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1.
Páraic ó Cuív Rajesh Gupta Hareshwar P. Goswami Mark Morrison 《Applied and environmental microbiology》2013,79(19):6173-6175
Clostridium thermocellum encodes a cellulosomal, modular, and thermostable serine protease inhibitor (serpin), PinA. PinA stability but not inhibitory activity is affected by the Fn(III) and Doc(I) domains, and PinA is a broad inhibitor of subtilisin-like proteases and may play a key role in protecting the cellulosome from protease attack. 相似文献
2.
Rajesh Narendran William G. Frankle Neale S. Mason Matthew F. Muldoon Bita Moghaddam 《PloS one》2012,7(10)
Studies in rodents indicate that diets deficient in omega-3 polyunsaturated fatty acids (n–3 PUFA) lower dopamine neurotransmission as measured by striatal vesicular monoamine transporter type 2 (VMAT2) density and amphetamine-induced dopamine release. This suggests that dietary supplementation with fish oil might increase VMAT2 availability, enhance dopamine storage and release, and improve dopamine-dependent cognitive functions such as working memory. To investigate this mechanism in humans, positron emission tomography (PET) was used to measure VMAT2 availability pre- and post-supplementation of n–3 PUFA in healthy individuals. Healthy young adult subjects were scanned with PET using [11C]-(+)-α-dihydrotetrabenzine (DTBZ) before and after six months of n–3 PUFA supplementation (Lovaza, 2 g/day containing docosahexaenonic acid, DHA 750 mg/d and eicosapentaenoic acid, EPA 930 mg/d). In addition, subjects underwent a working memory task (n-back) and red blood cell membrane (RBC) fatty acid composition analysis pre- and post-supplementation. RBC analysis showed a significant increase in both DHA and EPA post-supplementation. In contrast, no significant change in [11C]DTBZ binding potential (BPND) in striatum and its subdivisions were observed after supplementation with n–3 PUFA. No correlation was evident between n–3 PUFA induced change in RBC DHA or EPA levels and change in [11C]DTBZ BPND in striatal subdivisions. However, pre-supplementation RBC DHA levels was predictive of baseline performance (i.e., adjusted hit rate, AHR on 3-back) on the n-back task (y = 0.19+0.07, r2 = 0.55, p = 0.009). In addition, subjects AHR performance improved on 3-back post-supplementation (pre 0.65±0.27, post 0.80±0.15, p = 0.04). The correlation between n-back performance, and DHA levels are consistent with reports in which higher DHA levels is related to improved cognitive performance. However, the lack of change in [11C]DBTZ BPND indicates that striatal VMAT2 regulation is not the mechanism of action by which n–3 PUFA improves cognitive performance. 相似文献
3.
Yu-Chi Su Goutham Venkata Naga Davuluri Cheng-Hao Chen Dong-Che Shiau Chien-Chin Chen Chia-Ling Chen Yee-Shin Lin Chih-Peng Chang 《PloS one》2016,11(2)
Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients. 相似文献
4.
Michael Jae-Yoon Chung Abram L. Friesen Dieter Fox Andrew N. Meltzoff Rajesh P. N. Rao 《PloS one》2015,10(11)
A fundamental challenge in robotics today is building robots that can learn new skills by observing humans and imitating human actions. We propose a new Bayesian approach to robotic learning by imitation inspired by the developmental hypothesis that children use self-experience to bootstrap the process of intention recognition and goal-based imitation. Our approach allows an autonomous agent to: (i) learn probabilistic models of actions through self-discovery and experience, (ii) utilize these learned models for inferring the goals of human actions, and (iii) perform goal-based imitation for robotic learning and human-robot collaboration. Such an approach allows a robot to leverage its increasing repertoire of learned behaviors to interpret increasingly complex human actions and use the inferred goals for imitation, even when the robot has very different actuators from humans. We demonstrate our approach using two different scenarios: (i) a simulated robot that learns human-like gaze following behavior, and (ii) a robot that learns to imitate human actions in a tabletop organization task. In both cases, the agent learns a probabilistic model of its own actions, and uses this model for goal inference and goal-based imitation. We also show that the robotic agent can use its probabilistic model to seek human assistance when it recognizes that its inferred actions are too uncertain, risky, or impossible to perform, thereby opening the door to human-robot collaboration. 相似文献
5.
Bibek Yumnam Yadvendradev V. Jhala Qamar Qureshi Jesus E. Maldonado Rajesh Gopal Swati Saini Y. Srinivas Robert C. Fleischer 《PloS one》2014,9(11)
Even with global support for tiger (Panthera tigris) conservation their survival is threatened by poaching, habitat loss and isolation. Currently about 3,000 wild tigers persist in small fragmented populations within seven percent of their historic range. Identifying and securing habitat linkages that connect source populations for maintaining landscape-level gene flow is an important long-term conservation strategy for endangered carnivores. However, habitat corridors that link regional tiger populations are often lost to development projects due to lack of objective evidence on their importance. Here, we use individual based genetic analysis in combination with landscape permeability models to identify and prioritize movement corridors across seven tiger populations within the Central Indian Landscape. By using a panel of 11 microsatellites we identified 169 individual tigers from 587 scat and 17 tissue samples. We detected four genetic clusters within Central India with limited gene flow among three of them. Bayesian and likelihood analyses identified 17 tigers as having recent immigrant ancestry. Spatially explicit tiger occupancy obtained from extensive landscape-scale surveys across 76,913 km2 of forest habitat was found to be only 21,290 km2. After accounting for detection bias, the covariates that best explained tiger occupancy were large, remote, dense forest patches; large ungulate abundance, and low human footprint. We used tiger occupancy probability to parameterize habitat permeability for modeling habitat linkages using least-cost and circuit theory pathway analyses. Pairwise genetic differences (F
ST) between populations were better explained by modeled linkage costs (r>0.5, p<0.05) compared to Euclidean distances, which was in consonance with observed habitat fragmentation. The results of our study highlight that many corridors may still be functional as there is evidence of contemporary migration. Conservation efforts should provide legal status to corridors, use smart green infrastructure to mitigate development impacts, and restore habitats where connectivity has been lost. 相似文献
6.
7.
Mark A. Pook Rekhaben Thakrar Bruce Pottinger Brian Harding David Porteous Veronica van Heningen John Cowell Carol Jones Sue Povey Kay E. Davies Rajesh V. Thakker 《Human genetics》1996,97(6):742-749
EagI and NotI linking libraries were prepared in the lambda vector, EMBL5, from the mouse-human somatic cell hybrid 1W1LA4.9, which contains
human chromosomes 11 and Xp as the only human component. Individual clones containing human DNA were isolated by their ability
to hybridise with total human DNA and digested with SalI and EcoRI to identify the human insert size and single-copy fragments. The mean (± SD) insert sizes of the EagI and NotI clones were 18.3 ± 3.2 kb and 16.6 ± 3.6 kb, respectively. Regional localisation of 66 clones (52 EagI, 14 NotI) was achieved using a panel of 20 somatic cell hybrids that contained different overlapping deletions of chromosomes 11
or Xp. Thirty-nine clones (36 EagI, 3 NotI) were localised to chromosome 11; 17 of these were clustered in 11q13 and another nine were clustered in 11q14–q23.1. Twenty-seven
clones (16 EagI, 11 NotI) were localised to Xp and 10 of these were clustered in Xp11. The 66 clones were assessed for seven different microsatellite
repetitive sequences; restriction fragment length polymorphisms for five clones from 11q13 were also identified. These EagI and NotI clones, which supplement those previously mapped to chromosome 11 and Xp, should facilitate the generation of more detailed
maps and the identification of genes that are associated with CpG-rich islands.
Received: 27 December 1995 / Revised: 30 January 1996 相似文献
8.
Chathurika Henpita Rajesh Vyas Chastity L. Healy Tra L. Kieu Aditi U. Gurkar Matthew J. Yousefzadeh Yuxiang Cui Aiping Lu Luise A. Angelini Ryan D. O'Kelly Sara J. McGowan Sanjay Chandrasekhar Rebecca R. Vanderpool Danielle Hennessy-Wack Mark A. Ross Timothy N. Bachman Charles McTiernan Smitha P. S. Pillai Warren Ladiges Mitra Lavasani Johnny Huard Donna Beer-Stolz Claudette M. St. Croix Simon C. Watkins Paul D. Robbins Ana L. Mora Eric E. Kelley Yinsheng Wang Timothy D. O'Connell Laura J. Niedernhofer 《Aging cell》2023,22(4):e13782
Cardiomyopathy is a progressive disease of the myocardium leading to impaired contractility. Genotoxic cancer therapies are known to be potent drivers of cardiomyopathy, whereas causes of spontaneous disease remain unclear. To test the hypothesis that endogenous genotoxic stress contributes to cardiomyopathy, we deleted the DNA repair gene Ercc1 specifically in striated muscle using a floxed allele of Ercc1 and mice expressing Cre under control of the muscle-specific creatinine kinase (Ckmm) promoter or depleted systemically (Ercc1−/D mice). Ckmm-Cre+/−;Ercc1−/fl mice expired suddenly of heart disease by 7 months of age. As young adults, the hearts of Ckmm-Cre+/−;Ercc1−/fl mice were structurally and functionally normal, but by 6-months-of-age, there was significant ventricular dilation, wall thinning, interstitial fibrosis, and systolic dysfunction indicative of dilated cardiomyopathy. Cardiac tissue from the tissue-specific or systemic model showed increased apoptosis and cardiac myocytes from Ckmm-Cre+/-;Ercc1−/fl mice were hypersensitive to genotoxins, resulting in apoptosis. p53 levels and target gene expression, including several antioxidants, were increased in cardiac tissue from Ckmm-Cre+/−;Ercc1−/fl and Ercc1−/D mice. Despite this, cardiac tissue from older mutant mice showed evidence of increased oxidative stress. Genetic or pharmacologic inhibition of p53 attenuated apoptosis and improved disease markers. Similarly, overexpression of mitochondrial-targeted catalase improved disease markers. Together, these data support the conclusion that DNA damage produced endogenously can drive cardiac disease and does so mechanistically via chronic activation of p53 and increased oxidative stress, driving cardiac myocyte apoptosis, dilated cardiomyopathy, and sudden death. 相似文献
9.
Piliang Hao Wei Meng Soak Kuan Lai Karthigayan Gunalan Trang T. Chu Ameya Sinha Julien Lescar Rajesh Chandramohanadas Hoi Yeung Li Siu Kwan Sze Peter R. Preiser 《Cellular microbiology》2017,19(9)
The successful invasion of Plasmodium is an essential step in their life cycle. The parasite reticulocyte‐binding protein homologues (RHs) and erythrocyte‐binding like proteins are two families involved in the invasion leading to merozoite‐red blood cell (RBC) junction formation. Ca2+ signaling has been shown to play a critical role in the invasion. RHs have been linked to Ca2+ signaling, which triggers the erythrocyte‐binding like proteins release ahead of junction formation, consistent with RHs performing an initial sensing function in identifying suitable RBCs. RH5, the only essential RHs, is a highly promising vaccine candidate. RH5‐basigin interaction is essential for merozoite invasion and also important in determining host tropism. Here, we show that RH5 has a distinct function from the other RHs. We show that RH5‐Basigin interaction on its own triggers a Ca2+ signal in the RBC resulting in changes in RBC cytoskeletal proteins phosphorylation and overall alterations in RBC cytoskeleton architecture. Antibodies targeting RH5 that block the signal prevent invasion before junction formation consistent with the Ca2+ signal in the RBC leading to rearrangement of the cytoskeleton required for invasion. This work provides the first time a functional context for the essential role of RH5 and will now open up new avenues to target merozoite invasion. 相似文献
10.