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161.
162.
Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes 总被引:13,自引:0,他引:13
Koehne G Doubrovin M Doubrovina E Zanzonico P Gallardo HF Ivanova A Balatoni J Teruya-Feldstein J Heller G May C Ponomarev V Ruan S Finn R Blasberg RG Bornmann W Riviere I Sadelain M O'Reilly RJ Larson SM Tjuvajev JG 《Nature biotechnology》2003,21(4):405-413
New technologies are needed to characterize the migration, survival, and function of antigen-specific T cells in vivo. Here, we demonstrate that Epstein-Barr virus (EBV)--specific T cells transduced with vectors encoding herpes simplex virus-1 thymidine kinase (HSV-TK) selectively accumulate radiolabeled 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (FIAU). After adoptive transfer, HSV-TK+ T cells labeled in vitro or in vivo with [131I]FIAU or [124I]FIAU can be noninvasively tracked in SCID mice bearing human tumor xenografts by serial images obtained by scintigraphy or positron emission tomography (PET), respectively. These T cells selectively accumulate in EBV+ tumors expressing the T cells' restricting HLA allele but not in EBV- or HLA-mismatched tumors. The concentrations of transduced T cells detected in tumors and tissues are closely correlated with the concentrations of label retained at each site. Radiolabeled transduced T cells retain their capacity to eliminate targeted tumors selectively. This technique for imaging the migration of ex vivo-transduced antigen-specific T cells in vivo is informative, nontoxic, and potentially applicable to humans. 相似文献
163.
164.
Prabhjeet K. Phalora Nathan M. Sherer Steven M. Wolinsky Chad M. Swanson Michael H. Malim 《Journal of virology》2012,86(21):11712-11724
The APOBEC3 cytidine deaminases play a critical role in host-mediated defense against exogenous viruses, most notably, human immunodeficiency virus type-1 (HIV-1) and endogenous transposable elements. APOBEC3G and APOBEC3F interact with numerous proteins that regulate cellular RNA metabolism, including components of the RNA-induced silencing complex (RISC), and colocalize with a subset of these proteins to mRNA processing bodies (P bodies), which are sites of mRNA translational repression and decay. We sought to determine the role of P bodies and associated proteins in HIV-1 replication and APOBEC3 antiviral activity. While we established a positive correlation between APOBEC3 protein incorporation into virions and localization to P bodies, depletion of the P-body components DDX6 or Lsm1 did not affect HIV-1 replication, APOBEC3 packaging into virions or APOBEC3 protein mediated inhibition of HIV-1 infectivity. In addition, neither HIV-1 genomic RNA nor Gag colocalized with P-body proteins. However, simultaneous depletion of multiple Argonaute family members, the effector proteins of RISC, could modestly increase viral infectivity. Because some APOBEC3 proteins interact with several Argonaute proteins, we also tested whether they could modulate microRNA (miRNA) activity. We found no evidence for the specific regulation of miRNA function by the APOBEC3 proteins, though more general effects on transfected gene expression were observed. In sum, our results indicate that P bodies and certain associated proteins do not regulate HIV-1 replication or APOBEC3 protein antiviral activity. Localization to P bodies may therefore provide a means of sequestering APOBEC3 enzymatic activity away from cellular DNA or may be linked to as yet unidentified cellular functions. 相似文献
165.
The century-long research on succession has bestowed us with a number of theories, but little agreement on what causes species
replacements through time. The majority of studies has explored the temporal trends of individual species in plant and much
less so in microbial communities, arguing that interspecific interactions, especially competition, play a key role in community
organization throughout succession. In this experimental investigation of periphytic succession in re-circulating laboratory
streams, we examined the density and the relative abundance of diatoms and soft algae for 35 days across gradients of low
to high nutrient supply (nitrogen + phosphorus) and low to intermediate current velocity (10 vs. 30 cm·s−1). All algal species were classified into trophic groups and morphological guilds, both of which responded more strongly to
nutrient than current velocity manipulations, as shown by regression analyses. We concluded that within the manipulated environmental
ranges: (1) Succession was a gradient of stress tolerance, driven primarily by nutrient supply and secondarily, by current
velocity. Nutrient supply had a qualitative effect in determining whether the contribution of species tolerant vs. sensitive
to nutrient limitation would increase through time, while current velocity had a quantitative influence and affected only
the rate of this increase. (2) The mechanism of algal succession at a functional level was a neutral coexistence, whereby
the tolerant low profile guild maintained high density when overgrown by sensitive species, while sensitive species, constituting
mostly the motile and high profile guilds, were neither facilitated nor inhibited by tolerant species but controlled by the
environment. It is suggested that the mechanism of succession may depend on the level of biological organization with interspecific
interactions giving way to neutral coexistence along the hierarchy from species to functional groups. Considering that the
functional makeup is strictly environmentally defined, while species composition reflects local and regional species pools
that may exhibit substantial geographic variability, succession is deterministic at a functional level but stochastic at a
species level. 相似文献
166.
Galo Garcia III Gregory C. Finnigan Lydia R. Heasley Sarah M. Sterling Adeeti Aggarwal Chad G. Pearson Eva Nogales Michael A. McMurray Jeremy Thorner 《The Journal of cell biology》2016,212(5):515-529
Septin complexes display remarkable plasticity in subunit composition, yet how a new subunit assembled into higher-order structures confers different functions is not fully understood. Here, this question is addressed in budding yeast, where during meiosis Spr3 and Spr28 replace the mitotic septin subunits Cdc12 and Cdc11 (and Shs1), respectively. In vitro, the sole stable complex that contains both meiosis-specific septins is a linear Spr28–Spr3–Cdc3–Cdc10–Cdc10–Cdc3–Spr3–Spr28 hetero-octamer. Only coexpressed Spr3 and Spr28 colocalize with Cdc3 and Cdc10 in mitotic cells, indicating that incorporation requires a Spr28-Spr3 protomer. Unlike their mitotic counterparts, Spr28-Spr3–capped rods are unable to form higher-order structures in solution but assemble to form long paired filaments on lipid monolayers containing phosphatidylinositol-4,5-bisphosphate, mimicking presence of this phosphoinositide in the prospore membrane. Spr28 and Spr3 fail to rescue the lethality of a cdc11Δ cdc12Δ mutant, and Cdc11 and Cdc12 fail to restore sporulation proficiency to spr3Δ/spr3Δ spr28Δ/spr28Δ diploids. Thus, specific meiotic and mitotic subunits endow septin complexes with functionally distinct properties. 相似文献
167.
Chad K. Bush Dayaamayi Kurimella Lee J. S. Cross Katherine R. Conner Sheryl Martin-Schild Jiang He Changwei Li Jing Chen Tanika Kelly 《PloS one》2016,11(1)
Importance
Acute ischemic stroke is a leading cause of death and disability worldwide. Several recent clinical trials have shown that endovascular treatment improves clinical outcomes among patients with acute ischemic stroke.Objective
To provide an overall and precise estimate of the efficacy of endovascular treatment predominantly using second-generation mechanical thrombectomy devices (stent-retriever devices) compared to medical management on clinical and functional outcomes among patients with acute ischemic stroke.Data Sources
MEDLINE, EMBASE, Cochrane Collaboration Central Register of Controlled Clinical Trials, Web of Science, and NIH ClinicalTrials.gov were searched through November 2015.Study Selection
Searches returned 3,045 articles. After removal of duplicates, two authors independently screened titles and abstracts to assess eligibility of 2,495 potentially relevant publications. From these, 38 full-text publications were more closely assessed. Finally, 5 randomized controlled trials of endovascular treatment with predominant use of retrievable stents were selected.Data Extraction and Synthesis
Three authors independently extracted information on participant and trial characteristics and clinical events using a standardized protocol. Random effects models were used to pool endovascular treatment effects across outcomes.Main Outcomes and Measures
The primary outcome was better functional outcome as measured on the modified Rankin Scale at 90 days of follow-up. Secondary outcomes included all-cause mortality and symptomatic intra-cerebral hemorrhage.Results
Five trials representing 1,287 patients were included. Overall, patients randomized to endovascular therapy experienced 2.22 times greater odds of better functional outcome compared to those randomized to medical management (95% CI, 1.66 to 2.98; P < 0.0001). Endovascular therapy was not associated with mortality [OR (95% CI), 0.78 (0.54, 1.12); P = 0.1056] or symptomatic intracerebral hemorrhage [OR (95% CI), 1.19 (0.69, 2.05); P = 0.5348]. Meta-regression analysis suggested that shorter times from stroke onset to groin puncture and from stroke onset to reperfusion result in better functional outcomes in ischemic stroke patients (P = 0.0077 and P = 0.0089). There were no significant differences in the beneficial effects of endovascular treatment on functional outcomes across categories of gender, age, stroke severity, ischemic changes on computed tomography, or intravenous tissue plasminogen activator administration.Conclusions and Relevance
This meta-analysis demonstrated superior functional outcomes in subjects receiving endovascular treatment compared to medical management. Further, this analysis showed that acute ischemic stroke patients may receive enhanced functional benefit from earlier endovascular treatment. 相似文献168.
Joshua Allen Peterson Richard Vernon Oblad Jeffrey Chad Mecham Jason Donald Kenealey 《Biochemistry and Biophysics Reports》2016
Plasma membrane Ca2+-ATPase (PMCA) plays a vital role in maintaining cytosolic calcium concentration ([Ca2+]i). Given that many diseases have modified PMCA expression and activity, PMCA is an important potential target for therapeutic treatment. This study demonstrates that the non-toxic, naturally-occurring polyphenol resveratrol (RES) induces increases in [Ca2+]i via PMCA inhibition in primary dermal fibroblasts and MDA-MB-231 breast cancer cells. Our results also illustrate that RES and the fluorescent intracellular calcium indicator Fura-2, are compatible for simultaneous use, in contrast to previous studies, which indicated that RES modulates the Fura-2 fluorescence independent of calcium concentration. Because RES has been identified as a PMCA inhibitor, further studies may be conducted to develop more specific PMCA inhibitors from RES derivatives for potential therapeutic use. 相似文献
169.
The pro-apoptotic Ras effector Nore1 may serve as a Ras-regulated tumor suppressor in the lung 总被引:4,自引:0,他引:4
Vos MD Martinez A Ellis CA Vallecorsa T Clark GJ 《The Journal of biological chemistry》2003,278(24):21938-21943
Ras oncoproteins mediate multiple biological effects by activating multiple effectors. Classically, Ras activation has been associated with enhanced cellular growth and transformation. However, activated forms of Ras may also inhibit growth by inducing senescence, apoptosis, and differentiation. Induction of apoptosis by Ras may be mediated by its effector RASSF1, which appears to function as a tumor suppressor. We now show that the Ras effector Nore1, which is structurally related to RASSF1, can also mediate a Ras-dependent apoptosis. Moreover, an analysis of Nore1 protein expression showed that it is frequently down-regulated in lung tumor cell lines and primary lung tumors. Like RASSF1, this correlates with methylation of the Nore1 promoter rather than gene deletion. Finally, re-introduction of Nore1, driven by its own promoter, impairs the growth in soft agar of a human lung tumor cell line. Consequently, we propose that the Ras effector Nore1 is a member of a family of Ras effector/tumor suppressors that includes RASSF1. 相似文献
170.
Flockhart AF Tree JJ Xu X Karpiyevich M McAteer SP Rosenblum R Shaw DJ Low CJ Best A Gannon V Laing C Murphy KC Leong JM Schneiders T La Ragione R Gally DL 《Molecular microbiology》2012,83(1):208-223
This study has identified horizontally acquired genomic regions of enterohaemorrhagic Escherichia coli O157:H7 that regulate expression of the type III secretion (T3S) system encoded by the locus of enterocyte effacement (LEE). Deletion of O-island 51, a 14.93 kb cryptic prophage (CP-933C), resulted in a reduction in LEE expression and T3S. The deletion also had a reduced capacity to attach to epithelial cells and significantly reduced E. coli O157 excretion levels from sheep. Further characterization of O-island 51 identified a novel positive regulator of the LEE, encoded by ecs1581 in the E. coli O157:H7 strain Sakai genome and present but not annotated in the E. coli strain EDL933 sequence. Functionally important residues of ECs1581 were identified based on phenotypic variants present in sequenced E. coli strains and the regulator was termed RgdR based on a motif demonstrated to be important for stimulation of gene expression. While RgdR activated expression from the LEE1 promoter in the presence or absence of the LEE-encoded regulator (Ler), RgdR stimulation of T3S required ler and Ler autoregulation. RgdR also controlled the expression of other phenotypes, including motility, indicating that this new family of regulators may have a more global role in E. coli gene expression. 相似文献