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Acceptor activity, isoacceptor profiles and function in protein synthesis of transfer RNAs from regenerating skeletal muscle.

Transfer RNAs have been prepared from control and regenerating rat skeletal muscle. The yield of tRNA is highest during the early stages of the regeneration process (5 and 8 days following the induction of regeneration) and decreases to near control values thereafter. The amino acid acceptor activity (extent of aminoacylation) of tRNA from regenerating muscle was also found to be higher for some amino acids than the activity of control tRNA, and the maximum increase in activity was observed between 5 and 8 days following the initiation of regeneration with a decrease to control levels through 15 and 30 days. The isoacceptor pattern, determined by RPC-5 chromatography, for methionyl-tRNAs from control muscle and 5-day regenerating muscle were essentially indistinguishable, while a minor peak of prolyl-tRNA was observed in the population from 5-, 8- and 15-day regenerates which was apparently absent from the control tRNA. Lysyl-tRNAs from control muscle contain two major isoacceptors while a third isoacceptor is observed in the tRNA preparations from 5-, 8- and 15-day regenerating muscle. The relative amount of this third isoacceptor is highest in the 8-day population and decreases in amount in tRNAs from 15- and 30-day regenerates. Control muscle also contains two major glutamyl-tRNA species while a third isoacceptor can be detected in regenerates. The relative amount of this species increases during the early course of the regeneration process but is present at near control levels by 30 days following Marcaine injection. Cell-free protein synthesis using muscle polyribosomes showed that tRNAs from regenerating muscle were more effective in stimulating [35S]methionine incorporation than tRNAs from control muscle.

Amino Acids

Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones.

Functional subsets of human T cells were delineated by analyzing patterns of lymphokines produced by clones from individuals with leprosy and by T cell clones of known function. CD4 clones from individuals with strong cell-mediated immunity produced predominantly interferon-gamma, whereas those clones that enhanced antibody formation produced interleukin-4. CD8 cytotoxic T cells secreted interferon-gamma. Interleukin-4 was produced by CD8 T suppressor clones from immunologically unresponsive individuals with leprosy and was found to be necessary for suppression in vitro. Both the classic reciprocal relation between antibody formation and cell-mediated immunity and resistance or susceptibility to certain infections may be explained by T cell subsets differing in patterns of lymphokine production.

Antibody Formation

Phenotypic profile and functional characteristics of human gamma and delta T cells during acute toxoplasmosis.

Gamma and delta (gamma delta) T-cell receptor lymphocytes are increased during acute toxoplasmosis. These cells are BB3+ CD45RO+ CD8-. Purified gamma delta T cells failed to proliferate in response to Toxoplasma gondii antigen (stimulation index, 1.4 +/- 0.6) but were responsive to phytohemagglutinin stimulation (stimulation index, 20.8 +/- 1.9). Natural-killer-like cytotoxicity was strongly acquired only after in vitro culture of purified gamma delta T cells with recombinant interleukin 2 (40% +/- 7% specific lysis). Our data show that gamma delta T-cell receptor T cells with a peculiar phenotype are increased during human acute T. gondii infection.

Acute Disease

Size, CD4 and CD8 marker profiles and functions of lymphocyte subpopulations in mucosal-associated lymph nodes.

We analyzed phenotypic and functional characteristics of T cell populations in mucosal-associated supramammary and mesenteric lymph nodes in goats. Here we demonstrate, by flow cytometry, quantitative differences in CD4 and CD8 T cell subsets among large and small mucosal-associated lymphocyte populations and their differential regulatory activities on resident lymph node B cells stimulated with Staphylococcus aureus Cowan I or pokeweed mitogen. The CD4/CD8 T cell ratio was lower in mesenteric lymph nodes (1.46) when compared to that of supramammary lymph nodes (2.18). Analysis of large and small lymphocyte subpopulations from lymph nodes showed nearly 62% of the lymphocytes from mesenteric lymph nodes being of large cell phenotype with CD4/CD8 ratios of 1.34. In contrast, large cell subpopulations in supramammary lymph nodes showed a significantly lower number (50%) with a higher CD4/CD8 ratio of 2.05. Functionally, mesenteric lymph node T cells, isolated by nylon wool, showed heightened suppressive activity in mitogen-driven B cell proliferation responses, whereas T cells from supramammary lymph nodes were stimulatory. These findings clearly demonstrate distinctive functional properties between resident T cell populations of supramammary and mesenteric lymph nodes, suggesting that different proportions of T cell subsets in these nodes are activated and thus regulate regional immune responses via different pathways.

