272 research outputs found
The Pre-positioned Warehouse Location Selection for International Humanitarian Relief Logistics
Β© 2018 This study aims to identify the most appropriate pre-positioned warehouse location for international humanitarian relief organisations. A two-step methodology is structured using fuzzy AHP and fuzzy TOPSIS to evaluate pre-positioned warehouse locations for humanitarian relief organisations. The empirical case study analysis of a humanitarian relief organisation is conducted to illustrate the use of the proposed framework for ranking alternative locations. This framework provides a more accurate, effective, and systematic decision support tool for stepwise implementation of warehouse location selection in humanitarian relief operations to increase efficiency. National stability is considered the most crucial factor for warehouse selection followed by host country cooperation. Location A was identified as the optimal warehouse location, with Locations D and E being relatively close. However, the organisation operates at Location A due to the national stability and government incentives such as land costs and customs exemption
Comparison of the functional features of the pump organs of Anopheles sinensis and Aedes togoi
Mosquitoes act as vectors for severe tropical diseases. Mosquito-borne diseases are affected by various factors such as environmental conditions, host body susceptibility, and mosquito feeding behavior. Among these factors, feeding behavior is affected by the feeding pump system located inside the mosquito head and also depends on the species of mosquito. Therefore, the 3D morphological structures of the feeding pumps of Aedes togoi and Anopheles sinensis were comparatively investigated using synchrotron X-ray microscopic computed tomography. In addition, the feeding behaviors of their pumping organs were also investigated using a 2D X-ray micro-imaging technique. An. sinensis, a malarial vector mosquito, had a larger feeding pump volume than Ae. togoi in the static or resting position. Interestingly, the two species of mosquitoes exhibited different feeding behaviors. Ae. togoi had a higher feeding frequency and expansion ratio than An. sinensis. Ae. togoi also exhibited F-actin localization more clearly. These distinctive variations in feeding volumes and behaviors provide essential insight into the blood-feeding mechanisms of female mosquitoes as vectors for tropical diseases.1124Ysciescopu
Detection of Heparin in the Salivary Gland and Midgut of Aedes togoi
Mosquitoes secrete saliva that contains biological substances, including anticoagulants that counteract a host's hemostatic response and prevent blood clotting during blood feeding. This study aimed to detect heparin, an anticoagulant in Aedes togoi using an immunohistochemical detection method, in the salivary canal, salivary gland, and midgut of male and female mosquitoes. Comparisons showed that female mosquitoes contained higher concentrations of heparin than male mosquitoes. On average, the level of heparin was higher in blood-fed female mosquitoes than in non-blood-fed female mosquitoes. Heparin concentrations were higher in the midgut than in the salivary gland. This indicates presence of heparin in tissues of A. togoi.X111Ysciescopu
TNF-alpha differentially modulates subunit levels of respiratory electron transport complexes of ER/PR plus ve/-ve breast cancer cells to regulate mitochondrial complex activity and tumorigenic potential
Background: Tumor necrosis factor-Ξ± (TNF-Ξ±) is an immunostimulatory cytokine that is consistently high in the
breast tumor microenvironment (TME); however, its differential role in mitochondrial functions and cell survival in
ER/PR +ve and ER/PR βve breast cancer cells is not well understood.
Methods: In the current study, we investigated TNF-Ξ± modulated mitochondrial proteome using high-resolution
mass spectrometry and identified the differentially expressed proteins in two different breast cancer cell lines, ER/PR
positive cell line; luminal, MCF-7 and ER/PR negative cell line; basal-like, MDA-MB-231 and explored its implication in
regulating the tumorigenic potential of breast cancer cells. We also compared the activity of mitochondrial
complexes, ATP, and ROS levels between MCF-7 and MDA-MB-231 in the presence of TNF-Ξ±. We used Tumor
Immune Estimation Resource (TIMER) webserver to analyze the correlation between TNF-Ξ± and mitochondrial
proteins in basal and luminal breast cancer patients. Kaplan-Meier method was used to analyze the correlation
between mitochondrial protein expression and survival of breast cancer patients.
Results: The proteome analysis revealed that TNF-Ξ± differentially altered the level of critical proteins of
mitochondrial respiratory chain complexes both in MCF-7 and MDA-MB-231, which correlated with differential
assembly and activity of mitochondrial ETC complexes. The inhibition of the glycolytic pathway in the presence of
TNF-Ξ± showed that glycolysis is indispensable for the proliferation and clonogenic ability of MDA-MB-231 cells (ER/
PR βve) as compared to MCF-7 cells (ER/PR +ve). The TIMER database showed a negative correlation between the
expressions of TNF-Ξ± and key regulators of mitochondrial OXPHOS complexes in basal breast vs lobular carcinoma.
Conversely, patient survival analysis showed an improved relapse-free survival with increased expression of
identified proteins of ETC complexes and survival of the breast cancer patients.
Conclusion: The evidence presented in our study convincingly demonstrates that TNF-Ξ± regulates the survival and
proliferation of aggressive tumor cells by modulating the levels of critical assembly factors and subunits involved in
mitochondrial respiratory chain supercomplexes organization and function. This favors the rewiring of
mitochondrial metabolism towards anaplerosis to support the survival and proliferation of breast cancer cells.
Collectively, the results strongly suggest that TNF-Ξ± differentially regulates metabolic adaptation in ER/PR +ve (MCF-
7) and ER/PR βve (MDA-MB-231) cells by modulating the mitochondrial supercomplex assembly and activity
Gene expression profiling reveals differential effects of sodium selenite, selenomethionine, and yeast-derived selenium in the mouse
The essential trace mineral selenium is an important determinant of oxidative stress susceptibility, with several studies showing an inverse relationship between selenium intake and cancer. Because different chemical forms of selenium have been reported to have varying bioactivity, there is a need for nutrigenomic studies that can comprehensively assess whether there are divergent effects at the molecular level. We examined the gene expression profiles associated with selenomethionine (SM), sodium selenite (SS), and yeast-derived selenium (YS) in the intestine, gastrocnemius, cerebral cortex, and liver of mice. Weanling mice were fed either a selenium-deficient (SD) diet (<0.01Β mg/kg diet) or a diet supplemented with one of three selenium sources (1Β mg/kg diet, as either SM, SS or YS) for 100Β days. All forms of selenium were equally effective in activating standard measures of selenium status, including tissue selenium levels, expression of genes encoding selenoproteins (Gpx1 and Txnrd2), and increasing GPX1 enzyme activity. However, gene expression profiling revealed that SS and YS were similar (and distinct from SM) in both the expression pattern of individual genes and gene functional categories. Furthermore, only YS significantly reduced the expression of Gadd45b in all four tissues and also reduced GADD45B protein levels in liver. Taken together, these results show that gene expression profiling is a powerful technique capable of elucidating differences in the bioactivity of different forms of selenium
Serum levels of selenium and smoking habits at age 50 influence long term prostate cancer risk; a 34 year ULSAM follow-up
Background: Serum selenium level (s-Se) has been associated with prostate cancer (PrCa) risk. We investigated the relation between s-Se, smoking and non-screening detected PrCa and explored if polymorphisms in two DNA repair genes: OGG1 and MnSOD, influenced any effect of s-Se. Methods: ULSAM, a population based Swedish male cohort (n = 2322) investigated at age 50 for s-Se and s-Se influencing factors: serum cholesterol, erythrocyte sedimentation rate and smoking habits. At age 71 a subcohort, (n = 1005) was genotyped for OGG1 and MnSOD polymorphisms. Results: In a 34-year-follow-up, national registries identified 208 PrCa cases further confirmed in medical records. Participants with s-Se in the upper tertile had a non-significantly lower risk of PrCa. Smokers with s-Se in the two lower tertiles (<= 80 mu g/L) experienced a higher cumulative incidence of PrCa than smokers in the high selenium tertile (Hazard Ratio 2.39; 95% CI: 1.09-5.25). A high tertile selenium level in combination with non-wt rs125701 of the OGG1 gene in combination with smoking status or rs4880 related variation of MnSOD gene appeared to protect from PrCa. Conclusions: S-Se levels and smoking habits influence long-term risk of PrCa. Smoking as a risk factor for PrCa in men with low s-Se is relevant to explore further. Exploratory analyses of variations in OGG1 and MnSOD genes indicate that hypotheses about patterns of exposure to selenium and smoking combined with data on genetic variation in genes involved in DNA repair can be valuable to pursue
Electroacupuncture preconditioning reduces ROS generation with NOX4 down-regulation and ameliorates blood-brain barrier disruption after ischemic stroke
Fifteen-month follow up of an assertive community treatment program for chronic patients with mental illness
p53 Amino-Terminus Region (1β125) Stabilizes and Restores Heat Denatured p53 Wild Phenotype
BACKGROUND:The intrinsically disordered N-ter domain (NTD) of p53 encompasses approximately hundred amino acids that contain a transactivation domain (1-73) and a proline-rich domain (64-92) and is responsible for transactivation function and apoptosis. It also possesses an auto-inhibitory function as its removal results in remarkable reduction in dissociation of p53 from DNA. PRINCIPAL FINDINGS/METHODOLOGY:In this report, we have discovered that p53-NTD spanning amino acid residues 1-125 (NTD125) interacted with WT p53 and stabilized its wild type conformation under physiological and elevated temperatures, both in vitro and in cellular systems. NTD125 prevented irreversible thermal aggregation of heat denatured p53, enhanced p21-5'-DBS binding and further restored DBS binding activity of heat-denatured p53, in vitro, in a dose-dependent manner. In vivo ELISA and immunoprecipitation analysis of NTD125-transfected cells revealed that NTD125 shifted equilibrium from p53 mutant to wild type under heat stress conditions. Further, NTD125 initiated nuclear translocation of cytoplasmic p53 in transcriptionally active state in order to activate p53 downstream genes such as p21, Bax, PUMA, Noxa and SUMO. CONCLUSION/SIGNIFICANCE:Here, we showed that a novel chaperone-like activity resides in p53-N-ter region. This study might have significance in understanding the role of p53-NTD in p53 stabilization, conformational activation and apoptosis under heat-stress conditions
Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells
The platinum compound oxaliplatin has been shown to be an effective chemotherapeutic agent for the treatment of colorectal cancer. In this study, we investigate the molecular mechanisms of action of oxaliplatin to identify means of predicting response to this agent. Exposure of colon cancer cells to oxaliplatin resulted in G2/M arrest and apoptosis. Immunofluorescent staining demonstrated that the apoptotic cascade initiated by oxaliplatin is characterised by translocation of Bax to the mitochondria and cytochrome c release into the cytosol. Oxaliplatin treatment resulted in caspase 3 activation and oxaliplatin-induced apoptosis was abrogated by inhibition of caspase activity with z-VAD-fmk, but was independent of Fas/FasL association. Targeted inactivation of Bax or p53 in HCT116 cells resulted in significantly increased resistance to oxaliplatin. However, the mutational status of p53 was unable to predict response to oxaliplatin in a panel of 30 different colorectal cancer cell lines. In contrast, the expression profile of these 30 cell lines, assessed using a 9216-sequence cDNA microarray, successfully predicted the apoptotic response to oxaliplatin. A leave-one-out cross-validation approach was used to demonstrate a significant correlation between experimentally observed and expression profile predicted apoptosis in response to clinically achievable doses of oxaliplatin (R=0.53; P=0.002). In addition, these microarray experiments identified several genes involved in control of apoptosis and DNA damage repair that were significantly correlated with response to oxaliplatin
- β¦