Factor Activity Research Articles

A TriAdj-Adjuvanted Chlamydia trachomatis CPAF Protein Vaccine Is Highly Immunogenic in Pigs.

Chlamydia trachomatis (Ct) infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs, as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we used the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial-protease-like activity factor (CPAF) protein. We tested two weekly administration options-twice intranasal (IN) followed by twice intramuscular (IM) and twice IM followed by twice IN. We assessed the humoral immune response in both serum using CPAF-specific IgG (including antibody avidity determination) and also in cervical and rectal swabs using CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed following in vitro CPAF restimulation via IFN-γ and IL-17 ELISpots, as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity, as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response. Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response with CD4 T cells. In IM/IN-vaccinated pigs, these cells also significantly downregulated their CCR7 expression, a sign of differentiation into peripheral-tissue-homing effector/memory cells. Conclusively, this study demonstrates the strong immunogenicity of the IM/IN-administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test the vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates the suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

Gallic acid mitigates intestinal inflammation and loss of tight junction protein expression using a 2D-Caco-2 and RAW 264.7 co-culture model

A 2D-intestinal epithelial Caco-2/RAW 264.7 macrophage co-culture model was developed to demonstrate the relative efficacy of different phenolic acids to mitigate changes in Caco-2 epithelial cell redox state initiated both directly by autoxidation products, H2O2, and indirectly through cell communication events originating from cytokine stimulated macrophage. An inducer cocktail (lipopolysaccharide + interferon gamma) was used to activate RAW 264.7 cells in the 2D- Caco-2/RAW co-culture and intracellular changes in Caco-2 cell redox signaling occurred in response to positive changes (p < 0.05) in inflammatory biomarkers derived in macrophage that included IL-6, TNF-α, nitric oxide and peroxynitrite, respectively. Phenolic acids varied in relative capacity to reduce NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) in cocktail inflamed induced macrophage. This response in addition to the relative predisposition of gallic acid (GA) to undergo autoxidation to generate H2O2 activity (p < 0.05), culminated in downstream cell signaling in Caco-2 nuclear factor erythroid 2-related factor (Nrf2) activity (increase 26.9 %), altered monolayer integrity (increase 33.7 %), and release of interleukin 8 (IL-8) (decrease 80.5 %) (p < 0.05). It can be concluded that the co-culture model described herein was useful to assess the importance of communication between cytokine stimulated macrophage and intestinal cells. Moreover, the relative unique efficacy of GA, compared to other phenolic acids tested to protect against activated macrophage induced changes related to intestinal dysfunction were particularly relevant to epithelial redox signaling, intestinal permeability and regulation of tight junction proteins. This study concludes that phenolic acids are not equal in the capacity to protect against intestinal cell dysfunction despite some indication of biological activity.

Characterization of the metabolic contributions of cytochrome P450 isoforms to bicyclol using the relative activity factor method

Bicyclol is a hepatoprotective agent widely used for treating chronic hepatitis and drug-induced liver injuries in clinics. The purpose of the study was to elucidate the contribution of CYP450 enzymes to the metabolism of bicyclol using the relative activity factor approach. After incubation with human liver microsomes and recombinant human liver CYP450 enzymes, the calculated contribution of CYP3A4 and 2C19 to the metabolism of bicyclol was 85.6–90.3% and 9.2–9.7%, respectively. The metabolism was interrupted in the presence of CYP3A4 and 2C19 selective inhibitors. These findings help to predict or avoid metabolic drug–drug interactions or toxicity in clinical applications of bicyclol.

Abstract P15: Aberrant Non-canonical NF-κB Signalling Reprograms the Epigenome Landscape to Drive Oncogenic Transcriptomes in Multiple Myeloma

Abstract Activation of the NF-κB pathway is recognized to be necessary for the survival and progression of haematological cancers including Multiple Myeloma (MM). In particular, recurrent genetic lesions resulting in the chronic induction of non-canonical NF-κB (ncNF-κB) signalling have been exclusively linked to MM. Such mutations among patients are associated with significant proliferative and metastatic advantages and have been causally linked to treatment resistance. How the constitutive activity of ncNF-κB transcription factors can support such adaptations in this common haematological malignancy has been a fundamental question in cancer. In this study, we captured the epigenomic landscape of patient-derived MM cell lines harbouring recurrent NF-κB activating mutations through perturbation of nfkb2/p52 and integrated these cis-regulatory changes with MM patient epigenome data. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment of cis-regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of these cis-regulatory modules on cell and tumour phenotypes using in vitro and in vivo models, confirming RGS1 as a novel p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression. Citation Format: Daniel A. Ang, Jean-Michel Carter, Kamalakshi Deka, Joel H.L. Tan, Jianbiao Zhou, Qingfeng Chen, Wee Joo Chng, Nathan Harmston, Yinghui Li. Aberrant Non-canonical NF-κB Signalling Reprograms the Epigenome Landscape to Drive Oncogenic Transcriptomes in Multiple Myeloma [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P15.

Deciphering the prognostic landscape of osteosarcoma: Integrating the roles of hippo pathway genes, programmed cell death, and the tumor immune microenvironment.

Osteosarcoma is a highly aggressive cancer prevalent among adolescents and young adults, notorious for its tendency to metastasize to the lungs. This research delves into the molecular foundations of osteosarcoma by examining the role of the Hippo signaling pathway and its interaction with the tumor immune microenvironment (TME). Through analysis of transcriptomic data from the TARGET-OS dataset and control samples from GTEx, we identified a set of 131 genes that link high expression profiles in osteosarcoma with the Hippo pathway. A focused examination through univariate Cox regression analysis revealed eight key genes (DLG5, WNT11, TGFB2, DLG4, WNT16, ID2, WNT10B, and WNT10A) with a significant correlation to patient outcomes. Hierarchical clustering of these genes delineated two distinct patient groups with significantly different survival rates, a finding supported by Kaplan-Meier survival analysis. Further investigation into immune cell infiltration and expression profiles of immunoregulatory factors uncovered a notable pattern of immune evasion in the group with poorer prognosis, marked by reduced effector immune cell activity and lower levels of immunostimulatory factors. Single-cell sequencing highlighted the cellular diversity within osteosarcoma samples and identified markers differentiating malignant from nonmalignant cells, correlating these markers with prognostic risk scores. Our results emphasize the critical prognostic value of Hippo pathway genes and the TME in osteosarcoma, shedding light on new avenues for therapeutic intervention and patient-specific treatment strategies.

The Progress in the Occurrence and Treatment of NLRP3 Inflammasome in Bone and Joint Diseases

Inflammasomes play a pivotal role in the innate immune system, which regulates the activation and expression of inflammatory factors, has a profound impact on the occurrence and expression of various inflammatory diseases. In recent years, studies have demonstrated that the NLRP3 inflammasome is closely associated with many fields, such as cardiovascular diseases, metabolic disorders, and chronic diseases. Moreover, inflammatory diseases of bone and joints, which are more prevalent in the population, such as osteoarthritis and rheumatoid arthritis, can cause substantial damage to bone and cartilage, trigger pain and even dysfunction, and reduce the quality of life. Numerous studies have shown that the pathogenesis of multiple bone diseases and arthritic diseases, including osteoarthritis and rheumatoid arthritis, is closely associated with the NLRP3 inflammasome. Some progress has been made in the targeted treatment of the NLRP3 inflammasome, especially for small-molecule inhibitors. These inhibitors have potential therapeutic value by inhibiting the activation of the NLRP3 inflammasome, thereby reducing the inflammatory response. However, the research on the feasibility, safety, and drug metabolism of these small-molecule inhibitors in clinical application is still in the exploratory stage, and further research is urgently needed. This paper aims to review the NLRP3 inflammasome structure, function and its progress in bone-related diseases and treatment. Through this paper, we hope to improve the understanding of the NLRP3 inflammasome in the development and treatment of bone diseases, so as to provide a theoretical basis for clinical practice.

Photobleaching FRET-FLIM-ICS for quaternary structure quantification on cells. Theory and simulations

The oligomerization of proteins is an important biological control mechanism and has several functions in activity and stability of enzymes, structural proteins, ion channels and transcription factors. The determination of the relevant oligomeric states in terms of geometry (spatial extent), oligomer size (monomer or dimer or oligomer) and affinity (amounts of monomer, dimer and oligomer) is a challenging biophysical problem. Förster resonance energy transfer and fluorescence fluctuation spectroscopy are powerful tools that are sensitive to proximity and oligomerization respectively. Here it is proposed to combine image-based lifetime-detected Forster resonance energy transfer with image correlation spectroscopy and photobleaching to determine distances, oligomer sizes and oligomer distributions. Simulations for simple oligomeric forms illustrate the potential to improve the discrimination between different quaternary states in the cellular milieu.

