NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells

Simvastatin and lovastatin are statins traditionally used for lowering serum cholesterol levels. However, there exists evidence indicating their potential chemotherapeutic characteristics in cancer. In this study, we used bioinformatic analysis of publicly available data in order to systematically identify the genes involved in resistance to cytotoxic effects of these two drugs in the NCI60 cell line panel. We used the pharmacological data available for all the NCI60 cell lines to classify simvastatin or lovastatin resistant and sensitive cell lines, respectively. Next, we performed whole-genome single marker case-control association tests for the lovastatin and simvastatin resistant and sensitive cells using their publicly available Affymetrix 125K SNP genomic data. The results were then evaluated using RNAi methodology. After correction of the p-values for multiple testing using False Discovery Rate, our results identified three genes (NRP1, COL13A1, MRPS31) and six genes (EAF2, ANK2, AKAP7, STEAP2, LPIN2, PARVB) associated with resistance to simvastatin and lovastatin, respectively. Functional validation using RNAi confirmed that silencing of EAF2 expression modulated the response of HCT-116 colon cancer cells to both statins. In summary, we have successfully utilized the publicly available data on the NCI60 cell lines to perform whole-genome association studies for simvastatin and lovastatin. Our results indicated genes involved in the cellular response to these statins and siRNA studies confirmed the role of the EAF2 in response to these drugs in HCT-116 colon cancer cells

Functional clustering of yeast proteins from the protein-protein interaction network

BACKGROUND: The abundant data available for protein interaction networks have not yet been fully understood. New types of analyses are needed to reveal organizational principles of these networks to investigate the details of functional and regulatory clusters of proteins. RESULTS: In the present work, individual clusters identified by an eigenmode analysis of the connectivity matrix of the protein-protein interaction network in yeast are investigated for possible functional relationships among the members of the cluster. With our functional clustering we have successfully predicted several new protein-protein interactions that indeed have been reported recently. CONCLUSION: Eigenmode analysis of the entire connectivity matrix yields both a global and a detailed view of the network. We have shown that the eigenmode clustering not only is guided by the number of proteins with which each protein interacts, but also leads to functional clustering that can be applied to predict new protein interactions

In vitro influence of dietary protein and fructooligosaccharides on metabolism of canine fecal microbiota

BACKGROUND: The present in vitro study investigated whether the utilization of fructooligosaccharides (FOS) may influence canine fecal microbial population in presence of diets differing in their protein content and digestibility. Fresh fecal samples were collected from five adult dogs, pooled, and incubated for 24 h with the undigested residue of three diets: 1, Low protein high digestibility diet (LP HD, crude protein (CP) 229 g/kg); 2, High protein high digestibility diet (HP HD, CP 304 g/kg); 3, High protein low digestibility diet (HP LD, CP 303 g/kg) that had been previously subjected to enzymatic digestion. In the in vitro fermentation study, there were six treatments: 1) LP HD; 2) HP HD 3) HP LD; 4) LP HD + FOS; 5) HP HD + FOS; 6) HP LD + FOS. Fructooligosaccharides were added at the final concentration of 1.5 g/L. Samples of fermentation fluid were collected at 6 and 24 h of incubation. RESULTS: Values of pH were reduced by FOS at 6 and 24 h (P < 0.001); conversely, low protein digestibility and high dietary protein level resulted in higher pH at both sampling times (P < 0.001). At 24 h, FOS lowered ammonia (−10 %; P < 0.001) and resulted (P < 0.05) in higher concentrations of total volatile fatty acids (VFA) (+43 %), acetic acid (+14 %), propionic acid (+75 %) and n-butyric acid (+372 %). Conversely, at 24 h, low protein digestibility resulted (P < 0.01) in lower concentrations of acetic acid (−26 %), propionic acid (−37 %) and total VFA (−21 %). Putrescine concentrations were increased at 6 and 24 h of fermentation by low protein digestibility (+21 and 22 %, respectively; P < 0.05) and FOS (+18 and 24 %, respectively; P < 0.01). After 24 h of fermentation, high dietary protein level resulted in lower counts of lactobacilli and enterococci (−0.5 and −0.7 log cells/mL, respectively; P < 0.05) whereas low protein digestibility tended to increase counts of C. perfringens (+0.2 log cells/mL; P = 0.07). CONCLUSIONS: Results from the present study showed that diets rich in protein may exert negative influences on the canine intestinal ecosystem, slightly increasing the presence of ammonia and reducing counts of lactobacilli and enterococci. Moreover, the presence of poorly digestible protein resulted in lower concentrations of VFA. Conversely, administration of FOS may improve metabolism of canine intestinal microbiota, reducing ammonia concentrations and enhancing VFA production

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

Influence of the chemical functionalization of carbon nanotubes on low temperature ac conductivity with polyaniline composites

We report the ac conductivity measurement of polyaniline (PANI) composites with carbon nanotubes (CNT) and functionalized carbon nanotubes (fCNT) with different degrees of functionalization from 300 K-4.2 K in the frequency range 40 Hz-5 MHz. The ac conductivity of PANI follows the universal power law and the charge transport is dominated by small polaron tunneling. In the CNT/PANI composite, metallic behaviour emerges, and ac conductivity does not obey the power law which is explained by the Drude model. Due to the chemical functionalization of CNT, disordered semiconducting behaviour appears in the transport below 50 K and follows the Johnscher's power law. The enhancement of polaron formation due to the polar interaction between fCNT and PANI is reflected in the ac conductivity of the composites. The charge transport is manifested by single electron tunneling for a lower degree of fCNT/PANI (6 h) composite which changes to small polaron tunneling transport for a higher degree of fCNT/PANI (48 h) composite. The dc conductivity behaviour is explained by Mott's VRH model and the characteristic Mott temperature increases with an increasing degree of chemical functionalization

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Not AvailableSurra, a haemoprotozoan parasitic disease even in subclinical form poses a challenge in terms of diagnosis and management to animal health practitioners and policy makers as well; eventually imparting financial loss to the livestock holders. A systematic study was designed to assess the seroprevalence of surra in cattle and associated climatic risk factors, by collecting 480 serum samples across the eight districts of Mizoram during 2017–2019. The apparent and true seroprevalence detected by card agglutination test was 37.08% (CI at 95%: 32.88–41.49) and 36.59% (CI at 95%: 32.4–40.99) whereas by recombinant Variable Surface Glycoprotein based indirect ELISA was 41.88% (CI at 95%: 37.5–46.3) and 40.35% (CI at 95%: 36.02–44.76) respectively. Climate parameters which influence vector population were extracted from their respective database and were correlated with seroprevalence data. Linear discriminant analysis revealed that air temperature, relative humidity and diurnal temperature range, leaf area index and soil moisture as significant risk factors discriminating seropositive and seronegative data sets classified by indirect ELISA. This study is the first report on seroprevalence of surra in cattle of Mizoram and the situation demands deployment of intervention strategies in order to assess the endemicity of the disease and thereby preventing the economic losses.Not Availabl