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At least 235 records · Page 13Linked to original sources
PubMed2026

Feeding the epigenome: EZH2 as a metabolic integrator of cell fate in development and cancer.

Epigenetic regulation is intimately linked to cellular metabolism, enabling environmental and nutritional cues to shape gene expression programs through dynamic modifications of chromatin structure. This metabolism-epigenetics interface is mediated, in part, by the dependence of chromatin-modifying enzymes on key metabolites, including S-adenosylmethionine (SAM), acetyl-CoA, UDP-GlcNAc, and α-ketoglutarate, which serve as substrates or cofactors for DNA and histone modifications. Among these regulators, EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), has emerged as a key mediator linking metabolic state to epigenetic regulation by translating metabolic inputs into changes in chromatin architecture and gene expression. EZH2 governs developmental cell fate through H3K27me3-mediated gene repression and is frequently dysregulated in cancer, where it promotes dedifferentiation, tumor progression, and metabolic reprogramming. Importantly, EZH2 activity is itself modulated by cellular metabolic status through posttranslational modifications, including phosphorylation, acetylation, methylation, ubiquitination, and O-GlcNAcylation, which influence its stability, catalytic activity, and chromatin-binding capacity. These modifications are responsive to nutrient availability and signaling pathways involving glucose, SAM, NAD+, and other metabolic intermediates. Consequently, disruption of this finely tuned regulatory network can contribute to developmental abnormalities, metabolic dysfunction, and oncogenesis. In this review, we examine the molecular mechanisms governing EZH2 regulation and discuss how metabolic control of EZH2 shapes chromatin dynamics, cell fate decisions, and disease pathogenesis. Elucidating how metabolic signals modulate EZH2 activity will advance our understanding of development and disease while uncovering potential therapeutic opportunities to target metabolism-driven epigenetic dysregulation.

Humans↗
PubMed1986

Married women's dissatisfaction with tubal sterilization and vasectomy at first-year follow-up: effects of perceived spousal dominance.

Examination of first-year follow-up data obtained from 234 tubal ligation women and 154 vasectomy wives indicated a very low incidence of actual regret in both groups. However, use of a broader measure of satisfaction/dissatisfaction indicated that tubal ligation women had significantly more positive feelings about the sterilization decision than did vasectomy wives. Results of a series of multivariate statistical analyses demonstrated that group differences in satisfaction were related to (1) the disproportionate prevalence of perceived male control (particularly extensive control) over reproductive decisions among vasectomy wives and the negative effect it had upon subjects in both groups and (2) the disproportionate prevalence of female control over reproductive decision-making among tubal ligation women and the positive effect it had among subjects in this group. Study results point to the importance of couple counseling and exercising control over one's own body.

Adult↗
PubMed1992

Nonoperative management of multilevel lumbar disk herniations in an adolescent athlete.

Herniated lumbar nucleus pulposus is rare in the pediatric age-group; for surgically proven cases, the estimated prevalence is between 0.8 and 3.2%. Most of the current literature indicates that herniated nucleus pulposus in pediatric patients differs from that in adult patients in epidemiologic characteristics, clinical manifestations, and frequency of associated neurologic findings. To our knowledge, the current case is the first published report of lumbar disk herniations at three levels in a 15-year-old male adolescent, whose abnormalities were verified by computed tomography and myelography. Most investigators recommend surgical treatment; however, our patient had good results with nonoperative management that consisted of nonsteroid anti-inflammatory drugs, passive extension, lumbar traction, segmental mobilization, and a progressive program of dynamic lumbar stabilization exercises. The patient is now asymptomatic and able to participate in selected limited contact sports and most farm activities; however, contact sports are prohibited for 1 year. If follow-up computed tomographic imaging of the lumbar spine demonstrates no progression of the disk abnormalities and if the patient remains asymptomatic, he could consider participation in contact sports after necessary conditioning.

Adolescent↗
PubMed1992

A preliminary evaluation of education material prepared for the Safe Motherhood Initiative Educational Project.

Maternal death is a tragedy which is all too familiar in much of the world. As part of the Safe Motherhood Initiative the World Health Organization is developing and producing a learning package designed specifically for midwives. Through a modular system of learning incorporating aspects of community, prevention, treatment and follow-up the package seeks to address the five main causes of maternal mortality. In this paper the first pre-testing of the educational material in an African country is described. The extent of the evaluation is limited at this early stage but the initial analysis of the results is encouraging and have led to modifications of the original package. The evaluation has confirmed that a tool such as this package can be a valuable resource for midwife teachers attempting to improve the relevance of education for their midwifery students. The midwifery students whilst being 'with woman' in childbirth are also grappling with the realities of death in their everyday practice. The educational package has also reinforced the sense of urgency fundamental to completing this extensive project so that it can be made available to midwives throughout the developing world at the earliest opportunity.

Botswana↗
PubMed1992

Infant and child mortality in rural Egypt.

This research examines determinants of infant and child mortality in rural Egypt, primarily the effects of household economic status and the availability of health services. Certain features of the health service environment affect survival in the neonatal period. In early childhood, survival chances improve markedly as income increases and if the household depends almost exclusively on employment income. In infancy and in early childhood, mortality is strongly associated with region of residence and maternal demographic characteristics, and is weakly associated with parental schooling.

Child, Preschool↗
PubMed2026

Genomic and structural analysis of dacB variants associated with cephalosporin resistance in Pseudomonas aeruginosa.

The rise of resistance to fourth-generation cephalosporin in Pseudomonas aeruginosa (P. aeruginosa) is a global concern. The resistance is largely driven by variants of chromosomally encoded AmpC β-lactamase, known as Pseudomonas-derived cephalosporinase (PDC), which arise from the mutations in the ampC gene. In addition, alteration in dacB, which encode the penicillin-binding protein 4 (PBP4), can lead to the overexpression of ampC, thereby contributing to β-lactam resistance. Present work analyzed 208 clinical isolates of P. aeruginosa using whole-genome sequencing (WGS) and detected multiple nonsynonymous single nucleotide polymorphisms (nsSNPs), such as Y264C, G444D, and a double mutation (A394P-T428P). All nsSNPs were predicted to be deleterious by several prediction program. Molecular dynamics (MD) simulations suggested that these substitutions destabilize PBP4, increase structural flexibility, and contribute to the resistance mechanism, which favored their selection. To determine the effective therapeutics against these mutations, molecular docking was conducted with various antibiotics. Cefoperazone exhibited the highest binding affinity (-7.3 kcal/mol) among multiple PBP4 variants. The Molecular dynamics (MD) simulations and Molecular Mechanics Poisson Boltzmann Surface Area calculations (MMPBSA) further confirmed the favorable interactions between cefoperazone and PBP4 variants. In vitro MIC analyses supported these findings, indicating that cefoperazone displayed significant activity against clinical dacB mutants of P. aeruginosa. The study offers structural insight of dacB variants leading to antibiotic resistance and emphasizes the need to prioritize specific antibiotics to address the challenges arising from protein mutations.

Pseudomonas aeruginosa↗
PubMed1985

Contraception for the adolescent.

The primary care physician is in an excellent position to counsel adolescents about contraception. However, an adequate understanding of the biologic and psychosocial development of this particular age-group is imperative. In addition, communication skills are necessary to advise adolescents on use of contraceptives. The goal in counseling the adolescent about sexuality is to instill a sense of sexual responsibility and to provide individualized instruction in selecting the appropriate birth control method. General factors to remember in selecting the proper method include motivation, moral-ethical responsibility, frequency of intercourse, side effects of the various contraceptive methods, and patient's preference.

Adolescent↗
PubMed2025

CaLMPhosKAN: prediction of general phosphorylation sites in proteins via fusion of codon aware embeddings with amino acid aware embeddings and wavelet-based Kolmogorov-Arnold network.

MOTIVATION: The mapping from codon to amino acid is surjective due to codon degeneracy, suggesting that codon space might harbor higher information content. Embeddings from the codon language model have recently demonstrated success in various protein downstream tasks. However, predictive models for residue-level tasks such as phosphorylation sites, arguably the most studied Post-Translational Modification (PTM), and PTM sites prediction in general, have predominantly relied on representations in amino acid space. RESULTS: We introduce a novel approach for predicting phosphorylation sites by utilizing codon-level information through embeddings from the codon adaptation language model (CaLM), trained on protein-coding DNA sequences. Protein sequences are first reverse-translated into reliable coding sequences by mapping UniProt sequences to their corresponding NCBI reference sequences and extracting the exact coding sequences from their GenBank format using a dynamic programming-based global pairwise alignment. The resulting coding sequences are encoded using the CaLM encoder to generate codon-aware embeddings, which are subsequently integrated with amino acid-aware embeddings obtained from a protein language model, through an early fusion strategy. Next, a window-level representation of the site of interest, retaining the full sequence context, is constructed from the fused embeddings. A ConvBiGRU network extracts feature maps that capture spatiotemporal correlations between proximal residues within the window. This is followed by a prediction head based on a Kolmogorov-Arnold network (KAN) using the derivative of gaussian wavelet transform to generate the inference for the site. The overall model, dubbed CaLMPhosKAN, performs better than the existing approaches across multiple datasets. AVAILABILITY AND IMPLEMENTATION: CaLMPhosKAN is publicly available at https://github.com/KCLabMTU/CaLMPhosKAN.

Codon↗
PubMed1986

Area variation in mortality from diseases amenable to medical intervention: the contribution of differences in morbidity.

Several conditions, whose timely and appropriate therapy should decrease case fatality, have been proposed as indicators of medical care quality for the National Health Service. Mortality rates for these diseases vary widely within the UK. To evaluate the contribution of varying incidence rates to these mortality differences, routinely collected morbidity and mortality data for 1974-1978 were analysed for 98 Area Health Authorities (AHAs) in England and Wales. Although differences in morbidity (as measured by hospital discharge and disease registration rates) and socioeconomic factors account for some of the area variation in mortality, significant heterogeneity persists after these factors are taken into account. This finding suggests that morbidity and socioeconomic factors are not the only determinants of mortality variation among areas for these particular diseases. Variation in quality of medical care may account for this result, although regional diagnostic and reporting differences and variation in disease severity among areas must also be considered.

Analysis of Variance↗
PubMed1990

Black/white comparisons of deaths preventable by medical intervention: United States and the District of Columbia 1980-1986.

Blacks in the US experience increased mortality (1113 versus 745 per 100,000 males; 631 versus 411 per 100,000 females) and decreased life expectancy (63.7 years versus 70.7 years for males; 72.3 years versus 78.1 years for females); compared to Whites. In an effort to determine if the excess mortality among Black Americans might be explained by differences in access or quality of health care services, we performed a race-specific analysis of conditions for which mortality is largely avoidable given timely and appropriate medical care. Using methodology proposed by Rutstein and Charlton, mortality due to 12 causes was evaluated including tuberculosis, cervical cancer, Hodgkin's disease, rheumatic heart disease, hypertensive heart disease, acute respiratory disease, pneumonia and bronchitis, influenza, asthma, appendicitis, hernias and cholecystitis. In the US, during 1980 to 1986, an average of 17,366 deaths and 286,813 years of potential life (YPLL) before age 65 were lost each year due to all 12 sentinel causes combined. Of these causes, hypertensive heart disease, pneumonia and bronchitis, cervical cancer and asthma accounted for the greatest number of deaths. The mortality rate for all 12 causes combined among Blacks was 4.5 times that of Whites. The highest relative rates among Blacks compared to Whites were observed for tuberculosis, hypertensive heart disease and asthma. The overall mortality rate in the District of Columbia for the selected causes was 3.7 times the national rate. Compared to national rates, statistically significant elevated rates in the District were observed for tuberculosis, hypertensive heart disease and pneumonia and bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Female age, the length of involuntary infertility prior to investigation and fertility outcome.

The objectives of this study were two-fold: firstly to determine whether female age exerts an influence on the fertility outcome of couples attending an infertility clinic, independent of demographic and clinical details; and secondly to examine the relationship between the length of involuntary infertility prior to investigation and the subsequent chance of conception. Seven-hundred-and-thirty-one subjects whose partner did not have azoospermia were recruited to the study. Female age ranged from 20 to 46 (mean = 31.1). The range of involuntary infertility prior to investigation was 12-216 (mean = 62) months. One-hundred-and-twenty-four women conceived. The following variables achieved the 5% level of significance when a stepwise analysis was performed on all cases; the concentration of spermatozoa exhibiting slow or sluggish linear or non-linear motility (chi 2(1) = 17.57, P less than 0.0001, RR = 1.67 per 50 x 10(6)), female age (chi 2(1) = 12.44, P = 0.0004, RR = 0.92 per annum), tubal status (chi 2(1) = 12.22, P = 0.0005, RR = 2.15), length of infertility before investigation (chi 2(1) = 11.22, P = 0.0008, RR = 0.87 per annum) and past paternity (chi 2(1) = 8.43, P = 0.0037, RR = 1.81). Female age was found to be positively correlated with the incidence and severity of ovulatory dysfunction, tubal occlusive disease, pelvic adhesions and endometriosis. Where the female partner was 'normal' on investigation, all conceptions were independent of treatment to either partner.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1992

Pattern-induced multi-sequence alignment (PIMA) algorithm employing secondary structure-dependent gap penalties for use in comparative protein modelling.

A multiple sequence alignment algorithm is described that uses a dynamic programming-based pattern construction method to align a set of homologous sequences based on their common pattern of conserved sequence elements. This pattern-induced multi-sequence alignment (PIMA) algorithm can employ secondary-structure dependent gap penalties for use in comparative modelling of new sequences when the three-dimensional structure of one or more members of the same family is known. We show that the use of secondary structure information can significantly improve the accuracy of aligning structure boundaries in a set of homologous sequences even when the structure of only one member of the family is known.

Algorithms↗
PubMed2025

Cross-species phenotypic profiling uncovers functional determinants of bacterial cold shock adaptation.

Temperature shifts impose broad physiological stress, requiring precise and dynamic regulatory programs to restore cellular homeostasis. While the heat shock response is well characterized, the mechanisms underlying cold shock response (CSR) remain less understood. To identify genes critical for cold adaptation, we applied transposon sequencing (Tn-seq) to monitor mutant fitness across the full course of CSR and sustained low-temperature growth in two mesophilic bacteria, Escherichia coli and Bacillus subtilis. In B. subtilis, phenotypic profiling revealed a temporally structured program: membrane fluidity and cell wall remodeling were most critical in the early stage of CSR, whereas post-transcriptional regulation became essential during late-stage recovery to reprogram gene expression and restore growth. Cross-species comparison uncovered both conserved and species-specific mechanisms, with RNA metabolism and ribosome/translation regulators playing broad roles. Specifically, we identified a conserved synergy between two ribosomal RNA methyltransferases, RsmA and RsmH, in promoting cold adaptation. In B. subtilis, mutants lacking these enzymes exhibited significant delay in translation recovery following cold-induced global inhibition. Together, these findings provide a comparative, systems-level view of bacterial cold adaptation and establish a framework for exploring stress responses in pathogens and extremophiles.

Cell envelope↗