Editorial: Amino Acid Transport and Metabolism During Homeostasis and Inflammation.

DC is supported by grant from Ayudas Fundación BBVA a Equipos de Investigación Cientıfí ca (BIOMEDICINA-2018) and “La Caixa” Banking Foundation (HR17-00016). MP is supported by the Spanish Science, Innovation and University Ministry (RT2018—094211-B-100-FEDER), La Caixa Foundation (LCF/ PR/HR20/52400017) and La Marató-TV3.S

Procesos de titulación por diversas modalidades en la Facultad de Ingeniería Mecánica de la Universidad Nacional de Ingeniería (2012 – 2017)

La presente investigación tuvo como objetivo describir la problemática con la que suceden los procesos de titulación por diversas modalidades en la Facultad de Ingeniería Mecánica de la Universidad Nacional de Ingeniería (FIM-UNI) en el periodo 2012-2017, pues debido a la ley universitaria 30220-2014 en este periodo sucedió la problemática considerada en la presente investigación. Mediante un diseño de investigación no experimental transversal exploratorio descriptivo, se diseñó la estrategia de recopilación de información, con la aplicación de encuestas a alumnos y egresados; y, entrevistas a docentes y titulados; así también, se recabo información de archivos documentales de la UNI. Se consideró como única variable procesos de titulación. La investigación utilizó para su propósito los softwares MS Office y SPSS, con el fin de Interpretar los procesos secuenciales para la titulación en la FIM-UNI, para describir la problemática presentada en la obtención del Título Profesional. La investigación concluye que los procesos de titulación por diversas modalidades en la Facultad de Ingeniería Mecánica de la UNI se ven influenciado por los ingresantes y egresados, demoras en la obtención de un tema de tesis y los empirismos aplicativos

DOR undergoes nucleo-cytoplasmic shuttling, which involves passage through the nucleolus

AbstractDOR is a bi-functional protein that regulates transcription and enhances starvation-induced autophagy. While autophagy has been mostly described as a stress–response mechanism, cells also need autophagy to maintain homeostasis in basal conditions. However, the mechanisms regulating basal autophagy still remain unknown. Our results show that DOR acts in basal autophagy. Indeed, DOR already undergoes nucleo-cytoplasmic shuttling in basal conditions and, surprisingly, DOR exits continuously the nucleus and traverses the nucleolus. However, the nucleolus integrity is not essential for both DOR nucleo-cytoplasmic shuttling and DOR function on basal autophagy. Taken together, we propose that DOR exit from the nucleus is essential for basal autophagy stimulation even under nucleolus disruption

CATs and HATs: the SLC7 family of amino acid transporters

The SLC7 family is divided into two subgroups, the cationic amino acid transporters (the CAT family, SLC7A1-4) and the glycoprotein-associated amino acid transporters (the gpaAT family, SLC7A5-11), also called light chains or catalytic chains of the hetero(di)meric amino acid transporters (HAT). The associated glycoproteins (heavy chains) 4F2hc (CD98) or rBAT (D2, NBAT) form the SLC3 family. Members of the CAT family transport essentially cationic amino acids by facilitated diffusion with differential trans-stimulation by intracellular substrates. In some cells, they may regulate the rate of NO synthesis by controlling the uptake of l-arginine as the substrate for nitric oxide synthase (NOS). The heterodimeric amino acid transporters are, in contrast, quite diverse in terms of substrate selectivity and function (mostly) as obligatory exchangers. Their selectivity ranges from large neutral amino acids (system L) to small neutral amino acids (ala, ser, cys-preferring, system asc), negatively charged amino acid (system xc −) and cationic amino acids plus neutral amino acids (system y+L and b0,+-like). Cotransport of Na+ is observed only for the y+L transporters when they carry neutral amino acids. Mutations in b0,+-like and y+L transporters lead to the hereditary diseases cystinuria and lysinuric protein intolerance (LPI), respectivel

Los procedimientos empíricos en el proceso de titulación profesional en la universidad pública

This study describes the problem that happened in the titling processes by various modalities in the Faculty of Mechanical Engineering of the National University of Engineering (FIM-UNI) in the period 2012-2017, in reference to University Law 30220. The aforementioned law ponders the modalities to obtain the professional degree: first the Bachelor's degree must have been obtained, as well as having passed a thesis or in any case a work of professional sufficiency, and only in that university in which the degree was obtained Bachelor's degree. This research has followed the method of exploratory, descriptive and explanatory study; and the descriptive non-experimental transectional or transversal exploratory descriptive design was applied. All those actions that contribute to the motivation and realization of some thesis topic between the industry and the university benefit the students, which means that they do not feel oblivious to this reality and obtain the appropriate tools to experiment; and that way, avoid being part of the application empiricisms.En el presente estudio se describe la problemática que sucedió en los procesos de titulación por diversas modalidades en la Facultad de Ingeniería Mecánica de la Universidad Nacional de Ingeniería (FIM-UNI) en el periodo 2012-2017, en referencia a la Ley Universitaria 30220. La referida ley pondera las modalidades para obtener el título profesional: primero se debe haber obtenido el grado de Bachiller, así como también haber aprobado una tesis o en todo caso un trabajo de suficiencia profesional, y solamente en aquella universidad en la cual se consiguió el grado de bachiller. Esta investigación ha seguido el método de estudio exploratorio, descriptivo y explicativo; y se aplicó el diseño no experimental transeccional o transversal exploratorio descriptivo. Todas aquellas acciones que contribuyen a la motivación y realización de algún tema de tesis entre la industria y la universidad benefician a los alumnos, lo cual hace que no se sientan ajenos a tal realidad y logren obtener las herramientas adecuadas para experimentar; y de esa manera, evitar ser parte de los empirismos aplicativos

Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers

The levels, regulation and prognostic value of p21 in head and neck squamous cell carcinomas (HNSCC) has been puzzling for years. Here, we report a new mechanism of regulation of p21 by the mTORC1/4E-BP1 pathway. We find that non-phosphorylated 4E-BP1 interacts with p21 and induces its degradation. Accordingly, hyper-activation of mTORC1 results in phosphorylation of 4E-BP1 and stabilization of p21. In HNSCC, p21 levels strongly correlate with mTORC1 activity but not with p53 status. Finally, clinical data indicate that HNSCC patients with p21 and phospho-S6-double-positive tumours present a better disease-specific survival. We conclude that over-activation of the mTORC1/4E-BP1/p21 pathway is a frequent and clinically relevant alteration in HNSCC.We are grateful to Reidar Grenman, Silvio Gutkind, Nahum Sonenberg, Gordon Peters, David Sabatini and Mariano Barbacid for sharing critical reagents. We also thank Aurora Astudillo, Aitana Vallina, Laura Alonso-Dura ́n and Eva Allonca for excellent technical assistance. Work in the laboratory of M.S. is funded by the CNIO and by grants from the Spanish Ministry of Economy (SAF) co-funded by the European Regional Development Fund, the European Research Council (ERC Advanced Grant), the Regional Government of Madrid co-funded by the European Social Fund, the Botin Foundation and BancoSantander (Santander Universities Global Division), the Ramon Areces Foundation an the AXA Foundation. Work in the laboratory of J.M.G.-P. and J.P.R. was supported bygrants from Plan Nacional de DþI 2013–2016 ISCIII (CP13/00013 andPI13/00259),RD12/0036/0015 of Red Tematica de Investigacio ́n Cooperativa en Cancer (RTICC), Spain and the FEDER Funding Program from the European UnionS

Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action

Myotonic dystrophy 1 (DM1) is caused by a CTG expansion in the 3′-unstranslated region of the DMPK gene, which encodes a serine/threonine protein kinase. One of the common clinical features of DM1 patients is insulin resistance, which has been associated with a pathogenic effect of the repeat expansions. Here we show that DMPK itself is a positive modulator of insulin action. DMPK-deficient (dmpk−/−) mice exhibit impaired insulin signaling in muscle tissues but not in adipocytes and liver, tissues in which DMPK is not expressed. Dmpk−/− mice display metabolic derangements such as abnormal glucose tolerance, reduced glucose uptake and impaired insulin-dependent GLUT4 trafficking in muscle. Using DMPK mutants, we show that DMPK is required for a correct intracellular trafficking of insulin and IGF-1 receptors, providing a mechanism to explain the molecular and metabolic phenotype of dmpk−/− mice. Taken together, these findings indicate that reduced DMPK expression may directly influence the onset of insulin-resistance in DM1 patients and point to dmpk as a new candidate gene for susceptibility to type 2-diabetes

Pengaruh Solvabilitas dan Ukuran Perusahaan terhadap Nilai Perusahaan pada Perusahaan Restaurant, Hotel & Tourism Yang terdaftar di Bursa Efek Indonesia Tahun 2015-2017

Penelitian ini bertujuan untuk mengetahui pengaruh solvabilitas dan ukuran perusahaan terhadap nilai perusahaan, metodeyang digunakan penelitian sensus, yakni memasukkan semua perusahaan restaurant, hotel & tourism yang terdaftar di Bursa Efek Indonesia yang telah memenuhi kriteria ke dalam data pengamatan.Periode pengamatan data mulai tahun 2015 s.d 2017, berjumlah 66 perusahaan.Metode analisis data yang digunakan adalah regresi berganda linear.Hasil penelitian ini menyatakan bahwa solvabilitas dan ukuran perusahaan berpengaruh terhadap nilai perusahaan, baik secara individu (parsial) maupun bersama-sama (simultan)

Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism

Abstract The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused studies were also performed in tissues from ob/ob and db/db mice. We document that T2D, both early and late onset, are characterized by reduced muscle expression of genes involved in branched-chain amino acids (BCAA) metabolism. Weighted Co-expression Networks Analysis provided support to idea that the BCAA genes are relevant in the pathophysiology of type 2 diabetes, and that mitochondrial BCAA management is impaired in skeletal muscle from T2D patients. In diabetic mice model we detected alterations in skeletal muscle proteins involved in BCAA metabolism but not in obese mice. Metabolomic analysis revealed increased levels of branched-chain keto acids (BCKA), and BCAA in plasma of T2D patients, which may result from the disruption of muscle BCAA management. Our data support the view that inhibition of genes involved in BCAA handling in skeletal muscle takes place as part of the pathophysiology of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes