Cellular and subcellular localization of Marlin-1 in the brain

<p>Abstract</p> <p>Background</p> <p>Marlin-1 is a microtubule binding protein that associates specifically with the GABA_B1subunit in neurons and with members of the Janus kinase family in lymphoid cells. In addition, it binds the molecular motor kinesin-I and nucleic acids, preferentially single stranded RNA. Marlin-1 is expressed mainly in the central nervous system but little is known regarding its cellular and subcellular distribution in the brain.</p> <p>Results</p> <p>Here we have studied the localization of Marlin-1 in the rodent brain and cultured neurons combining immunohistochemistry, immunofluorescence and pre-embedding electron microscopy. We demonstrate that Marlin-1 is enriched in restricted areas of the brain including olfactory bulb, cerebral cortex, hippocampus and cerebellum. Marlin-1 is abundant in dendrites and axons of GABAergic and non-GABAergic hippocampal neurons. At the ultrastructural level, Marlin-1 is present in the cytoplasm and the nucleus of CA1 neurons in the hippocampus. In the cytoplasm it associates to microtubules in the dendritic shaft and occasionally with the Golgi apparatus, the endoplasmic reticulum (ER) and dendritic spines. In the nucleus, clusters of Marlin-1 associate to euchromatin.</p> <p>Conclusion</p> <p>Our results demonstrate that Marlin-1 is expressed in discrete areas of the brain. They also confirm the microtubule association at the ultrastructural level in neurons. Together with the abundance of the protein in dendrites and axons they are consistent with the emerging role of Marlin-1 as an intracellular protein linking the cytoskeleton and transport. Our study constitutes the first detailed description of the cellular and subcellular distribution of Marlin-1 in the brain. As such, it will set the basis for future studies on the functional implications of Marlin-1 in protein trafficking.</p

Ear photosynthesis in C3 cereals and its contribution to grain yield: Methodologies, controversies, and perspectives

In C3 cereals such as wheat and barley, grain filling was traditionally explained as being sustained by assimilates from concurrent leaf photosynthesis and remobilization from the stem. In recent decades, a role for ear photosynthesis as a contributor to grain filling has emerged. This review analyzes several aspects of this topic: (i) methodological approaches for estimation of ear photosynthetic contribution to grain filling; (ii) the existence of genetic variability in the contribution of the ear, and evidence of genetic gains in the past; (iii) the controversy of the existence of C4 metabolism in the ear; (iv) the response of ear photosynthesis to water deficit; and (v) morphological and physiological traits possibly related to ear temperature and thermal balance of the ear. The main conclusions are: (i) there are a number of methodologies to quantify ear photosynthetic activity (e.g. gas exchange and chlorophyll fluorescence) and the contribution of the ear to grain filling (individual ear shading, ear emergence in shaded canopies, and isotope composition); (ii) the contribution of ear photosynthesis seems to have increased in modern wheat germplasm; (iii) the contribution of the ear to grain filling increases under resource-limitation (water deficit, defoliation, or pathogen infection); (iv) there is genetic variability in the contribution of the ear in wheat, opening up the possibility to use this trait to ameliorate grain yield; (v) current evidence supports the existence of C3 metabolism rather than C4 metabolism; (vi) the ear is a 'dehydration avoider organ' under drought; and (vii) thermal balance in the ear is a relevant issue to explore, and more research is needed to clarify the underlying morphological and physiological traits.Fil: Tambussi, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; ArgentinaFil: Maydup, Maria Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; ArgentinaFil: Carrión, Cristian Antonio. Universidad Nacional de Tierra del Fuego. Instituto de Ciencias Polares, Recursos Naturales y Ambiente; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guiamet, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; ArgentinaFil: Araus, José L.. Universidad de Barcelona; Españ

Información mecanística en la evaluación de riesgos. Una aproximación desde las explicaciones basadas en mecanismos

RESUMENDesde la década pasada, en la evaluación de riesgos se ha propuesto utilizar la información mecanística con un doble propósito: seleccionar guías de inferencia y realizar extrapolaciones inter-químicas para establecer categorías de tóxicos. En este trabajo se utilizan aportaciones procedentes del análisis filosófico de las explicaciones mecanísticas para analizar el concepto de información mecanística utilizado en la evaluación de riesgos. Categorizamos la información mecanística de los modos de acción en términos de explicaciones etiológicas que emplean bosquejos de mecanismos. El grado de detalle que ha de incorporar la información mecanística en la evaluación de riesgos dependerá, entre otros factores, de consideraciones pragmáticas respecto del uso posterior de dicha información.PALABRAS CLAVEINFORMACIÓN MECANÍSTICA, EVAVALUACIÓN DE RIESGOS, MODELO, BOSQUEJO, EXPLICACIÓN.ABSTRACTSince the 2000s, in risk assessment studies it is usual to use mechanistic information with a double aim: to select inference guidelines and to make inter-chemical extrapolations to categorize toxics. Here, we use the contributions made in philosophical analysis of mechanistic explanations to analyze the concept of mechanistic information used in the risk assessment. We classify mechanistic information, specifically that concerning modes of action, in terms of etiological explanations employing sketches of mechanisms. The grade of the details that mechanistic information must incorporate to risk assessment depends on, among other factors, pragmatic considerations on the further use of such information.KEYWORDSMECHANISTIC INFORMATION, RISK ASSESSMENT, MODEL, SKETCH, EXPLANATION

