Identification of disulfidptosis-related genes and subgroups in Alzheimer’s disease

BackgroundAlzheimer’s disease (AD), a common neurological disorder, has no effective treatment due to its complex pathogenesis. Disulfidptosis, a newly discovered type of cell death, seems to be closely related to the occurrence of various diseases. In this study, through bioinformatics analysis, the expression and function of disulfidptosis-related genes (DRGs) in Alzheimer’s disease were explored.MethodsDifferential analysis was performed on the gene expression matrix of AD, and the intersection of differentially expressed genes and disulfidptosis-related genes in AD was obtained. Hub genes were further screened using multiple machine learning methods, and a predictive model was constructed. Finally, 97 AD samples were divided into two subgroups based on hub genes.ResultsIn this study, a total of 22 overlapping genes were identified, and 7 hub genes were further obtained through machine learning, including MYH9, IQGAP1, ACTN4, DSTN, ACTB, MYL6, and GYS1. Furthermore, the diagnostic capability was validated using external datasets and clinical samples. Based on these genes, a predictive model was constructed, with a large area under the curve (AUC = 0.8847), and the AUCs of the two external validation datasets were also higher than 0.7, indicating the high accuracy of the predictive model. Using unsupervised clustering based on hub genes, 97 AD samples were divided into Cluster1 (n = 24) and Cluster2 (n = 73), with most hub genes expressed at higher levels in Cluster2. Immune infiltration analysis revealed that Cluster2 had a higher level of immune infiltration and immune scores.ConclusionA close association between disulfidptosis and Alzheimer’s disease was discovered in this study, and a predictive model was established to assess the risk of disulfidptosis subtype in AD patients. This study provides new perspectives for exploring biomarkers and potential therapeutic targets for Alzheimer’s disease

Repeat expansion scanning of the NOTCH2NLC gene in patients with multiple system atrophy

© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. Objective: Trinucleotide GGC repeat expansion in the 5’UTR of the NOTCH2NLC gene has been recognized as the pathogenesis of neuronal intranuclear inclusion disease (NIID). Previous studies have described that some NIID patients showed clinical and pathological similarities with multiple system atrophy (MSA). This study aimed to address the possibility that GGC repeat expansion in NOTCH2NLC might be associated with some cases diagnosed as MSA. Methods: A total of 189 patients with probable or possible MSA were recruited to screen for GGC repeat expansion in NOTCH2NLC by repeat-primed PCR (RP-PCR). In addition, long-read sequencing (LRS) was performed for all patients with RP-PCR-positive expansion, five patients with RP-PCR-negative expansion, and five controls on the Nanopore platform. Skin biopsies were performed on two patients with GGC expansion. Results: Five of 189 patients (2.6%) were found to have GGC expansion in NOTCH2NLC. LRS results identified that the five patients had GGC expansion between 101 and 266, but five patients with RP-PCR-negative expansion and five controls had GGC expansion between 8 and 29. Besides the typical symptoms and signs of MSA, patients with GGC expansion might have longer disease duration, severe urinary retention, and prominent cognitive impairment. In the skin samples from the patients with GGC expansion, typical p62-postive but alpha-synuclein-negative intranuclear inclusions were found in fibroblasts, adipocyte and ductal epithelial cells of sweat glands. Conclusion: Trinucleotide GGC repeat expansion in NOTCH2NLC could be observed in patients with clinically diagnosed MSA. Adult-onset NIID should be considered as a differential diagnosis of MSA

Microarray-based gene expression profiles in multiple tissues of the domesticated silkworm, Bombyx mori

Using a genome-wide oligonucleotide microarray, gene expression was surveyed in multiple silkworm tissues on day 3 of the fifth instar, providing a new resource for annotating the silkworm genome

Penicillium marneffei-Stimulated Dendritic Cells Enhance HIV-1 Trans-Infection and Promote Viral Infection by Activating Primary CD4+ T Cells

Penicillium marneffei (P. marneffei) is considered an indicator pathogen of AIDS, and the endemicity and clinical features of P. marneffei have been described. While, how the co-infection of P. marneffei exacerbate deterioration of the immune response remains poorly understood. Here we isolated P. marneffei from the cutaneous lesions of AIDS patients and analyzed its effects on HIV-1-dendritic cells (DCs) interaction. We demonstrated that the monocyte-derived dendritic cells (MDDCs) could be activated by both thermally dimorphic forms of P. marneffei for significantly promoting HIV-1 trans-infection of CD4+ T cells, while these activated MDDCs were refractory to HIV-1 infection. Mechanistically, P. marneffei-activated MDDCs endocytosed large amounts of HIV-1 and sequestrated the internalized viruses into tetrapasnin CD81+ compartments potentially for proteolysis escaping. The activated MDDCs increased expression of intercellular adhesion molecule 1 and facilitated the formation of DC-T-cell conjunctions, where much more viruses were recruited. Moreover, we found that P. marneffei-stimulated MDDCs efficiently activated resting CD4+ T cells and induced more susceptible targets for viral infection. Our findings demonstrate that DC function and its interaction with HIV-1 have been modulated by opportunistic pathogens such as P. marneffei for viral dissemination and infection amplification, highlighting the importance of understanding DC-HIV-1 interaction for viral immunopathogenesis elucidation

Variants in MME are associated with autosomal-recessive distal hereditary motor neuropathy

© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. Objective: To identify a new genetic cause in patients segregating distal hereditary motor neuropathy (dHMN) with an autosomal recessive pattern. Methods: Whole-exome sequencing was conducted in two siblings and was combined with segregation analysis. Additionally, 83 unrelated dHMN patients with unknown genetic cause were screened. RNA analysis was performed using blood lymphocytes and HEK293 cells transfected with mutant plasmids. Immunohistochemistry and Western blot analysis was applied to the nerve tissue. The enzymatic activities of mutant proteins were measured in the cultured cells to verify the pathogenicity of variants. Results: The clinical features of the patients showed late-onset phenotype of distal motor neuropathy without sensory involvement. We identified that compound heterozygous variants of c.1342C\u27T and c.2071_2072delGCinsTT in the membrane metalloendopeptidase (MME) gene co-segregated with the phenotype in a dHMN family. In an additional group of 83 patients with dHMN, compound heterozygous variants of c.1416+2T\u27C and c.2027C\u27T in MME were identified in one patient. The splice site variant c.1416+2T\u27C results in skipping of exon 13. The stop variant c.1342C\u27T induces mRNA degradation via nonsense-mediated mRNA decay. Transcript levels of MME in the lymphocytes showed no significant differences between the patients and controls. We also identified that MME variants were associated with mild decrease in protein expression in the sural nerve and significant impairments of enzymatic activity. Interpretation: Variants in the MME gene were associated with not only a Charcot-Marie-Tooth neuropathy phenotype but also with an autosomal-recessive dHMN phenotype. Loss of function may play a role in the pathogenesis of dHMN

Chloroplast Genomes in Populus (Salicaceae): Comparisons From an Intensively Sampled Genus Reveal Dynamic Patterns of Evolution

The chloroplast is one of two organelles containing a separate genome that codes for essential and distinct cellular functions such as photosynthesis. Given the importance of chloroplasts in plant metabolism, the genomic architecture and gene content have been strongly conserved through long periods of time and as such are useful molecular tools for evolutionary inferences. At present, complete chloroplast genomes from over 4000 species have been deposited into publicly accessible databases. Despite the large number of complete chloroplast genomes, comprehensive analyses regarding genome architecture and gene content have not been conducted for many lineages with complete species sampling. In this study, we employed the genus Populus to assess how more comprehensively sampled chloroplast genome analyses can be used in understanding chloroplast evolution in a broadly studied lineage of angiosperms. We conducted comparative analyses across Populus in order to elucidate variation in key genome features such as genome size, gene number, gene content, repeat type and number, SSR (Simple Sequence Repeat) abundance, and boundary positioning between the four main units of the genome. We found that some genome annotations were variable across the genus owing in part from errors in assembly or data checking and from this provided corrected annotations. We also employed complete chloroplast genomes for phylogenetic analyses including the dating of divergence times throughout the genus. Lastly, we utilized re-sequencing data to describe the variations of pan-chloroplast genomes at the population level for P. euphratica. The analyses used in this paper provide a blueprint for the types of analyses that can be conducted with publicly available chloroplast genomes as well as methods for building upon existing datasets to improve evolutionary inference

Nanoscale pore characteristics of the Jurassic Dongyuemiao member lacustrine shale, Eastern Sichuan Basin, SW China: Insights from SEM, NMR, LTNA, and MICP experiments

The Jurassic Dongyuemiao Member is the most promising target for lacustrine shale gas exploration in Sichuan Basin. By integrating SEM, NMR, LTNA, and MICP experiments, and other basic measurements, the nanoscale pore category and structure and the corresponding controlling factors of Dongyuemiao lacustrine shale in Eastern Sichuan Basin are studied. The results denote that organic pores comprise primary pores within plant debris and secondary pores within bitumen. Inorganic pores are composed of intraparticle pores within calcite particles, intercrystalline pores between pyrite crystals, and interparticle pores between different minerals. The 4th Section lacustrine shale of Dongyuemiao Member has the best pore structure, exhibiting high organic pore proportion, large amounts of gas adsorption, and parallel plate-shaped pore morphology. Micropores (<2 nm) are the main contributors of the pore volume and surface area of Dongyuemiao lacustrine shale. Moreover, the enrichment of organic matter positively affects the formation of micropores and has no influence on the mesopore–macropore (>2 nm). Quartz does not significantly affect the nanoscale pore formation. The intraparticle pores within calcite particles constitute part of mesopore–macropore but not micropores. Clay minerals are conducive to the formation of micropores but play a negative role in the formation of mesopore–macropore

The chromosome-scale reference genome of black pepper provides insight into piperine biosynthesis

Black pepper (Piper nigrum), dubbed the ‘King of Spices’ and ‘Black Gold’, is one of the most widely used spices. Here, we present its reference genome assembly by integrating PacBio, 10x Chromium, BioNano DLS optical mapping, and Hi-C mapping technologies. The 761.2 Mb sequences (45 scaffolds with an N50 of 29.8 Mb) are assembled into 26 pseudochromosomes. A phylogenomic analysis of representative plant genomes places magnoliids as sister to the monocots-eudicots clade and indicates that black pepper has diverged from the shared Laurales-Magnoliales lineage approximately 180 million years ago. Comparative genomic analyses reveal specific gene expansions in the glycosyltransferase, cytochrome P450, shikimate hydroxycinnamoyl transferase, lysine decarboxylase, and acyltransferase gene families. Comparative transcriptomic analyses disclose berry-specific upregulated expression in representative genes in each of these gene families. These data provide an evolutionary perspective and shed light on the metabolic processes relevant to the molecular basis of species-specific piperine biosynthesis

Comprehensive transcriptional profiling of aging porcine liver

Background Aging is a major risk factor for the development of many diseases, and the liver, as the most important metabolic organ, is significantly affected by aging. It has been shown that the liver weight tends to increase in rodents and decrease in humans with age. Pigs have a genomic structure, with physiological as well as biochemical features that are similar to those of humans, and have therefore been used as a valuable model for studying human diseases. The molecular mechanisms of the liver aging of large mammals on a comprehensive transcriptional level remain poorly understood. The pig is an ideal model animal to clearly and fully understand the molecular mechanism underlying human liver aging. Methods In this study, four healthy female Yana pigs (an indigenous Chinese breed) were investigated: two young sows (180-days-old) and two old sows (8-years-old). High throughput RNA sequencing was performed to evaluate the expression profiles of messenger RNA, long non-coding RNAs, micro RNAs, and circular RNAs during the porcine liver aging process. Gene Ontology (GO) analysis was performed to investigate the biological functions of age-related genes. Results A number of age-related genes were identified in the porcine liver. GO annotation showed that up-regulated genes were mainly related to immune response, while the down-regulated genes were mainly related to metabolism. Moreover, several lncRNAs and their target genes were also found to be differentially expressed during liver aging. In addition, the multi-group cooperative control relationships and constructed circRNA-miRNA co-expression networks were assessed during liver aging. Conclusions Numerous age-related genes were identified and circRNA-miRNA co-expression networks that are active during porcine liver aging were constructed. These findings contribute to the understanding of the transcriptional foundations of liver aging and also provide further references that clarify human liver aging at the molecular level