Regulation of inflammatory response by LINC00346 via miR-25-3p-mediated modulation of the PTEN/PI3K/AKT/NF-κB pathway.

Long intergenic non-coding RNA 346 (LINC00346) has been reported to be involved in the development of atherosclerosis and specific cancers by affecting signaling pathways. However, its function in inflammation has not been thoroughly studied. Therefore, its expression pattern and function were determined in the human macrophage-like cell line THP-1. Lipopolysaccharide (LPS) treatment induced the expression of LINC00346. LPS-induced NF-κB activation and proinflammatory cytokine expression were suppressed or enhanced by the overexpression or knockdown of LINC00346, respectively. Analyses using dual luciferase assay and decoy RNAs that could block RNA-RNA interactions indicated that LINC00346 improves phosphatase and tensin homolog (PTEN) expression by sponging miR-25-3p. Subsequently, PTEN suppresses phosphoinositide-3 kinase (PI3K)-mediated conversion of phosphatidylinositol-4,5-bisphosphate (PIP2) into phosphatidylinositol-3,4,5-trisphosphate (PIP3) as well as consequent activation of protein kinase B (AKT) and NF-κB. Interestingly, database analysis revealed that the expression levels of LINC00346 and PTEN were simultaneously decreased in breast cancer tissues. Further analyses conducted using a breast cancer cell line, MDA-MB-231, confirmed the functional relationship among LINC00346, miR-25-3p, and PTEN in LPS-induced activation of NF-κB. These results indicate that miR-25-3p-sponging activity of LINC00346 affects the balance between PTEN and PI3K as well as the downstream activation of AKT/NF-κB pathway in inflammatory conditions.

Early life exposure to perfluorooctanesulfonate (PFOS) impacts vital biological processes in Xenopus laevis: Integrated morphometric and transcriptomic analyses.

Perfluorooctanesulfonate (PFOS) is a ubiquitous environmental pollutant associated with increasing health concerns and environmental hazards. Toxicological analyses of PFOS exposure are hampered by large interspecies variations and limited studies on the mechanistic details of PFOS-induced toxicity. We investigated the effects of PFOS exposure on Xenopus laevis embryos based on the reported developmental effects in zebrafish. X. laevis was selected to further our understanding of interspecies variation in response to PFOS, and we built upon previous studies by including transcriptomics and an assessment of ciliogenic effects. Midblastula-stage X. laevis embryos were exposed to PFOS using the frog embryo teratogenesis assay Xenopus (FETAX). Results showed teratogenic effects of PFOS in a time- and dose-dependent manner. The morphological abnormalities of skeleton deformities, a small head, and a miscoiled gut were associated with changes in gene expression evidenced by whole-mount in situ hybridization and transcriptomics. The transcriptomic profile of PFOS-exposed embryos indicated the perturbation in the expression of genes associated with cell death, and downregulation in adenosine triphosphate (ATP) biosynthesis. Moreover, we observed the effects of PFOS exposure on cilia development as a reduction in the number of multiciliated cells and changes in the directionality and velocity of the cilia-driven flow. Collectively, these data broaden the molecular understanding of PFOS-induced developmental effects, whereby ciliary dysfunction and disrupted ATP synthesis are implicated as the probable modes of action of embryotoxicity. Furthermore, our findings present a new challenge to understand the links between PFOS-induced developmental toxicity and vital biological processes.

Conserved dual-mode gene regulation programs in higher eukaryotes.

Recent genomic data analyses have revealed important underlying logics in eukaryotic gene regulation, such as CpG islands (CGIs)-dependent dual-mode gene regulation. In mammals, genes lacking CGIs at their promoters are generally regulated by interconversion between euchromatin and heterochromatin, while genes associated with CGIs constitutively remain as euchromatin. Whether a similar mode of gene regulation exists in non-mammalian species has been unknown. Here, through comparative epigenomic analyses, we demonstrate that the dual-mode gene regulation program is common in various eukaryotes, even in the species lacking CGIs. In cases of vertebrates or plants, we find that genes associated with high methylation level promoters are inactivated by forming heterochromatin and expressed in a context-dependent manner. In contrast, the genes with low methylation level promoters are broadly expressed and remain as euchromatin even when repressed by Polycomb proteins. Furthermore, we show that invertebrate animals lacking DNA methylation, such as fruit flies and nematodes, also have divergence in gene types: some genes are regulated by Polycomb proteins, while others are regulated by heterochromatin formation. Altogether, our study establishes gene type divergence and the resulting dual-mode gene regulation as fundamental features shared in a broad range of higher eukaryotic species.

Dose Optimization of Cefpirome Based on Population Pharmacokinetics and Target Attainment during Extracorporeal Membrane Oxygenation.

To obtain the optimal dosage regimen in patients receiving extracorporeal membrane oxygenation (ECMO), we developed a population pharmacokinetics model for cefpirome and performed pharmacodynamic analyses. This prospective study included 15 patients treated with cefpirome during ECMO. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF) at predose and 0.5 to 1, 2 to 3, 4 to 6, 8 to 10, and 12 h after cefpirome administration. The population pharmacokinetic model was developed using nonlinear mixed effects modeling and stepwise covariate modeling. Monte Carlo simulation was used to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) according to the MIC distribution. Cefpirome pharmacokinetics were best described by a two-compartment model. Covariate analysis indicated that serum creatinine concentration (SCr) was negatively correlated with clearance, and the presence of ECMO increased clearance and the central volume of distribution. The simulations showed that patients with low SCr during ECMO-ON had lower PTA than patients with high SCr during ECMO-OFF; so, a higher dosage of cefpirome was required. Cefpirome of 2 g every 8 h for intravenous bolus injection or 2 g every 12 h for extended infusion over 4 h was recommended with normal kidney function receiving ECMO. We established a population pharmacokinetic model for cefpirome in patients with ECMO, and appropriate cefpirome dosage regimens were recommended. The impact of ECMO could be due to the change in patient status on consideration of the small population and uncertainty in covariate relationships. Dose optimization of cefpirome may improve treatment success and survival in patients receiving ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.).

Artificially designed recombinant protein composed of multiple epitopes of foot-and-mouth disease virus as a vaccine candidate.

BACKGROUND: Concerns regarding the safety of inactivated foot-and-mouth disease (FMD) vaccine have been raised since it is produced from cultured live FMD virus (FMDV). To overcome this issue, recombinant protein has been studied as an alternative vaccine. RESULTS AND CONCLUSION: We designed a chimerical multi-epitope recombinant protein (5BT), which is comprised of tandem repeats of five B cell epitopes (residue of VP1 136-162) derived from different FMDV variants and one T-cell epitope (residue of 3A 21-35). To increase solubility and stability of 5BT, it was conjugated with BmpB, the membrane protein B of Brachyspira hyodysenteriae (B5BT). Our results indicated that 5BT was susceptible to degradation by host protease and produced with substantial fraction of inclusion body. The stability and solubility of 5BT was greatly increased by conjugating to BmpB. FMDV specific antibodies were observed in the serum of mice immunized with 5BT and B5BT comparable to inactivated FMD vaccine. Sera from 5BT and B5BT groups also exhibited high epitope-specific antibody titers in peptide specific ELISA, indicating that all five epitopes are exposed to the B cell receptor for the antibody reaction. Thus the multi-epitope recombinant protein designed in this study may be a potential candidate as an alternative vaccine against FMDV epidemic variants.

Pan-Genomic Approaches in Lactobacillus reuteri as a Porcine Probiotic: Investigation of Host Adaptation and Antipathogenic Activity.

After the introduction of a ban on the use of antibiotic growth promoters (AGPs) for livestock, reuterin-producing Lactobacillus reuteri is getting attention as an alternative to AGPs. In this study, we investigated genetic features of L. reuteri associated with host specificity and antipathogenic effect. We isolated 104 L. reuteri strains from porcine feces, and 16 strains, composed of eight strains exhibiting the higher antipathogenic effect (group HS) and eight strains exhibiting the lower effect (group LS), were selected for genomic comparison. We generated draft genomes of the 16 isolates and investigated their pan-genome together with the 26 National Center for Biotechnology Information-registered genomes. L. reuteri genomes organized six clades with multi-locus sequence analysis, and the clade IV includes the 16 isolates. First, we identified six L. reuteri clade IV-specific genes including three hypothetical protein-coding genes. The three annotated genes encode transposases and cell surface proteins, indicating that these genes are the result of adaptation to the host gastrointestinal epithelia and that these host-specific traits were acquired by horizontal gene transfer. We also identified differences between groups HS and LS in the pdu-cbi-cob-hem gene cluster, which is essential for reuterin and cobalamin synthesis, and six genes specific to group HS are revealed. While the strains of group HS possessed all genes of this cluster, LS strains have lost many genes of the cluster. This study provides a deeper understanding of the relationship between probiotic properties and genomic features of L. reuteri.

Evaluating the association between body weight and the intestinal microbiota of weaned piglets via 16S rRNA sequencing.

Due to the ban on the use of antimicrobial growth promoters in livestock feeds, understanding the relationship between intestinal microbiota and the physiology of the host has become very important for improving livestock performance. In this study, we investigated the relationship between intestinal microbiota and body weights of weaned piglets. Lighter (n = 9) and heavier (n = 9) 9-week-old weaned piglets were selected from approximately one hundred individuals based on their body weights. Their fecal microbial communities were analyzed by sequencing the V4 region of the 16S rRNA gene. The microbial richness estimators of the heavier piglets were significantly higher than those of the lighter piglets. At the phylum level, the microbiota of the heavier group had significantly higher levels of Firmicutes and a higher Firmicutes-to-Bacteroidetes ratio than that of the lighter group. At the genus level, the levels of several genera, such as Anaerococcus and Lactococcus, were significantly different in the two groups. In particular, the lighter group had significantly higher levels of opportunistic pathogenic bacteria, such as Anaerotruncus and Bacteroides, compared with those of the heavier group. Moreover, the levels of bacteria expressing the components of several metabolic pathways were significantly different in the two groups. The microbiota of the heavier group had a significantly higher involvement in three KEGG pathways concerned with xenobiotic degradation than that of the lighter group. These results may provide insights into host-microbe interactions occurring in the piglet intestine and will be useful in establishing a strategy for improving growth performance in the swine industry.

Influence of Flaxseed Oil on Fecal Microbiota, Egg Quality and Fatty Acid Composition of Egg Yolks in Laying Hens.

Although there have been many attempts to produce ω-3 fatty acid-rich eggs using alpha-linolenic acid (ALA) that is a popular fatty acid in the poultry feed industry, only limited knowledge about the effects of ALA-enriched diets on chicken fecal microbiota is currently available. Herein we examined the changes in the fecal microbiota composition, egg quality traits and fatty acid composition of the egg yolks of laying hens fed ALA-rich flaxseed oil for 8 weeks. The animals fed the experimental diets that contained 0 % (group C), 0.5 % (group T1), and 1.0 % (group T2) of flaxseed oil, respectively, and eggs and feces were obtained for the analyses. ω-3 fatty acids, including ALA, were increased in T1 and T2 compared with C. Furthermore, the freshness of eggs was improved with no side effects on the eggs. The diet also changed the fecal microbiota; Firmicutes was increased in T1 and T2 (48.6 to 83 and 79.6 %) and Bacteroidetes was decreased (40.2 to 8.8 and 4.2 %). Principal coordinate analysis revealed that Lactobacillus, among the 56 examined genera, was the most influenced bacterial group in terms of the fecal microbial community shifts. These results indicate that ALA-rich diets influenced both the egg and fecal microbiota in beneficial manners in laying hens although the association between the fatty acid composition of the egg yolk and the fecal microbiota was not clear. This study is a first step to understand the effect of flaxseed oil as well as intestinal microbiota of laying hens.

Soluble RANKL expression in Lactococcus lactis and investigation of its potential as an oral vaccine adjuvant.

BACKGROUND: To initiate mucosal immune responses, antigens in the intestinal lumen must be transported into gut-associated lymphoid tissue through M cells. Recently, it has been increasingly recognized that receptor activator of NF-kB ligand (RANKL) controls M cell differentiation by interacting with RANK expressed on the sub-epithelium of Peyer's patches. In this study, we increased the number of M cells using soluble RANKL (sRANKL) as a potent mucosal adjuvant. RESULTS: For efficient oral delivery of sRANKL, we constructed recombinant Lactococcus lactis (L. lactis) IL1403 secreting sRANKL (sRANKL-LAB). The biological activity of recombinant sRANKL was confirmed by observing RANK-RANKL signaling in vitro. M cell development in response to oral administration of recombinant L. lactis was determined by 1.51-fold higher immunohistochemical expression of M cell marker GP-2, compared to that of non-treatment group. In addition, an adjuvant effect of sRANKL was examined by immunization of mice with M-BmpB as a model antigen after treatment with sRANKL-LAB. Compared with the wild-type L. lactis group, the sRANKL-LAB group showed significantly increased systemic and mucosal immune responses specific to M-BmpB. CONCLUSIONS: Our results show that the M cell development by sRANKL-LAB can increase the antigen transcytotic capability of follicle-associated epithelium, and thereby enhance the mucosal immune response, which implies that oral administration of sRANKL is a promising adjuvant strategy for efficient oral vaccination.

Impact of nsSNPs in human AIM2 and IFI16 gene: a comprehensive in silico analysis.

AIM2 and IFI16 are the most studied members of AIM2-like receptors (ALRs) in humans and share a common N-Terminal PYD domain and C-terminal HIN domain. The HIN domain binds to dsDNA in response to the invasion of bacterial and viral DNA, and the PYD domain directs apoptosis-associated speck-like protein via protein-protein interactions. Hence, activation of AIM2 and IFI16 is crucial for protection against pathogenic assaults, and any genetic variation in these inflammasomes can dysregulate the human immune system. In this study, different computational tools were used to identify the most deleterious and disease-causing non-synonymous single nucleotide polymorphisms (nsSNPs) in AIM2 and IFI16 proteins. Molecular dynamic simulation was performed for the top damaging nsSNPs to study single amino acid substitution-induced structural alterations in AIM2 and IFI16. The observed results suggest that the variants G13V, C304R, G266R, and G266D for AIM2, and G13E and C356F are deleterious and affect structural integrity. We hope that the suggested deleterious nsSNPs and structural dynamics of AIM2 and IFI16 variants will guide future research to better understand the function of these variants with large-scale studies and may assist in fresher therapeutics focusing on these polymorphisms.Communicated by Ramaswamy H. Sarma.

Synergy effect of silicate fertilizer and iron slag: A sustainable approach for mitigating methane emission in rice farming.

Although silicate fertilizer has been recently recognized for its ability to suppress methane (CH4) emissions in paddy fields, the effects of its consecutive application during the rice farming period are still a subject of debate. Moreover, while it was known that silicate fertilizer can mitigate CH4 emissions through several electron acceptors, the effect of additional application of electron acceptors have not been extensively studied. This study evaluated the effect of silicate fertilizer with varying concentrations of iron slag on CH4 emissions and rice yield over the 3 years rice farming period. Seasonal CH4 fluxes exhibited a significant decrease with the application of silicate fertilizer, with the treatment containing 2.5 % iron slag showing the maximum reduction of 35 % in 2020. Additionally, in 2021 and 2022, the application of silicate fertilizer with 2.5 % iron slag resulted in a decrease of total seasonal CH4 emission by 22 % and 23 %, respectively. Rice grain yield exhibited a significant increase with the inclusion of iron slag in the silicate fertilizer, which resulted in a 37 % and 16 % higher yield compared to no-silicate fertilization and no­iron slag silicate fertilization, respectively. Therefore, iron slag-based silicate fertilizer could be a beneficial soil amendment to mitigate CH4 emissions in rice paddy fields and improve rice productivity without negative effects on the atmospheric and soil ecosystem.

Pyrolysis temperature and time of rice husk biochar potentially control ammonia emissions and Chinese cabbage yield from urea-fertilized soils.

Current agricultural practices are increasingly favoring the biochar application to sequester carbon, enhance crop growth, and mitigate various environmental pollutants resulting from nitrogen (N) loss. However, since biochar's characteristics can vary depending on pyrolysis conditions, it is essential to determine the optimal standard, as they can have different effects on soil health. In this study, we categorized rice husk biochars basis on their pH levels and investigated the role of each rice husk biochar in reducing ammonia (NH3) emissions and promoting the growth of Chinese cabbage in urea-fertilized fields. The findings of this study revealed that the variation in pyrolysis conditions of rice husk biochars and N rates affected both the NH3 emissions and crop growth. The neutral (pH 7.10) biochar exhibited effective NH3 volatilization reduction, attributed to its high surface area (6.49 m2 g-1), outperforming the acidic (pH 6.10) and basic (pH 11.01) biochars, particularly under high N rates (640 kg N ha-1). Chinese cabbage yield was highest, reaching 4.00 kg plant-1, with the basic biochar application with high N rates. Therefore, the neutral rice husk biochar effectively mitigate the NH3 emissions from urea-treated fields, while the agronomic performance of Chinese cabbage enhanced in all biochar amendments.

Production of Plant-Based, Film-Type Scaffolds Using Alginate and Corn Starch for the Culture of Bovine Myoblasts.

Natural scaffolds have been the cornerstone of tissue engineering for decades, providing ideal environments for cell growth within extracellular matrices. Previous studies have favored animal-derived materials, including collagen, gelatin, and laminin, owing to their superior effects in promoting cell attachment, proliferation, and differentiation compared to non-animal scaffolds, and used immortalized cell lines. However, for cultured meat production, non-animal-derived scaffolds with edible cells are preferred. Our study represents the first research to describe plant-derived, film-type scaffolds to overcome limitations associated with previously reported thick, gel-type scaffolds completely devoid of animal-derived materials. This approach has been employed to address the difficulties of fostering bovine muscle cell survival, migration, and differentiation in three-dimensional co-cultures. Primary bovine myoblasts from Bos Taurus Coreanae were harvested and seeded on alginate (Algi) or corn-derived alginate (AlgiC) scaffolds. Scaffold functionalities, including biocompatibility and the promotion of cell proliferation and differentiation, were evaluated using cell viability assays, immunofluorescence staining, and reverse transcription-quantitative polymerase chain reaction. Our results reveal a statistically significant 71.7% decrease in production time using film-type scaffolds relative to that for gel-type scaffolds, which can be maintained for up to 7 days. Film-type scaffolds enhanced initial cell attachment owing to their flatness and thinness relative to gel-type scaffolds. Algi and AlgiC film-type scaffolds both demonstrated low cytotoxicity over seven days of cell culture. Our findings indicated that PAX7 expression increased 16.5-fold in alginate scaffolds and 22.8-fold in AlgiC from day 1 to day 3. Moreover, at the differentiation stage on day 7, MHC expression was elevated 41.8-fold (Algi) and 32.7-fold (AlgiC), providing initial confirmation of the differentiation potential of bovine muscle cells. These findings suggest that both Algi and AlgiC film scaffolds are advantageous for cultured meat production.

The Principles and Applications of High-Throughput Sequencing Technologies.

The advancement in high-throughput sequencing (HTS) technology has revolutionized the field of biology, including genomics, epigenomics, transcriptomics, and metagenomics. This technology has become a crucial tool in many areas of research, allowing scientists to generate vast amounts of genetic data at a much faster pace than traditional methods. With this increased speed and scale of data generation, researchers can now address critical questions and gain new insights into the inner workings of living organisms, as well as the underlying causes of various diseases. Although the first HTS technology have been introduced about two decades ago, it can still be challenging for those new to the field to understand and use effectively. This review aims to provide a comprehensive overview of commonly used HTS technologies these days and their applications in terms of genome sequencing, transcriptome, DNA methylation, DNA-protein interaction, chromatin accessibility, three-dimensional genome organization, and microbiome.

A genomic estimated breeding value-assisted reduction method of single nucleotide polymorphism sets: a novel approach for determining the cutoff thresholds in genome-wide association studies and best linear unbiased prediction.

Traditionally, the p-value is the criterion for the cutoff threshold to determine significant markers in genome-wide association studies (GWASs). Choosing the best subset of markers for the best linear unbiased prediction (BLUP) for improved prediction ability (PA) has become an interesting issue. However, when dealing with many traits having the same marker information, the p-values' themselves cannot be used as an obvious solution for having a confidence in GWAS and BLUP. We thus suggest a genomic estimated breeding value-assisted reduction method of the single nucleotide polymorphism (SNP) set (GARS) to address these difficulties. GARS is a BLUP-based SNP set decision presentation. The samples were Landrace pigs and the traits used were back fat thickness (BF) and daily weight gain (DWG). The prediction abilities (PAs) for BF and DWG for the entire SNP set were 0.8 and 0.8, respectively. By using the correlation between genomic estimated breeding values (GEBVs) and phenotypic values, selecting the cutoff threshold in GWAS and the best SNP subsets in BLUP was plausible as defined by GARS method. 6,000 SNPs in BF and 4,000 SNPs in DWG were considered as adequate thresholds. Gene Ontology (GO) analysis using the GARS results of the BF indicated neuron projection development as the notable GO term, whereas for the DWG, the main GO terms were nervous system development and cell adhesion.

Molecular dynamics of the ERRγ ligand-binding domain bound with agonist and inverse agonist.

Estrogen-related receptor gamma (ERRγ), the latest member of the ERR family, does not have any known reported natural ligands. Although the crystal structures of the apo, agonist-bound, and inverse agonist-bound ligand-binding domain (LBD) of ERRγ have been solved previously, their dynamic behavior has not been studied. Hence, to explore the intrinsic dynamics of the apo and ligand-bound forms of ERRγ, we applied long-range molecular dynamics (MD) simulations to the crystal structures of the apo and ligand-bound forms of the LBD of ERRγ. Using the MD trajectories, we performed hydrogen bond and binding free energy analysis, which suggested that the agonist displayed more hydrogen bonds with ERRγ than the inverse agonist 4-OHT. However, the binding energy of 4-OHT was higher than that of the agonist GSK4716, indicating that hydrophobic interactions are crucial for the binding of the inverse agonist. From principal component analysis, we observed that the AF-2 helix conformation at the C-terminal domain was similar to the initial structures during simulations, indicating that the AF-2 helix conformation is crucial with respect to the agonist or inverse agonist for further functional activity of ERRγ. In addition, we performed residue network analysis to understand intramolecular signal transduction within the protein. The betweenness centrality suggested that few of the amino acids are important for residue signal transduction in apo and ligand-bound forms. The results from this study may assist in designing better therapeutic compounds against ERRγ associated diseases.

Evaluating methane emissions from rice paddies: A study on the cultivar and transplanting date.

Climate change, driven by increased greenhouse gas emissions, is a pressing environmental issue worldwide. Flooded rice paddy soils are a predominant source of methane (CH4) emissions, accounting for approximately 11 % of global emissions. Factors such as rice (Oryza sativa L.) cultivar, transplanting date, water management, and soil characteristics significantly influence these emissions. This study aimed to evaluate the CH4 emissions from rice paddies in relation to the cultivar and transplanting date. The experiment included two rice cultivars (an early-maturing cultivar, Unkwang, and a medium-late-maturing cultivar, Samkwang) and four transplanting dates (Times 1-4). In the present study, CH4 emissions were higher with earlier transplanting dates and decreased significantly with delayed transplanting. Weather conditions, such as cumulative mean air temperature, cumulative soil temperature, and total sunshine hours, were positively correlated with total CH4 emissions. The recommended regional transplanting date (Time 3) resulted in the highest rice grain yields for both cultivars. However, the earlier transplanting dates (Time 1 and Time 2) were more effective in improving plant growth characteristics such as rice straw weight, root biomass weight, and chlorophyll content. A significant positive correlation was observed between the root biomass weight of the rice and CH4 emissions in both cultivars, implying that an increase in root biomass weight led to an increase in CH4 emissions. Consequently, adhering to the advised regional transplanting dates is the most sensible approach for transplanting rice seedlings. This ensured lower CH4 emissions without compromising rice productivity or quality for both cultivars. Further research should focus on identifying the most appropriate rice-transplanting dates and management practices to effectively reduce CH4 emissions without compromising rice production.

Histone modification in Saccharomyces cerevisiae: A review of the current status.

The budding yeast Saccharomyces cerevisiae is a well-characterized and popular model system for investigating histone modifications and the inheritance of chromatin states. The data obtained from this model organism have provided essential and critical information for understanding the complexity of epigenetic interactions and regulation in eukaryotes. Recent advances in biotechnology have facilitated the detection and quantitation of protein post-translational modification (PTM), including acetylation, methylation, phosphorylation, ubiquitylation, sumoylation, and acylation, and led to the identification of several novel modification sites in histones. Determining the cellular function of these new histone markers is essential for understanding epigenetic mechanisms and their impact on various biological processes. In this review, we describe recent advances and current views on histone modifications and their effects on chromatin dynamics in S. cerevisiae.

Employment impacts of the COVID-19 pandemic across metropolitan status and size.

We use individual-level data from the United States Current Population Survey to examine effects of the COVID-19 pandemic on employment losses across metropolitan area status and population size. Job losses spiked in April 2020, and partially recovered in subsequent months. Non-metropolitan and metropolitan areas of all sizes experienced significant employment losses, but the impacts were much larger in large metropolitan areas. The COVID-19 infection rate was initially higher in large metropolitan areas and this is a significant factor explaining the higher early employment losses in large metropolitan areas. However, higher job losses for large metropolitan areas persisted through summer and fall 2020 even after COVID-19 infection rates became higher in less populous areas. We find evidence of persistent effects of early COVID-19 infection rates on later employment.

Misexpression of genes lacking CpG islands drives degenerative changes during aging.

Cellular aging is characterized by disruption of the nuclear lamina and its associated heterochromatin. How these structural changes within the nucleus contribute to age-related degeneration of the organism is unclear. Genes lacking CpG islands (CGI− genes) generally associate with heterochromatin when they are inactive. Here, we show that the expression of these genes is globally activated in aged cells and tissues. This CGI− gene misexpression is a common feature of normal and pathological aging in mice and humans. We report evidence that CGI− gene up-regulation is directly responsible for age-related physiological deterioration, notably for increased secretion of inflammatory mediators.