排序方式: 共有105条查询结果,搜索用时 15 毫秒
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Ryan M. Bradley Darin Bloemberg Juan J. Aristizabal Henao Ashkan Hashemi Andrew S. Mitchell Val A. Fajardo Catherine Bellissimo Emily B. Mardian Eric Bombardier Marie-France Paré Katherine A. Moes Ken D. Stark A. Russell Tupling Joe Quadrilatero Robin E. Duncan 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(7):700-711
Lysophosphatidic acid acyltransferase (LPAAT) δ/acylglycerophosphate acyltransferase 4 is a mitochondrial enzyme and one of five homologues that catalyze the acyl-CoA-dependent synthesis of phosphatidic acid (PA) from lysophosphatidic acid. We studied skeletal muscle LPAATδ and found highest levels in soleus, a red oxidative fibre-type that is rich in mitochondria, and lower levels in extensor digitorum longus (EDL) (white glycolytic) and gastrocnemius (mixed fibre-type). Using Lpaatδ-deficient mice, we found no change in soleus or EDL mass, or in treadmill time-to-exhaustion compared to wildtype littermates. There was, however, a significant reduction in the proportion of type I and type IIA fibres in EDL but, surprisingly, not soleus, where these fibre-types predominate. Also unexpectedly, there was no impairment in force generation by EDL, but a significant reduction by soleus. Oxidative phosphorylation and activity of complexes I, I?+?II, III, and IV in soleus mitochondria was unchanged and therefore could not explain this effect. However, pyruvate dehydrogenase activity was significantly reduced in Lpaatδ?/? soleus and EDL. Analysis of cellular lipids indicated no difference in soleus triacylglycerol, but specific elevations in soleus PA and phosphatidylethanolamine levels, likely due to a compensatory upregulation of Lpaatβ and Lpaatε in Lpaatδ?/? mice. An anabolic effect for PA as an activator of skeletal muscle mTOR has been reported, but we found no change in serine 2448 phosphorylation, indicating reduced soleus force generation is unlikely due to the loss of mTOR activation by a specific pool of LPAATδ-derived PA. Our results identify an important role for LPAATδ in soleus and EDL. 相似文献
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Kathy Trieu Daisy H. Coyle Ashkan Afshin Bruce Neal Matti Marklund Jason H. Y. Wu 《PLoS medicine》2021,18(10)
BackgroundThe Australian Government recently established sodium targets for packaged foods to encourage voluntary reformulation to reduce population sodium consumption and related diseases. We modeled the health impact of Australia’s sodium reformulation targets and additional likely health gains if more ambitious, yet feasible sodium targets had been adopted instead.Methods and findingsUsing comparative risk assessment models, we estimated the averted deaths, incidence, and disability-adjusted life years (DALYs) from cardiovascular disease (CVD), chronic kidney disease (CKD) and stomach cancer after implementation of (a) Australia’s sodium targets (overall and by individual companies); (b) United Kingdom’s targets (that covers more product categories); and (c) an optimistic scenario (sales-weighted 25th percentile sodium content for each food category included in the UK program). We used nationally representative data to estimate pre- and post-intervention sodium intake, and other key data sources from the Global Burden of Disease study. Full compliance with the Australian government’s sodium targets could prevent approximately 510 deaths/year (95% UI, 335 to 757), corresponding to about 1% of CVD, CKD, and stomach cancer deaths, and prevent some 1,920 (1,274 to 2,600) new cases and 7,240 (5,138 to 10,008) DALYs/year attributable to these diseases. Over half (59%) of deaths prevented is attributed to reformulation by 5 market-dominant companies. Compliance with the UK and optimistic scenario could avert approximately an additional 660 (207 to 1,227) and 1,070 (511 to 1,856) deaths/year, respectively, compared to Australia’s targets. The main limitation of this study (like other modeling studies) is that it does not prove that sodium reformulation programs will prevent deaths and disease events; rather, it provides the best quantitative estimates and the corresponding uncertainty of the potential effect of the different programs to guide the design of policies.ConclusionsThere is significant potential to strengthen Australia’s sodium reformulation targets to improve its health impact. Promoting compliance by market-dominant food companies will be critical to achieving the potential health gains.Kathy Trieu and colleagues model the estimated health impact of sodium reformulation targets in Australia. 相似文献
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Ashkan Fakharzadeh Jiahui Zhang Christopher Roland Celeste Sagui 《Nucleic acids research》2022,50(9):4860
The expansion of d(CGG) trinucleotide repeats (TRs) lies behind several important neurodegenerative diseases. Atypical DNA secondary structures have been shown to trigger TR expansion: their characterization is important for a molecular understanding of TR disease. CD spectroscopy experiments in the last decade have unequivocally demonstrated that CGG runs adopt a left-handed Z-DNA conformation, whose features remain uncertain because it entails accommodating GG mismatches. In order to find this missing motif, we have carried out molecular dynamics (MD) simulations to explore all the possible Z-DNA helices that potentially form after the transition from B- to Z-DNA. Such helices combine either CpG or GpC Watson-Crick steps in Z-DNA form with GG-mismatch conformations set as either intrahelical or extrahelical; and participating in BZ or ZZ junctions or in alternately extruded conformations. Characterization of the stability and structural features (especially overall left-handedness, higher-temperature and steered MD simulations) identified two novel Z-DNA helices: the most stable one displays alternately extruded Gs, and is followed by a helix with symmetrically extruded ZZ junctions. The G-extrusion favors a seamless stacking of the Watson-Crick base pairs; extruded Gs favor syn conformations and display hydrogen-bonding and stacking interactions. Such conformations could have the potential to hijack the MMR complex, thus triggering further expansion. 相似文献
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Mousavi Seyedeh Zahra Rahmanian Mojdeh Sami Ashkan 《Functional & integrative genomics》2022,22(3):429-433
Functional & Integrative Genomics - Although extrapulmonary manifestations of coronavirus disease 2019 (COVID-19) are increasingly reported, no effective therapeutic strategy for these... 相似文献
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We propose and study an augmented variant of the estimator proposed by Wang, Tchetgen Tchetgen, Martinussen, and Vansteelandt. 相似文献
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Nazari Soltan Ahmad Saeed Kalantary-Charvadeh Ashkan Hamzavi Masoud Ezzatifar Fatemeh Aboutalebi Vand Beilankouhi Elmira Toofani-Milani Attabak Geravand Faezeh Golshadi Zakieh Mesgari-Abbasi Mehran 《Journal of molecular histology》2022,53(4):691-698
Journal of Molecular Histology - Renal fibrosis is characterized by accumulation of extracellular matrix components and collagen deposition. TGF-β1 acts as a master switch promoting renal... 相似文献
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Sanjay Sarin Ashkan Javidan Felix Boivin Iakovina Alexopoulou Dusan Lukic Bruno Svajger Stephanie Chu Alireza Baradaran-Heravi Cornelius F. Boerkoel Norman D. Rosenblum Darren Bridgewater 《The journal of histochemistry and cytochemistry》2015,63(1):32-44
Schimke immuno-osseous dysplasia (SIOD) is a pleiotropic disorder caused by mutations in the SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like-1 (SMARCAL1) gene, with multiple clinical features, notably end-stage renal disease. Here we characterize the renal pathology in SIOD patients. Our analysis of SIOD patient renal biopsies demonstrates the tip and collapsing variants of focal segmental glomerulosclerosis (FSGS). Additionally, electron microscopy revealed numerous glomerular abnormalities most notably in the podocyte and Bowman’s capsule. To better understand the role of SMARCAL1 in the pathogenesis of FSGS, we defined SMARCAL1 expression in the developing and mature kidney. In the developing fetal kidney, SMARCAL1 is expressed in the ureteric epithelium, stroma, metanephric mesenchyme, and in all stages of the developing nephron, including the maturing glomerulus. In postnatal kidneys, SMARCAL1 expression is localized to epithelial tubules of the nephron, collecting ducts, and glomerulus (podocytes and endothelial cells). Interestingly, not all cells within the same lineage expressed SMARCAL1. In renal biopsies from SIOD patients, TUNEL analysis detected marked increases in DNA fragmentation. Our results highlight the cells that may contribute to the renal pathogenesis in SIOD. Further, we suggest that disruptions in genomic integrity during fetal kidney development contribute to the pathogenesis of FSGS in SIOD patients. 相似文献
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