Adrenomedullin as a potential biomarker involved in patients with hereditary hemorrhagic telangiectasia

Background: Adrenomedullin (AM) is a vasoactive peptide mostly secreted by endothelial cells with an important role in preserving endothelial integrity. The relationship between AM and hereditary hemorrhagic telangiectasia (HHT) is unknown. We aimed to compare the serum levels and tissue expression of AM between HHT patients and controls. Methods: Serum AM levels were measured by radioimmunoassay and compared between control and HHT groups. AM levels were also compared among HHT subgroups according to clinical characteristics. The single nucleotide polymorphism (SNP) rs4910118 was assessed by restriction analysis and sequencing. AM immunohistochemistry was performed on biopsies of cutaneous telangiectasia from eight HHT patients and on the healthy skin from five patients in the control group. Results: Forty-five HHT patients and 50 healthy controls were included, mean age (SD) was 50.7 (14.9) years and 46.4 (9.9) years (p = 0.102), respectively. HHT patients were mostly female (60% vs 38%, p = 0.032). Median [Q1-Q3] serum AM levels were 68.3 [58.1-80.6] pg/mL in the HHT group and 47.7 [43.2-53.8] pg/mL in controls (p<0.001), with an optimal AM cut-off according to Youden's J statistic of 55.32 pg/mL (J:0.729). Serum AM levels were similar in the HHT subgroups. No patient with HHT had the SNP rs4910118. AM immunoreactivity was found with high intensity in the abnormal blood vessels of HHT biopsies

Impulso al desarrollo de grupos vulnerables y marginados a través de apoyos económicos

Derivado de las iniciativas gubernamentales, emergen programas que van más allá del asistencialismo, es decir, se busca detonar el emprendedurismo y autoempleo de grupos sociales que en el mayor de los casos se encuentran por debajo de la línea del bienestar que anualmente estima el Consejo Nacional de Evaluación de la Política de Desarrollo Social (CONEVAL, 2016). Como mecanismo de control y seguimiento  a  estos  grupos  sociales,  los  programas  mismos  contemplan  una  posterior  y  nueva inyección de recursos para detonar el empleo  en las comunidades correspondientes  a los citados grupos

Fortification and bioaccessibility of saffron apocarotenoids in potato tubers

Carotenoids are C40 isoprenoids with well-established roles in photosynthesis, pollination, photoprotection, and hormone biosynthesis. The enzymatic or ROS-induced cleavage of carotenoids generates a group of compounds named apocarotenoids, with an increasing interest by virtue of their metabolic, physiological, and ecological activities. Both classes are used industrially in a variety of fields as colorants, supplements, and bio-actives. Crocins and picrocrocin, two saffron apocarotenoids, are examples of high-value pigments utilized in the food, feed, and pharmaceutical industries. In this study, a unique construct was achieved, namely O6, which contains CsCCD2L, UGT74AD1, and UGT709G1 genes responsible for the biosynthesis of saffron apocarotenoids driven by a patatin promoter for the generation of potato tubers producing crocins and picrocrocin. Different tuber potatoes accumulated crocins and picrocrocin ranging from 19.41–360 to 105–800 μg/g DW, respectively, with crocetin, crocin 1 [(crocetin-(β-D-glucosyl)-ester)] and crocin 2 [(crocetin)-(β-D-glucosyl)-(β-D-glucosyl)-ester)] being the main compounds detected. The pattern of carotenoids and apocarotenoids were distinct between wild type and transgenic tubers and were related to changes in the expression of the pathway genes, especially from PSY2, CCD1, and CCD4. In addition, the engineered tubers showed higher antioxidant capacity, up to almost 4-fold more than the wild type, which is a promising sign for the potential health advantages of these lines. In order to better investigate these aspects, different cooking methods were applied, and each process displayed a significant impact on the retention of apocarotenoids. More in detail, the in vitro bioaccessibility of these metabolites was found to be higher in boiled potatoes (97.23%) compared to raw, baked, and fried ones (80.97, 78.96, and 76.18%, respectively). Overall, this work shows that potatoes can be engineered to accumulate saffron apocarotenoids that, when consumed, can potentially offer better health benefits. Moreover, the high bioaccessibility of these compounds revealed that potato is an excellent way to deliver crocins and picrocrocin, while also helping to improve its nutritional value

Abriendo las compuertas del aula: la fisiología vegetal en el viaje de campaña

La experiencia educativa durante el viaje de campaña adquiere características singulares que en parte podrían explicarse por una temporalidad diferente a la usual en el aula. También, el hecho de que nuestra propuesta no supuso abordar contenidos específicos de la disciplina sino integrar los ya vistos durante la cursada contribuyó a deshacernos de estructuras conceptuales o esquemas de razonamiento rígidos y, por lo tanto, a hacernos de ideas propias. La estrategia de utilizar un proceso de investigación como hilo conductor del trabajo grupal implicó colocarnos a docentes y alumnos en una misma situación de incertidumbre, acercándonos a una construcción colectiva del conocimiento disciplinar.Eje 1: La enseñanza universitaria en el contexto actual: transformaciones y propuestas. Reflexiones y experiencias en la enseñanza de las Ciencias NaturalesSecretaría de Asuntos Académico

Impacto de la intervención con una adaptación grupal del método de musicoterapia BMGIM en pacientes con Enfermedad Inflamatoria Intestinal (Enfermedad de Crohn y COLITIS Ulcerosa)

Las terapias complementarias no farmacológicas han demostrado las mejoras que producen en pacientes crónicos, en especial las terapias psicológicas (Gracie et al., 2017), dentro de las cuales se encuentra la Musicoterapia (MT). Uno de los métodos de Musicoterapia reconocidos a nivel mundial es el método Bonny de Imaginación Guiada con Música (BMGIM), cuya aplicación ha mostrado la mejora al tratar pacientes con ciertas enfermedades crónicas, como artritis reumatoide (Jacobi & Eisenberg, 2001) y fibromialgia (Torres, 2015a, 2015b). Aun así, no hay estudios específicos que evalúen el impacto de un tratamiento basado en una adaptación grupal del BMGIM en pacientes con enfermedad inflamatoria intestinal (EII), concretamente Colitis Ulcerosa (CU y Enfermedad de Crohn (EC), y ese ha sido el objeto de este estudio de tesis doctoral. El objetivo consiste en determinar la eficacia de la intervención con una adaptación grupal del método de MT BMGIM, en la mejora del estado de salud de pacientes con EII (CU y EC).Medicin

Mucoidy, Quorum Sensing, Mismatch Repair and Antibiotic Resistance in Pseudomonas aeruginosa from Cystic Fibrosis Chronic Airways Infections

Survival of Pseudomonas aeruginosa in cystic fibrosis (CF) chronic infections is based on a genetic adaptation process consisting of mutations in specific genes, which can produce advantageous phenotypic switches and ensure its persistence in the lung. Among these, mutations inactivating the regulators MucA (alginate biosynthesis), LasR (quorum sensing) and MexZ (multidrug-efflux pump MexXY) are the most frequently observed, with those inactivating the DNA mismatch repair system (MRS) being also highly prevalent in P. aeruginosa CF isolates, leading to hypermutator phenotypes that could contribute to this adaptive mutagenesis by virtue of an increased mutation rate. Here, we characterized the mutations found in the mucA, lasR, mexZ and MRS genes in P. aeruginosa isolates obtained from Argentinean CF patients, and analyzed the potential association of mucA, lasR and mexZ mutagenesis with MRS-deficiency and antibiotic resistance. Thus, 38 isolates from 26 chronically infected CF patients were characterized for their phenotypic traits, PFGE genotypic patterns, mutations in the mucA, lasR, mexZ, mutS and mutL gene coding sequences and antibiotic resistance profiles. The most frequently mutated gene was mexZ (79%), followed by mucA (63%) and lasR (39%) as well as a high prevalence (42%) of hypermutators being observed due to loss-of-function mutations in mutL (60%) followed by mutS (40%). Interestingly, mutational spectra were particular to each gene, suggesting that several mechanisms are responsible for mutations during chronic infection. However, no link could be established between hypermutability and mutagenesis in mucA, lasR and mexZ, indicating that MRS-deficiency was not involved in the acquisition of these mutations. Finally, although inactivation of mucA, lasR and mexZ has been previously shown to confer resistance/tolerance to antibiotics, only mutations in MRS genes could be related to an antibiotic resistance increase. These results help to unravel the mutational dynamics that lead to the adaptation of P. aeruginosa to the CF lung

A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Background: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. Objectives: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. Medthods: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. Results: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. Conclusions: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors