BayesAge 2.0: a maximum likelihood algorithm to predict transcriptomic age.

Aging is a complex biological process influenced by various factors, including genetic and environmental influences. In this study, we present BayesAge 2.0, an upgraded version of our maximum likelihood algorithm designed for predicting transcriptomic age (tAge) from RNA-seq data.

DNA-methylation age and accelerated epigenetic aging in blood as a tumor marker for predicting breast cancer susceptibility.

Background: DNA methylation (DNAm)-based marker of aging, referred to as 'epigenetic age' or 'DNAm age' is a highly accurate multi-tissue biomarker for aging, associated with age-related disease risk, including cancer. Breast cancer (BC), an age-associated disease, is associated with older DNAm age and epigenetic age acceleration (age accel) at tissue levels. But this raises a question on the predictability of DNAm age/age accel in BC development, emphasizing the importance of studying DNAm age in pre-diagnostic peripheral blood (PB) in BC etiology and prevention.

Epigenetic aging of semen is associated with inflammation.

Male infertility has been a primary cause of global infertility, affecting 8-12% of couples worldwide. Previous studies have shown that semen quality decreases with advanced aging with an increased presence of inflammatory cells. In this study, we examined changes in the epigenome across a diverse cohort that includes both fertile and infertile men.

Complete genomes of SNA2 and sp. cycad4: microbes with the potential for plant growth promotion.

species have been isolated from various environments, often in association with plants. Here, we report the complete genomes of SNA2 and sp. cycad4.

The Multi-State Epigenetic Pacemaker enables the identification of combinations of factors that influence DNA methylation.

Epigenetic clocks, DNA methylation-based predictive models of chronological age, are often utilized to study aging associated biology. Despite their widespread use, these methods do not account for other factors that also contribute to the variability of DNA methylation data. For example, many CpG sites show strong sex-specific or cell-type-specific patterns that likely impact the predictions of epigenetic age.

A genomic analysis reveals the diversity of cellulosome displaying bacteria.

Introduction: Several species of cellulolytic bacteria display cellulosomes, massive multi-cellulase containing complexes that degrade lignocellulosic plant biomass (LCB). A greater understanding of cellulosome structure and enzyme content could facilitate the development of new microbial-based methods to produce renewable chemicals and materials.

Methods: To identify novel cellulosome-displaying microbes we searched 305,693 sequenced bacterial genomes for genes encoding cellulosome proteins; dockerin-fused glycohydrolases (DocGHs) and cohesin domain containing scaffoldins.

Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients.

Clinical trials for Duchenne muscular dystrophy (DMD) are assessing the therapeutic efficacy of systemically delivered adeno-associated virus (AAV) carrying a modified transgene. High vector doses (>1E14 vg/kg) are needed to globally transduce skeletal muscles; however, such doses trigger immune-related adverse events. Mitigating these immune responses is crucial for widespread application of AAV-based therapies.

Complete genome of sp. EBFNA2, isolated from a surface-sterilized fava bean nodule.

We report the complete genome sequence of sp. EBFNA2, a fava bean nodule endophyte. The strain appears to be a new species, and its genome provides insight into its interactions with host plants and potential to promote plant growth and crop yield.

Extracellular vesicles from human breast cancer-resistant cells promote acquired drug resistance and pro-inflammatory macrophage response.

Introduction: Breast cancer is a significant public health problem around the world, ranking first in deaths due to cancer in females. The therapy to fight breast cancer involves different methods, including conventional chemotherapy. However, the acquired resistance that tumors develop during the treatment is still a central cause of cancer-associated deaths.

Bone-marrow macrophage-derived GPNMB protein binds to orphan receptor GPR39 and plays a critical role in cardiac repair.

Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein initially identified in nonmetastatic melanomas and has been associated with human heart failure; however, its role in cardiac injury and function remains unclear. Here we show that GPNMB expression is elevated in failing human and mouse hearts after myocardial infarction (MI). Lineage tracing and bone-marrow transplantation reveal that bone-marrow-derived macrophages are the main source of GPNMB in injured hearts.

A humanized monoclonal antibody targeting an ectonucleotidase rescues cardiac metabolism and heart function after myocardial infarction.

Myocardial infarction (MI) results in aberrant cardiac metabolism, but no therapeutics have been designed to target cardiac metabolism to enhance heart repair. We engineer a humanized monoclonal antibody against the ectonucleotidase ENPP1 (hENPP1mAb) that targets metabolic crosstalk in the infarcted heart. In mice expressing human ENPP1, systemic administration of hENPP1mAb metabolically reprograms myocytes and non-myocytes and leads to a significant rescue of post-MI heart dysfunction.

BayesAge 2.0: A Maximum Likelihood Algorithm to Predict Transcriptomic Age.

Aging is a complex biological process influenced by various factors, including genetic and environmental influences. In this study, we present BayesAge 2.0, an improved version of our maximum likelihood algorithm designed for predicting transcriptomic age (tAge) from RNA-seq data.

Dysfunctional β-cell longevity in diabetes relies on energy conservation and positive epistasis.

Long-lived PFKFB3-expressing β-cells are dysfunctional partly because of prevailing glycolysis that compromises metabolic coupling of insulin secretion. Their accumulation in type 2 diabetes (T2D) appears to be related to the loss of apoptotic competency of cell fitness competition that maintains islet function by favoring constant selection of healthy "winner" cells. To investigate how PFKFB3 can disguise the competitive traits of dysfunctional "loser" β-cells, we analyzed the overlap between human β-cells with bona fide "loser signature" across diabetes pathologies using the HPAP scRNA-seq and spatial transcriptomics of PFKFB3-positive β-cells from nPOD T2D pancreata.

Genome of 55, a desert-isolated microbe with plant growth-promoting properties for grain crops.

Here, we report the genome sequence of 55, isolated from the Negev Desert, Israel. 55 was found to promote the growth of several cereal crops (corn, wheat, and pearl millet) in greenhouse and field studies.

The evolution of computational research in a data-centric world.

Computational data-centric research techniques play a prevalent and multi-disciplinary role in life science research. In the past, scientists in wet labs generated the data, and computational researchers focused on creating tools for the analysis of those data. Computational researchers are now becoming more independent and taking leadership roles within biomedical projects, leveraging the increased availability of public data.

The response to influenza vaccination is associated with DNA methylation-driven regulation of T cell innate antiviral pathways.

Background: The effect of vaccination on the epigenome remains poorly characterized. In previous research, we identified an association between seroprotection against influenza and DNA methylation at sites associated with the RIG-1 signaling pathway, which recognizes viral double-stranded RNA and leads to a type I interferon response. However, these studies did not fully account for confounding factors including age, gender, and BMI, along with changes in cell-type composition.

Role of Forkhead Box P3 in IFNγ-Mediated PD-L1 Expression and Bladder Cancer Epithelial-to-Mesenchymal Transition.

Unlabelled: Antagonism of the PD-1/PD-L1 axis is a critical therapeutic strategy for patients with advanced bladder cancer. IFNγ functions as a key regulator of PD-L1 in both immune as well as cancer cells. Forkhead box P3 (FOXP3) is a transcription factor synonymous in T regulatory cell function but with increasingly described functions in cancer cells.

Age-correlated changes in the canine oral microbiome.

Introduction: Canine oral disease has been associated with significant changes in the oral microbiome rather than the presence or absence of individual species. In addition, most studies focus on a single age group of canines and as of yet, the relationship between canine microbiomes and age is poorly understood.

Methods: This study used a shotgun whole gene sequencing approach in tandem with the Aladdin Bioinformatics platform to profile the microbiomes of 96 companion dogs, with the sourmash-zymo reference database being used to perform taxonomic profiling.

Clinical Factors on Dental Implant Fractures: A Systematic Review.

Dental implant fractures pose a significant challenge to long-term treatment success. This systematic review aims to comprehensively examine the clinical factors influencing dental implant fractures (IFs). Furthermore, strategies to choose the right type of implant and prevent this complication are addressed.

Adenovirus small E1A directs activation of Alu transcription at YAP/TEAD- and AP-1-bound enhancers through interactions with the EP400 chromatin remodeler.

Alu retrotransposons, which form the largest family of mobile DNA elements in the human genome, have recently come to attention as a potential source of regulatory novelties, most notably by participating in enhancer function. Even though Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, their expression has long been known to increase in response to various types of stress, including viral infection. Here we show that, in primary human fibroblasts, adenovirus small e1a triggered derepression of hundreds of individual Alus by promoting TFIIIB recruitment by Alu-bound TFIIIC.

Complete genomes of two endophytes isolated from surface-sterilized alfalfa nodules.

species catabolize a wide range of natural and industrial products and have been shown to be integral rhizosphere inhabitants. Here, we report the complete genomes of 2u118 and . sp.

Non-coding RNA yREX3 from human extracellular vesicles exerts macrophage-mediated cardioprotection via a novel gene-methylating mechanism.

Background And Aims: Extracellular vesicles (EVs) secreted by cardiosphere-derived cells exert immunomodulatory effects through the transmission of small non-coding RNAs.

Methods: The mechanism and role of yREX3, a small Y RNA abundant in EVs in myocardial injury, was investigated.

Results: yREX3 attenuates cardiac ischaemic injury by selective DNA methylation.