A novel stoploss mutation CYB5R3 c.906A>G(p.*302Trpext*42) involved in the pathogenesis of hereditary methemoglobinemia.

Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

Exposición a temperaturas extremas y su efecto en la gestación en un departamento de Colombia / Exposure to extreme temperatures and its effect on pregnancy in a department of Colombia

Introducción: Diversas investigaciones han establecido la relación entre temperatura y duración del embarazo, la exposición a temperaturas altas durante el embarazo plantea interrogantes en especial el papel que esta juega frente a los partos prematuros y partos de bajo peso, es indispensable determinar si las temperaturas altas o bajas tienen un comportamiento protector o de riesgo sobre el feto durante la gestación en regiones tropicales. Objetivo: describir la relación entre la exposición a temperaturas altas y bajas durante el embarazo y su efecto en la edad gestacional y peso al momento del parto en los recién nacidos del departamento del Guaviare-Colombia. Metodología: Estudio tipo observacional, analítico, retrospectivo de corte transversal que busco determinar la relación entre exposición a temperaturas altas y bajas durante el embarazo y su efecto en la edad gestacional y peso al momento del parto en los recién nacidos, el universo estuvo conformado por 10.137 nacidos vivos, de los cuales 9.932 cumplieron los criterios de inclusión. Se determinó Odds Ratio para estimar la asociación entre las variables. Resultados: Dentro de la semana de retraso 3 el estar expuesto a temperaturas máximas percentil 90 es un factor protector para la ganancia ponderal de peso OR < 1, la exposición a temperaturas mínimas percentil 10 se asoció como factor protector para el parto prematuro en la semana de retraso 1 y 2 OR < 1.Conclusión: A pesar del beneficio de las altas y bajas temperaturas durante el embarazo en la ganancia ponderal de peso y disminución del parto prematuro, es recomendable prevenir la exposición a temperaturas extremas durante el periodo de gestación[AU]

Introduction: Various investigations have established the relationship between temperature and duration of pregnancy. Exposure to high temperatures during pregnancy raises questions, especially the role it plays in premature births and low-weight births. It is essential to determine whether high temperatures or low have a protective or risky behavior on the fetus during pregnancy in tropical regions.Objective: to describe the relationship between exposure to high and low temperatures during pregnancy and its effect on gestational age and weight at the time of delivery in newborns in the department of Guaviare-Colombia.Methodology:Observational, analytical, retrospective cross-sectional study that sought to determine the relationship between exposure to high and low temperatures during pregnancy and its effect on gestational age and weight at the time of delivery in newborns. The universe was made up of 10,137 births. alive, of which 9,932 met the inclusion criteria. Odds Ratio was determined to estimate the association between the variables.Results:Within the 3rd week of delay, being exposed to maximum temperatures at the 90th percentile is a protective factor for weight gain OR < 1, exposure to minimum temperatures at the 10th percentile was associated as a protective factor for premature birth in the week. of delay 1 and 2 OR < 1. Conclusion: Despite the benefit of high and low temperatures during pregnancy in weight gain and reduction in premature birth, it is advisable to prevent exposure to extreme temperatures during the gestation period[AU]

Introdução: Várias investigações estabeleceram a relação entre temperatura e duração da gravidez. A exposição a altas temperaturas durante a gravidez levanta questões, especialmente o papel que desempenha nos partos prematuros e nos nascimentos de baixo peso. É essencial determinar se as temperaturas altas ou baixas têm um comportamento protetor ou de risco para o feto durante a gravidez em regiões tropicais. Objetivo:descrever a relação entre a exposição a altas e baixas temperaturas durante a gravidez e seu efeito na idade gestacional e no peso no momento do parto em recém-nascidos no departamento de Guaviare-Colômbia. Metodologia: Estudo observacional, analítico, retrospectivo e transversal que buscou determinar a relação entre a exposição a altas e baixas temperaturas durante a gravidez e seu efeito na idade gestacional e no peso no momento do parto em recém-nascidos. O universo foi composto por 10.137 nascimentos. vivos, dos quais 9.932 preencheram os critérios de inclusão. O Odds Ratio foi determinado para estimar a associação entre as variáveis. Resultados:Na 3ª semana de atraso, a exposição a temperaturas máximas no percentil 90 é fator de proteção para ganho de peso OR < 1, a exposição a temperaturas mínimas no percentil 10 foi associada como fator de proteção para parto prematuro na semana. de atraso 1 e 2 OR < 1.Conclusão:Apesar do benefício das altas e baixas temperaturas durante a gravidez no ganho de peso e redução do parto prematuro, é aconselhável evitar a exposição a temperaturas extremas durante o período de gestação[AU]

