Early-life programming is a major determinant of lifelong metabolic health, yet current preventive strategies focus almost exclusively on maternal factors. Emerging experimental and preclinical data reveal that a father's diet before conception, particularly high-fat intake, also shapes offspring physiology. Here, we synthesize the latest evidence on how such diets remodel the sperm epigenome during two discrete windows of vulnerability: (i) testicular spermatogenesis, via DNA methylation and histone modifications, and (ii) post-testicular epididymal maturation, where small non-coding RNAs are selectively gained.
View Article and Find Full Text PDFBlack American women suffer from disproportionately high rates of cardiovascular disease (CVD). This disparity may be related to psychosocial stress and cardiometabolic risk factors. Therefore, the objective of this trial was to evaluate the efficacy of a stress-reducing meditation technique compared with health education on cardiometabolic disease endpoints in high CVD risk Black women.
View Article and Find Full Text PDFClin J Am Soc Nephrol
July 2025
Increased rates of adverse health conditions across the spectrum of cardiovascular, kidney, and metabolic disease have been linked to social, psychologic, and environmental stressors. Stress from daily living can elicit protective responses from multiple physiologic systems that include psychologic/neurocognitive and biologic/cellular pathways. Excessive exposures to noxious stress overwhelms normally protective responses and lead to maladaptive psychologic and biologic consequences that trigger and/or exacerbate multiple disease processes including CKD and CKD risk factors.
View Article and Find Full Text PDFIn eukaryotic cells, the genetic material is organized into chromatin, which consists mainly of DNA, histones and chromatin-associated proteins. An important regulator of chromatin structure and function are histone post-translational modifications, which can shape gene expression patterns and control the epigenetic landscape. Here, we summarize the role of some key histone modifications in animal development, with a focus on the two best-studied types of histone modifications: lysine methylation and acylations, specifically, acetylation.
View Article and Find Full Text PDFIntroduction: Black Americans suffer from disproportionately high rates of cardiovascular disease (CVD). Psychosocial stress contributes to this disparity. Previous studies reported that the Transcendental Meditation (TM) technique reduced CVD risk factors, surrogate endpoints, and clinical events in high-risk populations.
View Article and Find Full Text PDFMental health complaints have significantly increased in Europe over recent years. This study evaluated the effects and safety of a 4-month online, multimodal, complementary intervention on the mental and physical health of home-based adults. Ninety-eight home-based adults with mild to severe mental health and related physical symptoms were recruited across Europe through digital advertisements.
View Article and Find Full Text PDFIntrinsically disordered proteins and protein regions are central to many biological processes but difficult to characterize at atomic resolution. Nuclear magnetic resonance is particularly well-suited for providing structural and dynamical information on intrinsically disordered proteins, but existing NMR methodologies need to be constantly refined to provide greater sensitivity and resolution, particularly to capitalise on the potential of high magnetic fields to investigate large proteins. In this paper, we describe how N-detected 2D NMR experiments can be optimised for better performance.
View Article and Find Full Text PDFWe study monolayer WSe using ultrafast electron diffraction. We introduce an approach to quantitatively extract atomic-site-specific information, providing an element-specific view of incoherent atomic vibrations following femtosecond excitation. Via differences between W and Se vibrations, we identify stages in the nonthermal evolution of the phonon population.
View Article and Find Full Text PDFBackground: Patients with scoliosis often require multiple imaging modalities. The aim of this study was to find out whether primary diagnosis, including surgical planning, could be carried out entirely without computed tomography (CT) scans and whether follow-up could be replaced with alternative methods without the use of X-rays. In order to reduce the radiation exposure in the diagnosis and treatment of severe scoliosis, we expect to replace X-rays with radiation-free or less-intensive radiation examinations.
View Article and Find Full Text PDFMethods Mol Biol
August 2024
In eukaryotes, DNA is packaged into chromatin with the help of highly conserved histone proteins. Together with DNA-binding proteins, posttranslational modifications (PTMs) on these histones play crucial roles in regulating genome function, cell fate determination, inheritance of acquired traits, cellular states, and diseases. While most studies have focused on individual DNA-binding proteins, chromatin proteins, or histone PTMs in bulk cell populations, such chromatin features co-occur and potentially act cooperatively to accomplish specific functions in a given cell.
