Impact of The Ageing on Oxidant/Antioxidant Balance And Hematology of Indigenous Cow and Its Amelioration by Ascorbic Acid

Ageing is a complex biological process of all flora and fauna. It leads to a gradual reduction in the ability to maintain homeostasis under internal physiological and external environmental stresses, hence reducing the viability of individual's and increasing their vulnerability to diseases. The objective of this study was to investigate the alteration in the oxidant /antioxidant balance and hematology in four different age group of indigenous Tharparkar cattle and its amelioration by ascorbic acid. A total 24 female Tharparkar cattle were included and were categorized into 4 groups of six cows in each group. Animals below 1 year-age were kept in group I, between 1 to 8 year-age in group II, between 8-10 year-age in group III and above 10 year-age in group IV. The oxidant/antioxidant markers (LPO, SOD, GSH, GPX and catalase activity) and haematological panels (Hb, TEC, TLC, Platelet and DLC) were determined on day 0, before ascorbic acid supplementation, and on day 6, 12, 18 and 24 post ascorbic acid supplementation. In the present study LPO and SOD levels were significantly (P < 0.05) increased with the ageing. GSH and GPX activities significantly (P < 0.05) decreased with ageing in different age groups. Variations in hematological parameters were also observed with ageing in different age groups. The geriatric cattle (> 10 years) exhibited remarkable alteration in oxidative stress indices, and haematological panels when compared to other groups. Supplementation of ascorbic acid reduced the oxidative stress and improved hemoglobin, PCV, TEC and TLC levels. From the findings of this study, it can be inferred that administration of ascorbic acid is helpful in ameliorating altered oxidant/antioxidant balance and hematological parameters with ageing in various age groups of cattle.

Dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis

Folliculogenesis is a complex biological process involving a central oocyte and its surrounding somatic cells. Three-dimensional chromatin architecture is an important transcription regulator; however, little is known about its dynamics and role in transcriptional regulation of granulosa cells during chicken folliculogenesis. We investigate the transcriptomic dynamics of chicken granulosa cells over ten follicular stages and assess the chromatin architecture dynamics and how it influences gene expression in granulosa cells at three key stages: the prehierarchical small white follicles, the first largest preovulatory follicles, and the postovulatory follicles. Our results demonstrate the consistency between the global reprogramming of chromatin architecture and the transcriptomic divergence during folliculogenesis, providing ample evidence for compartmentalization rearrangement, variable organization of topologically associating domains, and rewiring of the long-range interaction between promoter and enhancers. These results provide key insights into avian reproductive biology and provide a foundational dataset for the future in-depth functional characterization of granulosa cells.

Biomarkers of ageing in the study of occupational harm impacts (literature review)

Aging is an individual, complex biological process, modulated by internal and external factors, characterized by a progressive loss of biological / physiological integrity, which leads to body dysfunction, increases vulnerability and death. Influence of activity type on aging rate has been convincingly shown in many studies, which makes it possible assess differences in aging rate of workers, exposed various occupational factors, conditions, work nature and intensity in certain professional and seniority groups, adequately reflects health state and can predict effectiveness of human labor activity. As integral indicator, it can help identify individuals at risk of age-related disorders, serving as a measure of relative fitness and predicting later life disability and mortality, regardless of chronological age. The article provides an overview of the main measuring ageing rate methods based on biomarkers, such as functional (“Kiev model”, WAI) and molecular genetic biomarkers (determination of telomere length, β-galactosidase enzyme activity) of human ageing, applicable in occupational medicine. The review discusses the main requirements for biomarker sets compilation, methods applicability and reliability, mathematical approaches to biological age calculating, and some workers biological age calculating problems. This allows assuming the great potential for using biological age to assess the impact of working conditions and work nature on workers’ ageing rate to prevent disability and improve quality of life.

Transcriptional and mutational signatures of the aging germline

Aging is a complex biological process which is accompanied by changes in gene expression and mutational load. In many species including humans, old fathers pass on more paternally-derived de novo mutations, however, the cellular basis and cell types driving this pattern are still unclear. To understand the root causes of this phenomenon, we performed single-cell RNA-sequencing (scRNA-seq) on testes from young and old male Drosophila, as well as genomic sequencing (DNA-seq) on somatic tissue from the same flies. We found that early germ cells from old and young flies have similar mutational loads, but older flies are less able to remove mutations during spermatogenesis. This indicates that germline mutations arise from primarily non-replicative factors, and that the increased mutational load of older males is due to differences in genome maintenance activities such as repairs to DNA damage. We also found that T>A mutations are enriched in older flies, and transcription-related enrichment terms are depleted in older males. Early spermatogenesis-enriched genes have lower dN/dS than late spermatogenesis-enriched genes, supporting the hypothesis that late spermatogenesis is the source of evolutionary innovation. This transcriptional disruption is reflected in the decreased expression of genome maintenance genes in early germ cells of older flies, as well as potentially aberrant transcription of transposable elements in the aging germline. Our results provide novel insights into the transcriptional and mutational signatures of the male germline.

Phosphoproteome Profiling of Mouse Liver During Normal Aging

BackgroundAging is a complex biological process accompanied by a time-dependent functional decline that affects most living organisms. Omics studies help to comprehensively understand the mechanism of aging and discover potential intervention methods. Old mice were frequently obese with a fatty liver. MethodsWe applied mass spectrometry-based phosphoproteomics to obtain a global phosphorylation profile of liver in mice aged 2 or 18 months. A total of 5,685 phosphosites in 2,335 proteins were filtered for quantitative analysis. Phosphoproteome weakly separated young and old mice. ResultsCombining kinase prediction, kinase-substrate interaction analysis, and KEGG functional enrichment analysis, we observed high phosphorylation of fatty acid biosynthesis, b-oxidation, and potential secretory process, together with low phosphorylation of Egfr-Sos1-Araf/Braf-Map2k1-Mapk1 pathway and Ctnnb1 during aging. Proteins with differentially expressed phosphosites seemed more directly related to aging-associated fatty liver phenotype compared to the differentially expressed transcripts. Phosphoproteome may observe distinctive biological functions lost in transcriptome and proteome. ConclusionsIn summary, we constructed a phosphorylation-associated network in the liver of mice during normal aging, which may help to discover novel anti-aging strategies.

Regulation of Milk Protein Synthesis by Free and Peptide-Bound Amino Acids in Dairy Cows

Milk protein (MP) synthesis in the mammary gland of dairy cows is a complex biological process. As the substrates for protein synthesis, amino acids (AAs) are the most important nutrients for milk synthesis. Free AAs (FAAs) are the main precursors of MP synthesis, and their supplies are supplemented by peptide-bound AAs (PBAAs) in the blood. Utilization of AAs in the mammary gland of dairy cows has attracted the great interest of researchers because of the goal of increasing MP yield. Supplying sufficient and balanced AAs is critical to improve MP concentration and yield in dairy cows. Great progress has been made in understanding limiting AAs and their requirements for MP synthesis in dairy cows. This review focuses on the effects of FAA and PBAA supply on MP synthesis and their underlying mechanisms. Advances in our knowledge in the field can help us to develop more accurate models to predict dietary protein requirements for dairy cows MP synthesis, which will ultimately improve the nitrogen utilization efficiency and lactation performance of dairy cows.

Physically Consistent Scar Tissue Dynamics from Scattered Set of Data: A Novel Computational Approach to Avoid the Onset of the Runge Phenomenon

The foreign body reaction is a complex biological process leading to the insulation of implanted artificial materials through a capsule of scar tissue. In particular, in chronic implantations of neural electrodes, the prediction of the scar tissue evolution is crucial to assess the implant reliability over time. Indeed, the capsule behaves like an increasing insulating barrier between electrodes and nerve fibers. However, no explicit and physically based rules are available to computationally reproduce the capsule evolution. In addition, standard approaches to this problem (i.e., Vandermonde-based and Lagrange interpolation) fail for the onset of the Runge phenomenon. More specifically, numerical oscillations arise, thus standard procedures are only able to reproduce experimental detections while they result in non physical values for inter-interval times (i.e., times before and after experimental detections). As a consequence, in this work, a novel framework is described to model the evolution of the scar tissue thickness, avoiding the onset of the Runge phenomenon. This approach is able to provide novel approximating functions correctly reproducing experimental data (R2≃0.92) and effectively predicting inter-interval detections. In this way, the overall performances of previous approaches, based on phenomenological fitting polynomials of low degree, are improved.

CALANGO: an annotation-based, phylogeny-aware comparative genomics framework for exploring and interpreting complex genotypes and phenotypes

The increasing availability of high-quality genomic, annotation and phenotypic data for different species contrasts with the lack of general software for comparative genomics that integrates these data types in a statistically sound framework in order to produce biologically meaningful knowledge. In this work, we present CALANGO (Comparative AnaLysis with ANnotation-based Genomic cOmponentes), a first-principles comparative genomics tool to search for annotation terms, such as GO terms or Pfam domain IDs, associated with a quantitative variable used to rank species data, after correcting for phylogenetic relatedness. This information can be used to annotate genomes at any level, including protein domains, genes, or promoters, allowing comparative analyses of genomes at several resolutions and from distinct functional and evolutionary angles. CALANGO outputs a set of HTML5 files that can be opened in any conventional web browser, featuring interactive heatmaps, scatter plots, and tables, stimulating scientific reproducibility, data sharing, and exploratory analysis. Detailed results and a reproducibility-focused data structure are also returned after each run of the tool. CALANGO provides classic association statistics used in comparative genomics, including correlation coefficients, probabilities, and phylogeny-aware linear models. To illustrate how CALANGO can be used to produce biologically meaningful, statistically sound knowledge, we present a case study of the co-evolution of Escherichia coli and their integrated bacteriophages (prophages). Through controlled in silico experiments, we demonstrate that terms from a functional annotation are both more prevalent across genomes and more abundant than the homology-based annotation terms commonly used in traditional comparative genomics studies. This result demonstrates how GO-based annotation captures information of non-homologous sequences fulfilling the same biological roles. Most homologous regions positively associated with prophage occurrence are found in genes of viral origin (e.g. capsids, lysozymes, and integrases), as expected, while the second most abundant category is virulence factors. The removal of viral genes demonstrated that most of the virulence factors associated with prophage density are located outside viral genes, suggesting a more complex biological process than the archetypal bacteriophage-mediated horizontal gene transfer of virulence factors. The functional annotation performed by CALANGO revealed several GO terms describing general and specific aspects of viral biology (e.g. "viral life cycle", "DNA integration"). We also found an association of the GO term "pathogenicity", used to annotate several non-homologous virulence factors, as well as terms describing several known virulence mechanisms in pathogenic E. coli (e.g. "Type III secretion system"). Moreover, CALANGO also detected previously unknown associations that unveil a richer scenario of the bacteriophage-host biological interaction. An interesting example is the association of GO term "response to stress", used to annotate several classes of non-homologous genes components of distinct stress response mechanisms (e.g. peroxidases, DNA repair enzymes, heat shock proteins), indicating that the horizontal transfer of such genes may be adaptive for host cells and, consequently, advantageous for the integrated prophages as well. CALANGO is provided as a fully operational, out-of-the-box R package that can be freely installed directly from CRAN. Usage examples and longer-format documentation are also available at maintainer's github page.

Long Non-coding RNA MSTRG.24008.1 Regulates the Regeneration of the Sciatic Nerve via the miR-331-3p–NLRP3/MAL Axis

Peripheral nerve injury (PNI) is a common clinical problem, which can cause severe disability and dramatically affect a patient’s quality of life. Neural regeneration after PNI is a complex biological process that involves a variety of signaling pathways and genes. Emerging studies demonstrated that long non-coding RNAs (lncRNAs) were abnormally expressed after PNI and played pivotal roles in peripheral nerve regeneration. Based on the rat sciatic nerve injury model, we found that the expression levels of several lncRNAs were increased significantly in the sciatic nerve after injury. Software prediction prompted us to focus on one up-regulated lncRNA, MSTRG.24008.1. Dual-luciferase reporter assay, RNA pull-down assay and RNA interference approach verified that MSTRG.24008.1 regulated neuroregeneration via the miR-331-3p/nucleotide-binding oligomerization domain-like pyrin domain containing 3 (NLRP3)/myelin and lymphocyte protein (MAL) axis in vitro. Subsequently, we performed gastrocnemius muscle gravity and sciatic functional index experiments to evaluate the recovery of injured sciatic nerves after MSTRG.24008.1 siRNA interference in vivo. In conclusion, knockdown of MSTRG.24008.1 promotes the regeneration of the sciatic nerve via the miR-331-3p/NLRP3/MAL axis, which may provide a new strategy to evaluate and repair injured peripheral nerves clinically.

Sex differences in biological aging with a focus on human studies

Aging is a complex biological process characterized by hallmark features accumulating over the life course, shaping the individual's aging trajectory and subsequent disease risks. There is substantial individual variability in the aging process between men and women. In general, women live longer than men, consistent with lower biological ages as assessed by molecular biomarkers, but there is a paradox. Women are frailer and have worse health at the end of life, while men still perform better in physical function examinations. Moreover, many age-related diseases show sex-specific patterns. In this review, we aim to summarize the current knowledge on sexual dimorphism in human studies, with support from animal research, on biological aging and illnesses. We also attempt to place it in the context of the theories of aging, as well as discuss the explanations for the sex differences, for example, the sex-chromosome linked mechanisms and hormonally driven differences.