Formación docente para la educación inclusiva en instituciones públicas del Quindío / Teacher training for inclusive education in public institutions of Quindío

La formación docente es esencial dentro del proceso de educación inclusiva permitiendo responder a la diversidad de los estudiantes a partir de estrategias que promuevan su aprendizaje y participación. Este estudio analiza la formación en inclusión de 253 docentes de instituciones públicas mediante el Cuestionario de Valoración Docente de la Inclusión Educativa (CEFI-R). Los resultados indican niveles bajos de formación en las dimensiones concepciones, apoyos y metodologías. Lo que sugiere que no existe una preparación integral del profesorado para la inclusión y los planes de formación deben abordar desde aspectos conceptuales hasta la implementación de ajustes en el aula. (AU)

Teacher training is essential within the inclusive education process, allowing students to respond to diversity through strategies that promote their learning and participation. This study analyzes the inclusion training of 253 teachers in public institutions, through the Cuestionario de Valoración Docente de la Inclusión Educativa (CEFI-R). The results indicate low levels of training in the conceptual dimensions, supports and methodologies. This suggests that there is no comprehensive preparation of teachers for inclusion and training plans should address conceptual aspects to the implementation of adjustments in the classroom. (AU)

Formación docente para la educación inclusiva en instituciones públicas del Quindío / Teacher training for inclusive education in public institutions of Quindío

La formación docente es esencial dentro del proceso de educación inclusiva permitiendo responder a la diversidad de los estudiantes a partir de estrategias que promuevan su aprendizaje y participación. Este estudio analiza la formación en inclusión de 253 docentes de instituciones públicas mediante el Cuestionario de Valoración Docente de la Inclusión Educativa (CEFI-R). Los resultados indican niveles bajos de formación en las dimensiones concepciones, apoyos y metodologías. Lo que sugiere que no existe una preparación integral del profesorado para la inclusión y los planes de formación deben abordar desde aspectos conceptuales hasta la implementación de ajustes en el aula. (AU)

Teacher training is essential within the inclusive education process, allowing students to respond to diversity through strategies that promote their learning and participation. This study analyzes the inclusion training of 253 teachers in public institutions, through the Cuestionario de Valoración Docente de la Inclusión Educativa (CEFI-R). The results indicate low levels of training in the conceptual dimensions, supports and methodologies. This suggests that there is no comprehensive preparation of teachers for inclusion and training plans should address conceptual aspects to the implementation of adjustments in the classroom. (AU)

Synergic effects of DL-limonene, R-limonene, and cisplatin on AKT, PI3K, and mTOR gene expression in MDA-MB-231 and 5637 cell lines.

The anticancer and cytotoxic effects of DL-Limonene and R-Limonene are well-documented. However, the role of natural compounds in enhancing the efficacy of platinum-based drugs like Cisplatin (CisPt) remains debated. This study aims to boost Cisplatin's impact on breast (MDA-MB-231) and bladder (5637) cancer cells using DL-Limonene and R-Limonene. Different concentrations of DL-Limonene, R-Limonene, and Cisplatin, combined, were used to treat MDA-MB-231 and 5637 cells in this experimental study. The cell's viability was evaluated using an MTT assay. AnnexinV- PI staining was applied to evaluate the percentage of apoptotic cells. Cytotoxicity results showed that combining DL-Limonene, R-Limonene, and Cisplatin significantly improved outcomes in MDA-MB-231 cells (P < 0.05). Annexin/PI staining revealed apoptosis rates of 74 %, 28 %, 43 %, 81 %, and 91 % for Cisplatin40, R-Limonen1000, DL-Limonen1000, R-Limonen1000/DL-Limonen1000, and the combined treatment, respectively, versus 13 % in the control. The combination also resulted in the greatest reduction of AKT, PI3K, and mTOR gene expression. Our results show that R-Limonene and DL-Limonene enhance Cisplatin's cancer-inhibiting effects in breast and bladder cancer cell lines. These compounds may be promising for combination therapy, potentially allowing for lower doses of chemotherapy and reducing side effects like nephrotoxicity.

The Safewards Model and I.R.O.N. Interventions in a No-Restraint Ward.

The psychiatry inpatient ward of Trento (SPDC: italian acronym for Servizio Psichiatrico di Diagnosi e Cura - i.e. Psychiatric Service for Diagnosis and Treatment) operates with an open-door policy, emphasising a recovery-oriented approach. The professionals are capable of adopting the patient's perspective as a "person" rather than seeing them as a "patient", allowing them the freedom and responsibility to make decisions about their own lives. The SPDC of Trento is a no-restraint psychiatric ward, where relational restraint is prioritised, and patients' responsibility is maximised, avoiding, where possible, the use of physical restraint. In 2022, our SPDC introduced the so-called I.R.O.N. interventions (Italian: Interventi Relazionali prolungati ad Orientamento No restraint - no-restraint-oriented relational interventions). These interventions are used in situations of patient agitation to ease tension and resolve crises by employing methods that are both "gentle" and "iron" at the same time, highlighting the determination, patience, and 'relational time' required from the work team. At the end of the intervention, the strategies implemented are described in a register and later shared with the work team. At the end of the year, individuals who have demonstrated their commitment to supporting their colleagues will be awarded an "IRON parchment". A special "Talk Down Champion" parchment will be awarded to the person who manages to consistently maintain this style of work, always in agreement with the team and the safety of all (operators and patients).

Big data analysis reveals significant increases in complications, costs, and hospital stay in revision total knee arthroplasty compared to primary TKA.

INTRODUCTION: Despite significant advancements in total knee arthroplasty (TKA), some patients require revision surgery (R-TKA) due to complications such as infection, mechanical loosening, instability, periprosthetic fractures, and persistent pain. This study aimed to explore the specific causes leading to R-TKA, associated complications, including infection, mechanical failure, and wound issues, as well as costs, mortality rates, and hospital length of stay (LOS) using data from a large national database. METHODS: Data from the nationwide inpatient sample (NIS), the largest publicly available all-payer inpatient care database in the United States were analysed from 1 January 2016 to 31 December 2019. The study included 44,649 R-TKA cases, corresponding to 223,240 patients, with exclusions for nonelective admissions. Various statistical analyses were used to assess clinical outcomes, including in-hospital mortality, postoperative complications, LOS, and hospitalization costs. RESULTS: Among 2,636,880 TKA patients, 8.4% underwent R-TKA. R-TKA patients had higher rates of chronic conditions, including mental disorders (36.4%) and renal disease (9.9%). Additionally, these patients often experienced instability, necessitating revision surgery. Infection (22.3%) was the primary reason for R-TKA, followed by mechanical loosening (22.9%) and instability. Compared to primary TKA patients, R-TKA patients exhibited higher in-hospital mortality (0.085% vs. 0.025%), longer LOS (3.1 vs. 2.28 days), and higher total charges ($97,815 vs. $62,188). Postoperative complications, including blood transfusion (4.6% vs. 1.3%), acute kidney injury (4.4% vs. 1.8%), venous thromboembolism (0.55% vs. 0.29%), infection, and wound problems, were significantly higher in R-TKA patients. CONCLUSIONS: This study provides detailed insights into t LOS, costs, and complications associated with specific etiologies of revision TKA. Our findings emphasize the need for targeted preoperative optimization and patient education. This approach can help reduce the incidence and burden of R-TKA, improve patient care, optimize resource allocation, and potentially decrease the overall rates of complications in revision surgeries. LEVEL OF EVIDENCE: Level III.

Phenotypic, genetic, variation, and molecular function of CaMYB113 in pepper (Capsicum annuum L.).

