Vertical sleeve gastrectomy lowers SGLT2/Slc5a2 expression in the mouse kidney

Bariatric surgery improves glucose homeostasis but the underlying mechanisms are not fully elucidated. Here, we show that the expression of sodium glucose cotransporter-2 (SGLT2/Slc5a2) is reduced in the kidney of lean and obese mice following vertical sleeve gastrectomy (VSG). Indicating an important contribution of altered cotransporter expression to the impact of surgery, inactivation of the SGLT2/Slc5a2 gene by CRISPR/Cas9 attenuated the effects of VSG, with glucose excursions following intraperitoneal injection lowered by ∼30% in wild-type mice but by ∼20% in SGLT2 null animals. The effects of the SGLT2 inhibitor dapaglifozin were similarly blunted by surgery. Unexpectedly, effects of dapaglifozin were still observed in SGLT2 null mice, consistent with the existence of metabolically beneficial off-target effects of SGLT2 inhibitors. Thus, we describe a new mechanism involved in mediating the glucose lowering effects of bariatric surgery

Functional effect of miR-1307-3p on breast cancer progression

Background: MiRNAs are non-coding RNA molecules and its function is the regulation of gene expression. In cancer, the deregulation of miRNAs allows them to act as oncogenes or tumor suppressors. From an analysis of the expression of miRNAs in breast cancer (BC) in The Cancer Genome Atlas (TCGA), it was identified that miR-1307-3p is significantly overexpressed in the tumor tissue compared to healthy tissue from patients. So far, in BC, it has only been reported that this miRNA inhibits SMYD4 and that it is involved in resistance to cisplatin through its effect on Mdm4. In this project we propose to identify the role of miR-1307-3p in proliferation, migration, invasion, angiogenesis, and possible targets involved in these processes in BC cells. Methods: RT-qPCR was used to evaluate basal levels of miR-1307-3p in the BC cell lines MDA-MB-231 and MCF-7, and the human epithelial breast MCF-10A cells. Later, we determined the effect of miR-1307-3p on proliferation, migration, and invasion in MDA-MB-231 and MCF-7, and angiogenesis in the HUVEC endothelial cells. All assays were carried out using the miR-1307-3p inhibitor. Then, nine miRNA-target prediction databases were analyzed to identify potential miR-1307-3p target genes, and their expression was analyzed by RT-qPCR in a designed 384-well plate. Finally, the targets that presented an alteration in their expression were evaluated by western blot. Results: We found that miR-1307-3p is overexpressed in MDA-MB-231 and MCF-7, compared to MCF-10A cells. We also identified that transfection with the miR-1307-3p inhibitor causes a significant decrease in the processes of proliferation, migration, invasion, and angiogenesis, when compared with untreated or negative control transfected cells. For its part, prediction databases analysis allowed us to identify 19 potential targets of miR-1307-3p. We also found that 2 genes were overexpressed, CIC and PRM2. Finally, we found an overexpression of PRM2 protein. Conclusions: MiR-1307-3p is overexpressed in BC cells. Furthermore, miR-1307-3p induces the processes of proliferation, migration and invasion in BC cells, and angiogenesis in HUVEC cells. These observations suggest that miR-1307-3p can acts as an onco-miRNA. In addition, a potential new target of miR-1307-3p was found, PRM2 which has not been previously reported in breast cancer. Further analysis to verify and validate the implication of this miR-1307-3p target are needed to understand its importance in BC

Effect of miR-660-5p in breast cancer progression

Background: Breast cancer (BC) is the most diagnosed cancer in women worldwide. MicroRNAs (miRNAs) participate in different processes of BC and their deregulation can cause them to act as oncogenes or tumor suppressors, participating in cancer progression. Using the TCGA (The Cancer Genome Atlas) database, we found that miR-660-5p significantly overexpressed and associated with poor survival in patients with this pathology. Moreover, it is reported that miR-660-5p can induce BC progression through transcription factor CP2 (TFCP2) and the downregulation of tet methylcytosine dioxygenase 2 (TET2). In this project, we propose to identify the role of miR-660-5p in proliferation, migration, invasion, angiogenesis, and the possible targets involved in these processes in BC cell lines. Methods: Basal levels of miR-660-5p were determined in BC cells MDA-MB-231 and MCF-7, and in human epithelial breast cells MCF-10A by RT-qPCR. The effect of miR-660-5p was evaluated on proliferation, migration, and invasion processes in MDA-MB-231 and MCF-7 cells. HUVEC cells were used to assess angiogenesis. All cell lines were transfected with miR-660-5p inhibitor. Analysis of nine miRNA-target prediction databases was made to identify targets of miR-660-5p. We selected the targets genes predicted by at least three of these programs, and their expression were evaluated in MDA-MB-231 cells by RT-qPCR in a customized plate. We validated those results with Western blot. Results: We found that miR-660-5p is significantly upregulated in MDA-MB-231 and MCF-7, compared to MCF-10A cells. In addition, we observed a significant decrease in proliferation, migration, and invasion in BC cells transfected with miR-660-5p inhibitor, compared to nontreated cells and miRNA inhibitor negative control cells. Similarly, we observed a significant decrease in angiogenesis of HUVEC cells transfected with miR-660-5p inhibitor. Furthermore, of all the miR-660-5p target genes identified by prediction databases, 17 were selected, and of these, three were observed upregulated and one downregulated. We found that CD8A, LIFR and TMEM41B are reported as tumor suppressors in different types of cancer. We validated those results by Western blot, observing an increase in TMEM41B protein levels in the group of cells transfected with miR-660 inhibitor compared to nontreated cells and miRNA inhibitor negative control cells. Conclusions: The results show that miR-660-5p is upregulated and involved in proliferation, migration, invasion, and angiogenesis of BC, which may lead us to suggest that this miRNA act as an onco-miRNA. In addition, we found that TMEM41B could be a potential target of miR-660-5p

Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats

This study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy, and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets

The Physics of turbulent and dynamically unstable Herbig-Haro jets

The overall properties of the Herbig-Haro objects such as centerline velocity, transversal profile of velocity, flow of mass and energy are explained adopting two models for the turbulent jet. The complex shapes of the Herbig-Haro objects, such as the arc in HH34 can be explained introducing the combination of different kinematic effects such as velocity behavior along the main direction of the jet and the velocity of the star in the interstellar medium. The behavior of the intensity or brightness of the line of emission is explored in three different cases : transversal 1D cut, longitudinal 1D cut and 2D map. An analytical explanation for the enhancement in intensity or brightness such as usually modeled by the bow shock is given by a careful analysis of the geometrical properties of the torus.Comment: 17 pages, 10 figures. Accepted for publication in Astrophysics & Spac

The 2HWC HAWC Observatory Gamma Ray Catalog

We present the first catalog of TeV gamma-ray sources realized with the recently completed High Altitude Water Cherenkov Observatory (HAWC). It is the most sensitive wide field-of-view TeV telescope currently in operation, with a 1-year survey sensitivity of ~5-10% of the flux of the Crab Nebula. With an instantaneous field of view >1.5 sr and >90% duty cycle, it continuously surveys and monitors the sky for gamma ray energies between hundreds GeV and tens of TeV. HAWC is located in Mexico at a latitude of 19 degree North and was completed in March 2015. Here, we present the 2HWC catalog, which is the result of the first source search realized with the complete HAWC detector. Realized with 507 days of data and represents the most sensitive TeV survey to date for such a large fraction of the sky. A total of 39 sources were detected, with an expected contamination of 0.5 due to background fluctuation. Out of these sources, 16 are more than one degree away from any previously reported TeV source. The source list, including the position measurement, spectrum measurement, and uncertainties, is reported. Seven of the detected sources may be associated with pulsar wind nebulae, two with supernova remnants, two with blazars, and the remaining 23 have no firm identification yet.Comment: Submitted 2017/02/09 to the Astrophysical Journa

The Sensitivity of HAWC to High-Mass Dark Matter Annihilations

The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC will observe gamma rays and cosmic rays with an array of water Cherenkov detectors. The full HAWC array is scheduled to be operational in Spring 2015. In this paper, we study the HAWC sensitivity to the gamma-ray signatures of high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be sensitive to diverse searches for dark matter annihilation, including annihilation from extended dark matter sources, the diffuse gamma-ray emission from dark matter annihilation, and gamma-ray emission from non-luminous dark matter subhalos. Here we consider the HAWC sensitivity to a subset of these sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the Galactic center. We simulate the HAWC response to gamma rays from these sources in several well-motivated dark matter annihilation channels. If no gamma-ray excess is observed, we show the limits HAWC can place on the dark matter cross-section from these sources. In particular, in the case of dark matter annihilation into gauge bosons, HAWC will be able to detect a narrow range of dark matter masses to cross-sections below thermal. HAWC should also be sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The constraints placed by HAWC on the dark matter cross-section from known sources should be competitive with current limits in the mass range where HAWC has similar sensitivity. HAWC can additionally explore higher dark matter masses than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR