CD36-Mediated Metabolic Rewiring of Breast Cancer Cells Promotes Resistance to HER2-Targeted Therapies

The functional significance of lipid metabolism in cancer cells is not fully understood. Feng et al. show that the fatty acid transporter CD36 is essential for survival of breast cancer cells during anti-HER2 therapy, highlighting the role of lipid metabolism in acquired resistance to targeted therapy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Role of C-reactive protein in complement-mediated hemolysis in Malaria

HumanC-reactive protein (CRP) is a clinically important classical acute phase protein. Although CRP has been reported to bind with many nucleated cells, the direct binding of CRP to erythrocytes in diseases remains largely unexplored. The main focus of the present studywas to investigate the binding of disease-specific CRP to erythrocytes of same patients. Distinct molecular variant of disease-specific CRP was affinity purified from sera of malaria patients (CRPMal). This CRP showed strong binding with malaria erythrocytes (RBCMal) as confirmed by flow cytometric analysis (FACS), enzyme-linked immunosorbent assays (ELISA), and radio binding assays. Calcium and phosphoryl choline (PC) were found to be essential for this interaction.A2.3-fold increased binding of induced CRP to RBCMal as compared to normal erythrocytes (RBCN) confirmed disease-specificity. Preincubation of RBCMal with unconjugated CRP showed 3–5 fold inhibition. The association constant of CRP and RBCMal was 4.7 × 106 cpm/μg with the corresponding number of receptors/ cell being 4.3 × 105. The effector function of CRPMal has been demonstrated by its potency to activate the complement pathway. An optimal dose of 10 μg/ml of CRP induced three-fold higher hemolysis of patient erythrocytes as compared to RBCN. These studies provide direct evidence for an important phagocytic functional interaction of this acutephase protein by triggering the CRP-complement pathway after the binding of CRPMal with RBCMal. Hemolysis as triggered by this pathway may be one of the causative factors of anemia, a common clinical manifestation of this diseas

Desempenho e qualidade dos ovos de poedeiras comerciais alimentadas com rações contendo farelo de coco tratado ou não com antioxidante Performance and egg quality of laying hens fed diets containing coconut meal treated with and without antioxidant

Este experimento foi conduzido para avaliar a estabilidade oxidativa do farelo de coco (FC) tratado ou não com butil-hidroxitolueno (BHT) e armazenado por 35 dias e estudar o efeito de rações contendo esse ingrediente sobre o desempenho e a qualidade do ovo de poedeiras. Um lote de 200 kg de farelo de coco foi dividido em cinco partes: uma foi armazenada sem a adição de antioxidante e as demais tratadas com 500 ppm de BHT nos dias 0, 7, 14 e 21. A estabilidade oxidativa do farelo de coco foi acompanhada por meio dos índices de acidez e de peróxidos, determinados semanalmente. Após 35 dias de armazenamento, 10% de farelo de coco tratado e não tratado com BHT nos diferentes tempos de armazenamento foi usado na formulação de rações isonutrientes para poedeiras comerciais. Foram utilizadas 180 poedeiras da linhagem Hisex White, distribuídas ao acaso em 5 tratamentos e 6 repetições de 6 aves cada. Os índices de acidez e de peróxidos do farelo de coco armazenado com ou sem BHT aumentaram com o tempo de armazenamento. Contudo, os tratamentos não afetaram o desempenho nem a qualidade dos ovos das aves. O farelo de coco armazenado por 35 dias sem antioxidante, embora sofra oxidação, pode ser usado em níveis de até 10% na ração para poedeiras comerciais.<br>This experiment was conducted to evaluate the oxidative stability of coconut meal treated with or without butylated hydroxytoluene (BHT) at different storage times and the effect of diets containing this ingredient on laying hens' performance and egg quality. A 200-kg batch of freshly produced coconut meal was divided into five equal portions. One portion was stored without BHT and the others were treated with BHT at zero, 7, 14 and 21 days. The oxidative stability of coconut meal was measured by the acidity index and peroxide index determined weekly. At the end of the 35-day storage time, this ingredient was used in the formulation of diets for laying hen. One hundred and eighty Hisex White laying hens were randomly distributed among five treatments with six repetitions of six birds each. The acidity index and peroxide index of coconut meal treated with or without BHT at different periods of time increased with storage time. Nevertheless, treatments did not affect laying hens' performance or egg quality. Coconut meal stored for 35 days, although showing lipid peroxidation, can be included at 10% level in the diet for commercial poultry

Selection of variables in exploratory factor analysis: An empirical comparison of a stepwise and traditional approach

Stepwise variable selection, exploratory factor analysis, goodness-of-fit, varimax rotation, statistical bias, selection accuracy, pattern accuracy,

Activation of Mitogen-activated Protein Kinase (Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase) Cascade by Aldosterone

Aldosterone in some tissues increases expression of the mRNA encoding the small monomeric G protein Ki-RasA. Renal A6 epithelial cells were used to determine whether induction of Ki-ras leads to concomitant increases in the total as well as active levels of Ki-RasA and whether this then leads to subsequent activation of its effector mitogen-activated protein kinase (MAPK/extracellular signal-regulated kinase) cascade. The molecular basis and cellular consequences of this action were specifically investigated. We identified the intron 1-exon 1 region (rasI/E1) of the mouse Ki-ras gene as sufficient to reconstitute aldosterone responsiveness to a heterologous promotor. Aldosterone increased reporter gene activity containing rasI/E1 threefold. Aldosterone increased the absolute and GTP-bound levels of Ki-RasA by a similar extent, suggesting that activation resulted from mass action and not effects on GTP binding/hydrolysis rates. Aldosterone significantly increased Ki-RasA and MAPK activity as early as 15 min with activation peaking by 2 h and waning after 4 h. Inhibitors of transcription, translation, and a glucocorticoid receptor antagonist attenuated MAPK signaling. Similarly, rasI/E1-driven luciferase expression was sensitive to glucocorticoid receptor blockade. Overexpression of dominant-negative RasN17, addition of antisense Ki-rasA and inhibition of mitogen-activated protein kinase kinase also attenuated steroid-dependent increases in MAPK signaling. Thus, activation of MAPK by aldosterone is dependent, in part, on a genomic mechanism involving induction of Ki-ras transcription and subsequent activation of its downstream effectors. This genomic mechanism has a distinct time course from activation by traditional mitogens, such as serum, which affect the GTP-binding state and not absolute levels of Ras. The result of such a genomic mechanism is that peak activation of the MAPK cascade by adrenal corticosteroids is delayed but prolonged