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151.
El Ghamrasni S Pamidi A Halaby MJ Bohgaki M Cardoso R Li L Venkatesan S Sethu S Hirao A Mak TW Hande MP Hakem A Hakem R 《PLoS genetics》2011,7(5):e1001385
Chk2 is an effector kinase important for the activation of cell cycle checkpoints, p53, and apoptosis in response to DNA damage. Mus81 is required for the restart of stalled replication forks and for genomic integrity. Mus81(Δex3-4/Δex3-4) mice have increased cancer susceptibility that is exacerbated by p53 inactivation. In this study, we demonstrate that Chk2 inactivation impairs the development of Mus81(Δex3-4/Δex3-4) lymphoid cells in a cell-autonomous manner. Importantly, in contrast to its predicted tumor suppressor function, loss of Chk2 promotes mitotic catastrophe and cell death, and it results in suppressed oncogenic transformation and tumor development in Mus81(Δex3-4/Δex3-4) background. Thus, our data indicate that an important role for Chk2 is maintaining lymphocyte development and that dual inactivation of Chk2 and Mus81 remarkably inhibits cancer. 相似文献
152.
Soumhya Venkatesan 《Ethnos》2013,78(3):400-424
This paper explores the ways in which particular individuals or groups are cast as problematically other at certain times by exploring the relationship between empathy and antipathy – identified as products of ‘resonance’, or a certain kind of responsiveness to embodied encounters with others and also to concerns, ideas and discourses that originate locally or from elsewhere. Consequent effects on subject-formation and affordances of social possibilities are explored through an intensive focus on one Muslim man. The notion of a ‘laminated subjectivity’ is presented and elucidated. The paper draws on ethnography conducted in a Tamil town and is set against the backdrop of Hindu–Muslim relations in India. 相似文献
153.
Vasuki Venkatesan Sugeerappa Laxmanappa Hoti Nagalakshmi Kamaraj Somnath Ghosh Kaushik Rajaram 《Memórias do Instituto Oswaldo Cruz》2013,108(6):804-807
Single-stranded DNA (ssDNA) is a prerequisite for electrochemical sensor-based
detection of parasite DNA and other diagnostic applications. To achieve this
detection, an asymmetric polymerase chain reaction method was optimised. This
method facilitates amplification of ssDNA from the human lymphatic filarial
parasite Wuchereria bancrofti. This procedure produced ssDNA
fragments of 188 bp in a single step when primer pairs (forward and reverse)
were used at a 100:1 molar ratio in the presence of double-stranded template
DNA. The ssDNA thus produced was suitable for immobilisation as probe onto the
surface of an Indium tin oxide electrode and hybridisation in a system for
sequence-specific electrochemical detection of W. bancrofti.
The hybridisation of the ssDNA probe and target ssDNA led to considerable
decreases in both the anodic and the cathodic currents of the system''s redox
couple compared with the unhybridised DNA and could be detected via cyclic
voltammetry. This method is reproducible and avoids many of the difficulties
encountered by conventional methods of filarial parasite DNA detection; thus, it
has potential in xenomonitoring. 相似文献
154.
Wojciech Pulawski Slawomir Filipek Anna Zwolinska Aleksander Debinski Krystiana Krzysko Ramón Garduño-Juárez Sowmya Viswanathan Venkatesan Renugopalakrishnan 《European biophysics journal : EBJ》2013,42(4):291-300
Molecular dynamics (MD) simulation combined with inelastic neutron scattering can provide information about the thermal dynamics of proteins, especially the low-frequency vibrational modes responsible for large movement of some parts of protein molecules. We performed several 30-ns MD simulations of cytochrome c (Cyt c) in a water box for temperatures ranging from 110 to 300 K and compared the results with those from experimental inelastic neutron scattering. The low-frequency vibrational modes were obtained via dynamic structure factors, S(Q, ω), obtained both from inelastic neutron scattering experiments and calculated from MD simulations for Cyt c in the same range of temperatures. The well known thermal transition in structural movements of Cyt c is clearly seen in MD simulations; it is, however, confined to unstructured fragments of loops Ω1 and Ω2; movement of structured loop Ω3 and both helical ends of the protein is resistant to thermal disturbance. Calculated and experimental S(Q, ω) plots are in qualitative agreement for low temperatures whereas above 200 K a boson peak vanishes from the calculated plots. This may be a result of loss of crystal structure by the protein–water system compared with the protein crystal. 相似文献
155.
