Future in the past: paternal reprogramming of offspring phenotype and the epigenetic mechanisms.

That certain preconceptual paternal exposures reprogram the developmental phenotypic plasticity in future generation(s) has conceptualized the "paternal programming of offspring health" hypothesis. This transgenerational effect is transmitted primarily through sperm epigenetic mechanisms-DNA methylation, non-coding RNAs (ncRNAs) and associated RNA modifications, and histone modifications-and potentially through non-sperm-specific mechanisms-seminal plasma and circulating factors-that create 'imprinted' memory of ancestral information. The epigenetic landscape in sperm is highly responsive to environmental cues, due to, in part, the soma-to-germline communication mediated by epididymosomes. While human epidemiological studies and experimental animal studies have provided solid evidences in support of transgenerational epigenetic inheritance, how ancestral information is memorized as epigenetic codes for germline transmission is poorly understood. Particular elusive is what the downstream effector pathways that decode those epigenetic codes into persistent phenotypes. In this review, we discuss the paternal reprogramming of offspring phenotype and the possible underlying epigenetic mechanisms. Cracking these epigenetic mechanisms will lead to a better appreciation of "Paternal Origins of Health and Disease" and guide innovation of intervention algorithms to achieve 'healthier' outcomes in future generations. All this will revolutionize our understanding of human disease etiology.

Retinoic acid signaling in development and differentiation commitment and its regulatory topology.

Retinoic acid (RA), the derivative of vitamin A/retinol, is a signaling molecule with important implications in health and disease. It is a well-known developmental morphogen that functions mainly through the transcriptional activity of nuclear RA receptors (RARs) and, uncommonly, through other nuclear receptors, including peroxisome proliferator-activated receptors. Intracellular RA is under spatiotemporally fine-tuned regulation by synthesis and degradation processes catalyzed by retinaldehyde dehydrogenases and P450 family enzymes, respectively. In addition to dictating the transcription architecture, RA also impinges on cell functioning through non-genomic mechanisms independent of RAR transcriptional activity. Although RA-based differentiation therapy has achieved impressive success in the treatment of hematologic malignancies, RA also has pro-tumor activity. Here, we highlight the relevance of RA signaling in cell-fate determination, neurogenesis, visual function, inflammatory responses and gametogenesis commitment. Genetic and post-translational modifications of RAR are also discussed. A better understanding of RA signaling will foster the development of precision medicine to improve the defects caused by deregulated RA signaling.

Unlocking gut microbiota potential of dairy cows in varied environmental conditions using shotgun metagenomic approach.

Food security and environmental pollution are major concerns for the expanding world population, where farm animals are the largest source of dietary proteins and are responsible for producing anthropogenic gases, including methane, especially by cows. We sampled the fecal microbiomes of cows from varying environmental regions of Pakistan to determine the better-performing microbiomes for higher yields and lower methane emissions by applying the shotgun metagenomic approach. We selected managed dairy farms in the Chakwal, Salt Range, and Patoki regions of Pakistan, and also incorporated animals from local farmers. Milk yield and milk fat, and protein contents were measured and correlated with microbiome diversity and function. The average milk protein content from the Salt Range farms was 2.68%, with an average peak milk yield of 45 litters/head/day, compared to 3.68% in Patoki farms with an average peak milk yield of 18 litters/head/day. Salt-range dairy cows prefer S-adenosyl-L-methionine (SAMe) to S-adenosyl-L-homocysteine (SAH) conversion reactions and are responsible for low milk protein content. It is linked to Bacteroides fragilles which account for 10% of the total Bacteroides, compared to 3% in the Patoki region. The solid Non-Fat in the salt range was 8.29%, whereas that in patoki was 6.34%. Moreover, Lactobacillus plantarum high abundance in Salt Range provided propionate as alternate sink to [H], and overcoming a Methanobrevibacter ruminantium high methane emissions in the Salt Range. Furthermore, our results identified ruminant fecal microbiomes that can be used as fecal microbiota transplants (FMT) to high-methane emitters and low-performing herds to increase farm output and reduce the environmental damage caused by anthropogenic gases emitted by dairy cows.

Effectiveness of herbal plants on rumen fermentation, methane gas emissions, in vitro nutrient digestibility, and population of protozoa.

Background and Aim: Herbal plants have the potential to reduce the population of metagonic bacteria and protozoa due to the bioactive compound contained in herbal plants. This study aimed to evaluate the effect of herbal plant supplementation on rumen fermentation characteristics, methane (CH4) gas emissions, in vitro nutrient digestibility, and protozoan populations. Materials and Methods: This study consisted of two stages. Stage I involved determining the potential of herbal plants to increase total gas production (Orskov and McDonald methods) and reduce the protozoan population (Hristov method). Three potential herbs were selected at this stage and used in Stage II as supplements in the palm kernel cake (PKC)-based diet (30% herbal plants + 70% PKC). Proximate and Van Soest analyses were used to determine the chemical composition. In vitro dry matter digestibility (IVDMD), organic matter (IVOMD), and rumen fermentation characteristics were determined using Theodorous method. Conway microdiffusion was used to determine ammonia concentration (NH3). Gas chromatography was used to determine the total and partial volatile fatty acid production. Results: The results of the first stage showed that seven herbal plants (Moringa oleifera, Rhodomyrtus tomentosa, Clerodendron serratum, Curcuma longa Linn., Urena lobata, Uncaria, and Parkia timoriana) significantly differed in terms of total gas production (p < 0.05). Herbal plants can increase gas production and reduce protozoan populations. The highest total gas production was observed using P. timoriana, M. oleifera, and C. longa Linn. Moringa oleifera plants were the most effective in lowering protozoa population. In Stage 2, the supplementation of herbal plants in PKC-based-diet significantly increased IVDMD, that was ranged from 56.72% to 65.77%, IVOMD that was ranged from 52.10% to 59.54%, and NH3, that was ranged from 13.20 mM to 17.91 mM. Volatile fatty acid partial and total gas production potential and CH4 gas emissions were also significantly different from those of the control (p < 0.05). Conclusion: Supplementation of M. oleifera, C. longa Linn., and P. timoriana in ruminant diet effectively increased total gas production, IVDMD percentage, and IVOMD, and reduced CH4 gas emissions and protozoa populations during rumen fermentation.