Pepper (Capsicum annuum L.) is widely consumed vegetables worldwide, and F1 hybrids are highly sought after in the pepper seed industry. However, studies on gene mutations affecting the color of cotyledon are rare, and the same is true for peppers. In this study, a segregating population was developed by crossing the pepper accession 21C1344 with purple cotyledon and accession 21C912 with green cotyledon. Initially, a target genomic region was identified by screening polymorphic SSR markers distributed across 12 chromosomes. Subsequently, polymorphic markers were developed based on resequencing data from the two parental lines, and genetic linkage analysis was performed. This approach ultimately identified Capana10g001433 (CaMYB113) as the candidate gene responsible for the purple cotyledons. The gene mutation type in 21C912 represents a new mutation type distinct from the reported missense mutation types, and this mutation affects the biosynthesis of anthocyanins. Virus-induced gene silencing (VIGS) of CaMYB113 substantially decreased anthocyanin accumulation in the cotyledons. Subsequent overexpression of CaMYB113 resulted in purple callus and leaves of pepper, and changed the expression levels of downstream genes involved in anthocyanin synthesis. Yeast one-hybrid and dual-luciferase transient expression assays demonstrated the binding of CaMYB113 to anthocyanin biosynthesis-related genes, thereby regulating anthocyanin accumulation in pepper cotyledons.

Experimental considerations for precise RNA-mediated insertion of transgenes.

Precise RNA-mediated insertion of transgenes (PRINT) is a pioneering method for site-specific, safe-harbor transgene supplementation of the human genome that harnesses a eukaryotic retroelement protein and relies solely on the delivery of RNA. Here we outline important considerations in the design of the two required RNAs, details for the production and transfection of these RNAs to cells, and read-outs for successful transgene addition. Throughout, tips and key concepts are laid out to enable general use of this method.

Expression, purification, and biochemical analysis of the RNA-DNA hybrid helicase Sen1/SETX from Chaetomium thermophilum.

Yeast Sen1 and its vertebrate ortholog Senataxin (also known as SETX) are RNA-DNA resolving helicases. Sen1 and SETX are implicated in multiple critical nuclear functions not limited to but including DNA replication and repair, RNA processing, and transcription. These> 200 kDa helicases have a two-domain architecture with an N-terminal regulatory helical repeat array linked to an SF1b helicase motor core via a variable sized central linker of low complexity sequence. Given the size of these proteins, production of milligram quantities of protein that is suitable for biochemical, biophysical, and protein structural analysis has been challenging. To overcome these limitations, we developed a robust selectable high-yield YFP-fusion protein expression method for Sen1 production in mammalian cells, followed by purification on a high-affinity YFP-binding camelid nanobody support. Herein, we detail methods and protocols for the expression and purification of recombinant Sen1 from the thermophilic fungus Chaetomium thermophilum, and the quantitative characterization of its RNA-DNA duplex resolution activity.

Simultaneous probing of transcription, G-quadruplex, and R-loop.

DNA and RNA can form various non-canonical secondary structures, including G-quadruplex (G4) and R-loops. These structures are considered transcriptional regulatory elements due to their enrichment at regulatory regions. During transcription, G-rich sequences in the non-template strand promote R-loop formation in the DNA template strand. These R-loops induce G4 structures in the non-template DNA strand, further stabilizing them. Additionally, the high rG: dC base-pairing within the R-loop contributes to the stability of DNA/RNA hybridization. Our previous study investigated the interplay between G4s and R-loops and its impact on transcription. We employed two techniques to demonstrate transcription-mediated G4 and R-loop formation. The single-molecule method allows us to detect intricate details of transcription initiation, elongation, and co-transcriptional R-loop and G4 formation. It provides a high-resolution view of the dynamic processes involved in transcriptional regulation. As an orthogonal approach, a gel-based assay enables the detection of the transcription-mediated R-loops and the RNA product. We can measure the progressive formation of R-loop and total RNA produced from transcription by analyzing gel electrophoresis patterns. In summary, these techniques provide valuable insights into the non-canonical nucleic acid structures and their impact on gene expression.

Improved antitumor effectiveness of oncolytic HSV-1 viruses engineered with IL-15/IL-15Rα complex combined with oncolytic HSV-1-aPD1 targets colon cancer.

Oncolytic virotherapy is emerging as a promising therapeutic avenue for cancer treatment, harnessing both innate and tumor-specific immune responses for targeted tumor elimination. In this study, we present a novel oncolytic virus (oHSV1-IL15B) derived from herpes simplex virus-1 (HSV-1), armed with IL-15/IL-15Rα complex, with a focus on treating colon cancer combined with oncolytic HSV-1 expressing anti-PD-1 antibody (oHSV1-aPD1). Results from our study reveal that recombinant oHSV-1 virus equipped with IL-15/IL-15Rα complex exhibited significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Notably, oHSV1-IL15B combined with oHSV-1-aPD1 demonstrates superior tumor inhibition and prolonged overall survival compared to oHSV1-mock and monotherapy groups. Further exploration highlights the impact of oHSV1-IL15B, oHSV-1-aPD1 and combined group on antitumor capacity, revealing a substantial increase in CD8+ T and CD4+ T cell proportions of CT26-bearing BALB/c mice and promoting apoptosis in tumor tissue. The study emphasizes the pivotal role of cytotoxic CD8+T cells in oncolytic virotherapy, demonstrating that recombinant oHSV1-IL15B combined with oncolytic HSV-1-aPD1 induces a robust tumor-specific T cell response. RNA sequence analysis highlighted oHSV1-IL15B combined with oHSV1-aPD1 improved tumors immune microenvironment on immune response, antiviral response-related genes and apoptosis-related genes, which contributed to anti-tumor immunotherapy. The findings underscore the promising antitumor activity achieved through the combination of IL-15/IL-15Rα complex and anti-PD-1 antibody with oHSV-1. This research opens avenues for diverse therapeutic strategies, suggesting the potential of synergistically utilizing cytokines and anti-PD-1 antibody with oncolytic viruses to enhance immunotherapy for cancer management.

KLF4 regulates trophoblast function and associates with unexplained recurrent spontaneous abortion.

BACKGROUND: Recurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous abortions before 20 weeks with the same spouse [1]. However, approximately 50% of RSA cases of unknown cause are classified as unexplained recurrent spontaneous abortion (URSA). Potential factors include decreased trophoblast cell migration and invasion, leading to impaired placental implantation and maintenance of the normal maternal-fetal interface. However, the mechanism of this pathogenesis remains unknown. In this study, we investigated the potential role and mechanism of KLF4 in regulating URSA by influencing the invasion and migration ability of trophoblast cells. METHODS: We firstly identified 817 differentially expressed genes by performing a difference analysis of the dataset GSE121950 [2] related to recurrent abortion, and intersected the top 10 genes obtained respectively by the three algorithms: DMNC, MNC, and EPC using Venn Diagram.To detect the expression levels of core genes, villi samples were obtained from normal pregnant women and patients with URSA. RT-qPCR analysis revealed a significant difference in KLF4 mRNA expression and KLF4 was then analyzed. Trophoblast cell lines HTR8 and JEG3 were used to investigate the effect of KLF4 on trophoblastic function. Wound healing and transwell assays was performed to detect the invasion and migration of trophoblast cells. The expression of epithelial-mesenchymal transition(EMT) molecules were detected by RT-qPCR and western blot. Promoter detection and epigenetic modification were detected by chromatin immunoprecipitation (ChIP) assay. Molecular nuclear localization was detected by immunofluorescence and subcellular fractionation. Miscarried mice model was used to study the effects of KLF4 on URSA induced by reduced trophoblast invasion and migration. RESULTS: KLF4 is highly expressed in the villi of patients with URSA. KLF4 inhibits the expression level of H3R2ME2a in trophoblast cells by regulating the transcriptional level and nuclear translocation of PRMT6, thereby inhibiting the possible regulatory mechanism of trophoblastic invasion and providing a potential treatment strategy for URSA in vivo. CONCLUSIONS: The KLF4/PRMT6/H3R2ME2a axis regulates mechanisms associated with unexplained recurrent spontaneous abortion by regulating trophoblast function.

Prospective associations between Sleep, Sensation-Seeking and Mature Screen Usage in Early Adolescents: Findings from the Adolescent Brain Cognitive Development (ABCD) Study.

STUDY OBJECTIVES: Early exposure to mature content is linked to high-risk behaviors. This study aims to prospectively investigate how sleep and sensation-seeking behaviors influence the consumption of mature video games and R-rated movies in early adolescents. A secondary analysis examines the bidirectional relationships between sleep patterns and mature screen usage. METHODS: Data were obtained from a subsample of 3,687 early adolescents (49.2% female; mean age: 11.96 years) participating in the Adolescent Brain and Cognitive Development study. At Year 2 follow-up, participants wore Fitbit wearables for up to 21 nights to assess objective sleep measures and completed a scale about sensation-seeking traits. At Year 3 follow-up, they answered questions about mature screen usage. RESULTS: Of the sample, 41.8% of the sample reported playing mature-rated video games and 49% reported watching R-rated movies. Sensation-seeking traits were associated with R-rated movie watching one year later. Shorter sleep duration, later bedtime, more bedtime variability, and more social jetlag (discrepancy between the mid-sleep on weekdays and weekends) were associated with mature-rated video gaming and R-rated movie watching one year later. Sleep duration variability was associated with mature-rated video gaming. There was also an interaction effect: those with higher sensation-seeking scores and shorter sleep duration reported more frequent R-rated movie usage than those with longer sleep duration. Secondary analyses showed bidirectional associations between later bedtimes, more variability in bedtimes, and more social jetlag with mature screen usage. CONCLUSION: Early adolescents with sensation-seeking traits and poorer sleep health were more likely to engage in mature screen usage.

Huang Lian Jie Du decoction attenuated colitis via suppressing the macrophage Csf1r/Src pathway and modulating gut microbiota.

Introduction: Ulcerative colitis, a subtype of chronic inflammatory bowel disease (IBD), is characterized by relapsing colonic inflammation and ulcers. The traditional Chinese herbal formulation Huang Lian Jie Du (HLJD) decoction is used clinically to treat diarrhea and colitis. However, the mechanisms associated with the effects of treatment remain unclear. This study aims to elucidate the molecular mechanistic effects of HLJD formulation on colitis. Methods: Chronic colitis in mice was induced by adding 1% dextran sulfate sodium (DSS) to their drinking water continuously for 8 weeks, and HLJD decoction at the doses of 2 and 4 g/kg was administered orally to mice daily from the second week until experimental endpoint. Stool consistency scores, blood stool scores, and body weights were recorded weekly. Disease activity index (DAI) was determined before necropsy, where colon tissues were collected for biochemical analyses. In addition, the fecal microbiome of treated mice was characterized using 16S rRNA amplicon sequencing. Results: HLJD decoction at doses of 2 and 4 g/kg relieved DSS-induced chronic colitis in mice by suppressing inflammation through compromised macrophage activity in colonic tissues associated with the colony-stimulating factor 1 receptor (Csf1r)/Src pathway. Furthermore, the HLJD formula could modify the gut microbiota profile by decreasing the abundance of Bacteroides, Odoribacter, Clostridium_sensu_stricto_1, and Parasutterella. In addition, close correlations between DAI, colon length, spleen weight, and gut microbiota were identified. Discussion: Our findings revealed that the HLJD formula attenuated DSS-induced chronic colitis by reducing inflammation via Csf1r/Src-mediated macrophage infiltration, as well as modulating the gut microbiota profile.

Leveraging Open-Source Geographic Databases to Enhance the Representation of Landscape Heterogeneity in Ecological Models.

Wildlife abundance and movement are strongly impacted by landscape heterogeneity, especially in cities which are among the world's most heterogeneous landscapes. Nonetheless, current global land cover maps, which are used as a basis for large-scale spatial ecological modeling, represent urban areas as a single, homogeneous, class. This often requires urban ecologists to rely on geographic resources from local governments, which are not comparable between cities and are not available in underserved countries, limiting the spatial scale at which urban conservation issues can be tackled. The recent expansion of community-based geographic databases, for example, OpenStreetMap (OSM), represents an opportunity for ecologists to generate large-scale maps geared toward their specific research needs. However, computational differences in language and format, and the high diversity of information within, limit the access to these data. We provide a framework, using R, to extract geographic features from the OSM database, classify, and integrate them into global land cover maps. The framework includes an exhaustive list of OSM features describing urban and peri-urban landscapes and is validated by quantifying the completeness of the OSM features characterized, and the accuracy of its final output in 34 cities in North America. We portray its application as the basis for generating landscape variables for ecological analysis by using the OSM-enhanced map to generate an urbanization index, and subsequently analyze the spatial occupancy of six mammals throughout Chicago, Illinois, USA. The OSM features characterized had high completeness values for impervious land cover classes (50%-100%). The final output, the OSM-enhance map, provided an 89% accurate representation of the landscape at 30m resolution. The OSM-derived urbanization index outperformed other global spatial data layers in the spatial occupancy analysis and concurred with previously seen local response trends, whereby lagomorphs and squirrels responded positively to urbanization, while skunks, raccoons, opossums, and deer responded negatively. This study provides a roadmap for ecologists to leverage the fine resolution of open-source geographic databases and apply it to spatial modeling by generating research-specific landscape variables. As our occupancy results show, using context-specific maps can improve modeling outputs and reduce uncertainty, especially when trying to understand anthropogenic impacts on wildlife populations.

ER-mitochondria contact sites regulate hepatic lipogenesis via Ip3r-Grp75-Vdac complex recruiting Seipin.

BACKGROUND: Mitochondria and endoplasmic reticulum (ER) contact sites (MERCS) constitute a functional communication platform for ER and mitochondria, and they play a crucial role in the lipid homeostasis of the liver. However, it remains unclear about the exact effects of MERCs on the neutral lipid synthesis of the liver. METHODS: In this study, the role and mechanism of MERCS in palmitic acid (PA)-induced neutral lipid imbalance in the liver was explored by constructing a lipid metabolism animal model based on yellow catfish. Given that the structural integrity of MERCS cannot be disrupted by the si-mitochondrial calcium uniporter (si-mcu), the MERCS-mediated Ca2+ signaling in isolated hepatocytes was intercepted by transfecting them with si-mcu in some in vitro experiments. RESULTS: The key findings were: (1) Hepatocellular MERCs sub-proteome analysis confirmed that, via activating Ip3r-Grp75-voltage-dependent anion channel (Vdac) complexes, excessive dietary PA intake enhanced hepatic MERCs. (2) Dietary PA intake caused hepatic neutral lipid deposition by MERCs recruiting Seipin, which promoted lipid droplet biogenesis. (3) Our findings provide the first proof that MERCs recruited Seipin and controlled hepatic lipid homeostasis, depending on Ip3r-Grp75-Vdac-controlled Ca2+ signaling, apart from MERCs's structural integrity. Noteworthy, our results also confirmed these mechanisms are conservative from fish to mammals. CONCLUSIONS: The findings of this study provide a new insight into the regulatory role of MERCS-recruited SEIPIN in hepatic lipid synthesis via Ip3r-Grp75-Vdac complex-mediated Ca2+ signaling, highlighting the critical contribution of MERCS in hepatic lipid homeostasis.

Complex Coronary Artery Lesions in a Young Woman With an Acute Myocardial Infarction and Genetically Confirmed Familial Hypercholesterolemia: A Case Report and Literature Review From a Developing Country.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) in the blood from an incredibly early age. This condition leads to the early development of atherosclerotic arterial diseases, which can manifest even in the first few decades of life. Mutations in genes related to the LDL receptor (LDL-R), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) are the main molecular mechanisms causing familial hypercholesterolemia. This case involves a 44-year-old Vietnamese female who presented at the emergency department with chest pain and was diagnosed with acute myocardial infarction (AMI) complicated by cardiogenic shock. Clinical signs and an elevated LDL-C level pointed to prolonged exposure to high cholesterol. A Dutch Lipid Clinic Network (DLCN) score of 10 further supported the diagnosis of FH. The reverse T-stenting and small protrusion (TAP) technique was selected and successfully employed to stent the LMCA, left anterior descending artery (LAD) and left circumflex artery (LCx). This technique was chosen due to its simplicity and rapid execution, making it particularly suitable in situations of cardiogenic shock where time-consuming procedures should be avoided. Genetic testing confirmed a heterozygous pathogenic mutation in the LDL-R gene, corroborating the clinical diagnosis of FH. The patient's condition has gradually stabilized, and they have been discharged from the hospital. The patient is currently being monitored as an outpatient at the cardiology clinic. This case emphasizes the importance of considering FH in patients with premature cardiovascular events by applying the clinical diagnostic criteria and confirming by genetic analysis. It also highlights advanced interventional techniques for managing complex coronary lesions, such as reverse TAP.

Bibliometric analysis of microRNAs and Parkinson's disease from 2014 to 2023.

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons. Recent research has emphasized a significant correlation between microRNAs (miRNAs) and PD. To identify key research areas, provide a comprehensive overview of current research in various fields, and propose potential directions for future studies, a bibliometric analysis was conducted on the involvement of miRNAs in Parkinson's disease from 2014 to 2023. Methods: Relevant literature records were collected from the Web of Science Core Collection on February 29, 2024. Subsequently, the data underwent analysis using the Bibliometrix R package and VOSviewer (version 1.6.19). Results: The annual scientific publications on miRNAs and Parkinson's disease demonstrated an increasing trend, with an annual growth rate of 12.67%. China, the United States, and India emerged as the top three most productive countries/regions. The University of Barcelona had the highest annual publications, followed by Central South University and the Helmholtz Association. The INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES held the top position in terms of H-index and total citations, reflecting its extensive influence and prolific publication output. Kim, J., Junn, E., Hébert, S.S., and Doxakis, E. were the most frequently co-cited authors in the field. Based on the analysis of keywords, the most frequently occurring terms included "alpha-synuclein," "neurodegenerative disease," "exosome," "neuroinflammation," "oxidative stress," "autophagy," and "amyotrophic lateral sclerosis," which have emerged as prominent research topics. Concurrently, there has been notable interest in topics such as "ceRNA," "lncRNAs," "mitochondrial dysfunction," and "circular RNA." Conclusion: This study focused on identifying emerging trends and critical research topics in the bibliometric analysis of microRNAs related to Parkinson's disease. These findings highlight the diverse research landscape and evolving trend of miRNA-related research in PD. The field of miRNA research in Parkinson's disease is actively exploring the underlying mechanisms of miRNA function, identifying potential diagnostic markers, and developing innovative therapeutic strategies. The results of our study offer significant contributions to researchers' ability to track contemporary developments and guide the trajectory of future research in this domain.

Personality and COMT gene: molecular-genetic and epigenetic associations with NEO-PI-R personality domains and facets in monozygotic twins.

Background: This study investigates the relationship between MB-COMT DNA methylation (DNAm) and the personality traits outlined in the NEO-PI-R model through an epigenetic study of monozygotic twins. DNAm, a critical epigenetic mechanism, regulates gene expression and has been linked to various biological processes and disorders. By leveraging the genetic similarities of monozygotic twins, this research explores how epigenetic variations influenced by environmental factors correlate with personality differences. Methods: The study utilized the Five-Factor Model (FFM) to categorize personality traits into five domains: Neuroticism, Extraversion, Conscientiousness, Agreeableness, and Openness to Experience. Each domain comprises six facets, providing a granular view of personality. The research centered on the catechol-O-methyltransferase (COMT) gene, focusing on its role in dopamine metabolism, which is hypothesized to influence personality traits through the dopaminergic system. DNAm status in the MB-COMT promoter region was examined to determine its association with personality facets. Results: Preliminary findings suggest a complex interaction between MB-COMT DNAm patterns and personality traits. Specific methylation patterns at different CpG sites were linked to varying expressions of traits such as impulsivity and aggression, highlighting the nuanced impact of epigenetics on personality. Conclusion: This study underscores the potential of integrating genetic, epigenetic, and environmental data to enhance our understanding of personality formation. The results contribute to a broader understanding of how genetic predispositions shaped by environmental factors manifest in complex trait differences, paving the way for future research in genetic psychiatry and personalized medicine.