Neuregulin, an effector on mitochondria metabolism that preserves insulin sensitivity

Various external factors modulate the metabolic efficiency of mitochondria. This review focuses on the impact of the growth factor neuregulin and its ErbB receptors on mitochondria and their relationship with several physiopathological alterations. Neuregulin is involved in the differentiation of heart, skeletal muscle and the neuronal system, among others, and its deficiency is deleterious for the health. Information gathered over the last two decades suggests that neuregulin plays a key role regulating mitochondrial oxidative machinery, which sustain cell survival and insulin sensitivity

Functional characterization of the alanine-serine-cysteine exchanger of Carnobacterium sp AT7

Many key cell processes require prior cell uptake of amino acids from the environment, which is facilitated by cell membrane amino acid transporters such as those of the L-type amino acid transporter (LAT) subfamily. Alterations in LAT subfamily amino acid transport are associated with several human diseases, including cancer, aminoacidurias, and neurodegenerative conditions. Therefore, from the perspective of human health, there is considerable interest in obtaining structural information about these transporter proteins. We recently solved the crystal structure of the first LAT transporter, the bacterial alanine-serine-cysteine exchanger of Carnobacterium sp AT7 (BasC). Here, we provide a complete functional characterization of detergent-purified, liposome-reconstituted BasC transporter to allow the extension of the structural insights into mechanistic understanding. BasC is a sodium- and proton-independent small neutral amino acid exchanger whose substrate and inhibitor selectivity are almost identical to those previously described for the human LAT subfamily member Asc-1. Additionally, we show that, like its human counterparts, this transporter has apparent affinity asymmetry for the intra- and extracellular substrate binding sites a key feature in the physiological role played by these proteins. BasC is an excellent paradigm of human LAT transporters and will contribute to our understanding of the molecular mechanisms underlying substrate recognition and translocation at both sides of the plasma membrane

What DNA barcodes reveal: microhabitat preference, hunting strategy and dispersal ability drive genetic variation across Iberian spider species

1. The current rate of species loss calls for immediate actions to preserve biodiversity and ecosystem functioning. Cataloguing species richness and composition, and revealing how diversity is geographically distributed are the first steps towards designing efficient conservation strategies. 2. Here, we aim to determine diversity patterns and potential drivers of taxonomic and genetic diversity and population structure of Iberian spiders. We used a community level perspective, analysing more than 3000 DNA barcode sequences representing 370 spider species dwelling in white-oak forest habitats across the Spanish National Park network. 3. By combining and comparing morphological and DNA barcode-based species delimitation methods, we assessed their performance and identified putative factors behind cases of incongruence. Our findings uncovered potential overlooked diversity as suggested by the geographic patterns of genetic variation and put a red flag on those taxa that may be undergoing overlooked evolutionary or ecological processes. 4. Spider functional traits associated with foraging strategy, microhabitat preference, ballooning ability and circadian activity explained the observed patterns of population structure across species but did not explain variation in genetic diversity. Overall, our study represents a major step forward in the understanding of large-scale diversity patterns in Iberian spiders at the community level and provides relevant information to guide future conservation strategies of the so-far largely overlooked invertebrate diversit

Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction

Mitochondrial dynamics is a term that encompasses the movement of mitochondria along the cytoskeleton, regulation of their architecture, and connectivity mediated by tethering and fusion/fission. The importance of these events in cell physiology and pathology has been partially unraveled with the identification of the genes responsible for the catalysis of mitochondrial fusion and fission. Mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause neurodegenerative diseases, namely Charcot-Marie Tooth type 2A and autosomal dominant optic atrophy (ADOA). Alterations in mitochondrial dynamics may be involved in the pathophysiology of prevalent neurodegenerative conditions. Moreover, impairment of the activity of mitochondrial fusion proteins dysregulates the function of hypothalamic neurons, leading to alterations in food intake and in energy homeostasis. Here we review selected findings in the field of mitochondrial dynamics and their relevance for neurodegeneration and hypothalamic dysfunction

Diversidad de mariposas (Lepidoptera, Papilionoidea) y su relación con el paisaje de alta montaña en los Andes nororientales de Colombia