Recent advances in chromosome capture techniques unraveling 3D genome architecture in germ cells, health, and disease.

In eukaryotes, the genome does not emerge in a specific shape but rather as a hierarchial bundle within the nucleus. This multifaceted genome organization consists of multiresolution cellular structures, such as chromosome territories, compartments, and topologically associating domains, which are frequently defined by architecture, design proteins including CTCF and cohesin, and chromatin loops. This review briefly discusses the advances in understanding the basic rules of control, chromatin folding, and functional areas in early embryogenesis. With the use of chromosome capture techniques, the latest advancements in technologies for visualizing chromatin interactions come close to revealing 3D genome formation frameworks with incredible detail throughout all genomic levels, including at single-cell resolution. The possibility of detecting variations in chromatin architecture might open up new opportunities for disease diagnosis and prevention, infertility treatments, therapeutic approaches, desired exploration, and many other application scenarios.

A meta-analysis of the effects of clay mineral supplementation on alkaline phosphatase, broiler health, and performance.

The crucial constraint in the broiler production sector is feed efficiency; many feed additives have been widely employed to increase broiler growth. Nonetheless, some of these substances exacerbate health and animal-based food product safety concerns. This meta-analysis examines the effect of clay minerals on alkaline phosphatase (ALP), broiler health, and performance. Metadata was constructed from 369 data items that were harvested from 86 studies. The addition of clay minerals was set as a fixed effect and the difference between experiments was established as a random effect. The metadata were fitted using a linear mixed model. Due to the presence of clay minerals, growth performance as assessed by body weight (BW), average daily gain (ADG), and performance efficiency index (PEI) increased significantly (P < 0.01). In the total period, the increases of BW, ADG, and PEI were 4.12 g, 0.0714 g/d, and 0.648, respectively, per unit of clay minerals added. Clay minerals did not affect blood serum parameters (e.g., ALP and calcium). The IgA and IgM concentrations in the jejunum and ileum were significantly greater (P < 0.01) in the starter phase. Among clay minerals, broilers fed diets with aluminosilicate, halloysite, kaolin, and zeolite consistently exhibited higher (P < 0.05) BW, ADG, PEI, and lower feed conversion ratio (P < 0.05) in the finisher phase. Aluminosilicate was the only clay that increased (P < 0.05) secretory IgA concentration in both jejunum and ileum. In conclusion, clay minerals could be used as a growth promoter, especially during the finisher phase, without adversely affecting feed intake, liver function, and mineral metabolism in broiler chickens. Aluminosilicate was superior in improving the mucosal immunity status of broiler chickens.

Molecular Evolution of the Bactericidal/Permeability-Increasing Protein (BPIFA1) Regulating the Innate Immune Responses in Mammals.

Bactericidal/permeability-increasing protein, a primary factor of the innate immune system of mammals, participates in natural immune protection against invading bacteria. BPIFA1 actively contributes to host defense via multiple mechanisms, such as antibacterial, surfactant, airway surface liquid control, and immunomodulatory activities. However, the evolutionary history and selection forces on the BPIFA1 gene in mammals during adaptive evolution are poorly understood. This study examined the BPIFA1 gene of humans compared with that of other mammalian species to estimate the selective pressure derived by adaptive evolution. To assess whether or not positive selection occurred, we employed several different possibility tests (M1 vs. M2 and M7 vs. M8). The proportions of positively selected sites were significant, with a likelihood log value of 93.63 for the BPIFA1 protein. The Selecton server was used on the same dataset to reconfirm positive selection for specific sites by employing the Mechanistic-Empirical Combination model, thus providing additional evidence supporting the findings of positive selection. There was convincing evidence for positive selection signals in the BPIFA1 genes of mammalian species, which was more significant for selection signs and creating signals. We performed probability tests comparing various models based on dN/dS ratios to recognize specific codons under positive selection pressure. We identified positively selected sites in the LBP-BPI domain of BPIFA1 proteins in the mammalian genome, including a lipid-binding domain with a very high degree of selectivity for DPPC. BPIFA1 activates the upper airway's innate immune system in response to numerous genetic signals in the mammalian genome. These findings highlight evolutionary advancements in immunoregulatory effects that play a significant role in the antibacterial and antiviral defenses of mammalian species.