Animals

Turner syndrome patients as adults: a study of their cognitive profile, psychosocial functioning and psychopathological findings.

In this study we collected data on the cognitive abilities, psychosocial adjustment and psychopathology of 20 non-institutionalized adult Turner syndrome patients. The majority of them had a normal intelligence, most were socially well adapted and no high prevalence of psychopathology was noted. In only one patient evidence of a serious bipolar hypomanic disorder and antisocial personality was found, and in one other an episode of anorexia nervosa. Nevertheless, 50% of the women expressed feelings of low self-confidence, depression and social insecurity i.e. achieving a mature level of psycho-social functioning remains a problem for a number of Turner individuals. In the counseling process of adult Turner patients special attention should be given to the social and psychological functioning so that intervention can be made if social awkwardness and psychological well-being becomes a problem.

Adaptation, Psychological

Metabolic reprogramming and taxonomic drivers in bacterial vaginosis: A large-scale metagenomic meta-analysis.

OBJECTIVE: Bacterial vaginosis (BV) represents a profound ecological shift from a Lactobacillus-dominated microbiota to a diverse polymicrobial biofilm associated with adverse outcomes. While taxonomic signatures are well-documented, the functional mechanisms driving this transition remain obscured. This study elucidates the genomic potential for metabolic reprogramming and the putative "functional handover" underpinning the stability of the dysbiotic state. METHODS: A computational meta-analysis of 3557 vaginal microbiomes from diverse global cohorts was performed using the standardized MGnify pipeline. A high-resolution subset of 187 whole-genome shotgun (WGS) metagenomes was stratified to compare functional potential across demographic groups. Taxon-function interaction networks were constructed, utilizing a dual-filter statistical approach (p&#x202f;<&#x202f;0.05 and effect size ranking), to map the shift from homeostatic maintenance to dysbiotic metabolic potential. RESULTS: BV was characterized by a fundamental shift from "maintenance" pathways to high-turnover "growth-oriented" genomic repertoires. While ABC transporter-like domains were present in healthy communities, dysbiosis was marked by a quantitative expansion and diversification of these systems alongside P-loop NTPases. Network analysis revealed a putative "functional handover": while Gardnerella serves as the adherent structural scaffold, the metabolic burden appears to be associated with secondary anaerobes, specifically BVAB1 and Sneathia, which exhibit strong genomic correlations with nutrient transport and stress response pathways. Crucially, microbiomes from women of African ancestry (Black cohort) exhibited a distinct functional profile with genomic signatures consistent with functions previously associated with resistome expansion (e.g., tetracycline/macrolide resistance), contrasting with Asian cohorts. CONCLUSION: BV is a state of metabolic reprogramming where genomic functional dominance is transferred from Lactobacillus to a cooperative network of anaerobic opportunists. Identifying BVAB1 and Sneathia as candidate metabolic engines, supported by a Gardnerella scaffold, challenges current therapeutic paradigms and highlights the potential for precision medicine targeting specific functional drivers and resistome profiles across diverse populations.

Humans

A new description of the photon beam peak-depth profile as a function of field size.

The dose profile at peak depth in water is described as the product of an apparatus function and a source function. In principle, the source function is the circularly symmetric profile which would be measured at peak depth without any collimation. In practice, the peak-depth profile in the diagonal plane, measured for the largest collimator setting, is used for this purpose. The apparatus function represents the collimator acting upon the source function, and is referred to as the collimator function. The collimator function for any field size can be developed from the ratio of the peak-depth profile for a single medium-sized field and the source function. The method has been tested for a set of irregularly flattened 4-MV x-ray beams as well as for practically flat 15-MV x-ray beams. The model requires as basic data only three peak-depth profiles: one in each principal plane of a medium-sized square field and the peak-depth profile in the diagonal plane for the largest field. It replaces the peak-depth transformation in the projective beam model.

Humans

Imaging-Guided Omics Technologies for Resolving Rare Cancer States and Advancing Nanomedicine.

The ability to resolve rare and transient cellular states is critical for understanding metastasis, immune evasion, and therapy resistance in cancer, yet these dynamic processes often escape detection by conventional sequencing and imaging approaches. Recent advances at the interface of nanotechnology, high-resolution live-cell imaging, and single-cell/spatial multiomics methods have enabled functional profiling of cells with unprecedented precision within their native microenvironment. In this Mini-Review, we highlight emerging nanoscale platforms that couple real-time phenotypic imaging with molecular readouts, such as FUNseq and CIN-seq, to directly link functional heterogeneity to transcriptomic, proteomic, and epigenomic information. By integrating nanoscale optical imaging, microengineered perturbation tools, and AI-driven computational analysis, these technologies open up new avenues for dissecting rare metastatic, therapy-resistant, or immune-evasive subpopulations. We further discuss how these next-generation imaging-guided single-cell and spatial omics platforms not only advance fundamental cancer biology but also create opportunities to accelerate the development of nanomedicine applications.

Humans

Genetic profile of the transcriptional signals from the adenovirus major late promoter.

Identical functional profiles were obtained for in vivo and in vitro transcription assays of more than 30 site-directed point mutants within the adenovirus major late promoter. The functional limits of the functional regions encompassing upstream promoter element are defined (-51 to -61), as well as a region around the transcription start site (-1 to +1), flanked by regions insensitive to sequence alterations.

Adenoviridae

The role of pharmacological profiling in safety assessment.

The profiling of new drug candidates for general pharmacological properties requires a systematic examination of the functional effects of agents in a variety of in vitro and in vivo assays. Both the behavioral and physiological consequences of drug treatment are monitored in models of central nervous system, cardiovascular, autonomic, gastrointestinal, and renal functions. Broad functional profiling provides valuable information to the preclinical pharmacologist with respect to the selectivity of new agents and may serve to identify new and useful therapeutic indications of investigational drugs. At the same time, knowledge of the effects on these physiological systems can also play an important role in safety assessment. Pharmacological activity of a new agent that is both unintended and undesirable can be referred to as "pharmacological toxicity." In general, the spectrum of toxicities disclosed in pharmacological profiling includes a variety of acute functional or physiological effects which are not life-threatening and are readily reversible. On rare occasions, unanticipated and life-threatening pharmacological effects (e.g., convulsions, arrhythmias) are detected which can seriously detract from the usefulness of a new agent and may therefore deter the drug development process. It should also be noted that repeated exposure to acute pharmacological effects may lead to less obvious chronic findings, such as target organ effects or tumor formation in animals. The interpretation of pharmacological toxicity with respect to the safety profile of a new drug candidate is dependent not only upon the types of reactions observed and the doses at which they occur but also upon the nature of the effects elicited as to whether they represent expected extensions of the primary mechanism of action of a compound or constitute reactions unrelated to the primary pharmacological activity. The ultimate impact of pharmacological toxicity, as with all adverse findings in preclinical assessment, is dependent upon the projected therapeutic margin of safety as well as the risk-to-benefit ratio for new drug entities. In addition to supplementing the existing armamentarium of preclinical safety studies, pharmacological profiling can also play an important role in (1) the selection of new drug candidates with reduced toxic potential, (2) the design and conduct of preclinical toxicology studies, (3) the investigation of preclinical and clinical safety issues, and (4) the identification of potential functional effects to be monitored most closely in clinical trials of new drug entities.

Animals

Return to work after rehabilitation following traumatic brain injury.

The relationship of medical variables and discharge functional status to vocational and educational outcomes was examined in 79 closed head-injured patients who were consecutively admitted to an inpatient rehabilitation hospital during a two-year period. A follow-up study, conducted after hospital discharge (median, 16.5 months), found that 66% (n = 52) of the patients had returned to work or school, while 34% (n = 27) did not. Patients were divided into return and non-return to work groups. Traditional variables included age, severity of brain-damage as characterized by CT head scan, duration of post-traumatic amnesia, duration of coma, length of stay and acute inpatient rehabilitation program. Discharge functional scores were analysed by t-tests and chi-square analysis. Results suggest that traditional factors of younger age, shorter length of coma, minimal CT head scan findings and shorter length of stay were significant contributors to educational/vocational outcome. Their significance was enhanced by discharge functional profile measurement of medical, physical and psychological/neuropsychological integrity. Those functional measures not significant were in social, vocational, recreational and communication areas. These factors may continue to improve over a longer period of time and should be tracked in the post-acute rehabilitation phase for their significance in return to work/school.

Activities of Daily Living