Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing

It was shown previously that abnormal prohormone processing or inactive proconverting enzymes that are responsible for this processing cause profound obesity. Our laboratory demonstrated earlier that in the diet-induced obesity (DIO) state, the appetite-suppressing neuropeptide -melanocyte-stimulating hormone ( -MSH) is reduced, yet the mRNA of its precursor protein proopiomelanocortin (POMC) remained unaltered. It was also shown that the DIO condition promotes the development of endoplasmic reticulum (ER) stress and leptin resistance. In the current study, using an in vivo model combined with in vitro experiments, we demonstrate that obesity-induced ER stress obstructs the post-translational processing of POMC by decreasing proconverting enzyme 2, which catalyzes the conversion of adrenocorticotropin to -MSH, thereby decreasing -MSH peptide production. This novel mechanism of ER stress affecting POMC processing in DIO highlights the importance of ER stress in regulating central energy balance in obesity.Fil: Cakir, Isin. Brown University; Estados UnidosFil: Cyr, Nicole E.. Brown University; Estados UnidosFil: Perello, Mario. Brown University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Litvinov, Bogdan Patedakis. Brown University; Estados UnidosFil: Romero, Amparo. Brown University; Estados UnidosFil: Stuart, Ronald C.. Brown University; Estados UnidosFil: Nillni, Eduardo A.. Brown University; Estados Unido

Presencia de metales pesados en un suelo aledaño a una escombrera polimetálica en mina la ferrocarrilera, Lago Fontana. Chubut, Argentina

En la provincia de Chubut, Argentina, se desarrollaron actividades extractivas polimetálicas anteriores a las leyes ambientales vigentes desde hace unas décadas. En muchos casos, esas explotaciones fueron abandonadas sin haberse llevarse a cabo tareas de remediación-restauración, y deben realizarse estudios para determinar si constituyen pasivos ambientales mineros. En este trabajo se determinaron los impactos generados sobre el suelo por una escombrera de la Mina La Ferrocarrilera, ubicada sobre la margen sur del Lago Fontana, Chubut. La Ferrocarrilera es una estructura vetiforme emplazada en las rocas andesíticas de la Formación Lago La Plata., que posee sulfuros de Pb, Ag y Zn y escaso Au en ganga de cuarzo. Se describieron dos perfiles de suelo, uno de control ubicado en un área aledaña a la mina (PLF1) y otro a 1 metro del pie de la escombrera (PLF2). Se determinaron propiedades físicas y químicas, y los contenidos de Cu, Zn As y Pb en los horizontes del suelo. Los suelos de ambos perfiles son similares en cuanto a la secuencia de horizontes que presentan, las texturas, la conductividad eléctrica y el contenido de materia orgánica; en cambio PLF2 presenta menor pH y mayores contenidos de Pb, Zn, Cu y As que PFL1. Esto se explica porque el pH de la escombrera es fuertemente ácido, permitiendo la disolución de los metales pesados y metaloides contenidos en los sulfuros, que son movilizados por el drenaje superficial o sub superficial desde la escombrera hacia el suelo ubicado topográficamente por debajo, generando drenaje ácido de mina.For several decades, polymetallic extractive activities were carried on in Chubut province, prior to the environmental laws in force. In many cases, these mines were abandoned without remediation-restoration works, consequently they should be studied to determine whether they constitute mining environmental liabilities. In this work, the impacts generated on the soils by one of the wastes of La Ferrocarrilera mine, at southern margin of Fontana Lake, were determined. La Ferrocarrilera is a vein-type deposit located in andesitic rocks of Lago La Plata Formation, whit of Pb, Ag y Zn sulfides, and scarce gold in quartz gangue. Two soil profiles were described, one in an area adjacent to the mine (PLF1) and the other at 1 meter from the base of the dump (PLF2).Physical and chemical properties and Cu, Zn, As and Pb contents were determined in the different soil horizons. Both profiles are similar in terms of the sequence of horizons they present, textures, electrical conductivity and organic matter content; in contrast PLF2 presents lower pH and higher contents of Pb, Zn, Cu and As than PFL1. This can be explained because the pH of the dump is strongly acid, allowing the dissolution of heavy metals and metalloids contained in the sulfides, which are mobilized by surface or sub-surface drainage from the dump to the soil located topographically below, generating mine acid drainage.Fil: Rack, Mónica Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Patagonia; ArgentinaFil: Nillni, Adriana Mónica. Universidad Nacional de la Patagonia; ArgentinaFil: Do Campo, Margarita Diana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotopica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: Valenzuela, María Fernanda. Universidad Nacional de la Patagonia; ArgentinaFil: Ferro, Leonardo Fabio. Universidad Nacional de la Patagonia; Argentin

