MicroRNA Profiling and Bioinformatics Target Analysis in Dorsal Hippocampus of Chronically Stressed Rats: Relevance to Depression Pathophysiology

Indexación: Scopus.1Laboratory of Neuroplasticity and Neurogenetics, Faculty of Chemical and Pharmaceutical Sciences, Department of Biochemistry and Molecular Biology, Universidad de Chile, Santiago, Chile, 2National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Durham, NC, United States, 3Centro de Genómica y Bioinformática, Facultad de Ciencias, Universidad Mayor, Santiago, Chile, 4Millennium Institute for Integrative Biology (iBio), FONDAP Center for Genome Regulation, Departamento de Genética Molecular y Microbiología, Pontificia Universidad Católica de Chile, Santiago, Chile, 5Department of Kinesiology, Faculty of Health Sciences, Universidad Católica del Maule, Talca, Chile, 6Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.This study was supported by the following grants: FONDECYT 1120528 (JLF), Fondo Central de Investigación, Universidad de Chile ENL025/16 (JLF), ES090079 (JAC). Research in RG and EV laboratories is funded by Instituto Milenio iBio – Iniciativa Científica Milenio MINECON.Studies conducted in rodents subjected to chronic stress and some observations in humans after psychosocial stress, have allowed to establish a link between stress and the susceptibility to many complex diseases, including mood disorders. The studies in rodents have revealed that chronic exposure to stress negatively affects synaptic plasticity by triggering changes in the production of trophic factors, subunit levels of glutamate ionotropic receptors, neuron morphology, and neurogenesis in the adult hippocampus. These modifications may account for the impairment in learning and memory processes observed in chronically stressed animals. It is plausible then, that stress modifies the interplay between signal transduction cascades and gene expression regulation in the hippocampus, therefore leading to altered neuroplasticity and functioning of neural circuits. Considering that miRNAs play an important role in post-transcriptional-regulation of gene expression and participate in several hippocampus-dependent functions; we evaluated the consequences of chronic stress on the expression of miRNAs in dorsal (anterior) portion of the hippocampus, which participates in memory formation in rodents. Here, we show that male rats exposed to daily restraint stress (2.5 h/day) during 7 and 14 days display a differential profile of miRNA levels in dorsal hippocampus and remarkably, we found that some of these miRNAs belong to the miR-379-410 cluster. We confirmed a rise in miR-92a and miR-485 levels after 14 days of stress by qPCR, an effect that was not mimicked by chronic administration of corticosterone (14 days). Our in silico study identified the top-10 biological functions influenced by miR-92a, nine of which were shared with miR-485: Nervous system development and function, Tissue development, Behavior, Embryonic development, Organ development, Organismal development, Organismal survival, Tissue morphology, and Organ morphology. Furthermore, our in silico study provided a landscape of potential miRNA-92a and miR-485 targets, along with relevant canonical pathways related to axonal guidance signaling and cAMP signaling, which may influence the functioning of several neuroplastic substrates in dorsal hippocampus. Additionally, the combined effect of miR-92a and miR-485 on transcription factors, along with histone-modifying enzymes, may have a functional relevance by producing changes in gene regulatory networks that modify the neuroplastic capacity of the adult dorsal hippocampus under stress. © 2018 Muñoz-Llanos, García-Pérez, Xu, Tejos-Bravo, Vidal, Moyano, Gutiérrez, Aguayo, Pacheco, García-Rojo, Aliaga, Rojas, Cidlowski and Fiedler.https://www.frontiersin.org/articles/10.3389/fnmol.2018.00251/ful

Deleterious effects of litter on marine life

In this review we report new findings concerning interaction between marine debris and wildlife. Deleterious effects and consequences of entanglement, consumption and smothering are highlighted and discussed. The number of species known to have been affected by either entanglement or ingestion of plastic debris has doubled since 1997, from 267 to 557 species among all groups of wildlife. For marine turtles the number of affected species increased from 86 to 100 % (now 7 of 7 species), for marine mammals from 43 to 66 % (now 81 of 123 species) and for seabirds from 44 to 50 % of species (now 203 of 406 species). Strong increases in records were also listed for fish and invertebrates, groups that were previously not considered in detail. In future records of interactions between marine debris and wildlife we recommend to focus on standardized data on frequency of occurrence and quantities of debris ingested. In combination with dedicated impact studies in the wild or experiments, this will allow more detailed assessments of the deleterious effects of marine debris on individuals and populations

Some histopathological and clinical correlations in oral squamous cell carcinoma

Oral squamous cell carcinoma (SCC) is an important health problem that causes high mortality and morbidity. Correlations between some clinical and histopathological parameters were studied in 37 oral SCC. Some interesting aspects in oral SCC arising from precancerous lesions were found such as smaller size and a lower TNM stage at the moment of diagnosis. Histological and clinical differences were also found between tumors invading deep tissues by little groups of dissociated malignant cells and those invading by big masses of malignant cells. The possible significance of the intensity of peritumoral eosinophilic infiltrate was also studied.Le carcinome squameux de la cavité orale constitue un problème important de santé, qui est responsable d’une mortalité et d’une morbidité élevées. Nous avons étudié 37 carcinomes squameux de la cavité orale à travers un suivi clinique et une étude des corrélations entre les variables cliniques et histopathologiques. Nous avons relevé différents aspects intéressants en ce qui concerne les carcinomes squameux de la cavité orale qui procédaient de lésions précancéreuses comme leur petite dimention et le bas stade TNM au moment du diagnostic. Nous avons également trouvé des différences cliniques et histopathologiques entre les tumeurs qui envahissent les tissus adjecents en petits groupes et ceux qui le font en grandes masses de cellules malignes. Finalement, nous avons étudié la signification possible de l’intensité de l’infiltrat à eosinophiles peritumoral

Fulmar Litter EcoQO monitoring in the Netherlands - Update 2012 and 2013

Fulmars are purely offshore foragers that ingest all sorts of litter from the sea surface and do not regurgitate poorly degradable diet components like plastics. Initial size of ingested debris is usually in the range of millimetres to centimeters, but may be considerably larger for flexible items as for instance threadlike or sheetlike materials. Items must gradually wear down in the muscular stomach to a size small enough for passage to the intestines. During this process, plastics accumulate in the stomach to a level that integrates litter levels encountered in their foraging area for a period of probably up to a few weeks. The Dutch monitoring approach using beached fulmars was developed for international implementation by OSPAR

Transmission properties of a single metallic slit: From the subwavelength regime to the geometrical-optics limit

In this work we explore the transmission properties of a single slit in a metallic screen. We analyze the dependence of these properties on both slit width and angle of incident radiation. We study in detail the crossover between the subwavelength regime and the geometrical-optics limit. In the subwavelength regime, resonant transmission linked to the excitation of waveguide resonances is analyzed. Linewidth of these resonances and their associated electric field intensities are controlled by just the width of the slit. More complex transmission spectra appear when the wavelength of light is comparable to the slit width. Rapid oscillations associated to the emergence of different propagating modes inside the slit are the main features appearing in this regime.Comment: Accepted for publication in Phys. Rev.

Osteocondritis disecante de primera cuña en la infancia: presentación de 1 caso

Se presenta un caso de osteocondritis disecante de la primera cuña en la infancia, patología no descrita hasta el momento en la literatura mundial. Se trata de una niña de 11 años que se estudió por dolor de 1 año de evolución y tras llegar al diagnóstico se trató mediante artrodesis de la primera articulación escafocuneana, encontrándose la paciente asintomática tras 10 meses de seguimiento.We report a case of osteochondritis dissecans of the first cuneiform bone in a child. We have not found a similar case in world literature. She is an 11 years old girl with 1 year of pain in her foot. After the diagnosis was made, the treatment was an arthrodesis of the first naviculo-cuneiform joint. The patient is now asympthomatic after 10 months of follow-u

Fracturas de estrés en la infancia

Aportamos 13 casos de fracturas de estrés diagnosticadas en nuestro centro en los últimos 5 años ocurridas en niños entre 4 y 15 años de edad. Encontramos una mayor incidencia en el sexo masculino (9 de los 13 casos), así como un claro predominio de la localización en el tercio proximal de la diáfisis tibial (7 casos), hallazgos que concuerdan con los referidos en la literatura. Uno de los aspectos más interesantes de este tipo de fracturas es su similitud tanto clínica como radiológica con procesos de origen infeccioso y neoplásico, por lo que la realización de un correcto diagnóstico diferencial, apoyado en las radiografías simples, tomografías, gammagrafía, TAC y, más recientemente, RMN, resulta crucial.We present 13 cases of stress fractures in children, collected in our center during the last 5 years. The age of patients ranged from 4 to 15 years old. In agreement with literature, we found a greater incidence on males (9 of 13 cases), and a predominant location on the proximal shaft of the tibia (7 cases). One of the most interesting aspects of this type of fractures is their clinical and radiological similarity with infections and tumors. Therefore, it is essential to achieve a right diagnosis based on standard radiographs, tomography, radionuclide bone scan, CT-scan and, most recently, MRI

Platelet serotonin levels are associated with plasma soluble leptin receptor concentrations in normoglycemic women

Most peripheral serotonin (5-hydroxytryptamine (5HT)) is synthetized in the gut with platelets being its main circulating reservoir. 5HT is acting as a hormone in key organs to regulate glucose and lipid metabolism. However, the relation between platelet 5HT levels and traits related to glucose homeostasis and lipid metabolism in humans remains poorly explored. The objectives of this study were (a) to assess the association between platelet 5HT levels and plasma concentration of nonesterified fatty acids (NEFAs) and some adipokines including leptin and its soluble leptin receptor (sOb-R), (b) to assess the association between platelet 5HT levels and anthropometric traits and indexes of insulin secretion/sensitivity derived from oral glucose tolerance test (OGTT), and (c) to evaluate changes in platelet 5HT levels in response to OGTT. In a cross-sectional study, 59 normoglycemic women underwent a standard 2-hour OGTT. Plasma leptin, sOb-R, total and high molecular weight adiponectin, TNFα, and MCP1 were determined by immunoassays. Platelet 5HT levels and NEFAs were measured before and after OGTT. The free leptin index was calculated from leptin and sOb-R measurements. Insulin sensitivity indexes derived from OGTT (HOMA-S and Matsuda ISICOMP) and plasma NEFAs (Adipose-IR, Revised QUICKI) were also calculated. Our data show that among metabolic traits, platelet 5HT levels were associated with plasma sOb-R (r = 0 39, p = 0 003, corrected p = 0 018). Platelet 5HT levels were reduced in response to OGTT (779 ± 237 vs 731 ± 217 ng/109 platelets, p = 0 005). In conclusion, platelet 5HT levels are positively associated with plasma sOb-R concentrations and reduced in response to glucose intake possibly indicating a role of peripheral 5HT in leptin-mediated appetite regulation

PPARGC1A gene promoter methylation as a biomarker of insulin secretion and sensitivity in response to glucose challenges

Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31; p = 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose