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61.
SUMOylation of proteins is an important regulatory element in modulating protein function and has been implicated in the pathogenesis of numerous human diseases such as cancers, neurodegenerative diseases, brain injuries, diabetes, and familial dilated cardiomyopathy. Growing evidence has pointed to a significant role of SUMO in kidney diseases such as DN, RCC, nephritis, AKI, hypertonic stress and nephrolithiasis. Recently, emerging studies in podocytes demonstrated that SUMO might have a protective role against podocyte apoptosis. However, the SUMO code responsible for beneficial outcome in the kidney remains to be decrypted. Our recent experiments have revealed that the expression of both SUMO and SUMOylated proteins is appreciably elevated in hypoxia‐induced tubular epithelial cells (TECs) as well as in the unilateral ureteric obstruction (UUO) mouse model, suggesting a role of SUMO in TECs injury and renal fibrosis. In this review, we attempt to decipher the SUMO code in the development of kidney diseases by summarizing the defined function of SUMO and looking forward to the potential role of SUMO in kidney diseases, especially in the pathology of renal fibrosis and CKD, with the goal of developing strategies that maximize correct interpretation in clinical therapy and prognosis. 相似文献
62.
Phosphoinositides are a group of phospholipids whose inositol headgroups can be phosphorylated at three distinct positions thereby generating seven different isotypes. The conversion between these lipid species depends on the activity of specific sets of phosphoinositide kinases and phosphatases whose targeting and activity is critical to establish the landscape of phosphoinositides on the cytosol-facing hemi-membrane of all organelles and plasmalemma. Phosphoinositides play pleiotropic roles ranging from signalling and membrane trafficking to modulation of ion channels and survival. In neurons and neurosecretory cells, whose main function is to communicate through the release of neurotransmitter, most of the work has focused on the role played by phosphatidylinositol (4,5) bisphosphate in controlling the mechanism underpinning neurotransmitter release through the fusion of secretory vesicles with the plasmalemma. Emerging evidence supports a multi-faceted regulation of neuroexocytosis by 3-phosphorylated phosphoinositides. In this review, we summarise the molecular mechanism by which these lipids control exocytosis and how minute changes in their metabolism can have devastating effects in the nervous system and lead to neurodegeneration. 相似文献
63.
Evidence for long-distance dispersal in a sedentary passerine, Gymnorhina tibicen (Artamidae) 总被引:1,自引:0,他引:1
ANDREW M. BAKER PETER B. MATHER JANE M. HUGHES 《Biological journal of the Linnean Society. Linnean Society of London》2001,72(2):333-343
Australian magpies (Gymnorhina tibicen) are group-living birds found across much of mainland Australia. Adults commonly remain in a breeding territory until death. Young of the year either remain on the natal (birth) site or are forced by their parents to disperse. Observational studies in south-eastern Australia suggest that most dispersing juveniles settle within 7 km of their natal territory. Therefore, despite potential for considerable gene flow (via flight), social organization predisposes magpies towards local population structuring. In this study, we measured genetic variation at both nuclear (allozyme) and mitochondrial loci and found evidence of substantial gene flow over very large distances (up to 1599 km). Thus, some juvenile magpies may disperse much greater distances than was previously thought. For mtDNA, geographic and genetic distance were strongly correlated, consistent with a pattern of isolation by distance. Therefore, although female gene flow is substantial it is apparently geographically restricted over large distances, in approximately a stepping-stone fashion. We conclude that a strong relationship between gene flow and geographic distance can develop even over large distances if populations have experienced no major historical disturbances to gene flow. 相似文献
64.
Maria C Romay Mark J Millard Jeffrey C Glaubitz Jason A Peiffer Kelly L Swarts Terry M Casstevens Robert J Elshire Charlotte B Acharya Sharon E Mitchell Sherry A Flint-Garcia Michael D McMullen James B Holland Edward S Buckler Candice A Gardner 《Genome biology》2013,14(6):R55
Background
Genotyping by sequencing, a new low-cost, high-throughput sequencing technology was used to genotype 2,815 maize inbred accessions, preserved mostly at the National Plant Germplasm System in the USA. The collection includes inbred lines from breeding programs all over the world.Results
The method produced 681,257 single-nucleotide polymorphism (SNP) markers distributed across the entire genome, with the ability to detect rare alleles at high confidence levels. More than half of the SNPs in the collection are rare. Although most rare alleles have been incorporated into public temperate breeding programs, only a modest amount of the available diversity is present in the commercial germplasm. Analysis of genetic distances shows population stratification, including a small number of large clusters centered on key lines. Nevertheless, an average fixation index of 0.06 indicates moderate differentiation between the three major maize subpopulations. Linkage disequilibrium (LD) decays very rapidly, but the extent of LD is highly dependent on the particular group of germplasm and region of the genome. The utility of these data for performing genome-wide association studies was tested with two simply inherited traits and one complex trait. We identified trait associations at SNPs very close to known candidate genes for kernel color, sweet corn, and flowering time; however, results suggest that more SNPs are needed to better explore the genetic architecture of complex traits.Conclusions
The genotypic information described here allows this publicly available panel to be exploited by researchers facing the challenges of sustainable agriculture through better knowledge of the nature of genetic diversity. 相似文献65.
Bone marrow mesenchymal stem cells (BMSC) can differentiate into diverse cell types, including adipogenic, osteogenic, chondrogenic and myogenic lineages. There are lots of BMSC accumulated in atherosclerosis vessels and differentiate into VSMC. However, it is unclear whether VSMC originated from BMSC (BMSC-SMC) could remodel the vessel in new tunica intima or promote the pathogenesis of atherosclerosis. In this study, BMSC were differentiated into VSMC in response to the transforming growth factor β (TGF-β) and shown to express a number of VSMC markers, such as α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain1 (SM-MHC1). BMSC-SMC became foam cells after treatment with 80 mg/L ox-LDL for 72 hours. Ox-LDL could upregulate scavenger receptor class A (SR-A) but downregulate the ATP-binding cassette transporter A1 (ABCA1) and caveolin-1 protein expression, suggesting that modulating relative protein activity contributes to smooth muscle foam cell formation in BMSC-SMC. Furthermore, we found that BMSC-SMC have some biological characteristics that are similar to VSMC, such as the ability of proliferation and secretion of extracellular matrix, but, at the same time, retain some biological characteristics of BMSC, such as a high level of migration. These results suggest that BMSC-SMC could be induced to foam cells and be involved in the development of atherosclerosis. 相似文献
66.
67.
二维斑点追踪技术评价犬心梗后自体骨髓CD34+干细胞移植对心肌功能的影响 总被引:1,自引:0,他引:1
目的应用二维斑点追踪成像超声心动图(2D-STE),评价犬心梗后自体骨髓CD34+干细胞移植对心肌功能的影响。方法 12只杂种犬行冠脉左前降支结扎术,导致前壁心肌梗死,随机分为两组,A组为对照组,结扎术后两周二次开胸手术,经心肌注射磷酸盐缓冲液(PBS)1 mL;B组为治疗组,结扎术后两周二次开胸手术,经心肌注射含自体骨髓CD34+干细胞的磷酸盐缓冲液1 mL。应用STE对12只犬结扎术前、术后左室短轴基底段及心尖段心室节段径向应变(RS)、圆周方向应变(CS)以及局部心肌旋转(Rot)进行分析,并对对照组和治疗组治疗后的RS、CS及Rot变化进行比较。结果心肌梗死后梗死节段的RS、CS以及Rot均下降,治疗后治疗组梗死段RS及Rot较对照组好转。结论 STE能够评价左室短轴局部心肌的收缩功能,心肌梗死后梗死段短轴各方向应变减低,自体骨髓CD34+干细胞移植能够提高局部心肌的收缩功能。 相似文献
68.
Dai Sik Ko Junho Kang Hye Jin Heo Eun Kyoung Kim Kihun Kim Jin Mo Kang YunJae Jung Seung Eun Baek Yun Hak Kim 《International journal of biological sciences》2022,18(13):5154
Vascular smooth muscle cell (VSMC) proliferation is a hallmark of neointimal hyperplasia (NIH) in atherosclerosis and restenosis post-balloon angioplasty and stent insertion. Although numerous cytotoxic and cytostatic therapeutics have been developed to reduce NIH, it is improbable that a multifactorial disease can be successfully treated by focusing on a preconceived hypothesis. We, therefore, aimed to identify key molecules involved in NIH via a hypothesis-free approach. We analyzed four datasets (, GSE28829, GSE43292, and GSE100927), evaluated differentially expressed genes (DEGs) in wire-injured femoral arteries of mice, and determined their association with VSMC proliferation in vitro. Moreover, we performed RNA sequencing on platelet-derived growth factor (PDGF)-stimulated human VSMCs (hVSMCs) post-phosphoenolpyruvate carboxykinase 2 (PCK2) knockdown and investigated pathways associated with PCK2. Finally, we assessed NIH formation in Pck2 knockout (KO) mice by wire injury and identified PCK2 expression in human femoral artery atheroma. Among six DEGs, only PCK2 and RGS1 showed identical expression patterns between wire-injured femoral arteries of mice and gene expression datasets. PDGF-induced VSMC proliferation was attenuated when hVSMCs were transfected with PCK2 siRNA. RNA sequencing of PCK2 siRNA-treated hVSMCs revealed the involvement of the Akt-FoxO-PCK2 pathway in VSMC proliferation via Akt2, Akt3, FoxO1, and FoxO3. Additionally, NIH was attenuated in the wire-injured femoral artery of Pck2-KO mice and PCK2 was expressed in human femoral atheroma. PCK2 regulates VSMC proliferation in response to vascular injury via the Akt-FoxO-PCK2 pathway. Targeting PCK2, a downstream signaling mediator of VSMC proliferation, may be a novel therapeutic approach to modulate VSMC proliferation in atherosclerosis. GSE120521相似文献
69.
