排序方式: 共有198条查询结果,搜索用时 15 毫秒
21.
The structure and function of the PTEN phosphatase is investigated by studying its membrane affinity and localization on in-plane fluid, thermally disordered synthetic membrane models. The membrane association of the protein depends strongly on membrane composition, where phosphatidylserine (PS) and phosphatidylinositol diphosphate (PI(4,5)P2) act pronouncedly synergistic in pulling the enzyme to the membrane surface. The equilibrium dissociation constants for the binding of wild type (wt) PTEN to PS and PI(4,5)P2 were determined to be Kd∼12 µM and 0.4 µM, respectively, and Kd∼50 nM if both lipids are present. Membrane affinities depend critically on membrane fluidity, which suggests multiple binding sites on the protein for PI(4,5)P2. The PTEN mutations C124S and H93R show binding affinities that deviate strongly from those measured for the wt protein. Both mutants bind PS more strongly than wt PTEN. While C124S PTEN has at least the same affinity to PI(4,5)P2 and an increased apparent affinity to PI(3,4,5)P3, due to its lack of catalytic activity, H93R PTEN shows a decreased affinity to PI(4,5)P2 and no synergy in its binding with PS and PI(4,5)P2. Neutron reflection measurements show that the PTEN phosphatase “scoots" along the membrane surface (penetration <5 Å) but binds the membrane tightly with its two major domains, the C2 and phosphatase domains, as suggested by the crystal structure. The regulatory C-terminal tail is most likely displaced from the membrane and organized on the far side of the protein, ∼60 Å away from the bilayer surface, in a rather compact structure. The combination of binding studies and neutron reflection allows us to distinguish between PTEN mutant proteins and ultimately may identify the structural features required for membrane binding and activation of PTEN. 相似文献
22.
Christoph J. Meinrenken Scott M. Kaufman Siddharth Ramesh Klaus S. Lackner 《Journal of Industrial Ecology》2012,16(5):669-679
Publicly Available Specification 2050‐2011 (PAS 2050), the Green House Gas Product Protocol (GHGPP) standard and forthcoming guideline 14067 from the International Organization for Standardization (ISO) have helped to propel carbon footprinting from a subdiscipline of life cycle assessment (LCA) to the mainstream. However, application of carbon footprinting to large portfolios of many distinct products and services is immensely resource intensive. Even if achieved, it often fails to inform company‐wide carbon reduction strategies because footprint data are disjointed or don't cover the whole portfolio. We introduce a novel approach to generate standard‐compliant product carbon footprints (CFs) for companies with large portfolios at a fraction of previously required time and expertise. The approach was developed and validated on an LCA dataset covering 1,137 individual products from a global packaged consumer goods company. Three novel techniques work in concert in a single approach that enables practitioners to calculate thousands of footprints virtually simultaneously: (i) a uniform data structure enables footprinting all products and services by looping the same algorithm; (ii) concurrent uncertainty analysis guides practitioners to gradually improve the accuracy of only those data that materially impact the results; and (iii) a predictive model generates estimated emission factors (EFs) for materials, thereby eliminating the manual mapping of a product or service's inventory to EF databases. These autogenerated EFs enable non‐LCA experts to calculate approximate CFs and alleviate resource constraints for companies embarking on large‐scale product carbon footprinting. We discuss implementation roadmaps for companies, including further road‐testing required to evaluate the effectiveness of the approach for other product portfolios, limitations, and future improvements of the fast footprinting methodology. 相似文献
23.
Thrombospondin-1 interacts with Trypanosoma cruzi surface calreticulin to enhance cellular infection
CA Johnson YY Kleshchenko AO Ikejiani AN Udoko TC Cardenas S Pratap MA Duquette MF Lima J Lawler F Villalta PN Nde 《PloS one》2012,7(7):e40614
Trypanosoma cruzi causes Chagas disease, which is a neglected tropical disease that produces severe pathology and mortality. The mechanisms by which the parasite invades cells are not well elucidated. We recently reported that T. cruzi up-regulates the expression of thrombospondin-1 (TSP-1) to enhance the process of cellular invasion. Here we characterize a novel TSP-1 interaction with T. cruzi that enhances cellular infection. We show that labeled TSP-1 interacts specifically with the surface of T. cruzi trypomastigotes. We used TSP-1 to pull down interacting parasite surface proteins that were identified by mass spectrometry. We also show that full length TSP-1 and the N-terminal domain of TSP-1 (NTSP) interact with T. cruzi surface calreticulin (TcCRT) and other surface proteins. Pre-exposure of recombinant NTSP or TSP-1 to T. cruzi significantly enhances cellular infection of wild type mouse embryo fibroblasts (MEF) compared to the C-terminal domain of TSP-1, E3T3C1. In addition, blocking TcCRT with antibodies significantly inhibits the enhancement of cellular infection mediated by the TcCRT-TSP-1 interaction. Taken together, our findings indicate that TSP-1 interacts with TcCRT on the surface of T. cruzi through the NTSP domain and that this interaction enhances cellular infection. Thus surface TcCRT is a virulent factor that enhances the pathogenesis of T. cruzi infection through TSP-1, which is up-regulated by the parasite. 相似文献
24.
Nayden G. Naydenov Supriya Joshi Alex Feygin Siddharth Saini Larisa Litovchick 《Cell cycle (Georgetown, Tex.)》2018,17(14):1812-1831
Vesicle trafficking regulates epithelial cell migration by remodeling matrix adhesions and delivering signaling molecules to the migrating leading edge. Membrane fusion, which is driven by soluble N-ethylmaleimide-sensitive factor associated receptor (SNARE) proteins, is an essential step of vesicle trafficking. Mammalian SNAREs represent a large group of proteins, but few have been implicated in the regulation of cell migration. Ykt6 is a unique SNARE existing in equilibrium between active membrane-bound and inactive cytoplasmic pools, and mediating vesicle trafficking between different intracellular compartments. The biological functions of this protein remain poorly understood. In the present study, we found that Ykt6 acts as a negative regulator of migration and invasion of human prostate epithelial cells. Furthermore, Ykt6 regulates the integrity of epithelial adherens and tight junctions. The observed anti-migratory activity of Ykt6 is mediated by a unique mechanism involving the expressional upregulation of microRNA 145, which selectively decreases the cellular level of Junctional Adhesion Molecule (JAM) A. This decreased JAM-A expression limits the activity of Rap1 and Rac1 small GTPases, thereby attenuating cell spreading and motility. The described novel functions of Ykt6 could be essential for the regulation of epithelial barriers, epithelial repair, and metastatic dissemination of cancer cells. 相似文献
25.
Dong-chuan Guo Ellen S. Regalado Amelie Pinard Jiyuan Chen Kwanghyuk Lee Christina Rigelsky Lior Zilberberg Ellen M. Hostetler Micheala Aldred Stephanie E. Wallace Siddharth K. Prakash Suzanne M. Leal Michael J. Bamshad Deborah A. Nickerson Marvin Natowicz Daniel B. Rifkin Dianna M. Milewicz 《American journal of human genetics》2018,102(4):706-712
26.
Víctor Faundes William G. Newman Laura Bernardini Natalie Canham Jill Clayton-Smith Bruno Dallapiccola Sally J. Davies Michelle K. Demos Amy Goldman Harinder Gill Rachel Horton Bronwyn Kerr Dhavendra Kumar Anna Lehman Shane McKee Jenny Morton Michael J. Parker Julia Rankin Siddharth Banka 《American journal of human genetics》2018,102(1):175-187
27.
Ankita Kumari Charu Bahl Navneet Singh Digambar Behera Siddharth Sharma 《Molecular biology reports》2016,43(12):1383-1394
p53 helps in maintaining genomic stability by undergoing cellular arrest, DNA repair or cellular apoptosis during DNA damage. So, as to find the association of p53Arg 72 Pro towards lung carcinogenesis and overall survival of North Indian lung cancer patients, single nucleotide polymorphic variant (rs1042522) was analyzed. 840 subjects including 420 cases and 420 controls were recruited and genotyped using PCR-RFLP technique for p53Arg 72 Pro polymorphic site. Association was analyzed using adjusted odds ratio along with its confidence intervals (95?% CI) and p value predicted from logistic regression whereas overall survival for lung cancer patients was obtained using Kaplan–Meir and Cox regression model for different parameters to obtain hazard ratio and survival time with statistical significance (log-rank p value). None of the variant genotypes for p53Arg 72 Pro showed any association towards lung cancer risk or any specific histological subtype. Lung cancer subjects with Pro/Pro genotype had better median survival time as compared to Arg/Pro genotype (10 months; HR?=?0.65; 95?% CI?=?0.45–0.95; p?=?0.03). Furthermore, female lung cancer patients with Arg/Pro (HR?=?0.08; 95?% CI?=?0.02–0.34; p?=?0.0005) and Pro/Pro (HR?=?0.21; 95?% CI?=?0.06–0.67; p?=?0.008) genotypes showed a better overall survival and hence a better prognosis as compared to males. Our data also reveals that lung cancer patients with ECOG scores between 0 and 1 and carrying the Pro/Pro had better chances of survival. p53 codon 72 polymorphism could play a role as a prognostic marker in lung cancer patients. 相似文献
28.
We hereby report studies that suggest a role for serum exosomes in the anchorage-independent growth (AIG) of tumor cells. In AIG assays, fetal bovine serum is one of the critical ingredients. We therefore purified exosomes from fetal bovine serum and examined their potential to promote growth of breast carcinoma cells in soft agar and Matrigel after reconstituting them into growth medium (EEM). In all the assays, viable colonies were formed only in the presence of exosomes. Some of the exosomal proteins we identified, have been documented by others and could be considered exosomal markers. Labeled purified exosomes were up-taken by the tumor cells, a process that could be competed out with excess unlabeled vesicles. Our data also suggested that once endocytosed by a cell, the exosomes could be recycled back to the conditioned medium from where they can be up-taken by other cells. We also demonstrated that low concentrations of exosomes activate MAP kinases, suggesting a mechanism by which they maintain the growth of the tumor cells in soft agar. Taken together, our data demonstrate that serum exosomes form a growth promoting platform for AIG of tumor cells and may open a new vista into cancer cell growth in vivo. 相似文献
29.
Siddharth Bharath Iyengar Sumanta Bagchi Deepak Barua Charudutt Mishra Mahesh Sankaran 《Plant Ecology》2017,218(7):843-854
Plant communities are structured by both competition and facilitation. The interplay between the two interactions can vary depending on environmental factors, nature of stress, and plant traits. However, whether positive or negative interactions dominate in regions of high biotic and abiotic stress remains unclear. We studied herbaceous plant communities associated with a dwarf shrub Caragana versicolor in semi-arid, high altitude Trans-Himalayan rangelands of Spiti, India. We surveyed 120 pairs of plots (within and outside shrub canopies) across four watersheds differing in altitude, aspect, and dominant herbivores. Herbaceous communities within shrub canopies had 25% higher species richness, but similar abundance when compared to communities outside the canopy, with the shrub edge having higher diversity than the centre of the canopy. Grasses and erect forbs showed positive associations with the shrub, while prostrate plants occurred at much lower abundance within the canopy. Rare species showed stronger positive associations with Caragana than abundant species. Experimental removal of herbaceous vegetation from within shrub canopies led to 42% increase in flowering in Caragana, indicating a cost to the host shrubs. Our study indicates a robust pattern of a dwarf shrub facilitating local community diversity across this alpine landscape, increasing diversity at the plot level, facilitating rare species, and yet incurring a cost to hosts from the presence of herbaceous plants. Given these large influences of this shrub on the vegetation of these high altitude rangelands, we suggest that the shrub microhabitat be explicitly considered in any analyses of ecosystem health in such rangelands. 相似文献
30.
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling 总被引:2,自引:0,他引:2
Randall J. Platt Sidi Chen Yang Zhou Michael J. Yim Lukasz Swiech Hannah R. Kempton James E. Dahlman Oren Parnas Thomas M. Eisenhaure Marko Jovanovic Daniel B. Graham Siddharth Jhunjhunwala Matthias Heidenreich Ramnik J. Xavier Robert Langer Daniel G. Anderson Nir Hacohen Aviv Regev Guoping Feng Phillip A. Sharp Feng Zhang 《Cell》2014