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Afagh Alavi Shahriar Nafissi Mohammad Rohani Babak Zamani Behnaz Sedighi Hosein Shamshiri Jian-Bing Fan Mostafa Ronaghi Elahe Elahi 《Neurobiology of aging》2013,34(5):1516.e1-1516.e8
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, and the most common in European populations. Results of genetic analysis and mutation screening of SOD1 in a cohort of 60 Iranian ALS patients are here reported. Initially, linkage analysis in 4 families identified a disease-linked locus that included the known ALS gene, SOD1. Screening of SOD1 identified homozygous p.Asp90Ala causing mutations in all the linked families. Haplotype analysis suggests that the p.Asp90Ala alleles in the Iranian patients might share a common founder with the renowned Scandinavian recessive p.Asp90Ala allele. Subsequent screening in all the patients resulted in identification of 3 other mutations in SOD1, including p.Leu84Phe in the homozygous state. Phenotypic features of the mutation-bearing patients are presented. SOD1 mutations were found in 11.7% of the cohort, 38.5% of the familial ALS probands, and 4.25% of the sporadic ALS cases. SOD1 mutations contribute significantly to ALS among Iranians. 相似文献
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p63 regulates proliferation and differentiation of developmentally mature keratinocytes 总被引:1,自引:0,他引:1 下载免费PDF全文
p63 is a multi-isoform p53 family member required for epidermal development. Contrasting roles for p63 in either the initial commitment to the stratified epithelial cell fate or in stem cell-based self-renewal have been proposed. To investigate p63 function in a post-developmental context, we used siRNAs directed against p63 to down-regulate p63 expression in regenerating human epidermis. Loss of p63 resulted in severe tissue hypoplasia and inhibited both stratification and differentiation in a cell-autonomous manner. Although p63-deficient cells exhibited hypoproliferation, differentiation defects were not due to tissue hypoplasia. Simultaneous p63 and p53 knockdown rescued the cell proliferation defect of p63 knockdown alone but failed to restore differentiation, suggesting that defects in epidermal proliferation and differentiation are mediated via p53-dependent and -independent mechanisms, respectively. Furthermore, DeltaNp63 isoforms are the main mediators of p63 effects, although TAp63 isoforms may contribute to late differentiation. These data indicate that p63 is required for both the proliferative and differentiation potential of developmentally mature keratinocytes. 相似文献
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Sustainable correction of severe human genetic disorders of self-renewing tissues, such as the blistering skin disease junctional epidermolysis bullosa (JEB), is facilitated by stable genomic integration of therapeutic genes into somatic tissue stem cells. While integrating viral vectors can achieve this, they suffer from logistical and biosafety concerns. To circumvent these limitations, we used the Sleeping Beauty transposable element to integrate the LAMB3 cDNA into genomes of epidermal holoclones from six unrelated JEB patients. These cells regenerate human JEB skin that is normalized at the level of laminin 5 protein expression, hemidesmosome formation and blistering. Transposon-mediated gene delivery therefore affords an opportunity for stable gene delivery in JEB and other human diseases. 相似文献
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Fatemeh Haidari Behnaz Abiri Masood Iravani Seyyed-Mohsen Razavi 《Nutrition and cancer》2019,71(5):709-717
The solar ultraviolet B–vitamin D-cancer hypothesis was first suggested in 1980 based on a geographical ecological study. Since then, several ecological and observational studies, as well as researches of mechanisms have supported the hypothesis. Also, the association between vitamin D condition and cancer risk has been assessed in a number of epidemiologic studies, while data from interventional studies remain scant. In regard of cancer locations, the body of evidence is most substantial for colorectal cancer, for which support comes from studies of 25(OH)D, vitamin D intake, and region of residence in a sunny weather. Collectively evidence demonstrates that vitamin D has a potent and beneficial effect at antagonizing and blocking several mitogenic mechanisms related to tumorigenesis. Taken together with the epidemiological studies and limited clinical trials, individuals may need to consider elevating 25(OH)D levels via sun exposure and/or vitamin D supplementation to decrease risk of colorectal cancer, in addition to standard care, treat cancer. 相似文献
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