View Article and Find Full Text PDFTriple negative breast cancer (TNBC) represents a therapeutic challenge in which standard chemotherapy is limited to paclitaxel. MBQ167, a clinical stage small molecule inhibitor that targets Rac and Cdc42, inhibits tumor growth and metastasis in mouse models of TNBC. Herein, we investigated the efficacy of MBQ167 in combination with paclitaxel in TNBC preclinical models, as a prelude to safety trials of this combination in patients with advanced breast cancer.
View Article and Find Full Text PDFPsychological distress has a demonstrable impact on cardiovascular diseases (CVD) and risk factors. Transcendental Meditation (TM) has been shown to reduce stress and improve health and well-being. The current review aimed to synthesize the evidence on the effects of TM on cardiometabolic outcomes and identify gaps for future research.
View Article and Find Full Text PDFMethylation of cytosine 32 in the anticodon loop of tRNAs to 3-methylcytosine (mC) is crucial for cellular translation fidelity. Misregulation of the RNA methyltransferases setting this modification can cause aggressive cancers and metabolic disturbances. Here, we report the cryo-electron microscopy structure of the human mC tRNA methyltransferase METTL6 in complex with seryl-tRNA synthetase (SerRS) and their common substrate tRNA.
View Article and Find Full Text PDFThe now well described canonical mRNA translation initiation mechanism of mG 'cap' recognition by cap-binding protein eIF4E and assembly of the canonical pre-initiation complex consisting of scaffolding protein eIF4G and RNA helicase eIF4A has historically been thought to describe all cellular mRNA translation. However, the past decade has seen the discovery of alternative mechanisms to canonical eIF4E mediated mRNA translation initiation. Studies have shown that non-canonical alternate mechanisms of cellular mRNA translation initiation, whether cap-dependent or independent, serve to provide selective translation of mRNAs under cell physiological and pathological stress conditions.
View Article and Find Full Text PDFThe development of targeted anti-cancer therapeutics offers the potential for increased efficacy of drugs and diagnostics. Utilizing modalities agnostic to tumor type, such as the hypoxic tumor microenvironment (TME), may assist in the development of universal tumor targeting agents. The hypoxia-inducible factor (HIF), in particular HIF1, plays a key role in tumor adaptation to hypoxia, and inhibiting its interaction with p300 has been shown to provide therapeutic potential.
View Article and Find Full Text PDFIn the midst of global armed conflicts, notably the Israel-Hamas and Ukraine-Russia wars, there is an urgent need for innovative public health strategies in peacebuilding. The devastating impact of wars, including mortality, injury, disease, and the diversion of healthcare resources, necessitates effective and durable interventions. This perspective aligns with WHO recommendations and examines the role of evidence-based meditation from Ayurveda and Yoga in public health to mitigate collective stress and prevent collective violence and war.
View Article and Find Full Text PDFTriple-negative breast cancer (TNBC) lacks expressed protein targets, making therapy development challenging. Hydrogels offer a promising new route in this regard by improving the chemotherapeutic efficacy through increased solubility and sustained release. Moreover, subcutaneous hydrogel administration reduces patient burden by requiring less therapy and shorter treatment times.
View Article and Find Full Text PDFControl over the optical properties of atomically thin two-dimensional (2D) layers, including those of transition metal dichalcogenides (TMDs), is needed for future optoelectronic applications. Here, the near-field coupling between TMDs and graphene/graphite is used to engineer the exciton line shape and charge state. Fano-like asymmetric spectral features are produced in WS, MoSe, and WSe van der Waals heterostructures combined with graphene, graphite, or jointly with hexagonal boron nitride (-BN) as supporting or encapsulating layers.
View Article and Find Full Text PDFDNA and histone modifications combine into characteristic patterns that demarcate functional regions of the genome. While many 'readers' of individual modifications have been described, how chromatin states comprising composite modification signatures, histone variants and internucleosomal linker DNA are interpreted is a major open question. Here we use a multidimensional proteomics strategy to systematically examine the interaction of around 2,000 nuclear proteins with over 80 modified dinucleosomes representing promoter, enhancer and heterochromatin states.
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