Regulation of the Late Onset alzheimer’s Disease Associated HLA-DQA1/DRB1 Expression

(Genome-wide Association Studies) GWAS have identified ∼42 late-onset Alzheimer’s disease (LOAD)-associated loci, each of which contains multiple single nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) and most of these SNPs are in the non-coding region of human genome. However, how these SNPs regulate risk gene expression remains unknown. In this work, by using a set of novel techniques, we identified 6 functional SNPs (fSNPs) rs9271198, rs9271200, rs9281945, rs9271243, and rs9271247 on the LOAD-associated HLA-DRB1/DQA1 locus and 42 proteins specifically binding to five of these 6 fSNPs. As a proof of evidence, we verified the allele-specific binding of GATA2 and GATA3, ELAVL1 and HNRNPA0, ILF2 and ILF3, NFIB and NFIC, as well as CUX1 to these five fSNPs, respectively. Moreover, we demonstrate that all these nine proteins regulate the expression of both HLA-DQA1 and HLA-DRB1 in human microglial cells. The contribution of HLA class II to the susceptibility of LOAD is discussed

Gender-specific association between blood cell parameters and hyperuricemia in high-altitude areas

BackgroundHyperuricemia is a common metabolic disorder linked to various health conditions. Its prevalence varies among populations and genders, and high-altitude environments may contribute to its development. Understanding the connection between blood cell parameters and hyperuricemia in high-altitude areas can shed light on the underlying mechanisms. This study aimed to investigate the relationship between blood cell parameters and hyperuricemia in high-altitude areas, with a particular focus on gender differences.MethodsWe consecutively enrolled all eligible Tibetan participants aged 18–60 who were undergoing routine medical examinations at the People’s Hospital of Chaya County between January and December 2022. During this period, demographic and laboratory data were collected to investigate the risk factors associated with hyperuricemia.ResultsAmong the participants, 46.09% were diagnosed with hyperuricemia. In the male cohort, significant correlations were found between serum uric acid (SUA) levels and red blood cell (RBC) count, creatinine (Cr). Urea, alanine transaminase (ALT), and albumin (ALB). Notably, RBC exhibited the strongest association. Conversely, in the female cohort, elevated SUA levels were associated with factors such as white blood cell (WBC) count. Urea, ALT, and ALB, with WBC demonstrating the most significant association. Further analysis within the female group revealed a compelling relationship between SUA levels and specific white blood cell subtypes, particularly neutrophils (Neu).ConclusionThis study revealed gender-specific associations between SUA levels and blood cell parameters in high-altitude areas. In males, RBC count may play a role in hyperuricemia, while in females, WBC count appears to be a significant factor. These findings contribute to our understanding of metabolic dynamics in high-altitude regions but require further research for comprehensive mechanistic insights

Promoting longevity with less cancer: The 2022 International Conference on Aging and Cancer

Abstract Aging and cancer are increasingly becoming big challenges for public health worldwide due to increased human life expectancy. Meanwhile, aging is one of the major risk factors for cancer. In December 2019, the first International Conference on Aging and Cancer was held in Haikou, Hainan province (island), China, preluding the establishment of the International Center for Aging and Cancer (ICAC) at Hainan, an institute dedicated to the research at the intersection of aging and cancer. Since then, the ICAC has hosted the annual conference each December in Hainan. The 2022 ICAC conference, with the theme of “promoting longevity with less cancer,” invited 17 internationally renowned scientists to share their new research and insights. Topics included DNA methylation in rejuvenation, development, and cellular senescence; lifespan regulation and longevity manipulation; metabolism and aging; cellular senescence and diseases; and novel therapeutics for cancer and antiaging/anticancer drug discovery. The forum highlighted the interconnectedness of aging and senescence with cancer evolution and risk. Although there is hope for preventing diseases like cancer by modulating systems that also control lifespan, attention has to be paid to the conflicting needs and competing demands in human biology

Summary statistics of single nucleotide polymorphisms (SNPs) including indels from female and male <i>Eriocheir sinensis</i> unigenes.

<p>(A) Classification of SNPs. Distribution (%) of each SNP and indel type. (B) Venn diagram of common and unique SNPs and indels of female and male unigenes.</p

Primary sex determination pathway related genes detected in <i>Eriocheir sinensis</i> transcriptomes.

<p>Primary sex determination pathway related genes detected in <i>Eriocheir sinensis</i> transcriptomes.</p

qRT-PCR validation of selected differentially expressed genes identified by RNA-seq.

<p>Vertical bars represent the mean ± S.E. (n = 3). Significant differences are indicated with an asterisk at <i>P</i> < 0.05, and two asterisks at <i>P</i> < 0.01.</p

List of differentially expressed genes related to metabolism in female and male <i>Eriocheir sinensis</i> transcriptomes.

<p>List of differentially expressed genes related to metabolism in female and male <i>Eriocheir sinensis</i> transcriptomes.</p

Transcriptome Profiling Analysis on Whole Bodies of Microbial Challenged <i>Eriocheir sinensis</i> Larvae for Immune Gene Identification and SNP Development

<div><p>To study crab immunogenetics of individuals, newly hatched <i>Eriocheir sinensis</i> larvae were stimulated with a mixture of three pathogen strains (Gram-positive bacteria <i>Micrococcus luteus</i>, Gram-negative bacteria <i>Vibrio alginolyticus</i> and fungi <i>Pichia pastoris</i>; 10⁸ cfu·mL^-1). A total of 44,767,566 Illumina clean reads corresponding to 4.52 Gb nucleotides were generated and assembled into 100,252 unigenes (average length: 1,042 bp; range: 201-19,357 bp). 17,097 (26.09%) of 65,535 non-redundant unigenes were annotated in NCBI non-redundant protein (Nr) database. Moreover, 23,188 (35.38%) unigenes were assigned to three Gene Ontology (GO) categories, 15,071 (23.00%) to twenty-six Clusters of orthologous Groups (COG) and 8,574 (13.08%) to six Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. Numerous genes were further identified to be associated with multiple immune pathways, including Toll, immune deficiency (IMD), janus kinase (JAK)-signal transducers and activators of transcription (STAT) and mitogen-activated protein kinase (MAPK) pathways. Some of them, such as tumor necrosis factor receptor associated factor 6 (TRAF6), fibroblast growth factor (FGF), protein-tyrosine phosphatase (PTP), JNK-interacting protein 1 (JIP1), were first identified in <i>E. sinensis</i>. TRAF6 was even first discovered in crabs. Additionally, 49,555 single nucleotide polymorphisms (SNPs) were developed from over 13,309 unigenes. This is the first transcriptome report of whole bodies of <i>E. sinensis</i> larvae after immune challenge. Data generated here not only provide detail information to identify novel genes in genome reference-free <i>E. sinensis</i>, but also facilitate our understanding on host immunity and defense mechanism of the crab at whole transcriptome level.</p> </div