Diversitat de papallones (Lepidoptera, Papilionoidea) i la seva relació amb el paisatge d’alta muntanya als Andes nord-orientals de Colòmbia La regió andina es caracteritza per acollir una gran varietat d’ecosistemes entre els quals es compten les característiques zones d’alta muntanya, que mostren processos de transformació del sòl accelerats que han convertit els boscos natius en zones agrícoles i ramaderes, la qual cosa ha ocasionant un declivi de la diversitat biològica regional. L’ús d’indicadors de diversitat és adequat per avaluar els canvis en els paisatges d’alta muntanya i les papallones són un dels grups més importants per determinar els canvis que es produeixen en els diferents tipus d’ambients. A l’àrea d’estudi es van establir dotze punts de mostreig als complexos d’erms d’Almorzadero, Santurbán i Tamá de la regió nord-oriental de Colòmbia. Durant la fase de mostreig es van practicar captures d’individus adults de papallones en transsectes de 100 x 4 m en un gradient altitudinal de 500 m. Es van registrar 69 espècies, pertanyents a cinc famílies. Els valors de diversitat de la comunitat de papallones diürnes van variar a les diferents cobertures vegetals associades a cada transsecte. Així, les àrees amb cobertura vegetal conservada (per exemple, bosc dens, arbustos i matolls i erm i suberm) van presentar els valors més alts de diversitat, mentre que les zones amb cobertura alterada (per exemple, bosc fragmentat, pastures i àrees agrícoles) van presentar els valors de diversitat més baixos. Les anàlisis d’estructura de comunitats evidencien que les espècies de papallones endèmiques estan associades a àrees fragmentades a les zones d’alta muntanya. Aquest estudi és el primer del seu tipus que estableix canvis en la diversitat de les papallones en zones d’alta muntanya del nord-est de Colòmbia i s’ha fet amb el propòsit de generar estratègies de conservació en llocs que presenten un alt grau d’endemisme i diversitat.Diversity of butterflies (Lepidoptera, Papilionoidea) and their relationship with the highlands’ landscape in the northeastern Andes of Colombia The Andean region harbors a great variety of ecosystems, including the characteristic high mountain zones. The biological diversity in these zones, however, is declining as the result of changes in land use, particularly the introduction of agriculture and cattle ranching. Changes in the high mountain landscape can be appropriately monitored using diversity indicators such as butterflies, one of the most important indicator species. We chose twelve sampling points in the paramo (high altitude moor) complexes Almorzadero, Santurbán and El Tamá, located in the northeastern region of Colombia to collect adult butterflies within transects of 100 x 4 m, along an altitudinal gradient of 500 m. We recorded 69 species, from five families. Diversity values of the diurnal butterfly communities varied among  the different areas of vegetation coverage associated with each transect. Conserved vegetation coverage (i.e. dense forest, scrublands and scrublands, and paramo and subparamo) showed the highest values of diversity, while  perturbed coverage (i.e. fragmented forests, pastures and agriculture areas) presented the lowest values of diversity. Analysis of the community structure showed that endemic butterfly species were associated with fragmented areas in the high mountains. Findings from this study, the first of its kind to determine changes in butterfly diversity in highlands in northeastern Colombia, may help to generate conservation strategies in places where there is high endemism and diversityLa región andina se caracteriza por albergar una gran variedad de ecosistemas entre los que se cuentan las características zonas de alta montaña, que muestran acelerados procesos de transformación del suelo que han convertido los bosques nativos en zonas agrícolas y ganaderas ocasionando un declive de la diversidad biológica regional. El empleo de indicadores de diversidad es adecuado para evaluar los cambios en los paisajes de alta montaña, siendo las mariposas uno de los grupos más importantes para determinar los cambios que se producen en los diferentes tipos de ambientes. En el área de estudio se establecieron doce puntos de muestreo en los complejos de páramos del Almorzadero, Santurbán y Tamá de la región nororiental de Colombia. Durante la fase de muestreo se realizaron capturas de individuos adultos de mariposas en transectos de 100 x 4 m en un gradiente altitudinal de 500 m. Se registraron 69 especies, pertenecientes a cinco familias. Los valores de diversidad de la comunidad de mariposas diurnas variaron en las diferentes coberturas vegetales asociadas a cada transecto. Así, las áreas con cobertura vegetal conservada (por ejemplo, bosque denso, arbustos y matorrales y páramo y subpáramo) presentaron los valores más altos de diversidad, mientras que las zonas con cobertura alterada (por ejemplo, bosque fragmentado, pastos y áreas agrícolas) presentaron los valores de diversidad más bajos. Los análisis de estructura de comunidades evidencian que las especies de mariposas endémicas están asociadas a áreas fragmentadas en las zonas de alta montaña. Este estudio es el primero de su tipo que establece cambios en la diversidad de las mariposas en zonas de alta montaña del nordeste de Colombia y se ha realizado con el propósito de generar estrategias de conservación en lugares que presentan un alto grado de endemismo y diversidad

Identification of LAT4, a novel amino acid transporter with system L activity

System L amino acid transporters mediate the movement of bulky neutral amino acids across cell membranes. Until now three proteins that induce system L activity have been identified: LAT1, LAT2, and LAT3. The former two proteins belong to the solute carrier family 7 (SLC7), whereas the latter belongs to SLC43. In the present study we present a new cDNA, designated LAT4, which also mediates system L activity when expressed in Xenopus laevis oocytes. Human LAT4 exhibits 57% identity to human LAT3. Like LAT3, the amino acid transport activity induced by LAT4 is sodium-, chloride- and pH-independent, is not trans-stimulated, and shows two kinetic components. The low affinity component of LAT4 induced activity is sensitive to the sulfhydryl-specific reagent N-ethylmaleimide but not that with high affinity. Mutation in LAT4 of the SLC43 conserved serine 297 to alanine abolishes sensitivity to N-ethylmaleimide. LAT4 activity is detected at the basolateral membrane of PCT kidney cells. In situ hybridization experiments show that LAT4 mRNA is restricted to the epithelial cells of the distal tubule and the collecting duct in the kidney. In the intestine, LAT4 is mainly present in the cells of the crypt

A novel role of neuregulin in skeletal muscle. Neuregulin stimulates glucose uptake, glucose transporter translocation and transporter expression in muscle cells

Neuregulins regulate the expression of acetylcholine receptor genes and induce development of the neuromuscular junction in muscle. In studying whether neuregulins regulate glucose uptake in muscle, we analyzed the effect of a recombinant neuregulin, (r)heregulin-beta1-(177-244) (HRG), on L6E9 muscle cells, which express the neuregulin receptors ErbB2 and ErbB3. L6E9 responded acutely to HRG by a time- and concentration-dependent stimulation of 2-deoxyglucose uptake. HRG-induced stimulation of glucose transport was additive to the effect of insulin. The acute stimulation of the glucose transport induced by HRG was a consequence of the translocation of GLUT4, GLUT1, and GLUT3 glucose carriers to the cell surface. The effect of HRG on glucose transport was dependent on phosphatidylinositol 3-kinase activity. HRG also stimulated glucose transport in the incubated soleus muscle and was additive to the effect of insulin. Chronic exposure of L6E9 cells to HRG potentiated myogenic differentiation, and under these conditions, glucose transport was also stimulated. The activation of glucose transport after chronic HRG exposure was due to enhanced cell content of GLUT1 and GLUT3 and to increased abundance of these carriers at the plasma membrane. However, under these conditions, GLUT4 expression was markedly down-regulated. Muscle denervation is associated with GLUT1 induction and GLUT4 repression. In this connection, muscle denervation caused a marked increase in the content of ErbB2 and ErbB3 receptors, which occurred in the absence of alterations in neuregulin mRNA levels. This fact suggests that neuregulins regulate glucose transporter expression in denervated muscle. We conclude that neuregulins regulate glucose uptake in L6E9 muscle cells by mechanisms involving the recruitment of glucose transporters to the cell surface and modulation of their expression. Neuregulins may also participate in the adaptations in glucose transport that take place in the muscle fiber after denervation

Primer Reporte de leucismo en Artibeus lituratus (Olfers, 1818) (Phyllostomidae: Stenodermatinae) en el Caribe colombiano.

Leucism is a hypo-pigmentation of the tegument in which the individual has irregular patches or even the entire body depigmented, but maintains the normal coloration of the eyes and claws, which can be mistakenly described as partial albinism (Roncancio & Ramírez- Chaves 2008, Marín-Vásquez et al. 2010, Tabea-Treitler et al. 2013 & Velandia-Perilla et al. 2013).El leucismo es una hipo-pigmentación del tegumento en el que el individuo presenta parches irregulares o incluso la totalidad del cuerpo despigmentado, pero mantiene la coloración normal de los ojos y garras, lo cual puede ser descrito erróneamente como albinismo parcial (Roncancio & Ramírez-Chaves 2008, Marín-Vásquez et al. 2010, Tabea-Treitler et al. 2013 & Velandia-Perilla et al. 2013).&nbsp

Aquaglyceroporins are differenctially expressed in beige and white adipocytes

Browning of white adipocytes has been proposed as a powerful strategy to overcome metabolic complications, since brown adipocytes are more catabolic, expending energy as a heat form. However, the biological pathways involved in the browning process are still unclear. Aquaglyceroporins are a sub-class of aquaporin water channels that also permeate glycerol and are involved in body energy homeostasis. In the adipose tissue, aquaporin-7 (AQP7) is the most representative isoform, being crucial for white adipocyte fully differentiation and glycerol metabolism. The altered expression of AQP7 is involved in the onset of obesity and metabolic disorders. Herein, we investigated if aquaglyceroporins are implicated in beige adipocyte differentiation, similar to white cells. Thus, we optimized a protocol of murine 3T3-L1 preadipocytes browning that displayed increased beige and decreased white adipose tissue features at both gene and protein levels and evaluated aquaporin expression patterns along the differentiation process together with cellular lipid content. Our results revealed that AQP7 and aquaporin-9 (AQP9) expression was downregulated throughout beige adipocyte differentiation compared to white differentiation, which may be related to the beige physiological role of heat production from oxidative metabolism, contrasting with the anabolic/catabolic lipid metabolism requiring glycerol gateways occurring in white adipose cells

Spontaneous functional recovery after focal damage in neuronal cultures

Damage in biological neuronal networks triggers a complex functional reorganization whose mechanisms are still poorly understood. To delineate this reorganization process, here we investigate the functional alterations of in vitro rat cortical circuits following localized laser ablation. The analysis of the functional network configuration before and after ablation allowed us to quantify the extent of functional alterations and the characteristic spatial and temporal scales along recovery. We observed that damage precipitated a fast rerouting of information flow that restored network's communicability in about 15 min. Functional restoration was led by the immediate neighbors around trauma but was orchestrated by the entire network. Our in vitro setup exposes the ability of neuronal circuits to articulate fast responses to acute damage, and may serve as a proxy to devise recovery strategies in actual brain circuits. Moreover, this biological setup can become a benchmark to empirically test network theories about the spontaneous recovery in dynamical networks