Understanding Regulatory Mechanisms of Brain Function and Disease through 3D Genome Organization

The human genome has a complex and dynamic three-dimensional (3D) organization, which plays a critical role for gene regulation and genome function. The importance of 3D genome organization in brain development and function has been well characterized in a region- and cell-type-specific fashion. Recent technological advances in chromosome conformation capture (3C)-based techniques, imaging approaches, and ligation-free methods, along with computational methods to analyze the data generated, have revealed 3D genome features at different scales in the brain that contribute to our understanding of genetic mechanisms underlying neuropsychiatric diseases and other brain-related traits. In this review, we discuss how these advances aid in the genetic dissection of brain-related traits

Understanding the function of regulatory DNA interactions in the interpretation of non-coding GWAS variants

Genome-wide association studies (GWAS) have identified a vast number of variants associated with various complex human diseases and traits. However, most of these GWAS variants reside in non-coding regions producing no proteins, making the interpretation of these variants a daunting challenge. Prior evidence indicates that a subset of non-coding variants detected within or near cis-regulatory elements (e.g., promoters, enhancers, silencers, and insulators) might play a key role in disease etiology by regulating gene expression. Advanced sequencing- and imaging-based technologies, together with powerful computational methods, enabling comprehensive characterization of regulatory DNA interactions, have substantially improved our understanding of the three-dimensional (3D) genome architecture. Recent literature witnesses plenty of examples where using chromosome conformation capture (3C)-based technologies successfully links non-coding variants to their target genes and prioritizes relevant tissues or cell types. These examples illustrate the critical capability of 3D genome organization in annotating non-coding GWAS variants. This review discusses how 3D genome organization information contributes to elucidating the potential roles of non-coding GWAS variants in disease etiology

Intestinal microbiota: a new perspective on delaying aging?

The global aging situation is severe, and the medical pressures associated with aging issues should not be underestimated. The need and feasibility of studying aging and intervening in aging have been confirmed. Aging is a complex natural physiological progression, which involves the irreversible deterioration of body cells, tissues, and organs with age, leading to enhanced risk of disease and ultimately death. The intestinal microbiota has a significant role in sustaining host dynamic balance, and the study of bidirectional communication networks such as the brain–gut axis provides important directions for human disease research. Moreover, the intestinal microbiota is intimately linked to aging. This review describes the intestinal microbiota changes in human aging and analyzes the causal controversy between gut microbiota changes and aging, which are believed to be mutually causal, mutually reinforcing, and inextricably linked. Finally, from an anti-aging perspective, this study summarizes how to achieve delayed aging by targeting the intestinal microbiota. Accordingly, the study aims to provide guidance for further research on the intestinal microbiota and aging

Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity

Objectives Identify genetic loci of enhanced susceptibility to Chlamydial trachomatis (Ct) upper genital tract infection in women.MethodsWe performed an integrated analysis of DNA genotypes and blood-derived mRNA profiles from 200 Ct-exposed women to identify expression quantitative trait loci (eQTL) and determine their association with endometrial chlamydial infection using a mediation test. We further evaluated the effect of a lead eQTL on the expression of CD151 by immune cells from women with genotypes associated with low and high whole blood expression of CD151, respectively. Results We identified cis-eQTLs modulating mRNA expression of 81 genes (eGenes) associated with altered risk of ascending infection. In women with endometrial infection, eGenes involved in proinflammatory signaling were upregulated. Downregulated eGenes included genes involved in T cell functions pivotal for chlamydial control. eGenes encoding molecules linked to metabolism of tryptophan, an essential chlamydial nutrient, and formation of epithelial tight junctions were also downregulated in women with endometrial infection. A lead eSNP rs10902226 was identified regulating CD151, a tetrospanin molecule important for immune cell adhesion and migration and T cell proliferation. Further in vitro experiments showed that women with a CC genotype at rs10902226 had reduced rates of endometrial infection with increased CD151 expression in whole blood and T cells when compared to women with a GG genotype. Conclusions We discovered genetic variants associated with altered risk for Ct ascension. A lead eSNP for CD151 is a candidate genetic marker for enhanced CD4 T cell function and reduced susceptibility

Global gene expression profile progression in Gaucher disease mouse models

<p>Abstract</p> <p>Background</p> <p>Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide. The pathogenic pathways resulting from lipid laden macrophages (Gaucher cells) in visceral organs and their abnormal functions are obscure.</p> <p>Results</p> <p>To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinct <it>Gba1 </it>point-mutated mice (V394L/V394L and D409 V/null). About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change), representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk) of INFγ-regulated pro-inflammatory (13) and IL-4-regulated anti-inflammatory (11) cytokine/mediator networks showed tissue differential profiles in the lung and liver of the <it>Gba1 </it>mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with the <it>Gba1 </it>mutation.</p> <p>Conclusions</p> <p>Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.</p

A Study on Antibacterial Activity and Chemical Composition of the Petroleum Ether Extract from Aspergillusniger Mycelia

In order to develop natural antibacterial agents, the antibacterial activity of Aspergillusnigerxj was investigated. After being cultured in potato dextrose liquid medium liquid medium, mycelia was under heating reflux extraction with 90% ethanol. Removal of ethanol under reduced pressure gave a residue, to which water was added and then extracted with petroleum ether and ethyl acetate. In vacuo evaporation of the solvents yielded three crude extracts. Then the disc diffusion method was used to measure the antibacterial activity of these extracts. The petroleum ether extract with antibacterial activity was separated by silica gel column chromatography method, then separated and identified by GC-MS after been methyl esterified. At the concentration of 50 mg/mL, the petroleum ether extract of mycelia exhibited inhibitory effect against Staphylococcus aureus. The petroleum ether extract from Aspergillusnigerxj mycelia contained natural substances with antibacterial activity and fatty acids are the main constituents in it

Change of Human Footprint in China and Its Implications for Carbon Dioxide (CO₂) Emissions

Humans have altered the earth in unprecedented ways, and these changes have profound implications for global climate change. However, the impacts of human pressures on carbon dioxide (CO2) emissions over long time scales have not yet been clarified. Here, we used the human footprint index (HF), which estimates the ecological footprint of humans in a given location, to explore the impacts of human pressures on CO2 emissions in China from 2000 to 2017. Human pressures (+13.6%) and CO2 emissions (+198.3%) in China are still on the rise during 2000–2017 and are unevenly distributed spatially. There was a significant positive correlation between human pressures and CO2 emissions in China, and northern China is the main driver of this correlation. The increase of CO2 emissions in China slowed down after 2011. Although human pressures on the environment are increasing, high-quality development measures have already had noticeable effects on CO2 emission reductions

Characteristics of antioxidant capacity and metabolomics analysis of flavonoids in the bran layer of green glutinous rice (Oryza sativa L. var. Glutinosa Matsum)

Abstract Green glutinous rice is a unique genetic germplasm that has yet to be adequately studied. This study investigated antioxidant capacity and flavonoid metabolites in the bran layer of green glutinous rice (LvH) compared to purple (HeiH), red (HongH) and white (GJG) varieties. The results showed that LvH bran had significantly higher content of total flavonoids and anthocyanin than that of HongH (1.91-fold and 4.34-fold) and GJG (2.45-fold and 13.30-fold). LvH bran also showed significantly higher levels of vitamin B1 and vitamin E than that of HeiH (1.94-fold and 1.15-fold) and HongH (1.22-fold and 1.13-fold), indicating that green glutinous rice bran was rich in bioactive components. LvH bran showed significantly lower IC50 values for scavenging DPPH and ATBS radicals than GJG and even significantly lower IC50 value for scavenging DPPH radicals than HongH, highlighting its potential as an effective source of antioxidants. LvH bran had significantly different downstream metabolite synthesis in the flavonoid pathway compared to HeiH, HongH, and GJG, with 40, 26, and 22 different metabolites, 23, 20, and 33 up-regulated differentially expressed metabolites (DEMs), and 73, 50, and 13 down-regulated DEMs, respectively. Of the 139 flavonoid metabolites identified in colored rice bran, 26 metabolites showed significant positive correlation with both ABTS and DPPH radical scavenging capacity. Typically, quercetin derivatives showed potential for evaluating the antioxidant capacity of colored rice bran. These findings offer valuable insights into the antioxidant properties of green glutinous rice bran and provide references for better understanding of flavonoid metabolites in different colored rice bran

Mixotrophic Cultivation Optimization of Microalga <i>Euglena pisciformis</i> AEW501 for Paramylon Production

Euglena, a flagellated unicellular protist, has recently received widespread attention for various high-value metabolites, especially paramylon, which was only found in Euglenophyta. The limited species and low biomass of Euglena has impeded paramylon exploitation and utilization. This study established an optimal cultivation method of Euglena pisciformis AEW501 for paramylon production under mixotrophic cultivation. The results showed that the optimum mixotrophic conditions were 20 °C, pH 7.0, and 63 μmol photons m−2∙s−1, and the concentrations of sodium acetate and diammonium hydrogen phosphate were 0.98 g L−1 and 0.79 g L−1, respectively. The maximal biomass and paramylon content were 0.72 g L−1 and 71.39% of dry weight. The algal powder contained more than 16 amino acids, 6 vitamins, and 10 unsaturated fatty acids under the optimal cultivation. E. pisciformis paramylon was pure β-1,3-glucan-type polysaccharide (the purity was up to 99.13 ± 0.61%) composed of linear glucose chains linked together by β-1,3-glycosidic bonds. These findings present a valuable basis for the industrial exploitation of paramylon with E. pisciformis AEW501