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      • KCI등재

        Identification of Chaperones in Freeze Tolerance in Saccharomyces cerevisiae

        Mahendran Chinnamara Naicker,조이슬,임하나 한국미생물학회 2012 The journal of microbiology Vol.50 No.5

        Exposure to low temperatures reduces protein folding rates and induces the cold denaturation of proteins. Considering the roles played by chaperones in facilitating protein folding and preventing protein aggregation, chaperones must exist that confer tolerance to cold stress. Here, yeast strains lacking individual chaperones were screened for reduced freezing tolerance. In total, 19 of 82 chaperone-deleted strains tested were more sensitive to freeze-thaw treatment than wild-type cells. The reintroduction of the respective chaperone genes into the deletion mutants recovered the freeze tolerance. The freeze sensitivity of the chaperone-knockout strains was also retained in the presence of 20% glycerol.

      • KCI등재

        Yeast Cyclophilins Prevent Cold Denaturation of Proteins

        Mahendran Chinnamara Naicker,김양희,이경희,임하나 대한화학회 2016 Bulletin of the Korean Chemical Society Vol.37 No.3

        Freezing environments are one of the major challenges faced by many organisms, including Saccharomyces cerevisiae. Exposure to low temperatures reduces protein folding rates and induces the cold denaturation of proteins, necessitating aid from chaperones. In a previous study, we identified 19 chaperone genes, the deletion of which makes the host more vulnerable to freeze-and-thaw treatments. Among those, peptidyl–prolyl cis–trans isomerases (PPIases) were the most frequently identified. At low temperatures, peptidyl–prolyl isomerization is a rate-limiting step in protein folding, and folding intermediates, which are prone to protein aggregation, tend to accumulate. To characterize their mode of function, the identified PPIases were overexpressed in Escherichia coli. Not only did they increase the survival of E. coli during freeze-and-thaw treatment at –20 °C, but they also protected β-galactosidase against freeze-induced protein denaturation. Purified Cpr1p facilitated the refolding of a slow-folding substrate protein in vitro. These results suggest that the identified PPIases enhance cold survival of cells by preventing cold-induced protein denaturation and promoting protein folding.

      • Prognostic Factors and the Role of Adjuvant Chemotherapy in Post-curative Surgery for Dukes B and C Colon Cancers and Survival Outcomes: a Malaysian Experience

        Hassan, Astrid Sinarti,Naicker, Manimalar,Yusof, Khairul Hazdi,Ishak, Wan Zamaniah Wan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

        Background: Adjuvant chemotherapy improves survival in Dukes C colon cancers post-curative resection. However, the evidence for a role with Dukes B lesions remains unproven despite frequent use for disease characterized by poor prognostic features. In view of limited Asia-specific data, this study aimed to determine survival outcomes and identify prognostic factors in a tertiary teaching hospital in Malaysia. Materials and Methods: A total of 116 subjects who underwent curative surgery with and without adjuvant chemotherapy for Duke B and C primary colon adenocarcinomas diagnosed from 2004-2009 were recruited and data were collected retrospectively. Five-year overall survival (OS) and disease free survival (DFS) were analysed using Kaplan-Meier survival analysis and log-rank (Mantel-Cox) test. Prognostic factors were determined using Cox proportional hazards regression with both univariate and multivariate analyses. Results: The survival analysis demonstrated a 5-year OS of 74.0% for all patients, with 74.9% for Dukes C subjects receiving chemotherapy compared to 28.6% in those not receiving chemotherapy (p=0.001). For Dukes B disease, the 5-year survival rate was 82.6% compared to 75.0% for subjects receiving and not receiving chemotherapy, respectively (p=0.17). Independent prognostic factors identified included a CEA level more than 3.5 ng/ml (hazard ratio (HR)=4.78; p=0.008), serosal involvement (HR=3.75; p=0.028) and completion of chemotherapy (HR= 0.20; p=0.007). Conclusions: In a regional context, this study supports current evidence from the West that adjuvant chemotherapy improves survival in Dukes C colon cancers post curative surgery. However, although a clear benefit has yet to be proven for Dukes B disease, our results suggest survival improvement in selected cases.

      • KCI등재

        The complement system in preeclampsia: a review of its activation and endothelial injury in the triad of COVID-19 infection and HIV-associated preeclampsia

        Mikyle David,Thajasvarie Naicker 대한산부인과학회 2023 Obstetrics & Gynecology Science Vol.66 No.4

        This review assesses the complement system and its activation, with the pathological features of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human immunodeficiency virus (HIV) infection and preeclampsia (PE). The complement system is the first defensive response by the host innate immune system to viral pathogens, including SARS-CoV-2. SARS-CoV-2 entry results in the release of pro-inflammatory cytokines and chemical mediators to create a “cytokine storm”. Endothelial cell (EC) dysfunction and cell-mediated injury are also present. These factors cause an exacerbated inflammatory state. During HIV infection and PE, various complement components are elevated, causing a hyper-inflammatory state. Furthermore, EC dysfunction and cell-mediated injury are also present. The similarities in pathological aspects of these three disorders may emanate from excessive complement activation. This review serves as a platform for further research on the complement system, coronavirus disease 2019, HIV infection and PE.

      • KCI등재

        Transforming growth factor-beta and liver injury in an arginine vasopressin-induced pregnant rat model

        Nalini Govender,Sapna Ramdin,Rebecca Reddy,Thajasvarie Naicker 대한생식의학회 2021 Clinical and Experimental Reproductive Medicine Vol.48 No.2

        Objective: Approximately 30% of preeclamptic pregnancies exhibit abnormal liver function tests. We assessed liver injury-associated enzyme levels and circulating transforming growth factor beta (TGF-β) levels in an arginine vasopressin (AVP)-induced pregnant Sprague-Dawley rat model.Methods: Pregnant and non-pregnant Sprague-Dawley rats (n=24) received AVP (150 ng/hr) subcutaneously via mini-osmotic pumps for 18 days. Blood pressure was measured, urine samples were collected, and all animals were euthanized via isoflurane. Blood was collected to measure circulating levels of TGF-β1-3 isomers and liver injury enzymes in pregnant AVP (PAVP), pregnant saline (PS), non-pregnant AVP (NAVP), and non-pregnant saline (NS) rats. Results: The PAVP group showed significantly higher systolic and diastolic blood pressure than both saline-treated groups. The weight per pup was significantly lower in the AVP-treated group than in the saline group (p<0.05). Circulating TGF-β1-3 isomer levels were significantly higher in the PAVP rats than in the NS rats. However, similar TGF-1 and TGF-3 levels were noted in the PS and PAVP rats, while TGF-2 levels were significantly higher in the PAVP rats. Circulating liver-type arginase-1 and 5'-nucleotidase levels were higher in the PAVP rats than in the saline group. Conclusion: This is the first study to demonstrate higher levels of TGF-β2, arginase, and 5'-nucleotidase activity in PAVP than in PS rats. AVP may cause vasoconstriction and increase peripheral resistance and blood pressure, thereby elevating TGF-β and inducing the preeclampsia-associated inflammatory response. Future studies should explore the mechanisms through which AVP dysregulates liver injury enzymes and TGF-β in pregnant rats.

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