Abstract LT04: Dissecting Mediator Kinase Activity in Normal Tissue Homeostasis and Cancer

Abstract Cyclin-dependent kinase 8 (CDK8) and its paralog CDK19, collectively known as Mediator kinase, are part of the multimeric Mediator complex that fine-tune gene expression programs on multiple levels, most notably by controlling transcription factor (TF) activity at promoter- and enhancer regions as well as organising the chromatin landscape. While Mediator kinases have been predominantly studied as a therapeutic target in cancer cells, their functions in a physiologically relevant context remain poorly understood. To study in vivo functions of Mediator, we developed a comprehensive suite of genetically engineered mouse models (GEMMs), including conditional floxed alleles (Cdk8fl/fl/Cdk19fl/fl) and kinase-dead knock-ins (Cdk8D173A/fl/Cdk19D173A/fl), enabling the analysis of scaffolding and kinase-dependent functions of this critical transcriptional module. Herein, we show that Mediator kinase has distinct kinase-dependent functions in modulating homeostasis and tissue lineage specification in diverse organs. Moreover, using a proteo-genomic approach we show that the Mediator Kinase module functionally interacts with the SWI/SNF complex to mediate transcriptional output. Collectively, our work expands the understanding of how Mediator Kinase regulates tissue homeostasis and provides a framework for considering how Mediator Kinase inhibition may be effectively employed in the clinical setting. Citation Format: Marius Dannappel, Danxi Zhu, Claire Sun, Ron Firestein. Dissecting Mediator Kinase Activity in Normal Tissue Homeostasis and Cancer [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr LT04.

Metabolic Syndrome and Biotherapeutic Activity of Dairy (Cow and Buffalo) Milk Proteins and Peptides: Fast Food-Induced Obesity Perspective-A Narrative Review.

Metabolic syndrome (MS) is defined by the outcome of interconnected metabolic factors that directly increase the prevalence of obesity and other metabolic diseases. Currently, obesity is considered one of the most relevant topics of discussion because an epidemic heave of the incidence of obesity in both developing and underdeveloped countries has been reached. According to the World Obesity Atlas 2023 report, 38% of the world population are presently either obese or overweight. One of the causes of obesity is an imbalance of energy intake and energy expenditure, where nutritional imbalance due to consumption of high-calorie fast foods play a pivotal role. The dynamic interactions among different risk factors of obesity are highly complex; however, the underpinnings of hyperglycemia and dyslipidemia for obesity incidence are recognized. Fast foods, primarily composed of soluble carbohydrates, non-nutritive artificial sweeteners, saturated fats, and complexes of macronutrients (protein-carbohydrate, starch-lipid, starch-lipid-protein) provide high metabolic calories. Several experimental studies have pointed out that dairy proteins and peptides may modulate the activities of risk factors of obesity. To justify the results precisely, peptides from dairy milk proteins were synthesized under in vitro conditions and their contributions to biomarkers of obesity were assessed. Comprehensive information about the impact of proteins and peptides from dairy milks on fast food-induced obesity is presented in this narrative review article.

Chronic Administration of Exogenous Lactate Increases Energy Expenditure during Exercise through Activation of Skeletal Muscle Energy Utilization Capacity in Mice.

We compared the effects of chronic exogenous lactate and exercise training, which influence energy substrate utilization and body composition improvements at rest and during exercise, and investigated the availability of lactate as a metabolic regulator. The mice were divided into four groups: CON (sedentary + saline), LAC (sedentary + lactate), EXE (exercise + saline), and EXLA (exercise + lactate). The total experimental period was set at 4 weeks, the training intensity was set at 60-70% VO2max, and each exercise group was administered a solution immediately after exercise. Changes in the energy substrate utilization at rest and during exercise, the protein levels related to energy substrate utilization in skeletal muscles, and the body composition were measured. Lactate intake and exercise increased carbohydrate oxidation as a substrate during exercise, leading to an increased energy expenditure and increased protein levels of citrate synthase and malate dehydrogenase 2, key factors in the TCA(tricarboxylic acid) cycle of skeletal muscle. Exercise, but not lactate intake, induced the upregulation of the skeletal muscle glucose transport factor 4 and a reduction in body fat. Hence, chronic lactate administration, as a metabolic regulator, influenced energy substrate utilization by the skeletal muscle and increased energy expenditure during exercise through the activation of carbohydrate metabolism-related factors. Therefore, exogenous lactate holds potential as a metabolic regulator.

Molecular phenotyping of small cell lung cancer using targeted cfDNA profiling of transcriptional regulatory regions.

We report an approach for cancer phenotyping based on targeted sequencing of cell-free DNA (cfDNA) for small cell lung cancer (SCLC). In SCLC, differential activation of transcription factors (TFs), such as ASCL1, NEUROD1, POU2F3, and REST defines molecular subtypes. We designed a targeted capture panel that identifies chromatin organization signatures at 1535 TF binding sites and 13,240 gene transcription start sites and detects exonic mutations in 842 genes. Sequencing of cfDNA from SCLC patient-derived xenograft models captured TF activity and gene expression and revealed individual highly informative loci. Prediction models of ASCL1 and NEUROD1 activity using informative loci achieved areas under the receiver operating characteristic curve (AUCs) from 0.84 to 0.88 in patients with SCLC. As non-SCLC (NSCLC) often transforms to SCLC following targeted therapy, we applied our framework to distinguish NSCLC from SCLC and achieved an AUC of 0.99. Our approach shows promising utility for SCLC subtyping and transformation monitoring, with potential applicability to diverse tumor types.

АНАЛИЗ ИСПОЛЬЗОВАНИЯ ЧЕЛОВЕЧЕСКОГО КАПИТАЛА НА ПРИМЕРЕ АГРАРНОГО РЕГИОНА (РЕСПУБЛИКИ ТАТАРСТАН)

Human capital has always been of great importance for the stable economic and social progress of society. The way humanity accumulates experience and develops the potential of society in its various forms is the way of life of society. One of the forms of application of human capital is the agro-industrial complex, which is rightfully considered the foundation of any human economic activity. Purpose of the study: to determine the theoretical basis for the practical use of human capital in the agro-industrial complex of the Republic of Tatarstan and to develop recommendations for its implementation in specific conditions of economic activity. Methodology: analysis of statistical data, description, synthesis, systematic approach, etc. Scientific novelty: The level of socio-economic development of Tatarstan is largely determined by the presence of human capital that can compete with similar capital in other regions. In addition, it is human capital that contributes to the activation of production factors aimed at introducing innovation into production processes and increasing the efficiency of the economic system. The agro-industrial complex of modern Russia is an important industry, the level of development of which determines the country's food security. The political crisis and sanctions have necessitated changes in production technologies and requirements for the qualifications of relevant personnel with the necessary set of competencies, including digital competence.

Inferring gene regulatory networks from single-cell multiome data using atlas-scale external data.

Existing methods for gene regulatory network (GRN) inference rely on gene expression data alone or on lower resolution bulk data. Despite the recent integration of chromatin accessibility and RNA sequencing data, learning complex mechanisms from limited independent data points still presents a daunting challenge. Here we present LINGER (Lifelong neural network for gene regulation), a machine-learning method to infer GRNs from single-cell paired gene expression and chromatin accessibility data. LINGER incorporates atlas-scale external bulk data across diverse cellular contexts and prior knowledge of transcription factor motifs as a manifold regularization. LINGER achieves a fourfold to sevenfold relative increase in accuracy over existing methods and reveals a complex regulatory landscape of genome-wide association studies, enabling enhanced interpretation of disease-associated variants and genes. Following the GRN inference from reference single-cell multiome data, LINGER enables the estimation of transcription factor activity solely from bulk or single-cell gene expression data, leveraging the abundance of available gene expression data to identify driver regulators from case-control studies.

Roles of β-Cell Hypoxia in the Progression of Type 2 Diabetes.

Type 2 diabetes is a chronic disease marked by hyperglycemia; impaired insulin secretion by pancreatic β-cells is a hallmark of this disease. Recent studies have shown that hypoxia occurs in the β-cells of patients with type 2 diabetes and hypoxia, in turn, contributes to the insulin secretion defect and β-cell loss through various mechanisms, including the activation of hypoxia-inducible factors, induction of transcriptional repressors, and activation of AMP-activated protein kinase. This review focuses on advances in our understanding of the contribution of β-cell hypoxia to the development of β-cell dysfunction in type 2 diabetes. A better understanding of β-cell hypoxia might be useful in the development of new strategies for treating type 2 diabetes.

Neuroprotective effect of human cord blood-derived extracellular vesicles by improved neuromuscular function and reduced gliosis in a rat model of Huntington's disease

Huntington's disease (HD) is a hereditary condition characterized by the gradual deterioration of nerve cells in the striatum. Recent scientific investigations have revealed the promising potential of Extracellular vesicles (EVs) as a therapy to mitigate inflammation and enhance motor function. This study aimed to examine the impact of administering EVs derived from human umbilical cord blood (HUCB) on the motor abilities and inflammation levels in a rat model of HD. After ultracentrifugation to prepare EVs from HUCB to determine the nature of the obtained contents, the expression of CD markers 81 and 9, the average size and also the morphology of its particles were investigated by DLS and Transmission electron microscopy (TEM). Then, in order to induce the HD model, 3-nitropropionic acid (3-NP) neurotoxin was injected intraperitoneal into the rats, after treatment by HUCB-EVs, rotarod, electromyogram (EMG) and the open field tests were performed on the rats. Finally, after rat sacrifice and the striatum was removed, Hematoxylin and eosin staining (H&E), stereology, immunohistochemistry, antioxidant tests, and western blot were performed. Our results showed that the contents of the HUCB-EVs express the CD9 and CD81 markers and have spherical shapes. In addition, the injection of HUCB-EVs improved motor and neuromuscular function, reduced gliosis, increased antioxidant activity and inflammatory factor, and partially prevented the decrease of neurons. The findings generally show that HUCB-EVs have neuroprotective effects and reduce neuroinflammation from the toxic effects of 3-NP, which can be beneficial for the recovery of HD.

Completely Plant-Based Diets That Meet Energy Requirements for Resistance Training Can Supply Enough Protein and Leucine to Maximize Hypertrophy and Strength in Male Bodybuilders: A Modeling Study.

Despite increasing awareness of plant-based diets for health and athletic performance, athletes are cautioned that careful dietary monitoring is necessary. Whether commonly consumed plant-based diets are nutritionally adequate for maximal muscular hypertrophy remains unknown. This modeling study assessed the nutrient composition of completely plant-based diets scaled to the caloric demands of maximal muscle mass and strength development in adult male bodybuilders. To model calorie requirements, anthropometric data from bodybuilders were input into the Tinsley resting metabolic rate prediction equation, and an appropriate physical activity factor and calorie surplus were applied. Dietary data from a large cohort following completely plant-based diets were then scaled to meet these needs. Modeled intakes for nutrients of interest were calculated as 1.8 g/kg/day of protein and 2.75 g/meal of leucine, which surpass mean requirements for maximal increases in muscle mass and strength and muscle protein synthesis, respectively. Daily levels for all micronutrients, except vitamin D, also exceeded requirements. Saturated fat levels were aligned with dietary guidelines, although sodium levels exceeded recommended limits. Consumption of larger portions of commonplace plant-based diets, scaled to meet the energy demands of maximal accrual of muscle mass and strength, satisfied protein and leucine requirements without the need for additional planning.

Genome-wide DNA methylation-analysis of blastic plasmacytoid dendritic cell neoplasm identifies distinct molecular features

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) constitutes a rare and aggressive malignancy originating from plasmacytoid dendritic cells (pDCs) with a primarily cutaneous tropism followed by dissemination to the bone marrow and other organs. We conducted a genome-wide analysis of the tumor methylome in an extended cohort of 45 BPDCN patients supplemented by WES and RNA-seq as well as ATAC-seq on selected cases. We determined the BPDCN DNA methylation profile and observed a dramatic loss of DNA methylation during malignant transformation from early and mature DCs towards BPDCN. DNA methylation profiles further differentiate between BPDCN, AML, CMML, and T-ALL exhibiting the most striking global demethylation, mitotic stress, and merely localized DNA hypermethylation in BPDCN resulting in pronounced inactivation of tumor suppressor genes by comparison. DNA methylation-based analysis of the tumor microenvironment by MethylCIBERSORT yielded two, prognostically relevant clusters (IC1 and IC2) with specific cellular composition and mutational spectra. Further, the transcriptional subgroups of BPDCN (C1 and C2) differ by DNA methylation signatures in interleukin/inflammatory signaling genes but also by higher transcription factor activity of JAK-STAT and NFkB signaling in C2 in contrast to an EZH2 dependence in C1-BPDCN. Our integrative characterization of BPDCN offers novel molecular insights and potential diagnostic applications.

Insights into the Interaction between the Biocontrol Agent Bacillus amyloliquefaciens QST 713, the Pathogen Monilinia fructicola and Peach Fruit

Brown rot disease caused by Monilinia fructicola is one of the most important peach fruit threats in the world. The use of biological control agents (BCAs), instead of synthetic fungicides, to successfully inhibit postharvest disease development is a challenge in sustainable and efficient crop management. The commercially available BCA Bacillus amyloliquefaciens QST 713 (formerly Bacillus subtilis QST713) is able to inhibit a variety of fungal pathogens and suppress several plant diseases. Our results showed that this BCA inhibited mycelial growth in vitro, and was able to suppress the disease’s severity in peach fruits via delaying and reducing brown rot symptoms. A transcriptomic analysis of fruits during their pre-treatment with this biocontrol agent following M. fructicola challenge revealed a significant upregulation of specific differentially expressed genes (DEGs) at 48 h after inoculation (HAI). These genes are related to the activation of several transcriptional factors, such as members of the WRKY and NAC families, and receptors that are involved in pathogen recognition and signaling transduction (e.g., LRR-RLKs). Furthermore, the inhibition of M. fructicola by this biocontrol agent was confirmed by analyzing the expression profiles of specific fungal genes, which highlighted the direct antimicrobial impact of this bacterial strain against the fungus. Hence, these findings clearly suggest that B. amyloliquefaciens QST 713 is an efficient BCA against brown rot disease, which can directly inhibit M. fructicola and improve peach fruit tolerance.

Determinants of Risk for Type 2 Diabetes Mellitus Among the Community at The Birobuli Community Health Center

To identify the determinants of risk for type 2 diabetes mellitus among the community at the Birobuli Community Health Center. Type of quantitative research with a case-control approach at a confidence level of 95%. The sample size was taken using the Slovin formula with a result of 76 people and a 1:1 ratio and using gender matching with a total sample of 152 people. Sampling was done using the purposive sampling technique. The data source used secondary data in the form of medical records and primary data in the form of interviews using questionnaires measuring physical activity, unhealthy eating patterns, and sleep quality with the criteria that a doctor diagnosed the respondent as suffering from Type 2 DM and not suffering from other types of Diabetes Mellitus (DM). Data analysis used the odds ratio test, the results showed that physical activity (OR=4.455 and CI=2.250-8.819), unhealthy eating patterns (OR=3.145 and CI=1.616-6.120), sleep quality (OR=5.444 and CI= 2,703 10,966), and dyslipidemia (OR=4,287 and CI=2,121-8,667) are determinants of the risk of Type 2 DM. It is suggested that health workers should improve health services at each Integrated Development Post (known as POSBINDU), an integrated monitoring and early detection activity for NCD risk factors (heart and blood vessel disease, diabetes, acute obstructive pulmonary disease, and cancer) as well as disorders due to accidents and acts of domestic violence which are managed by the community through integrated guidance, meanwhile, provide education on healthy lifestyles to overcome the incidence of DM

PMF-GRN: a variational inference approach to single-cell gene regulatory network inference using probabilistic matrix factorization.

Inferring gene regulatory networks (GRNs) from single-cell data is challenging due to heuristic limitations. Existing methods also lack estimates of uncertainty. Here we present Probabilistic Matrix Factorization for Gene Regulatory Network Inference (PMF-GRN). Using single-cell expression data, PMF-GRN infers latent factors capturing transcription factor activity and regulatory relationships. Using variational inference allows hyperparameter search for principled model selection and direct comparison to other generative models. We extensively test and benchmark our method using real single-cell datasets and synthetic data. We show that PMF-GRN infers GRNs more accurately than current state-of-the-art single-cell GRN inference methods, offering well-calibrated uncertainty estimates.