Impact of GLP-1 receptor agonist versus omega-3 fatty acids supplement on obesity-induced alterations of mitochondrial respiration

ObjectiveTo compare administration of the glucagon-like peptide-1 (GLP-1) analogue, exenatide, versus dietary supplementation with the omega-3 fatty acid-rich Calanus oil on obesity-induced alterations in mitochondrial respiration. MethodsSix-week-old female C57BL/6JOlaHSD mice were given high fat diet (HFD, 45% energy from fat) for 12 weeks to induce obesity. Thereafter, they were divided in three groups where one received exenatide (10 mu g/kg/day) via subcutaneously implanted mini-osmotic pumps, a second group received 2% Calanus oil as dietary supplement, while the third group received HFD without any treatment. Animals were sacrificed after 8 weeks of treatment and tissues (skeletal muscle, liver, and white adipose tissue) were collected for measurement of mitochondrial respiratory activity by high-resolution respirometry, using an Oroboros Oxygraph-2k (Oroboros instruments, Innsbruck, Austria). ResultsIt was found that high-fat feeding led to a marked reduction of mitochondrial respiration in adipose tissue during all three states investigated - LEAK, OXPHOS and ETS. This response was to some extent attenuated by exenatide treatment, but not with Calanus oil treatment. High-fat feeding had no major effect on hepatic mitochondrial respiration, but exenatide treatment resulted in a significant increase in the various respiratory states in liver. Mitochondrial respiration in skeletal muscle was not significantly influenced by high-fat diet or any of the treatments. The precise evaluation of mitochondrial respiration considering absolute oxygen flux and ratios to assess flux control efficiency avoided misinterpretation of the results. ConclusionsExenatide increased hepatic mitochondrial respiration in high-fat fed mice, but no clear beneficial effect was observed in skeletal muscle or fat tissue. Calanus oil did not negatively affect respiratory activity in these tissues, which maintains its potential as a dietary supplement, due to its previously reported benefits on cardiac functio

Análisis de los metabolitos secundarios producidos por los agentes de control biológico Bacillus amyloliquefaciens CECT 8237 Y CECT 8238

Las cepas de Bacillus amyloliquefaciens CECT 8237 (UMAF6639) y CECT 8238 (UMAF6614) han sido ampliamente estudiadas en trabajos previos de nuestro grupo por su reseñable capacidad de biocontrol. Desde un principio ha destacado su actividad antagonista frente a Podosphaera fusca y ciertas bacterias patógenas de cucurbitáceas, siendo la antibiosis mediada por lipopéptidos tales como iturinas y fengicinas, uno de los principales mecanismos de acción. La secuenciación de los genomas de ambas cepas nos ha permitido localizar un amplio grupo de genes implicados en la síntesis de otros antibióticos ya descritos con anterioridad en otras cepas del género Bacillus. Sin embargo, las cepas CECT 8237 y CECT 8238 siguen mostrando mayor capacidad de biocontrol que otros agentes de biocontrol, lo que nos lleva a pensar en la producción de otras moléculas activas. Por ello, hemos desarrollado herramientas bioinformáticas que han facilitado la identificación de regiones poco conservadas con respecto al género Bacillus, así como regiones presentes solo en las cepas de estudio. También se pudo determinar si la adquisición de estas regiones genómicas por parte de estas bacterias se debía a procesos de transferencia horizontal, debido a las variaciones en el patrón de tripletes de aminoácidos y/o en el contenido en GC de dichas zonas. Actualmente, se está realizando la caracterización de algunas de las regiones identificadas en la cepa CECT 8237, cuyos genes parecen estar implicados en la síntesis de nuevos antibióticos no descritos hasta la fecha. Todos estos resultados refuerzan la hipótesis de que la producción de antibióticos es el mecanismo de acción determinante en la actividad de biocontrol de estas bacterias.Este trabajo ha sido financiado por ayudas del Plan Nacional de I+D+I del Ministerio de Ciencia e Innovación (AGL2010-21848-CO2-01) e Incentivos a Proyectos de Excelencia de la Junta de Andalucía (P10-AGR-5797), ambos cofinanciados con fondos FEDER (UE) y una ayuda del Plan Propio de Investigación de la Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tech

Physiological changes in retinal layers thicknesses measured with swept source optical coherence tomography

Purpose To evaluate the physiological changes related with age of all retinal layers thickness measurements in macular and peripapillary areas in healthy eyes. Methods Wide protocol scan (with a field of view of 12x9 cm) from Triton SS-OCT instrument (Topcon Corporation, Japan) was performed 463 heathy eyes from 463 healthy controls. This protocol allows to measure the thickness of the following layers: Retina, Retinal nerve fiber layer (RNFL), Ganglion cell layer (GCL +), GCL++ and choroid. In those layers, mean thickness was compared in four groups of ages: Group 1 (71 healthy subjects aged between 20 and 34 years); Group 2 (65 individuals aged 35–49 years), Group 3 (230 healthy controls aged 50–64 years) and Group 4 (97 healthy subjects aged 65–79 years). Results The most significant thinning of all retinal layers occurs particularly in the transition from group 2 to group 3, especially in temporal superior quadrant at RNFL, GCL++ and retinal layers (p=0.001), and temporal superior, temporal inferior, and temporal half in choroid layer (p<0.001). Curiously group 2 when compared with group 1 presents a significant thickening of RNFL in temporal superior quadrant (p = 0.001), inferior (p<0.001) and temporal (p = 0.001) halves, and also in nasal half in choroid layer (p = 0.001). Conclusions Excepting the RNFL, which shows a thickening until the third decade of life, the rest of the layers seem to have a physiological progressive thinning. Copyright

From Dimethylamine to Pyrrolidine: The Development of an Improved Nickel Pincer Complex for Cross-Coupling of Nonactivated Secondary Alkyl Halides

Replacement of a dimethyl amino group of the amidobis(amine) nickel(II) pincer complex (1), [((N2N)-N-Me)-Ni-Cl], by a pyrrolidino group resulted in a new nickel(II) pincer complex (2), [((PNNN)-N-yr-N-Me)Ni-Cl]. Complex 2 is an efficient catalyst for Kumada and Suzuki-Miyaura cross-coupling of nonactivated secondary alkyl halides, while complex 1 is largely inactive. The significant activity difference is tentatively attributed to a minimal structural difference, which leads to a more hemilabile ligand

Angiography with optical coherence tomography as a biomarker in multiple sclerosis

Purpose To investigate superficial retinal microvascular plexuses detected by optical coherence tomography angiography (OCT-A) in multiple sclerosis (MS) subjects and compare them with healthy controls. Methods A total of 92 eyes from 92 patients with relapsing-remitting MS and 149 control eyes were included in this prospective observational study. OCT-A imaging was performed using Triton Swept-Source OCT (Topcon Corporation, Japan). The vessel density (VD) percentage in the superficial retinal plexus and optic disc area (6 x 6 mm grid) was measured and compared between groups. Results MS patients showed a significant decrease VD in the superior (p = 0.005), nasal (p = 0.029) and inferior (p = 0.040) parafoveal retina compared with healthy subjects. Patients with disease durations of more than 5 years presented lower VD in the superior (p = 0.002), nasal (p = 0.017) and inferior (p = 0.022) parafoveal areas compared with healthy subjects. Patients with past optic neuritis episodes did not show retinal microvasculature alterations, but patients with an EDSS score of less than 3 showed a significant decrease in nasal (p = 0.024) and superior (p = 0.006) perifoveal VD when compared with healthy subjects. Conclusions MS produces a decrease in retinal vascularization density in the superficial plexus of the parafoveal retina. Alterations in retinal vascularization observed in MS patients are independent of the presence of optic nerve inflammation. OCT-A has the ability to detect subclinical vascular changes and is a potential biomarker for diagnosing the presence and progression of MS

Nickel-catalyzed diastereoselective alkyl-alkyl Kumada coupling

A nickel pincer complex is found to catalyze alkyl–alkyl Kumada coupling reactions of 1,3- and 1,4-substituted cyclohexyl halides and tetrahydropyrans with an excellent diastereoselectivity. The mechanistic investigation of the coupling reactions provides evidence that the activation of alkyl halides is reversible

Geographical variations in the risk of adverse birth outcomes in Spain

The objective of this study was to describe the spatial risk-patterns of prematurity and low birth weight in Spain. A descriptive spatial analysis of births registered in the Spanish Vital Statistics during 2004–2008 using municipalities as the observation unit was carried out. Besag-York-Mollié autoregressive spatial models were adjusted using the Integrated Nested Laplace approximation to calculate relative risks and posterior probabilities of having very and moderate preterm or low weight newborns. Results were represented in maps to assess geographic risk-patterns. Spatial analysis shows geographical variations in the risk of adverse reproductive outcomes in Spain highlighting three main high-risk zones, namely, municipalities in Asturias, Madrid City and Murcia. The specific risk patterns identified on each zone suggests some differences regarding the potential underlying risk factors and specific areas for future research. A differential exposure during pregnancy to some risks potentially related to industry or agriculture and other contextual factors could underlie an unequal vulnerability to adverse reproductive outcomes in some Spanish regions.Fondo de Investigación Sanitaria (PI081330); Spanish Ministry of Science and Innovation (SEJ 2005/07679); CIBER en Epidemiología y Salud Pública (CIBERESP), Spain.S

Autophagy-inducing peptides from mammalian VSV and fish VHSV rhabdoviral G glycoproteins (G) as models for the development of new therapeutic molecules

It has not been elucidated whether or not autophagy is induced by rhabdoviral G glycoproteins (G) in vertebrate organisms for which rhabdovirus infection is lethal. Our work provides the first evidence that both mammalian (vesicular stomatitis virus, VSV) and fish (viral hemorrhagic septicemia virus, VHSV, and spring viremia carp virus, SVCV) rhabdoviral Gs induce an autophagic antiviral program in vertebrate cell lines. The transcriptomic profiles obtained from zebrafish genetically immunized with either Gsvcv or Gvhsv suggest that autophagy is induced shortly after immunization and therefore, it may be an important component of the strong antiviral immune responses elicited by these viral proteins. Pepscan mapping of autophagy-inducing linear determinants of Gvhsv and Gvsv showed that peptides located in their fusion domains induce autophagy. Altogether these results suggest that strategies aimed at modulating autophagy could be used for the prevention and treatment of rhabdoviral infections such as rabies, which causes thousands of human deaths every year