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601.
602.
SCA8 RAN polySer protein preferentially accumulates in white matter regions and is regulated by eIF3F 下载免费PDF全文
Hannah K Shorrock Tao Zu Monica Banez‐Coronel Tammy Reid Hirokazu Furuya H Brent Clark Juan C Troncoso Christopher A Ross SH Subramony Tetsuo Ashizawa Eric T Wang Anthony T Yachnis Laura PW Ranum 《The EMBO journal》2018,37(19)
Spinocerebellar ataxia type 8 (SCA8) is caused by a bidirectionally transcribed CTG·CAG expansion that results in the in vivo accumulation of CUG RNA foci, an ATG‐initiated polyGln and a polyAla protein expressed by repeat‐associated non‐ATG (RAN) translation. Although RAN proteins have been reported in a growing number of diseases, the mechanisms and role of RAN translation in disease are poorly understood. We report a novel toxic SCA8 polySer protein which accumulates in white matter (WM) regions as aggregates that increase with age and disease severity. WM regions with polySer aggregates show demyelination and axonal degeneration in SCA8 human and mouse brains. Additionally, knockdown of the eukaryotic translation initiation factor eIF3F in cells reduces steady‐state levels of SCA8 polySer and other RAN proteins. Taken together, these data show polySer and WM abnormalities contribute to SCA8 and identify eIF3F as a novel modulator of RAN protein accumulation. 相似文献
603.
Xiao-Qin Luo Jia-Xi Duan Hui-Hui Yang Chen-Yu Zhang Chen-Chen Sun Xin-Xin Guan Jian-Bing Xiong Cheng Zu Jia-Hao Tao Yong Zhou Cha-Xiang Guan 《Journal of cellular physiology》2020,235(12):9910-9921
Epoxyeicosatrienoic acids (EETs) derived from arachidonic acid exert anti-inflammation effects. We have reported that blocking the degradation of EETs with a soluble epoxide hydrolase (sEH) inhibitor protects mice from lipopolysaccharide (LPS)-induced acute lung injury (ALI). The underlying mechanisms remain essential questions. In this study, we investigated the effects of EETs on the activation of nucleotide-binding domain leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3) inflammasome in murine macrophages. In an LPS-induced ALI murine model, we found that sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl), TPPU, profoundly attenuated the pathological injury and inhibited the activation of the NLRP3 inflammasome, characterized by the reduction of the protein expression of NLRP3, ASC, pro-caspase-1, interleukin precursor (pro-IL-1β), and IL-1β p17 in the lungs of LPS-treated mice. In vitro, primary peritoneal macrophages from C57BL/6 were primed with LPS and activated with exogenous adenosine triphosphate (ATP). TPPU treatment remarkably reduced the expression of NLRP3 inflammasome-related molecules and blocked the activation of NLRP3 inflammasome. Importantly, four EETs (5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET) inhibited the activation of NLRP3 inflammasome induced by LPS + ATP or LPS + nigericin in macrophages in various degree. While the inhibitory effect of 5,6-EET was the weakest. Mechanismly, EETs profoundly decreased the content of reactive oxygen species (ROS) and restored the calcium overload in macrophages receiving LPS + ATP stimulation. In conclusion, this study suggests that EETs inhibit the activation of the NLRP3 inflammasome by suppressing calcium overload and ROS production in macrophages, contributing to the therapeutic potency to ALI. 相似文献
604.
In the present study, the changes of the regulatory T cells (Treg) expression, endotoxin translocation, and the relationships in intestinal lymph nodes were investigated in porcine sepsis induced by severe burns. Flow cytometry, western blot, and Tachypleus amebocyte lysate were applied to study after the burn injury model was built. We found that the upregulated Treg expression was negatively related to the CD3+CD4+/CD3+CD8+ ratio (r = ?0.832, P < 0.05) after burn injury-induced sepsis. While Treg expression and portal venous plasma endotoxin translocation levels were positively correlated (r = 0.876, P < 0.05) when compared with the control group. Moreover, we detected a transforming of T cell subsets from T helper 1 cells to T helper 2 cells. Therefore, intestinal Treg cells expression exerts immunosuppressive effects on other intestinal T lymphocytes and was closely related to endotoxin translocation in porcine sepsis after severe burns injuries. Above all, the intestinal Treg cells may play an important role in the intestinal immune barrier system after severe burns injuries. 相似文献
605.
Sjoerd P Niehof Frank JPM Huygen Rick WP van der Weerd Mirjam Westra Freek J Zijlstra 《Biomedical engineering online》2006,5(1):30
Background
Complex Regional Pain Syndrome type 1 (CRPS1) is a clinical diagnosis based on criteria describing symptoms of the disease. 相似文献606.
Background
Many in vitro studies have demonstrated that silencing of cancerous genes by siRNAs is a potential therapeutic approach for blocking tumor growth. However, siRNAs are not cell type-selective, cannot specifically target tumor cells, and therefore have limited in vivo application for siRNA-mediated gene therapy. 相似文献607.
Orlando Schwery Breanna N. Sipley Mariana P. Braga Yan Yang Roberto Rebollo Pengjuan Zu 《植物分类学报:英文版》2023,61(3):465-486
The astonishing diversity of plants and insects and their entangled interactions are cornerstones in terrestrial ecosystems. Co-occurring with species diversity is the diversity of plant secondary metabolites (PSMs). So far, their estimated number is more than 200 000 compounds, which are not directly involved in plant growth and development but play important roles in helping plants handle their environment including the mediation of plant–insect interactions. Here, we use plant volatile organic compounds (VOCs), a key olfactory communication channel that mediates plant–insect interactions, as a showcase of PSMs. In spite of the cumulative knowledge of the functional, ecological, and microevolutionary roles of VOCs, we still lack a macroevolutionary understanding of how they evolved with plant–insect interactions and contributed to species diversity throughout the long coevolutionary history of plants and insects. We first review the literature to summarize the current state-of-the-art research on this topic. We then present various relevant types of phylogenetic methods suitable to answer macroevolutionary questions on plant VOCs and suggest future directions for employing phylogenetic approaches in studying plant VOCs and plant–insect interactions. Overall, we found that current studies in this field are still very limited in their macroevolutionary perspective. Nevertheless, with the fast-growing development of metabolome analysis techniques and phylogenetic methods, it is becoming increasingly feasible to integrate the advances of these two areas. We highlight promising approaches to generate new testable hypotheses and gain a mechanistic understanding of the macroevolutionary roles of chemical communication in plant–insect interactions. 相似文献
608.
Lin Lin Si‐Hui Zhong Xiao‐Feng Cui Jianming Li Zu‐Hua He 《The Plant journal : for cell and molecular biology》2012,72(5):707-720
The balance between cell proliferation and cell differentiation is essential for leaf patterning. However, identification of the factors coordinating leaf patterning and cell growth behavior is challenging. Here, we characterized a temperature‐sensitive Arabidopsis mutant with leaf blade and venation defects. We mapped the mutation to the sub‐2 allele of the SCRAMBLED/STRUBBELIG (SCM/SUB) receptor‐like kinase gene whose functions in leaf development have not been demonstrated. The sub‐2 mutant displayed impaired blade development, asymmetric leaf shape and altered venation patterning under high ambient temperature (30°C), but these defects were less pronounced at normal growth temperature (22°C). Loss of SCM/SUB function results in reduced cell proliferation and abnormal cell expansion, as well as altered auxin patterning. SCM/SUB is initially expressed throughout leaf primordia and becomes restricted to the vascular cells, coinciding with its roles in early leaf patterning and venation formation. Furthermore, constitutive expression of the SCM/SUB gene also restricts organ growth by inhibiting the transition from cell proliferation to expansion. We propose the existence of a SCM/SUB‐mediated developmental stage‐specific signal for leaf patterning, and highlight the importance of the balance between cell proliferation and differentiation for leaf morphogenesis. 相似文献
609.
Yong Feng Zhou Richard J. Abbott Zu Yao Jiang Fang K. Du Richard I. Milne Jian Quan Liu 《Evolution; international journal of organic evolution》2010,64(8):2342-2352
Species delimitation detected by molecular markers is complicated by introgression and incomplete lineage sorting between species. Recent modeling suggests that fixed genetic differences between species are highly related to rates of intraspecific gene flow. However, it remains unclear whether such differences are due to high levels of intraspecific gene flow overriding the spread of introgressed alleles or favoring rapid lineage sorting between species. In pines, chloroplast (cp) and mitochondrial (mt) DNAs are normally paternally and maternally inherited, respectively, and thus their relative rates of intraspecific gene flow are expected to be high and low, respectively. In this study, we used two pine species with overlapping geographical distributions in southeast China, P. massoniana and P. hwangshanensis, as a model system to examine the association between organelle gene flow and variation within and between species. We found that cpDNA variation across these two pine species is more species specific than mtDNA variation and almost delimits taxonomic boundaries. The shared mt/cp DNA genetic variation between species shows no bias in regard to parapatric versus allopatric species’ distributions. Our results therefore support the hypothesis that high intraspecific gene flow has accelerated cpDNA lineage sorting between these two pine species. 相似文献
610.
Dimethyl sulfide protects against oxidative stress and extends lifespan via a methionine sulfoxide reductase A‐dependent catalytic mechanism 下载免费PDF全文
Xin‐Lei Guan Peng‐Fei Wu Sheng Wang Juan‐Juan Zhang Zu‐Cheng Shen Han Luo Hao Chen Li‐Hong Long Jian‐Guo Chen Fang Wang 《Aging cell》2017,16(2):226-236
Methionine (Met) sulfoxide reductase A (MsrA) is a key endogenous antioxidative enzyme with longevity benefits in animals. Only very few approaches have been reported to enhance MsrA function. Recent reports have indicated that the antioxidant capability of MsrA may involve a Met oxidase activity that facilities the reaction of Met with reactive oxygen species (ROS). Herein, we used a homology modeling approach to search the substrates for the oxidase activity of MsrA. We found that dimethyl sulfide (DMS), a main metabolite that produced by marine algae, emerged as a good substrate for MsrA‐catalytic antioxidation. MsrA bounds to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72, Tyr103, and Glu115, followed by the release of dimethyl sulfoxide (DMSO). DMS reduced the antimycin A‐induced ROS generation in cultured PC12 cells and alleviated oxidative stress. Supplement of DMS exhibited cytoprotection and extended longevity in both Caenorhabditis elegans and Drosophila. MsrA knockdown abolished the cytoprotective effect and the longevity benefits of DMS. Furthermore, we found that the level of physiologic DMS was at the low micromolar range in different tissues of mammals and its level decreased after aging. This study opened a new window to elucidate the biological role of DMS and other low‐molecular sulfides in the cytoprotection and aging. 相似文献