The onset of Leber hereditary optic neuropathy is relatively rare in childhood and, interestingly, the rate of spontaneous visual recovery is very high in this group of patients. Here, we report a ...child harboring a rare pathological mitochondrial DNA mutation, present in heteroplasmy, associated with the disease. A patient follow-up showed a rapid recovery of the vision accompanied by a decrease of the percentage of mutated mtDNA. A retrospective study on the age of recovery of all childhood-onset Leber hereditary optic neuropathy patients reported in the literature suggested that this process was probably related with pubertal changes.
The isomerization of glucose to fructose and its subsequent dehydration to hydroxymethylfurfural (HMF) have been investigated on nanohybrid catalysts that stabilize emulsions comprising aqueous and ...organic phases. Significant improvement in catalyst stability was observed when NaX faujasite catalysts were functionalized with multiwalled carbon nanotubes (MWCNT-NaX), with a large fraction of the initial activity and selectivity preserved after several recycles. The combination of MWCNT-NaX, containing Lewis acid sites, and MWCNT-SO3H, containing Brønsted acid sites, enables glucose isomerization and fructose dehydration at high conversion and HMF selectivity. The use of a water/oil biphasic emulsion favors the continuous separation of the HMF product into the organic phase. Furthermore, selective conversion of HMF into added-value products can be accomplished in the same emulsion by incorporating a metallic function on the amphiphilic nanohybrids in the presence of hydrogen. Depending on the metal used, different final products can be obtained. For example, when Ru was added, the main product was 2,5-hexanedione (47.8 mol %), followed by 2,5-bis(hydroxymethyl)furan (15 mol %) and γ-hydroxyvaleric acid (7.8 mol %). When Pd was used, γ-hydroxyvaleric acid (84 mol %) dominated the product distribution, with only small amounts of 2,5-bis(hydroxymethyl)furan (2.9 mol %).
•Mutations in OXPHOS genes increase VEGF production and pathological angiogenesis.•OXPHOS inhibitors increase VEGF production and pathological angiogenesis.•OXPHOS dysfunction can be found in ...pathological angiogenesis-related diseases.•Increasing OXPHOS capacity could be a therapy against pathological angiogenesis.
Pathological mutations in subunits of the oxidative phosphorylation (OXPHOS) system, or inhibitors of this biochemical pathway, increase the production of vascular endothelial growth factor (VEGF) and pathological angiogenesis. In many angiogenesis-related diseases, such as retinal, rheumatoid diseases, or cancer, OXPHOS dysfunction can be found. Thus, enhancing OXPHOS might be a promising therapeutic approach for pathologic angiogenesis.
The role of wildlife as a brucellosis reservoir for humans and domestic livestock remains to be properly established. The aim of this work was to determine the aetiology, apparent prevalence, spatial ...distribution and risk factors for brucellosis transmission in several Iberian wild ungulates.
A multi-species indirect immunosorbent assay (iELISA) using Brucella S-LPS antigen was developed. In several regions having brucellosis in livestock, individual serum samples were taken between 1999 and 2009 from 2,579 wild bovids, 6,448 wild cervids and4,454 Eurasian wild boar (Sus scrofa), and tested to assess brucellosis apparent prevalence. Strains isolated from wild boar were characterized to identify the presence of markers shared with the strains isolated from domestic pigs.
Mean apparent prevalence below 0.5% was identified in chamois (Rupicapra pyrenaica), Iberian wild goat (Capra pyrenaica), and red deer (Cervus elaphus). Roe deer (Capreolus capreolus), fallow deer (Dama dama), mouflon (Ovis aries) and Barbary sheep (Ammotragus lervia) tested were seronegative. Only one red deer and one Iberian wild goat resulted positive in culture, isolating B. abortus biovar 1 and B. melitensis biovar 1, respectively. Apparent prevalence in wild boar ranged from 25% to 46% in the different regions studied, with the highest figures detected in South-Central Spain. The probability of wild boar being positive in the iELISA was also affected by age, age-by-sex interaction, sampling month, and the density of outdoor domestic pigs. A total of 104 bacterial isolates were obtained from wild boar, being all identified as B. suis biovar 2. DNA polymorphisms were similar to those found in domestic pigs.
In conclusion, brucellosis in wild boar is widespread in the Iberian Peninsula, thus representing an important threat for domestic pigs. By contrast, wild ruminants were not identified as a significant brucellosis reservoir for livestock.
Therapeutic potential of metformin in obese/diabetic patients has been associated to its ability to combat insulin resistance. However, it remains largely unknown the signaling pathways involved and ...whether some cell types are particularly relevant for its beneficial effects. M1-activation of macrophages by bacterial lipopolysaccharide (LPS) promotes a paracrine activation of hypoxia-inducible factor-1α (HIF1α) in brown adipocytes which reduces insulin signaling and glucose uptake, as well as β-adrenergic sensitivity. Addition of metformin to M1-polarized macrophages blunted these signs of brown adipocyte dysfunction. At the molecular level, metformin inhibits an inflammatory program executed by HIF1α in macrophages by inducing its degradation through the inhibition of mitochondrial complex I activity, thereby reducing oxygen consumption in a reactive oxygen species (ROS)-independent manner. In obese mice, metformin reduced inflammatory features in brown adipose tissue (BAT) such as macrophage infiltration, proinflammatory signaling and gene expression, and restored the response to cold exposure. In conclusion, the impact of metformin on macrophages by suppressing a HIF1α-dependent proinflammatory program is likely responsible for a secondary beneficial effect on insulin-mediated glucose uptake and β-adrenergic responses in brown adipocytes.
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•Macrophage-mediated inflammation in brown adipocytes stabilizes HIF1α.•Stabilization of HIF1α reduces brown adipocyte hormonal responses.•Metformin attenuates inflammation and BAT dysfunction in obese mice.•Mitochondrial complex I inhibition by metformin reduces HIF1α in macrophages.•Targeting macrophages HIF1α by metformin alleviates brown adipocyte inflammation.
Cocoa is a highly consumed food with beneficial effects on human health. Cocoa roasting has an important influence on its sensory and nutritional characteristics; therefore, roasting could also play ...a role in cocoa bioactivity. Thus, the aim of this paper is to unravel the effect of cocoa roasting conditions on its antioxidant capacity and modifications of gut microbiota after
digestion-fermentation. HMF and furfural, chemical markers of non-enzymatic browning, were analyzed in unroasted and roasted cocoa powder at different temperatures, as well as different chocolates. The antioxidant capacity decreased with roasting, most probably due to the loss of phenolic compounds during heating. In the case of the evaluated chocolates, the antioxidant capacity was 2-3 times higher in the fermented fraction. On the other hand, HMF and furfural content increased during roasting due to increasing temperatures. Moreover, unroasted and roasted cocoa powder have different effects on gut microbial communities. Roasted cocoa favored butyrate production, whereas unroasted cocoa favored acetate and propionate production in a significant manner. In addition, unroasted and roasted cocoa produced significantly different gut microbial communities in terms of composition. Although many bacteria were affected,
and
were some of the most discriminant ones; whereas the former is a propionate producer, the latter is a butyrate producer that has also been linked to positive effects on the inflammatory health of the gut and the immune system. Therefore, unroasted and roasted cocoa (regardless of the roasting temperature) promote different bacteria and a different SCFA production.
Mitochondrial oxidative phosphorylation disorders are extremely heterogeneous conditions. Their clinical and genetic variability makes the identification of reliable and specific biomarkers very ...challenging. Until now, only a few studies have focused on the effect of a defective oxidative phosphorylation functioning on the cell's secretome, although it could be a promising approach for the identification and pre-selection of potential circulating biomarkers for mitochondrial diseases. Here, we review the insights obtained from secretome studies with regard to oxidative phosphorylation dysfunction, and the biomarkers that appear, so far, to be promising to identify mitochondrial diseases. We propose two new biomarkers to be taken into account in future diagnostic trials.
Down syndrome is the most common genomic disorder of intellectual disability and is caused by trisomy of chromosome 21. Several genes in this chromosome repress mitochondrial biogenesis. The goal of ...this study was to evaluate whether early overexpression of these genes may cause a prenatal impairment of oxidative phosphorylation negatively affecting neurogenesis. Reduction in the mitochondrial energy production and a lower mitochondrial function have been reported in diverse tissues or cell types, and also at any age, including early fetuses, suggesting that a defect in oxidative phosphorylation is an early and general event in Down syndrome individuals. Moreover, many of the medical conditions associated with Down syndrome are also frequently found in patients with oxidative phosphorylation disease. Several drugs that enhance mitochondrial biogenesis are nowadays available and some of them have been already tested in mouse models of Down syndrome restoring neurogenesis and cognitive defects. Because neurogenesis relies on a correct mitochondrial function and critical periods of brain development occur mainly in the prenatal and early neonatal stages, therapeutic approaches intended to improve oxidative phosphorylation should be provided in these periods.
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•Several chromosome 21-encoded proteins repress mitochondrial biogenesis.•These proteins are overexpressed in fetal brains of Down syndrome (DS) individuals.•Oxidative phosphorylation function is essential for neurogenesis.•Upregulation of these proteins adversely impact on neurogenesis.•Prenatal therapy with drugs inhibiting these proteins would increase DS neurogenesis.
Dilated cardiomyopathy is a frequent and extremely heterogeneous medical condition. Deficits in the oxidative phosphorylation system have been described in patients suffering from dilated ...cardiomyopathy. Hence, mutations in proteins related to this biochemical pathway could be etiological factors for some of these patients. Here, we review the clinical phenotypes of patients harboring pathological mutations in genes related to the oxidative phosphorylation system, either encoded in the mitochondrial or in the nuclear genome, presenting with dilated cardiomyopathy. In addition to the clinical heterogeneity of these patients, the large genetic heterogeneity has contributed to an improper allocation of pathogenicity for many candidate mutations. We suggest criteria to avoid incorrect assignment of pathogenicity to newly found mutations and discuss possible therapies targeting the oxidative phosphorylation function.
Purpose
The purpose of this article is to explore the mediating role of both ethical climate and frontline employees' ethical intent on the relationship between store managers' ethical leadership and ...frontline employees’ customer orientation (FECO).
Design/methodology/approach
Original data on small and medium-sized enterprises in the Mexican retail industry were used. A survey provided a sample of 332 frontline employees. To test the hypotheses, the authors conducted a partial least squares (PLS) analysis.
Findings
The results show the positive effect of ethical leadership is mainly direct. This can primarily be explained through the mechanisms of social exchange theory. Additionally, the results show that ethical climate and ethical intent act as essential partial mediators.
Originality/value
Although managers' ethical leadership typically exercises a direct and positive influence on employees' work performance, the path linking the ethical leadership of the upper echelons to this outcome has not been frequently studied, especially in terms of its impact on meeting customers' needs (i.e. frontline employees' customer orientation, or FECO). This study expands on existing knowledge by considering that a true FECO is necessarily linked to being “oriented to others”, which is fostered by the perception that moral values (i.e. honesty) are embedded in an organization's culture.
Propósito
El propósito de este artículo es explorar el papel mediador del clima ético y la intención ética de los empleados de primera línea en la relación entre el liderazgo ético de los directores de tienda y la orientación al cliente de los empleados de primera línea (FECO).
Diseño/metodología/enfoque
Los autores utilizaron datos originales de pequeñas y medianas empresas ubicadas en la industria minorista mexicana. Una encuesta proporcionó una muestra de 332 empleados de primera línea. Para comprobar las hipótesis, los autores realizaron un análisis por mínimos cuadrados parciales (PLS).
Resultados
Los resultados muestran cómo el efecto positivo del liderazgo ético es principalmente directo. Esto puede ser explicado fundamentalmente a través de los mecanismos de la teoría del intercambio social. Adicionalmente, los resultados mostraron que el clima ético y la intención ética actúan como mediadores parciales esenciales.
Originalidad/valor
Aunque el liderazgo ético de los directivos suele ejercer una influencia directa y positiva en el rendimiento laboral de los empleados, no se ha estudiado con frecuencia la vía que relaciona el liderazgo ético de los mandos superiores con este resultado, especialmente en lo que se refiere a su impacto en la satisfacción de las necesidades de los clientes (es decir, la orientación al cliente de los empleados de primera línea, o FECO). Este estudio amplía los conocimientos actuales al considerar que un verdadero FECO está necesariamente vinculado a estar “orientado a los demás”, lo que se ve favorecido por la percepción de que los valores morales (es decir, la honestidad) están arraigados en la cultura de la organización.
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