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The objective is to characterize differentially expressed proteins (DEPs) in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) through high-throughput analysis. Sera from 11 healthy controls (HCs), 21 GBS and 19 CIDP patients were subjected to Olink Proteomics Analysis. In the comparison between CIDP and GBS groups, up-regulation of ITM2A and down-regulation of NTF4 were observed. Comparing GBS with HCs revealed 18 up-regulated and 4 down-regulated proteins. Comparing CIDP with the HCs identified 15 up-regulated and 4 down-regulated proteins. Additionally, the correlation between clinical characteristics and DEPs were uncovered. In conclusion, the DEPs have significant potential to advance our understanding of the pathogenesis in these debilitating neurological disorders.
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Spinocerebellar ataxia is a phenotypically and genetically heterogeneous group of autosomal dominant-inherited degenerative disorders. The gene mutation spectrum includes dynamic expansions, point mutations, duplications, insertions, and deletions of varying lengths. Dynamic expansion is the most common form of mutation. Mutations often result in indistinguishable clinical phenotypes, thus requiring validation using multiple genetic testing techniques. Depending on the type of mutation, the pathogenesis may involve proteotoxicity, RNA toxicity, or protein loss-of-function. All of which may disrupt a range of cellular processes, such as impaired protein quality control pathways, ion channel dysfunction, mitochondrial dysfunction, transcriptional dysregulation, DNA damage, loss of nuclear integrity, and ultimately, impairment of neuronal function and integrity which causes diseases. Many disease-modifying therapies, such as gene editing technology, RNA interference, antisense oligonucleotides, stem cell technology, and pharmacological therapies are currently under clinical trials. However, the development of curative approaches for genetic diseases remains a global challenge, beset by technical, ethical, and other challenges. Therefore, the study of the pathogenesis of spinocerebellar ataxia is of great importance for the sustained development of disease-modifying molecular therapies.
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Environmental stress at high altitudes drives the development of distinct adaptive mechanisms in plants. However, studies exploring the genetic adaptive mechanisms of high-altitude plant species are scarce. In the present study, we explored the high-altitude adaptive mechanisms of plants in the Himalayas through whole-genome resequencing. We studied two widespread members of the Himalayan endemic alpine genus Roscoea (Zingiberaceae): R. alpina (a selfing species) and R. purpurea (an outcrossing species). These species are distributed widely in the Himalayas with distinct non-overlapping altitude distributions; R. alpina is distributed at higher elevations, and R. purpurea occurs at lower elevations. Compared to R. purpurea, R. alpina exhibited higher levels of linkage disequilibrium, Tajima's D, and inbreeding coefficient, as well as lower recombination rates and genetic diversity. Approximately 96.3% of the genes in the reference genome underwent significant genetic divergence (FST ≥ 0.25). We reported 58 completely divergent genes (FST = 1), of which only 17 genes were annotated with specific functions. The functions of these genes were primarily related to adapting to the specific characteristics of high-altitude environments. Our findings provide novel insights into how evolutionary innovations promote the adaptation of mountain alpine species to high altitudes and harsh habitats.
Assuntos
Altitude , Zingiberaceae , Himalaia , Genômica , Evolução Biológica , Adaptação Fisiológica/genéticaRESUMO
Codon usage bias (CUB) refers to different codons exhibiting varying frequencies of usage in the genome. Studying CUB is crucial for understanding genome structure, function, and evolutionary processes. Herein, we investigated the codon usage patterns and influencing factors of protein-coding genes in the chloroplast genomes of four sister genera (monophyletic Roscoea and Cautleya, and monophyletic Pommereschea and Rhynchanthus) from the Zingiberaceae family with contrasting habitats in southwestern China. These genera exhibit distinct habitats, providing a unique opportunity to explore the adaptive evolution of codon usage. We conducted a comprehensive analysis of nucleotide composition and codon usage on protein-coding genes in the chloroplast genomes. The study focused on understanding the relationship between codon usage and environmental adaptation, with a particular emphasis on genes associated with photosynthesis. Nucleotide composition analysis revealed that the overall G/C content of the coding genes was Ë 48%, indicating an enrichment of A/T bases. Additionally, synonymous and optimal codons were biased toward ending with A/U bases. Natural selection is the primary factor influencing CUB characteristics, particularly photosynthesis-associated genes. We observed differential gene expressions related to light adaptation among sister genera inhabiting different environments. Certain codons were favored under specific conditions, possibly contributing to gene expression regulation in particular environments. This study provides insights into the adaptive evolution of these sister genera by analyzing CUB and offers theoretical assistance for understanding gene expression and regulation. In addition, the data support the relationship between RNA editing and CUB, and the findings shed light on potential research directions for investigating adaptive evolution.
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Immune thrombocytopenia (ITP) is a common acquired autoimmune hematological disorders. Platelet autoantibodies lead to the decrease of platelet production and (or) increase of its destruction. The latest researches showed that the abnormal tryptophan metabolism mediated by indoleamine-2, 3-dioxygenase(IDO) is related with the pathogenesis of ITP. The patients with ITP show less expression of IDO, reduction of Treg cells and increase of autoreactive T cells and autoantibodies. CTLA-4-Ig can improve the expression of IDO in the patients with ITP, which also can inhibit the proliferation and activation of self-reactive T cells. Thus, clarifying the abnormal tryptophan metabolism mediated by IDO may provide a new idea for improving the understand of the pathogenesis and treatment of ITP. This review focuses on reasearch progress of the tryptophan metabolism mediated by IDO and ITP.