drug users, animal models, papers published before 2005, co-infected patients, IBD and transplant patients, and finally secondary literature. Such criteria were incorporated due to the differences in TB immunology in these circumstances. 18 papers were included in this review and their risk of bias assessed using the QUADAS-2 guidelines. For analysis the papers’ sensitivities and specificities were examined. There was also a deeper look into the surrounding variables such as population differentiation, diagnostic technologies, clinical translation, and bias.FindingsWith thorough analysis of the data, it was determined that there are promising diagnostics for the precise identification of LTBI. Specifically, 2 studies one which used ELISA measuring the IgG response of LTBI and ATB patients when exposed to a combination of antigens and this resulted in a sensitivity and specificity of 93.33% and 93.10% respectively. The second study utilizes ESAT-6 SFC MSS (mean spot size) and the modified TBAg/PHA ratio diagnostic model to establish LTBI or ATB and using ROC curve analysis found a sensitivity of 90.12% and specificity of 91.02%.InterpretationTo conclude, specific diagnostics still being examined in the preliminary phase could in the future be used as adjuncts to already present diagnostics for the diagnosis of LTBI based on their strong sensitivities and specificities.No funding.SUMMARY BOXWhat is already known on this topic?The WHO guidelines for diagnosing LTBI include TST and IGRA, but neither can distinguish LTBI from ATB therefore a new diagnostic must be proposed for the specific detection of LTBIWhat this study addsOur review reveals new two specific new diagnostic tools for the diagnosis of LTBIHow this study might affect research, practice, or policyOur study can impact the future specific diagnosis of LTBI through proposing new ways of differentiating between ATB and LTBI and their possible further progression into clinical practice