Kandaswamy Ramya Kuppuswamy Ashok Ayyappa Saurabh Ghosh Viswanathan Mohan Venkatesan Radha 《Gene》2013
Objective
To investigate the genetic association of eight variants of the adiponectin gene with type 2 diabetes mellitus (T2DM), obesity and serum adiponectin level in the south Indian population.Methods
The study comprised of 1100 normal glucose tolerant (NGT) and 1100 type 2 diabetic, unrelated subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin levels were measured by radioimmunoassay. The variants were screened by polymerase chain reaction-restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotype frequencies.Results
Of the 8 variants, four SNPs namely, + 276 G/T (rs1501299), − 4522 C/T (rs822393), − 11365 C/G (rs266729), and + 712 G/A (rs3774261) were significantly associated with T2DM in our study population. The −3971 A/G (rs822396) and − 11391 G/A (rs17300539) SNPs' association with T2DM diabetes was mediated through obesity (where the association with type 2 diabetes was lost after adjusting for BMI). There was an independent association of + 276 G/T (rs1501299) and − 3971 A/G (rs822396) SNPs with generalized obesity and + 349 A/G (rs2241767) with central obesity. Four SNPs, −3971 A/G (rs822396), + 276 G/T (rs1501299), − 4522 C/T (rs822393) and Y111H T/C (rs17366743) were significantly associated with hypoadiponectinemia. The haplotypes GCCATGAAT and AGCGTGGGT conferred lower risk of T2DM in this south Indian population.Conclusion
The adiponectin gene variants and haplotype contribute to the genetic risk towards the development of type 2 diabetes, obesity and hypoadiponectinemia in the south Indian population. 相似文献156.
Myriam Gharbi Jennifer A. Flegg Bruno Pradines Ako Berenger Magatte Ndiaye Abdoulaye A. Djimdé Cally Roper Véronique Hubert Eric Kendjo Meera Venkatesan Philippe Brasseur Oumar Gaye André T. Offianan Louis Penali Jacques Le Bras Philippe J. Guérin Members of the French National Reference Center for Imported Malaria Study 《PloS one》2013,8(10)
Introduction
There are growing concerns about the emergence of resistance to artemisinin-based combination therapies (ACTs). Since the widespread adoption of ACTs, there has been a decrease in the systematic surveillance of antimalarial drug resistance in many malaria-endemic countries. The aim of this work was to test whether data on travellers returning from Africa with malaria could serve as an additional surveillance system of local information sources for the emergence of drug resistance in endemic-countries.Methodology
Data were collected from travellers with symptomatic Plasmodium falciparum malaria returning from Senegal (n = 1,993), Mali (n = 2,372), Cote d’Ivoire (n = 4,778) or Cameroon (n = 3,272) and recorded in the French Malaria Reference Centre during the period 1996–2011. Temporal trends of the proportion of parasite isolates that carried the mutant genotype, pfcrt 76T, a marker of resistance to chloroquine (CQ) and pfdhfr 108N, a marker of resistance to pyrimethamine, were compared for travellers and within-country surveys that were identified through a literature review in PubMed. The in vitro response to CQ was also compared between these two groups for parasites from Senegal.Results
The trends in the proportion of parasites that carried pfcrt 76T, and pfdhfr 108N, were compared for parasites from travellers and patients within-country using the slopes of the curves over time; no significant differences in the trends were found for any of the 4 countries. These results were supported by in vitro analysis of parasites from the field in Senegal and travellers returning to France, where the trends were also not significantly different.Conclusion
The results have not shown different trends in resistance between parasites derived from travellers or from parasites within-country. This work highlights the value of an international database of drug responses in travellers as an additional tool to assess the emergence of drug resistance in endemic areas where information is limited. 相似文献157.
Muthu Thiruvengadam Wei-Han Hsu Chang-Hsien Yang 《Plant Cell, Tissue and Organ Culture》2011,104(2):239-246
A transformation method using the phosphomannose-isomerase (pmi) gene as a selectable marker was developed for orchid Oncidium Gower Ramsey. The pmi-gene, which converts mannose-6-phosphate to fructose-6-phosphate allowing for selection of transgenic plants on mannose selective
medium. Genetically transformed plants of Oncidium were regenerated after cocultivating protocorm-like bodies with Agrobacterium tumefaciens strain GV3101 containing the vectors pEPYON-42P and pEPYON-42H with 35S::PMI and 35S::HPTII genes respectively. We observed that 35S::PMI (pEPYON-42P) produced high rate (27 plants) of mannose resistant transgenic plants compared to 35S::HPTII (pEPYON-42H) in which only fourteen hygromycin resistant transgenic plants were obtained. Mannose resistant transgenic plants
were confirmed by PCR and Southern blot. The pmi gene expression in 35S::PMI (pEPYON-42P) transgenic plants was confirmed by RT-PCR. Furthermore, the duration of regeneration time of transgenic plants
was significantly shorter in mannose selected system (4 months) than in hygromycin selected system (8 months). The pmi/mannose selection system is shown to be highly efficient for producing transgenic O. Gower Ramsey without using antibiotics or herbicides. For the first time, the pmi/mannose-based “positive” selection system has been used to obtain genetically engineered O. Gower Ramsey. 相似文献
158.
Ferreras JA Gupta A Amin ND Basu A Sinha BN Worgall S Jayaprakash V Quadri LE 《Bioorganic & medicinal chemistry letters》2011,21(21):6533-6537
Mycobacterium tuberculosis (Mtb) and Yersinia pestis (Yp) produce siderophores with scaffolds of nonribosomal peptide-polyketide origin. Compounds with structural similarities to these siderophores were synthesized and evaluated as antimicrobials against Mtb and Yp under iron-limiting conditions mimicking the iron scarcity these pathogens encounter in the host and under standard iron-rich conditions. Several new antimicrobials were identified, including some with increased potency in the iron-limiting condition. Our study illustrates the possibility of screening compound libraries in both iron-rich and iron-limiting conditions to identify antimicrobials that may selectively target iron scarcity-adapted bacteria and highlights the usefulness of building combinatorial libraries of compounds having scaffolds with structural similarities to siderophores to feed into antimicrobial screening programs. 相似文献
159.
160.
Venkatesan R Alahuhta M Pihko PM Wierenga RK 《Protein science : a publication of the Protein Society》2011,20(8):1387-1397
The key residue of the active site of triosephosphate isomerase (TIM) is the catalytic glutamate, which is proposed to be important (i) as a catalytic base, for initiating the reaction, as well as (ii) for the subsequent proton shuttling steps. The structural properties of this glutamate in the liganded complex have been investigated by studying the high resolution crystal structures of typanosomal TIM, complexed with three suicide inhibitors: (S)-glycidol phosphate ((S)-GOP, at 0.99 Å resolution), (R)-glycidol phosphate, ((R)-GOP, at 1.08 Å resolution), and bromohydroxyacetone phosphate (BHAP, at 1.97 Å resolution). The structures show that in the (S)-GOP active site this catalytic glutamate is in the well characterized, competent conformation. However, an unusual side chain conformation is observed in the (R)-GOP and BHAP complexes. In addition, Glu97, salt bridged to the catalytic lysine in the competent active site, adopts an unusual side chain conformation in these two latter complexes. The higher chemical reactivity of (S)-GOP compared with (R)-GOP, as known from solution studies, can be understood: the structures indicate that in the case of (S)-GOP, Glu167 can attack the terminal carbon of the epoxide in a stereoelectronically favored, nearly linear O–C–O arrangement, but this is not possible for the (R)-GOP isomer. These structures confirm the previously proposed conformational flexibility of the catalytic glutamate in its closed, liganded state. The importance of this conformational flexibility for the proton shuttling steps in the TIM catalytic cycle, which is apparently achieved by a sliding motion of the side chain carboxylate group above the enediolate plane, is also discussed. 相似文献