New synchronization method for <i>Plasmodium falciparum</i>

&lt;b&gt;Background&lt;/b&gt;: Plasmodium falciparum is usually asynchronous during in vitro culture. Although various synchronization methods are available, they are not able to narrow the range of ages of parasites. A newly developed method is described that allows synchronization of parasites to produce cultures with an age range as low as 30 minutes. &lt;b&gt;Methods&lt;/b&gt;: Trophozoites and schizonts are enriched using Plasmion. The enriched late stage parasites are immobilized as a monolayer onto plastic Petri dishes using concanavalin A. Uninfected erythrocytes are placed onto the monolayer for a limited time period, during which time schizonts on the monolayer rupture and the released merozoites invade the fresh erythrocytes. The overlay is then taken off into a culture flask, resulting in a highly synchronized population of parasites. &lt;b&gt;Results&lt;/b&gt;: Plasmion treatment results in a 10- to 13-fold enrichment of late stage parasites. The monolayer method results in highly synchronized cultures of parasites where invasion has occurred within a very limited time window, which can be as low as 30 minutes. The method is simple, requiring no specialized equipment and relatively cheap reagents. &lt;b&gt;Conclusions&lt;/b&gt;: The new method for parasite synchronization results in highly synchronized populations of parasites, which will be useful for studies of the parasite asexual cell cycle

Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing

It was shown previously that abnormal prohormone processing or inactive proconverting enzymes that are responsible for this processing cause profound obesity. Our laboratory demonstrated earlier that in the diet-induced obesity (DIO) state, the appetite-suppressing neuropeptide -melanocyte-stimulating hormone ( -MSH) is reduced, yet the mRNA of its precursor protein proopiomelanocortin (POMC) remained unaltered. It was also shown that the DIO condition promotes the development of endoplasmic reticulum (ER) stress and leptin resistance. In the current study, using an in vivo model combined with in vitro experiments, we demonstrate that obesity-induced ER stress obstructs the post-translational processing of POMC by decreasing proconverting enzyme 2, which catalyzes the conversion of adrenocorticotropin to -MSH, thereby decreasing -MSH peptide production. This novel mechanism of ER stress affecting POMC processing in DIO highlights the importance of ER stress in regulating central energy balance in obesity.Fil: Cakir, Isin. Brown University; Estados UnidosFil: Cyr, Nicole E.. Brown University; Estados UnidosFil: Perello, Mario. Brown University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Litvinov, Bogdan Patedakis. Brown University; Estados UnidosFil: Romero, Amparo. Brown University; Estados UnidosFil: Stuart, Ronald C.. Brown University; Estados UnidosFil: Nillni, Eduardo A.. Brown University; Estados Unido

Levodopa-Induced Dyskinesia Is Associated with Increased Thyrotropin Releasing Hormone in the Dorsal Striatum of Hemi-Parkinsonian Rats

Background Dyskinesias associated with involuntary movements and painful muscle contractions are a common and severe complication of standard levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) therapy for Parkinson's disease. Pathologic neuroplasticity leading to hyper-responsive dopamine receptor signaling in the sensorimotor striatum is thought to underlie this currently untreatable condition. Methodology/Principal Findings Quantitative real-time polymerase chain reaction (PCR) was employed to evaluate the molecular changes associated with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we determined that thyrotropin releasing hormone (TRH) was greatly increased in the dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal movements in response to L-DOPA therapy, relative to the levels measured in the contralateral non-dopamine-depleted striatum, and in the striatum of non-dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels were almost absent in the dopamine-depleted striatum of control rats that did not develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was dramatically up-regulated in the striatum, particularly in the sensorimotor striatum. This up-regulation of TRH peptide affected striatal medium spiny neurons of both the direct and indirect pathways, as well as neurons in striosomes. Conclusions/Significance TRH is not known to be a key striatal neuromodulator, but intrastriatal injection of TRH in experimental animals can induce abnormal movements, apparently through increasing dopamine release. Our finding of a dramatic and selective up-regulation of TRH expression in the sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper-responsivity in Parkinson's disease.Morris K. Udall Center for Excellence in Parkinson’s Research at MGH/MITNational Institutes of Health (U.S.) (NIH NS38372)American Parkinson Disease Association, Inc.University of Alabama at BirminghamMassachusetts General HospitalNational Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIDDK/NIH grant R01 DK58148)National Institute of Neurological Disorders and Stroke (U.S.) (R01 NINDS/NIH grant NS045231)Stanley H. and Sheila G. Sydney FundMichael J. Fox Foundation for Parkinson's Researc

Alteration of Hypothalamic–Pituitary–Thyroid Axis Function in Non-Small-Cell Lung Cancer Patients

The aim of this study was to evaluate the hypothalamic–pituitary–thyroid (HPT) axis function in patients suffering from lung cancer. Thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free thyroxine (FT4), interleukin (IL)-2, and melatonin serum levels were measured in blood samples collected every 4 hours for 24 hours from 11 healthy participants (H; ages 35-53 years) and 9 patients suffering from non-small-cell lung cancer (C; ages 43-63 years). Relationships between hormone levels overall and over time of day were evaluated within and among groups. A prominent circadian rhythm with peaks near midnight was present for TSH and melatonin serum levels in both H and C, indicating similar synchronization of the main body clock to the 24-hour environmental light–dark cycle. As regards 24-hour means in H and C, TSH was lower in C, whereas TRH, FT4, and IL-2 were higher in C, with no difference in melatonin levels. Simple linear regression, FT4 versus TRH, showed a positive correlation in H..

Explosive Volcanism in a tuff-dominated Intraplate Setting, Sarmiento Formation (Middle Eocene- lower Miocene), Patagonia Argentina

The Sarmiento Formation (middle Eocene to early Miocene) represents the distal record of the activity of the Andean volcanic arc in central Patagonia, mainly dominated by accumulation and reworking of fine ash in a low-gradient continental setting. Intraplate volcanism takes place in the Golfo San Jorge Basin during the deposition of the Sarmiento Formation, and shallow intrusives and basaltic lava flows occurs. An exposure of basaltic volcaniclastic deposits was analyzed in the proximity of the Cerro Dragón intrusive rocks. These deposits consist of eight volcaniclastic lithofacies, organized in three distinct lithofacies association: volcaniclastic debris flow (lahar), base surge, and scoriaceous breccias of a strombolian-style eruption. Explosive volcanism is evidenced by the fallout of ballistic bombs over base surge and scoriaceous deposits, which produced bedding sags in the plastic lapilli. These deposits constitute the first published record of explosive volcanism (Strombolian) associated to the emplacement of the Oligocene alkaline volcanic rocks in the Golfo San Jorge Basin, generally considered as subintrusive or hypabissal intrusions

Comparison of the in vitro invasive capabilities of Plasmodium falciparum schizonts isolated by Percoll gradient or using magnetic based separation

<p>Abstract</p> <p>Background</p> <p>Percoll gradient centrifugation is often used for synchronization, enrichment, or isolation of a particular stage of <it>Plasmodium falciparum</it>. However, Percoll, a hyperosmotic agent, may have harmful effects on the parasites. Magnetic bead column (MBC) separation has been used as an alternative. This is a report of a head-to-head comparison of the <it>in vitro </it>invasive capabilities of parasites isolated by either of the two methods.</p> <p>Methods</p> <p>The <it>P. falciparum </it>laboratory strain isolate 7G8 was grown <it>in vitro </it>using standard procedures and synchronized using 5% sorbitol. On separate days when the schizont parasitaemia was >1%, the culture was split and half was processed by Percoll gradient centrifugation and the other half by magnetic bead column separation. Both processed parasites were placed back in culture and allowed to invade new uninfected erythrocytes.</p> <p>Results</p> <p>In 10 paired assays, the mean efficiency of invasion of 7G8 parasites treated by Percoll gradient centrifugation was 35.8% that of those treated by magnetic bead column separation (95% CI, p = 0.00067) A paired <it>t </it>test with two tails was used for these comparisons.</p> <p>Conclusions</p> <p>In this comparison, magnetic bead column separation of 7G8 schizonts resulted in higher viability and efficiency of invasion than utilizing Percoll gradient centrifugation.</p

Preoptic leptin signaling modulates energy balance independent of body temperature regulation

© Yu et al. The adipokine leptin acts on the brain to regulate energy balance but specific functions in many brain areas remain poorly understood. Among these, the preoptic area (POA) is well known to regulate core body temperature by controlling brown fat thermogenesis, and we have previously shown that glutamatergic, long-form leptin receptor (Lepr)-expressing neurons in the POA are stimulated by warm ambient temperature and suppress energy expenditure and food intake. Here we further investigate the role of POA leptin signaling in body weight regulation and its relationship to body temperature regulation in mice. We show that POA Lepr signaling modulates energy expenditure in response to internal energy state, and thus contributes to body weight homeostasis. However, POA leptin signaling is not involved in ambient temperature-dependent metabolic adaptations. Our study reveals a novel cell population through which leptin regulates body weight

Fossil-diagenesis in dinosaurs remains preserved in fuvial deposits of the Lago Colhué Huapi Formation (Upper Cretaceous), Golfo San Jorge Basin, Argentina

En este trabajo se proporciona nueva información sedimentológica y fosildiagenética de restos de cuatro dinosaurios preservados en depósitos de diferentes subambientes fluviales de la sección media de la Formación Lago Colhué Huapi, en la Cuenca del Golfo San Jorge. En todos los casos, la estructura ósea originalmente constituida por hidroxiapatita fue modificada por sustitución iónica a francolita. Los restos fósiles contenidos en litoarenitas finas con alta participación de arcillas que sufrieron fuerte compactación, exhiben deformación plástica e intensa fracturación, que afectó la microestructura ósea. La francolita presenta una textura cavernosa con alto índice de cristalinidad y un menor contenido en carbonato que evidencia procesos de disolución del mineral en un medio ácido. La hematita presente externamente como costras y nódulos, e internamente en los bordes de los canales vasculares, se vincula a la precipitación de óxidos de hierro en zonas bien oxigenadas relacionadas con fluctuaciones del nivel freático. La permineralización de los canales vasculares con hematita, y con cristales bien desarrollados de fluorapatita de neoformación habría ocurrido durante la diagénesis temprana. En contraste, los restos fósiles contenidos en litoarenitas gruesas con escasas arcillas sufrieron menos compactación y están mejor preservados. En estos casos, la francolita presenta una textura maciza con menor índice de cristalinidad y mayor contenido en carbonato. La permineralización de los canales vasculares con hematita y con cristales bien desarrollados de calcita habría ocurrido en un medio alcalino y durante la diagénesis tardía. En los cuatro casos de estudio pudo determinarse que los índices de cristalinidad de la francolita y los contenidos en carbonato, suponen una correlación positiva del índice con el incremento relativo del contenido de flúor y el aumento de la fragilidad de los restos fósiles. De esta manera, los estudios sedimentológicos y fosildiagenéticos, en particular los procesos de permineralización en las cavidades vasculares, permiten aproximarnos al conocimiento de las condiciones físicas y químicas existentes durante la litificación y fosilización de los restos en diferentes subambientes fluviales de la Formación Lago Colhué Huapi.New sedimentological and fossil-diagenetic information from remains of four dinosaurs is herein provided. The fossil material was preserved in deposits of different fluvial sub-environments from the middle section of the Lago Colhué Huapi Formation, Golfo San Jorge Basin. In all the studied cases, the bone structure originally constituted by hydroxyapatite was modified by ionic substitution to francolite. The fossil remains contained in fine lithoarenites with high clay minerals content, affected by lithostatic compression, exhibit plastic deformation and intense fracturing which affected the bone microstructure. The francolite presents cavernous texture with high crystallinity index and a lower carbonate content, evidencing processes of mineral dissolution in an acidic environment. The hematite is present as crusts and nodules on the surface of the bones and internally at the edges of the vascular channels. It is related to the precipitation of iron oxide in well oxygenated areas with fluctuating water table. The permineralization of the vascular channels with hematite and well-developed crystals of fluorapatite of neoformation, would have occurred during the early diagenesis. By contrast, the fossil remains contained in coarse lithoarenites with scarce clay minerals, have been less affected by lithostatic compression and are better preserved. The francolite exhibits a massive texture with a lower index of crystallinity and higher carbonate concentration. The permineralization of the vascular channels with hematite and well-developed crystals of calcite would have occurred in an alkaline environment during the late diagenesis. In the four study-cases it could be determined that the crystallinity indexes of the francolite and the carbonate content, display a positive correlation with the relative increase of fluorine content and the fragility of the fossil remains. Therefore, the sedimentological and fossil-diagenetic studies, in particular the permineralization processes in the vascular channels, enhance our understanding of the physical and chemical conditions that prevailed during the lithification and fossilization of the remains in different fluvial sub-environments from the Lago Colhué Huapi Formation.Fil: Casal, Gabriel. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Comodoro. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nillni, Adriana Mónica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Comodoro. Departamento de Geología; ArgentinaFil: Valle, Mauro Nicolás. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Comodoro. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González Svoboda, Ezequiel. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Comodoro. Departamento de Geología; ArgentinaFil: Tiedemann, María Celina. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Comodoro; ArgentinaFil: Ciapparelli, Helena. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Comodoro. Departamento de Geología; ArgentinaFil: Ibiricu, Lucio Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Geología y Paleontología; ArgentinaFil: Luiz, Marta Mabel. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentin