SLC25A46 promotes mitochondrial fission and mediates resistance to lipotoxic stress in INS-1E insulin-secreting cells.

Glucose sensing in pancreatic ß-cells depends on oxidative phosphorylation and mitochondria-derived signals that promote insulin secretion. Using mass spectrometry-based phosphoproteomics to search for downstream effectors of glucose-dependent signal transduction in INS-1E insulinoma cells, we identified the outer mitochondrial membrane protein SLC25A46. Under resting glucose concentrations, SLC25A46 was phosphorylated on a pair of threonine residues (T44/T45) and was dephosphorylated in response to glucose-induced Ca2+ signals. Overexpression of SLC25A46 in INS-1E cells caused complete mitochondrial fragmentation, resulting in a mild mitochondrial defect associated with lowered glucose-induced insulin secretion. In contrast, inactivation of the Slc25a46 gene resulted in dramatic mitochondrial hyperfusion, without affecting respiratory activity or insulin secretion. Consequently, SLC25A46 is not essential for metabolism-secretion coupling under normal nutrient conditions. Importantly, insulin-secreting cells lacking SLC25A46 had an exacerbated sensitivity to lipotoxic conditions, undergoing massive apoptosis when exposed to palmitate. Therefore, in addition to its role in mitochondrial dynamics, SLC25A46 plays a role in preventing mitochondria-induced apoptosis in INS-E cells exposed to nutrient stress. By protecting mitochondria, SLC25A46 might help to maintain ß-cell mass essential for blood glucose control.

Using C. elegans as a model for neurodegenerative diseases: Methodology and evaluation.

Caenorhabditis elegans is a nematode that has been used as an animal model for almost 50years. It has primitive and simple tissues and organs, making it an ideal model for studying neurological pathways involved in neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD). C. elegans has conserved neurological pathways and is able to mimic human diseases, providing valuable insights into the human disease phenotype. This methodological review presents current approaches to generate neurodegenerative-like models of AD and PD in C. elegans, and evaluates the experiments commonly used to validate the diseases. These experimental approaches include assessing survival, fertility, mobility, electropharyngeogram assays, confocal mitochondrial imaging, RNA extraction for qRT-PCR or RT-PCR, and rate of defecation. This review also summarizes the current knowledge acquired on AD and PD using the aforementioned experimental approaches. Additionally, gaps in knowledge and future directions for research are also discussed in the review.

SERCA inhibition improves lifespan and healthspan in a chemical model of Parkinson disease in Caenorhabditis elegans.

Introduction: The high prevalence of neurodegenerative diseases in our population and the lack of effective treatments encourage the search for new therapeutic targets for these pathologies. We have recently described that submaximal inhibition of the Sarco-Endoplasmic Reticulum Ca2+ ATPase (SERCA), the main responsible for ER calcium storage, is able to increase lifespan in Caenorhabditis elegans worms by mechanisms involving mitochondrial metabolism and nutrient-sensitive pathways. Methods: We have studied here the effects of submaximal SERCA inhibition in a chemical model of Parkinson's disease (PD) induced in C. elegans worms by treatment with the mitochondrial complex I inhibitor rotenone. For specific SERCA inhibition, we treated worms with RNAi against sca-1, the sole orthologue of SERCA in C. elegans. Results and Discussion: Our results show that rotenone produces alterations in worms that include decreased lifespan, smaller size, reduced fertility, decreased motility, defecation and pumping rate, increased mitochondrial ROS production, reduced mitochondrial membrane potential and oxygen consumption rate, altered mitochondrial structure, and altered ethanol preference in behavioral studies. Most of these alterations were either fully or partially reversed in worms treated with sca-1 RNAi, suggesting that SERCA inhibition could be a novel pharmacological target in the prevention or treatment of neurodegeneration.

Angioedema Due to Acquired Deficiency of C1-Inhibitor: A Cohort Study in Spain and a Comparison With Other Series.

BACKGROUND: Data on acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) from 4 European countries (France, Italy, Germany, and Hungary) were recently published. OBJECTIVE: To report data from a group of 50 patients with acquired C1-INH deficiency from Spain, of whom 46 had angioedema, and compare them with other European series. METHODS: We performed a retrospective observational study of 46 patients with C1-INH-AAE and 4 asymptomatic patients. Clinical and biological characteristics and associated diseases were assessed and compared with other European series. RESULTS: Women accounted for 73.9% of cases. The prevalence of C1-INH-AAE related to hereditary forms was 1/10.1. Overall, 8.7% patients were aged <40 years. Diagnostic delay was 1.1 years. Angioedema mainly affected the face (91.3%), followed by the oropharynx (63%), extremities (50%), and abdomen (37%). Only 1 patient underwent orotracheal intubation. Erythema marginatum was present in 1 patient. A hematologic disorder was recorded in 50% of patients. Angioedema preceded all benign conditions, mostly monoclonal gammopathy of undetermined significance, but appeared very close to or after malignant hematologic diseases (median, 2.2 and 0.29 years). Autoimmune diseases were associated in 50% (autoimmune thyroiditis, 21.5%; systemic lupus erythematosus, 10.9%). Half of them coexisted with hematologic disorders. Anti-C1-INH antibodies were found in 67% of tested patients and were not related to the associated disease. Long-term prophylaxis was necessary in 52.2%, most of whom responded to tranexamic acid. CONCLUSIONS: This study emphasizes the possibility of C1-INH-AAE in patients younger than 40 and in autoimmune diseases other than systemic lupus erythematosus such as autoimmune thyroiditis.

A Binaural Neuromorphic Auditory Sensor for FPGA: A Spike Signal Processing Approach.

This paper presents a new architecture, design flow, and field-programmable gate array (FPGA) implementation analysis of a neuromorphic binaural auditory sensor, designed completely in the spike domain. Unlike digital cochleae that decompose audio signals using classical digital signal processing techniques, the model presented in this paper processes information directly encoded as spikes using pulse frequency modulation and provides a set of frequency-decomposed audio information using an address-event representation interface. In this case, a systematic approach to design led to a generic process for building, tuning, and implementing audio frequency decomposers with different features, facilitating synthesis with custom features. This allows researchers to implement their own parameterized neuromorphic auditory systems in a low-cost FPGA in order to study the audio processing and learning activity that takes place in the brain. In this paper, we present a 64-channel binaural neuromorphic auditory system implemented in a Virtex-5 FPGA using a commercial development board. The system was excited with a diverse set of audio signals in order to analyze its response and characterize its features. The neuromorphic auditory system response times and frequencies are reported. The experimental results of the proposed system implementation with 64-channel stereo are: a frequency range between 9.6 Hz and 14.6 kHz (adjustable), a maximum output event rate of 2.19 Mevents/s, a power consumption of 29.7 mW, the slices requirements of 11141, and a system clock frequency of 27 MHz.

Increased severity of Escherichia coli peritonitis in peritoneal dialysis patients independent of changes in in vitro antimicrobial susceptibility testing.

OBJECTIVE: Despite improvements in peritoneal dialysis (PD) technique, peritonitis continues to be one of the most frequent complications of PD. Nonresolving peritonitis remains a risk for severe anatomical peritoneal changes that may limit the viability of the membrane for dialysis purposes. We have observed remarkably poor outcome of peritonitis caused by Escherichia coli in the past 6 years. With its very low response rate to broad-spectrum antibiotics, the increased severity of E. coli peritonitis deteriorates peritoneal function and affects patient outcome. DESIGN: Retrospective study. SETTING: Two large PD units in two university hospitals. PATIENTS AND METHODS: The total number of patients reviewed was 456. The records of 49 E. coli peritonitis episodes were studied.The observation period started in 1980 and ended in March 2001. Sixteen males and 19 females were included. Severity was defined in terms of days of peritoneal inflammation, lack of response to a potentially useful antibiotic, requirement for catheter removal, and/or laparotomy. Study cases (study group) were those episodes appearing after 1996 (when the first severe cases appeared) and historic controls were episodes occurring before 1996. RESULTS: In the study group, 18 peritonitis episodes developed in 15 patients. In the control group, 31 peritonitis episodes developed in 20 patients. There were no significant differences in clinical presentation; however, the outcome was significantly poorer for the later period. A severe outcome occurred in 50% of study versus 10% of control patients. In fact, 68% of the episodes registered before 1996 were cured in 3 days or less. Concurring with this trend, the numbers of surgical interventions and catheter removals were also higher in the study group. Strikingly, E. coli did not show changes in in vitro susceptibility testing to antibiotics, although the in vivo response was much worse. CONCLUSIONS: We describe a change in the virulence of E. coli peritonitis episodes over the past 5 years leading to a high percentage of treatment failure, which does not depend on antibiotic sensitivity and seems to be dependent on changes in host response mechanisms.

Evaluación nutricional en estudiantes de enfermería / Nutricional assesment in nursing students

Objetivo: Conocer los hábitos dietéticos y conocimientos nutricionales de estudiantes de primero de enfermería. Material y métodos: Se estudio una muestra de 180 alumnas de 1er curso de enfermería que es el 95% de la población, el 5% restante se excluyó por razón de género o enfermedad crónica. A todas ellas se les realizó una encuesta de hábitos dietéticos y de frecuencia de consumo de alimentos de 3 días, incluyendo fin de semana. Asi mismo se realizó a todas las participantes medición de peso, talla, perímetro de cintura y cadera. Resultados: La ingesta energética media fue de1720 Kcal/día, siendo el aporte calórico proveniente de los hidratos de carbono inferior a las recomendaciones, mientras que el aporte de proteínas y lípidos eran superiores. La ingesta de ácidos grasos saturados (AGS)también era superior a las recomendaciones con significación estadística. En el 80% de las participantes el Índice de masa corporal (IMC) fue normal con un valor de 21,3 Kg/m2. El 11,1% presentaba bajo peso y el 8,9% sobrepeso / obesidad. Conclusiones: La información proporcionada por este estudio podría contribuir para reforzar los programas de formación en el área de Nutrición de las Escuelas de Enfermería (AU)

Objective: The aim of the study was to know dietary habits and nutritional knowledge of women nursing students. Material and methods: Participants of the study were a random sample composed of 180 female students of 1st curse of nursing studies. This sample represented the 95% of total, and the 5% was excluded (men and chronic illness). We studied three-day record study, including a weekend. At the same time, we measured the weight, the height, diameter of hip and diameter of waist. Results: The energy intake was 1720 Kcal/day, and as in similar studies the % energy from fat and proteins was higher than % energy from carbohydrates. Statured fatty acid intake was statistically significant higher than recommendations. Body mass index (BMI) was normal in 81,1% of women (21,3 Kg/m2). The rest was 10% underweight and 8,9% had overweight/obesity. Conclusions: This information provided by this study, should be used in order to improve Nutritional studies in nursing schools (AU)