Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant numbers 11/15682-4, 12/02270-2, 15/18121-4), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Regenera INCT Process Grant 465656/2014-5). JL is funded by the NIH/NIDDK R01DK106210. GDB is funded by the Wellcome Trust and the MRC Centre for Medical Mycology. Open access journalPeer reviewedPublisher PD

Cellular shortening and calcium dynamics are improved by noisy stimulus in a model of cardiomyopathy

Abstract Noise is present in cell biology. The capability of cells to respond to noisy environment have become essential. This study aimed to investigate whether noise can enhance the contractile response and Ca2+ handling in cardiomyocytes from a cardiomyopathy model. Experiments were conducted in an experimental setup with Gaussian white noise, frequency, and amplitude control to stimulate myocytes. Cell shortening, maximal shortening velocity, time to peak shortening, and time to half relaxation variables were recorded to cell shortening. Ca2+ transient amplitude and raise rate variables were registered to measure Ca2+ transients. Our results for cell shortening, Ca2+ transient amplitude, and raise rate suggest that cell response improve when myocytes are noise stimulated. Also, cell shortening, maximal shortening velocity, Ca2+ transient amplitude, and raise improves in control cells. Altogether, these findings suggest novel characteristics in how cells improve their response in a noisy environment

A critical tyrosine residue of the mitochondrial oxaloacetate carrier determines its uncoupling protein (UCP)-like function in yeast

9 páginas, 5 figuras, 1 tabla -- PAGS nros. 317-325The mitochondrial Oac (oxaloacetate carrier) found in some fungi and plants catalyses the uptake of oxaloacetate, malonate and sulfate. Despite their sequence similarity, transport specificity varies considerably between Oacs. Indeed, whereas ScOac (Saccharomyces cerevisiae Oac) is a specific anion–proton symporter, the YlOac (Yarrowia lipolytica Oac) has the added ability to transport protons, behaving as a UCP (uncoupling protein). Significantly, we identified two amino acid changes at the matrix gate of YlOac and ScOac, tyrosine to phenylalanine and methionine to leucine. We studied the role of these amino acids by expressing both wild-type and specifically mutated Oacs in an Oac-null S. cerevisiae strain. No phenotype could be associated with the methionine to leucine substitution, whereas UCP-like activity was dependent on the presence of the tyrosine residue normally expressed in the YlOac, i.e. Tyr-ScOac mediated proton transport, whereas Phe-YlOac lost its protonophoric activity. These findings indicate that the UCP-like activity of YlOac is determined by the tyrosine residue at position 146This work was partially supported by the CONACYT (Consejo Nacional de Ciencia y Tecnología) [grant numbers 79989 (to S.U.C.) and 80684 (to D.G.)], the DGAPA/UNAM (Dirección General Asuntos del Personal Académico/Universidad Nacional Autónoma de México) [grant numbers IN217109 (to S.U.C.) and IN219709-3 (to D.G.)], the ICGEB (International Centre for Genetic Engineering and Biotechnology) [grant number CRPMEX008-02 (to D.G.)] and the Spanish Consolider-Ingenio project [grant number CSD2007-00020 (to E.R.)]. L.A.L.-M., D.A.-O. and C.B.-O. are CONACYT fellows enrolled in the Biochemistry Graduate Program at UNAMPeer reviewe

Benefits of Cardamom (Elettaria cardamomum (L.) Maton) and Turmeric (Curcuma longa L.) Extracts for Their Applications as Natural Anti-Inflammatory Adjuvants

The genus Zingiberaceae has been widely used for phytotherapeutic purposes in traditional medicine throughout the world for its anti-inflammatory activity. Experimental studies have established that inflammation caused by chronic infections represents a risk factor for different forms of cancer. The objective of this study was focused on determining the anti-inflammatory capacity and cytotoxic activity of aqueous extracts of Elettaria cardamomum (cardamom) and Curcuma Longa (turmeric). The extracts were obtained by maceration and, through GC-MS/MS, a total of 11 different chemical components were determined in the aqueous extract of cardamom and 7 in the extract of turmeric. The main compounds found in cardamom and turmeric were α-terpinyl acetate (54.46%) and β-turmerone (33.45%), respectively. RT-qPCR results showed significantly lower gene expression levels of innate inflammatory cytokines (IL-6 and TNF-α) compared to the control (LPS). Also, it was observed that the extracts do not possess cytotoxic activity against different cell lines, where E. cardamomum showed EC50 (µg/mL) of 473.84 (HeLa cells), 237.36 (J774A.1 cells), 257.51 (Vero E6 cells), and 431.16 (Balb/C peritoneal cells) and C. longa showed EC50 (µg/mL) of 351.17 (HeLa cells), 430.96 (J774A.1 cells), 396.24 (Vero E6 cells), and 362.86 (Balb/C peritoneal cells). The results of this research suggest that natural extracts of E. cardamomum and C. longa possess anti-inflammatory effects and no cytotoxic activity against HeLa, J774A.1, Vero E6, and Balb/C peritoneal cell lines. Finally, it was observed that the extracts also decreased nitric oxide (NO) production in peritoneal macrophages

Identification of the mitochondrial carrier that provides Yarrowia lipolytica with a fatty acid-induced nucleotide-sensitive uncoupling protein-like activity

8 páginas, 7 figuras -- PAGS nros. 81-88Uncoupling proteins (UCPs) are mitochondrial carriers distributed throughout the eukaryotic kingdoms. While genes coding for UCPs have been identified in plants and animals, evidences for the presence of UCPs in fungi and protozoa are only functional. Here, it is reported that in the yeast Yarrowia lipolytica there is a fatty acid-promoted and GDP-sensitive uncoupling activity indicating the presence of a UCP. The uncoupling activity is higher in the stationary phase than in the mid-log growth phase. The in silico search on the Y. lipolytica genome led to the selection of two genes with the highest homology to the UCP family, XM_503525 and XM_500457. By phylogenetic analysis, XP_503525 was predicted to be an oxaloacetate carrier while XP_500457 would be a dicarboxylate carrier. Each of these two genes was cloned and heterologously expressed in Saccharomyces cerevisiae and the resulting phenotype was analyzed. The transport activity of the two gene products confirmed the phylogenetic predictions. In addition, only mitochondria isolated from yeasts expressing XP_503525 showed bioenergetic properties characteristic of a UCP: the proton conductance was increased by linoleic acid and inhibited by GDP. It is concluded that the XM_503525 gene from Y. lipolytica encodes for an oxaloacetate carrier although, remarkably, it also displays an uncoupling activity stimulated by fatty acids and inhibited by nucleotidesThis work was partially supported by grants from the Spanish Ministry of Science and Innovation to ER (BFU2006-08182 and Consolider-Ingenio CSD2007-00020). Research in Mexico was supported by grants from DGAPA/UNAM IN217109 and CONACyT 79989 to SU. The AECI, from the Spanish Ministry of Foreign Affairs and Cooperation, provided a visiting fellowship to LALM. LALM is a CONACyT fellow/Biochemistry PhD student at UNAMPeer reviewe