RESUMEN
BACKGROUND: Hereditary sensory and autonomic neuropathy type 2 (HSAN2; MIM 201300) is a rare recessive neuropathy typically diagnosed in the first decade. The 1973 study of a French Canadian family led to the definition of HSAN2. OBJECTIVES: To demonstrate that the apparent higher prevalence of HSAN2 in Quebec is due to the presence of two HSN2 mutations and that carriers of different mutations appear to have a similar phenotype. METHODS: Through attending physicians, the authors recruited French Canadian patients with HSAN2. Exclusion of linkage to the known HSAN loci and linkage to the HSAN2 was performed using standard methods. Sequencing of the HSN2 gene was used to uncover the causal mutations. RESULTS: A large cluster of HSAN2 patients comprising 16 affected individuals belonging to 13 families was identified. The mode of inheritance is clearly autosomal recessive. All patients originated from southern Quebec, and 75% are from the Lanaudière region. Whereas linkage to the HSAN1, 3, and 4 loci was excluded, linkage to the 12p13.33 HSAN2 locus was confirmed. Sequencing of the HSN2 gene uncovered two French Canadian mutations and a novel nonsense mutation in a patient of Lebanese origin, all predicted to lead to truncations of the HSN2 protein. The comparison of clinical variables between patients with different genotypes does not suggest any difference in phenotype. CONCLUSIONS: Two founder mutations are responsible for the apparently higher prevalence of HSAN2 in French Canadians. Genotype-phenotype correlation does not suggest any significant clinical variability.
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Predisposición Genética a la Enfermedad/genética , Neuropatías Hereditarias Sensoriales y Autónomas/epidemiología , Neuropatías Hereditarias Sensoriales y Autónomas/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Adulto , Anciano , Secuencia de Bases/genética , Niño , Preescolar , Mapeo Cromosómico , Cromosomas Humanos Par 12/genética , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Genotipo , Humanos , Lactante , Péptidos y Proteínas de Señalización Intracelular , Masculino , Persona de Mediana Edad , Antígenos de Histocompatibilidad Menor , Linaje , Nervios Periféricos/patología , Nervios Periféricos/fisiopatología , Fenotipo , Prevalencia , Proteínas Serina-Treonina Quinasas , Quebec/epidemiología , Proteína Quinasa Deficiente en Lisina WNK 1RESUMEN
We have constructed linkage maps for two parents of white spruce [ Picea glauca (Moench) Voss]. Haploid megagametophytes from 92 and 96 seeds of parents M2 and 80132, respectively, were analysed with RAPD, SCAR and ESTP markers. Fragments segregating in a 1:1 Mendelian ratio were classified and mapped using MAPMAKER, GMENDEL and JOINMAP. For M2, the analysis with JOINMAP resulted in 165 loci (152 RAPDs, 3 SCARs and 10 ESTPs) mapping to 23 linkage groups and covering 2,059.4 cM(Kosambi function, K). For 80132, the analysis resulted in 144 loci (137 RAPDs, 1 SCAR and 7 ESTPs) mapping to 19 linkage groups and covering 2,007.7 cM(K). The maps covered 87 and 73% of the entire genome of parents M2 and 80132, respectively. Similar results were obtained with MAPMAKER and GMENDEL. A comparison was made between the two individual maps and 16 loci were shared between the two maps.
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Numerous studies and reviews support an important contribution of endogenous opioid peptide systems in the mediation, modulation, and regulation of stress responses including endocrine (hypothalamopituitary-adrenal, HPA axis), autonomic nervous system (ANS axis), and behavioral responses. Although several discrepancies exist, the most consistent finding among such studies using different species and stressors is that opioids not only diminish stress-induced neuroendocrine and autonomic responses, but also stimulate these effector systems in the non-stressed state. A distinctive feature of the analgesic action of opioids is the blunting of the distressing, affective component of pain without dulling the sensation itself. Therefore, opioid peptides may diminish the impact of stress by attenuating an array of physiologic responses including emotional and affective states. The widespread distribution of enkephalin (ENK) throughout the limbic system (including the extended amygdala, cingulate cortex, entorhinal cortex, septum, hippocampus, and the hypothalamus) is consistent with a direct role in the modulation the stress responses. The predictability of stressful events reduces the impact of a wide range of stressors and ENK appears to play an important role in this process. Therefore, ENK and its receptors could represent a major modulatory system in the adaptation of an organism to stress, balancing the response that the stressor places on the central stress system with the potentially detrimental effects that a sustained stress may produce. Chronic neurogenic stressors will induce changes in specific components of the stress-induced ENKergic system, including ENK, delta- and mu-opioid receptors. This review presents evidences for adaptive cellular mechanisms underlying the response of the central stress system when assaulted by repeated psychogenic stress, and the involvement of ENK in these processes.
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Endorfinas/fisiología , Estrés Psicológico/fisiopatología , Adaptación Psicológica/fisiología , Animales , HumanosRESUMEN
Recycling of triose-phosphate and pentose-phosphate was previously reported on glucose in Sinorhizobium meliloti, a polysaccharide-synthesizing bacterium, but the metabolic basis of such processes remained unclear. In this work, we have used (13)C-labelling strategies to demonstrate that carbohydrate cycling in this organism is independent of the gluconate bypass, the alternative pathway for glucose assimilation involving its periplasmic oxidation into gluconate. Furthermore, carbohydrate cycling in S. meliloti is also observed on fructose, making the situation in this bacterium significantly different from that depicted for alginate-synthesizing species.
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Metabolismo de los Hidratos de Carbono , Sinorhizobium meliloti/metabolismo , Carbohidratos/química , Isótopos de Carbono , Fructosa/química , Fructosa/metabolismo , Fructosafosfatos/metabolismo , Eliminación de Gen , Glucanos/química , Glucanos/metabolismo , Gluconatos/química , Gluconatos/metabolismo , Glucosa/química , Glucosa/metabolismo , Glucosa 1-Deshidrogenasa , Glucosa Deshidrogenasas/genética , Glucosa Deshidrogenasas/metabolismo , Glucosa-6-Fosfato/metabolismo , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Sinorhizobium meliloti/enzimología , Sinorhizobium meliloti/genética , Sinorhizobium meliloti/crecimiento & desarrolloRESUMEN
This study tested the hypothesis that the activation pattern of enkephalinergic (ENKergic) neurons within the paraventricular nucleus of the hypothalamus (PVH) in response to psychogenic stress is identical whether in response to repeated exposure to the same stress (homotypic; immobilization) or to a novel stress (heterotypic; air jet puff). Rats were assigned to either acute or chronic immobilization stress paradigms (90 min/day for 1 or 10 days, respectively). The chronic group was then subjected to an additional 90-min session of either heterotypic or homotypic stress. A single 90-min stress session (immobilization or air jet) increased PVH-ENK heteronuclear (hn) RNA expression. In chronically stressed rats, exposure to an additional stress session (whether homotypic or heterotypic) continued to stimulate ENK hnRNA expression. Acute immobilization caused a marked increase in the numbers of Fos-immunoreactive and Fos-ENK double-labeled cells in the dorsal and ventral medial parvicellular, and lateral parvicellular subdivisions of the PVH. Chronic immobilization caused an attenuated Fos response ( approximately 66%) to subsequent immobilization. In contrast, chronic immobilization did not impair ENKergic neuron activation within the PVH following homotypic or heterotypic stress. These results indicate that within the PVH, chronic psychogenic stress markedly attenuates the Fos response, whereas ENKergic neurons resist habituation, principally within the ventral neuroendocrine portion of the nucleus. This suggests an increase in ENK effect during chronic stress exposure. Homotypic (immobilization) and heterotypic (air jet) psychogenic stressors produce similar responses, including Fos, ENK-Fos, and ENK hnRNA, within each subdivision of the PVH, suggesting similar processing for painless neurogenic stimuli.
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Encefalinas/biosíntesis , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Estrés Psicológico/metabolismo , Enfermedad Aguda , Hormona Adrenocorticotrópica/sangre , Animales , Enfermedad Crónica , Corticosterona/sangre , Encefalinas/genética , Prueba de Esfuerzo , Masculino , Neuronas/citología , Núcleo Hipotalámico Paraventricular/citología , Proteínas Proto-Oncogénicas c-fos/metabolismo , ARN Mensajero/biosíntesis , Ratas , Ratas Wistar , Restricción Física , Estrés Psicológico/sangreRESUMEN
Some pathways of hexose-6-phosphate recycling--those involving a breakdown of the hexose skeleton--through carbohydrate metabolism of micro-organisms were analyzed for both metabolic and isotopic effects. Two modes of recycling were proposed based on the degree of alteration of the hexose molecule through the catabolic part of the cycle. Simulated operation of most of these pathways resulted in increased synthesis of hexose-6-phosphate and NADPH, and reduced the NADH and moreover the ATP synthesis within the carbohydrate metabolism. A basic model for the quantitative assessment by means of isotopic studies of the processes of hexose-6-phosphate recycling is presented. The model was initially designed for the study of micro-organisms producing polysaccharides, but it can be extended to other situations.
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Bacterias/metabolismo , Hexosafosfatos/análisis , Hexosafosfatos/metabolismo , Espectroscopía de Resonancia Magnética , Modelos Químicos , Adenosina Trifosfato/biosíntesis , Bacterias/química , Isótopos de Carbono , Gluconatos/metabolismo , Gluconeogénesis/fisiología , NADP/metabolismo , Ácido Pirúvico/metabolismo , Ribulosafosfatos/metabolismoRESUMEN
Neurofilament proteins are highly phosphorylated molecules in the axonal compartment of the adult nervous system. We report the structural analysis of neurofilament proteins after oxidative damage. SDS-PAGE, immunoblotting, circular dichroism, and Fourier transform infrared spectroscopy were used to investigate the relative sensitivity of neurofilaments to oxidative stress and to identify changes in their molecular organization. An ascorbate-Fe+3-O2 buffer system as well as catechols were used to generate free radicals on a substrate of phosphorylated and dephosphorylated neurofilaments. By Fourier Transform Infrared spectroscopy and circular dichroism, we established that the neurofilament secondary structure is mainly composed of alpha-helices and that after free radical damage of the peptide backbone of neurofilaments, those helices are partly modified into beta-sheet and random coil structures. These characteristic reorganizations of the neurofilament structure after oxidative exposure suggest that free radical activity might play an important role in the biogenesis of the cytoplasmic inclusions found in several neurodegenerative diseases.
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Proteínas de Neurofilamentos/química , Estrés Oxidativo , Ácido 3,4-Dihidroxifenilacético/farmacología , Animales , Ácido Ascórbico/farmacología , Cloruros , Dicroismo Circular , Dopamina/farmacología , Electroforesis en Gel de Poliacrilamida , Compuestos Férricos/farmacología , Radicales Libres/farmacología , Levodopa/farmacología , Peso Molecular , Oxidación-Reducción , Fosforilación , Estructura Secundaria de Proteína , Espectroscopía Infrarroja por Transformada de Fourier , PorcinosRESUMEN
The pathways of polysaccharide biosynthesis were investigated in cells of Sinorhizobium meliloti (strain Su47) using a stable isotope approach. The isotopic labeling of the periplasmic beta-1,2-glucans synthesized from glucose labeled at various positions evidenced the involvement of catabolic pathways, namely the pentose-phosphate and Entner-Doudoroff pathways, into the early steps of polysaccharide synthesis. The exopolysaccharides produced at the same time had a labeling pattern similar to that of the beta-glucans, indicating similar early steps for both polysaccharides. The results emphasized a cyclic organization of the carbohydrate metabolism in S. meliloti, in which the carbons of the initial hexose were allowed to re-enter the catabolic pathways many times. The metabolic incidences of such metabolic topology are discussed.