The Radio Jet Associated with the Multiple V380 Ori System

The giant Herbig-Haro object 222 extends over $\sim$6$'$ in the plane of the sky, with a bow shock morphology. The identification of its exciting source has remained uncertain over the years. A non-thermal radio source located at the core of the shock structure was proposed to be the exciting source. However, Very Large Array studies showed that the radio source has a clear morphology of radio galaxy and a lack of flux variations or proper motions, favoring an extragalactic origin. Recently, an optical-IR study proposed that this giant HH object is driven by the multiple stellar system V380 Ori, located about 23$'$ to the SE of HH 222. The exciting sources of HH systems are usually detected as weak free-free emitters at centimeter wavelengths. Here we report the detection of an elongated radio source associated with the Herbig Be star or with its close infrared companion in the multiple V380 Ori system. This radio source has the characteristics of a thermal radio jet and is aligned with the direction of the giant outflow defined by HH~222 and its suggested counterpart to the SE, HH~1041. We propose that this radio jet traces the origin of the large scale HH outflow. Assuming that the jet arises from the Herbig Be star, the radio luminosity is a few times smaller than the value expected from the radio-bolometric correlation for radio jets, confirming that this is a more evolved object than those used to establish the correlation.Comment: 13 pages, 3 figure

Insulin secretion in health and disease: nutrients dictate the pace.

Insulin is a key hormone controlling metabolic homeostasis. Loss or dysfunction of pancreatic β-cells lead to the release of insufficient insulin to cover the organism needs, promoting diabetes development. Since dietary nutrients influence the activity of β-cells, their inadequate intake, absorption and/or utilisation can be detrimental. This review will highlight the physiological and pathological effects of nutrients on insulin secretion and discuss the underlying mechanisms. Glucose uptake and metabolism in β-cells trigger insulin secretion. This effect of glucose is potentiated by amino acids and fatty acids, as well as by entero-endocrine hormones and neuropeptides released by the digestive tract in response to nutrients. Glucose controls also basal and compensatory β-cell proliferation and, along with fatty acids, regulates insulin biosynthesis. If in the short-term nutrients promote β-cell activities, chronic exposure to nutrients can be detrimental to β-cells and causes reduced insulin transcription, increased basal secretion and impaired insulin release in response to stimulatory glucose concentrations, with a consequent increase in diabetes risk. Likewise, suboptimal early-life nutrition (e.g. parental high-fat or low-protein diet) causes altered β-cell mass and function in adulthood. The mechanisms mediating nutrient-induced β-cell dysfunction include transcriptional, post-transcriptional and translational modifications of genes involved in insulin biosynthesis and secretion, carbohydrate and lipid metabolism, cell differentiation, proliferation and survival. Altered expression of these genes is partly caused by changes in non-coding RNA transcripts induced by unbalanced nutrient uptake. A better understanding of the mechanisms leading to β-cell dysfunction will be critical to improve treatment and find a cure for diabetes

ALMA 690 GHz observations of IRAS 16293-2422B: Infall in a highly optically-thick disk

We present sensitive, high angular resolution ($\sim$ 0.2 arcsec) submillimeter continuum and line observations of IRAS 16293-2422B made with the Atacama Large Millimeter/Submillimeter Array (ALMA). The 0.45 mm continuum observations reveal a single and very compact source associated with IRAS 16293-2422B. This submillimeter source has a deconvolved angular size of about 400 {\it milli-arcseconds} (50 AU), and does not show any inner structure inside of this diameter. The H$^{13}$CN, HC$^{15}$N, and CH$_{3}$OH line emission regions are about twice as large as the continuum emission and reveal a pronounced inner depression or "hole" with a size comparable to that estimated for the submillimeter continuum. We suggest that the presence of this inner depression and the fact that we do not see inner structure (or a flat structure) in the continuum is produced by very optically thick dust located in the innermost parts of IRAS 16293-2422B. All three lines also show pronounced inverse P-Cygni profiles with infall and dispersion velocities larger than those recently reported from observations at lower frequencies, suggesting that we are detecting faster, and more turbulent gas located closer to the central object. Finally, we report a small east-west velocity gradient in IRAS 16293-2422B that suggests that its disk plane is likely located very close to the plane of the sky.Comment: Accepted to ApJ

Postnatal β-cell maturation is associated with islet-specific microRNA changes induced by nutrient shifts at weaning.

Glucose-induced insulin secretion is an essential function of pancreatic β-cells that is partially lost in individuals affected by Type 2 diabetes. This unique property of β-cells is acquired through a poorly understood postnatal maturation process involving major modifications in gene expression programs. Here we show that β-cell maturation is associated with changes in microRNA expression induced by the nutritional transition that occurs at weaning. When mimicked in newborn islet cells, modifications in the level of specific microRNAs result in a switch in the expression of metabolic enzymes and cause the acquisition of glucose-induced insulin release. Our data suggest microRNAs have a central role in postnatal β-cell maturation and in the determination of adult functional β-cell mass. A better understanding of the events governing β-cell maturation may help understand why some individuals are predisposed to developing diabetes and could lead to new strategies for the treatment of this common metabolic disease

Una Comparacion Sobre la Percepcion de la Utilidad del Modelo ITIL por Usuarios y Consultores en Mexico

Information technologies (IT) have become a key factor for the optimal implementation of business processes, to a degree in which the IT department becomes a service provider for the other departments in the organization. In Mexico several business have adopted the ITIL services standard created by the Office of Government Commerce of the United Kingdom. ITIL is a compendium of best practices of great dimensions, requiring extensive training. Given this, the perceived usefulness of adopting the standard may vary among IT professionals. In this work we are currently investigating about the perceived value of ITIL for both consultants and final users. Our research in progress intends to assess the current position about this standard in Mexico. The expected results should impact consultant efforts for supporting ITIL, as well as educational programs based on the standar

Roles of Noncoding RNAs in Islet Biology.

The discovery that most mammalian genome sequences are transcribed to ribonucleic acids (RNA) has revolutionized our understanding of the mechanisms governing key cellular processes and of the causes of human diseases, including diabetes mellitus. Pancreatic islet cells were found to contain thousands of noncoding RNAs (ncRNAs), including micro-RNAs (miRNAs), PIWI-associated RNAs, small nucleolar RNAs, tRNA-derived fragments, long non-coding RNAs, and circular RNAs. While the involvement of miRNAs in islet function and in the etiology of diabetes is now well documented, there is emerging evidence indicating that other classes of ncRNAs are also participating in different aspects of islet physiology. The aim of this article will be to provide a comprehensive and updated view of the studies carried out in human samples and rodent models over the past 15 years on the role of ncRNAs in the control of α- and β-cell development and function and to highlight the recent discoveries in the field. We not only describe the role of ncRNAs in the control of insulin and glucagon secretion but also address the contribution of these regulatory molecules in the proliferation and survival of islet cells under physiological and pathological conditions. It is now well established that most cells release part of their ncRNAs inside small extracellular vesicles, allowing the delivery of genetic material to neighboring or distantly located target cells. The role of these secreted RNAs in cell-to-cell communication between β-cells and other metabolic tissues as well as their potential use as diabetes biomarkers will be discussed. © 2020 American Physiological Society. Compr Physiol 10:893-932, 2020

Circular RNAs as novel regulators of β-cell functions in normal and disease conditions.

There is strong evidence for an involvement of different classes of non-coding RNAs, including microRNAs and long non-coding RNAs, in the regulation of β-cell activities and in diabetes development. Circular RNAs were recently discovered to constitute a substantial fraction of the mammalian transcriptome but the contribution of these non-coding RNAs in physiological and disease processes remains largely unknown. The goal of this study was to identify the circular RNAs expressed in pancreatic islets and to elucidate their possible role in the control of β-cells functions. We used a microarray approach to identify circular RNAs expressed in human islets and searched their orthologues in RNA sequencing data from mouse islets. We then measured the level of four selected circular RNAs in the islets of different Type 1 and Type 2 diabetes models and analyzed the role of these circular transcripts in the regulation of insulin secretion, β-cell proliferation, and apoptosis. We identified thousands of circular RNAs expressed in human pancreatic islets, 497 of which were conserved in mouse islets. The level of two of these circular transcripts, circHIPK3 and ciRS-7/CDR1as, was found to be reduced in the islets of diabetic db/db mice. Mimicking this decrease in the islets of wild type animals resulted in impaired insulin secretion, reduced β-cell proliferation, and survival. ciRS-7/CDR1as has been previously proposed to function by blocking miR-7. Transcriptomic analysis revealed that circHIPK3 acts by sequestering a group of microRNAs, including miR-124-3p and miR-338-3p, and by regulating the expression of key β-cell genes, such as Slc2a2, Akt1, and Mtpn. Our findings point to circular RNAs as novel regulators of β-cell activities and suggest an involvement of this novel class of non-coding RNAs in β-cell dysfunction under diabetic conditions

Scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation.

Glucose-induced insulin secretion, a hallmark of mature β-cells, is achieved after birth and is preceded by a phase of intense proliferation. These events occurring in the neonatal period are decisive for establishing an appropriate functional β-cell mass that provides the required insulin throughout life. However, key regulators of gene expression involved in functional maturation of β-cells remain to be elucidated. Here, we addressed this issue by mapping open chromatin regions in newborn versus adult rat islets using the ATAC-seq assay. We obtained a genome-wide picture of chromatin accessible sites (~ 100,000) among which 20% were differentially accessible during maturation. An enrichment analysis of transcription factor binding sites identified a group of transcription factors that could explain these changes. Among them, Scrt1 was found to act as a transcriptional repressor and to control β-cell proliferation. Interestingly, Scrt1 expression was controlled by the transcriptional repressor RE-1 silencing transcription factor (REST) and was increased in an in vitro reprogramming system of pancreatic exocrine cells to β-like cells. Overall, this study led to the identification of several known and unforeseen key transcriptional events occurring during β-cell maturation. These findings will help defining new strategies to induce the functional maturation of surrogate insulin-producing cells

Small RNAs derived from tRNA fragmentation regulate the functional maturation of neonatal β cells.

tRNA-derived fragments (tRFs) are an emerging class of small non-coding RNAs with distinct cellular functions. Here, we studied the contribution of tRFs to the regulation of postnatal β cell maturation, a critical process that may lead to diabetes susceptibility in adulthood. We identified three tRFs abundant in neonatal rat islets originating from 5' halves (tiRNA-5s) of histidine and glutamate tRNAs. Their inhibition in these islets reduced β cell proliferation and insulin secretion. Mitochondrial respiration was also perturbed, fitting with the mitochondrial enrichment of nuclear-encoded tiRNA-5 <sup>HisGTG</sup> and tiRNA-5 <sup>GluCTC</sup> . Notably, tiRNA-5 inhibition reduced Mpc1, a mitochondrial pyruvate carrier whose knock down largely phenocopied tiRNA-5 inhibition. tiRNA-5 <sup>HisGTG</sup> interactome revealed binding to Musashi-1, which was essential for the mitochondrial enrichment of tiRNA-5 <sup>HisGTG</sup> . Finally, tiRNA-5s were dysregulated in the islets of diabetic and diabetes-prone animals. Altogether, tiRNA-5s represent a class of regulators of β cell maturation, and their deregulation in neonatal islets may lead to diabetes susceptibility in adulthood