Rogelio Zamilpa Elizabeth F. Lopez Ying Ann Chiao Qiuxia Dai Gladys P. Escobar Kevin Hakala Susan T. Weintraub Merry L. Lindsey 《Proteomics》2010,10(11):2214-2223
Matrix metalloproteinase‐9 (MMP‐9) deletion has been shown to improve remodeling of the left ventricle post‐myocardial infarction (MI), but the mechanisms to explain this improvement have not been fully elucidated. MMP‐9 has a broad range of in vitro substrates, but relevant in vivo substrates are incompletely defined. Accordingly, we evaluated the infarct regions of wild‐type (wt) and MMP‐9 null (null) mice using a proteomic strategy. Wt and null groups showed similar infarct sizes (48±3 in wt and 45±3% in null), indicating that both groups received an equal injury stimulus. Left ventricle infarct tissue was homogenized and analyzed by 2‐DE and MS. Of 31 spot intensity differences, the intensities of 9 spots were higher and 22 spots were lower in null mice compared to wt (all p<0.05). Several extracellular matrix proteins were identified in these spots by MS, including fibronectin, tenascin‐C, thrombospondin‐1, and laminin. Fibronectin was observed on the gels at a lower than expected molecular weight in the wt group, which suggested substrate cleavage, and the lower molecular weight spot was observed at lower intensity in the MMP‐9 null group, which suggested cleavage by MMP‐9. Immunoblotting confirmed the presence of fibronectin cleavage products in the wt samples and lower levels in the absence of MMP‐9. In conclusion, examining infarct tissue from wt and MMP‐9 null mice by proteomic analysis provides a powerful and unique method to identify in vivo candidate MMP substrates. 相似文献
70.
Various mutants (oxa
s
) were isolated from Serratia marcescens SM-6 by selecting for hypersensitivity towards oxacillin. All mutants found are highly pleiotropic and able to yield spontaneous revertants which behave like the wild-type. Mutant W 1421 mostly studied shows the following phenotypic properties not found in the wild-type: (1) The growth is hypersensitive to various antibiotics, detergents and dyes which differ remarkably in their chemical structure and antibacterial action-mechanism, (2) the cells can be easily solubilized by 0.05% Sodium-dodecylsulfate, (3) the cells allow the adsorption of the roughmutant specific Salmonella phage 6SR, (4) strong cellular binding of crystal violet, (5) agglutination of the cells in 0.3% auramin solution and (6) reduced formation of red pigment. Strain W 1421 is assumed to be a lipopolysaccharide-defective mutant. The outer membrane of mutant W 1421 analyzed by Sodiumdodecylsulfate-polyacrylamide gel electrophoresis possesses a single protein less than that of the wild-type. Mutant W 1421 is further characterized by its low exolipase activity; exoprotease and exonuclease activities are as in the wild-type. This specific exoenzyme deficiency can be overcome either by backmutation to oxacillin-resistance or by growing mutant W 1421 in a medium supplemented with certain non-metabolizable polysaccharides, e.g. glycogen or pectin B. Both polysaccharides increase the exolipase activity of the wild-type too.List of Abbreviations amp
ampicillin
- LPS
lipopolysaccharide
- MIC
minimal inhibitory concentration
- NB
nutrient broth
- oxa
oxacillin
- str
streptomycin
- TBY
tryptone broth with yeast extract
- SDS
sodium-dodecylsulfate
- OD
optical density
This paper is dedicated to Prof. Dr. R. W. Kaplan, University of Frankfurt/M., on the occasion of his 65th birthday 相似文献