Resposta a longo prazo com sulfonilureia em um paciente com diabetes associado à mutação no gene KCNJ11

OBJECTIVE: To report the long-term (30-month) effect of the switch from insulin to sulfonylurea in a patient carrying the p.G53D (c.158G>A) mutation in KCNJ11 gene. SUBJECT AND METHOD: A 29-year-old male patient was diagnosed with diabetes in the third month of life and after identification of a heterozygous p.G53D mutation in the KCNJ11 gene, the therapy was switched from insulin to sulfonylurea. RESULTS: Long-term follow-up (30 months) showed that good metabolic control was maintained (HbA1c: 6.6%) and the glibenclamide dose could be reduced. CONCLUSION: Long-term therapy with sulfonylureas in patients with neonatal diabetes due to mutation in the KCNJ11 gene is safe and promotes sustained improvement of glycemic control.OBJETIVO: Reportar o efeito a longo prazo (30 meses) da substituição de insulina por sulfonilureia em um paciente com a mutação p.G53D (c.158G>A) no gene KCNJ11. SUJEITO E MÉTODO: Paciente do sexo masculino, atualmente com 29 anos de idade, foi diagnosticado com diabetes melito no terceiro mês de vida e, após identificação da mutação p.G53D (c.158G>A) em heterozigose no gene KCNJ11, a terapia foi substituída de insulina para sulfonilureia. RESULTADOS: Seguimento a longo prazo (30 meses) mostrou que o bom controle metabólico foi mantido (HbA1c: 6,6%) e a dose de glibenclamida pode ser reduzida. CONCLUSÃO: A terapia com sulfonilureia a longo prazo em pacientes com diabetes neonatal decorrente de mutações no gene KCNJ11 é segura e promove uma melhora persistente no controle metabólico.Universidade Federal de São Paulo (UNIFESP) Division of EndocrinologyUNIFESP, Division of EndocrinologySciEL

An appraisal on the source-to-sink relationship in plants: an application of desorption electrospray ionization mass spectrometry imaging

CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOAmino acids/ureides and carbohydrates are the main nutrients for the plants growth. These metabolites are continuously translocated through the plant organism via well-known transportation mechanisms. The well-established source-to-sink relationship invol2911723CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçãosem informaçã

Structure and functioning of a mountain grazed grassland and their response after exclosure

Se estudió el efecto del pastoreo por ganado doméstico y de distintos tiempos de exclusión sobre la composición florística y la diversidad, y sobre la dinámica de la biomasa aérea, el contenido de nitrógeno y la productividad primaria de diferentes formas de vida, en un pastizal semi-natural de montaña de la provincia de Córdoba. El pastoreo promovió una mayor diversidad de especies, aunque la biomasa total y la productividad fueron máximas en el sitio con mayor tiempo de exclusión. El pastoreo promovió la abundancia de especies rastreras y graminoides. Las gramíneas en penacho sólo aparecen a partir de los 4 años de exclusión y representan más del 90% de la biomasa total en el sitio excluido del pastoreo por 15 años. No hubo diferencias significativas en la dinámica estacional de la biomasa en pie ni del nitrógeno de las diferentes formas de crecimiento en los diferentes sitios estudiados, pero las formas de crecimiento rastreras y graminoides prolongaron su estación de crecimiento bajo pastoreo, y se observó un mayor contenido de nitrógeno en las plantas pastoreadas. La productividad primaria neta aérea estuvo limitada a la primavera y el verano, entre los meses de octubre y marzo. La productividad disminuyó ligeramente luego de la exclusión del pastizal, pero aumentó significativamente a partir de los 4 años sin pastoreo.The effect of grazing and different times of exclosure on floristic composition, biomass, plant nitrogen concentration and aboveground net plant productivity were studied in a mountain grassland of Córdoba, Argentina. Plant diversity was maximum at the grazed site and no invasion of alien species was recorded at any site, but total standing biomass and aboveground net plant productivity were maximum at the site excluded from grazing for 15 years. Prostrate, graminoid and annual growth forms accounted for more than 90% of live biomass at the grazed site. Rosettes increased their biomass with grazing exclusion and tussock grasses were apparent only after 4 years of exclusion and accounted for 90% of total biomass after 15 years of exclosure. There was no site effect on seasonal dynamics of standing biomass and plant nitrogen content of different plant growth forms, but prostrates and graminoids showed a prolonged growth season under grazing, and plant nitrogen content was higher in grazed plants. Aboveground net plant productivity (ANPP) was limited to spring and summer, from October to March. Two years of exclusion from grazing slightly decreased ANPP, but significatively increased after 4 years without livestock grazing.Universidad Nacional de La Plata (UNLP) - Facultad de Ciencias Agrarias y Forestales (FCAF

Effects of isoflavone-supplemented soy yogurt on lipid parameters and atherosclerosis development in hypercholesterolemic rabbits: a randomized double-blind study

<p>Abstract</p> <p>Background</p> <p>There is increasing interest in natural treatments to control dyslipidemia and reduce the risk of cardiovascular disease. Previous studies have demonstrated the beneficial effects of soy yogurt fermented with <it>Enterococcus faecium </it>CRL 183 and of dietary isoflavones on the lipid profile. The purpose of the present study was to investigate the effects of isoflavone-supplemented soy yogurt, fermented with <it>E. faecium </it>CRL183, on lipid parameters and atherosclerosis development in rabbits with induced hypercholesterolemia.</p> <p>Methods</p> <p>Forty-eight rabbits were randomly assigned to eight groups fed on the following diets for 60 days: C - control; IY - isoflavone-supplemented soy yogurt; H - hypercholesterolemic (1.0% cholesterol wt/wt diet); HY - hypercholesterolemic plus soy yogurt; HIY - hypercholesterolemic plus isoflavone-supplemented soy yogurt; HP - hypercholesterolemic plus placebo; HI - hypercholesterolemic plus isoflavone and HE - hypercholesterolemic plus pure culture of <it>E. faecium </it>CRL 183. Serum lipids and autoantibodies against oxLDL (oxLDL Ab) were analyzed on days 0, 30 and 60 of the treatment and the atherosclerotic lesions were quantified at the end of the experiment.</p> <p>Results</p> <p>Soy yogurt, soy yogurt supplemented with isoflavones and placebo promoted significant reductions in total cholesterol level (38.1%, 27.0% and 26.6%, respectively). Significant increases in serum HDL-C concentration relative to group H were detected in animals that ingested soy yogurt, with or without the isoflavone supplement (55.2%), <it>E. faecium </it>culture (43.3%) or placebo (35.8%). Intake of soy yogurt and soy yogurt supplemented with isoflavones prevented the rise of oxLDL Ab during the study period. The extent of atherosclerosis in the thoracic and abdominal aortas was reduced in the HIY, HY and HP groups. However, when the whole aorta was analyzed, animals treated with soy yogurt supplemented with isoflavones exhibited the greatest reduction (51.4%, P < 0.05) in atherosclerotic lesion area, compared to group H.</p> <p>Conclusion</p> <p>Soy yogurt could be consumed as an alternative means of reducing the risk of cardiovascular disease by improving the lipid profile and inhibiting oxLDL Ab formation. Our findings also suggest that isoflavone supplementation may enhance the antiatherosclerotic effect of soy yogurt.</p

SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation

Chronic lymphocytic leukemia (CLL) is characterized by a low CD20 expression, in part explained by an epigenetic-driven downregulation triggered by mutations of the NOTCH1 gene. In the present study, by taking advantage of a wide and well-characterized CLL cohort (n=537), we demonstrate that CD20 expression is downregulated in SF3B1-mutated CLL in an extent similar to NOTCH1-mutated CLL. In fact, SF3B1-mutated CLL cells show common features with NOTCH1-mutated CLL cells, including a gene expression profile enriched of NOTCH1-related gene sets and elevated expression of the active intracytoplasmic NOTCH1. Activation of the NOTCH1 signaling and down-regulation of surface CD20 in SF3B1-mutated CLL cells correlate with over-expression of an alternatively spliced form of DVL2, a component of the Wnt pathway and negative regulator of the NOTCH1 pathway. These findings are confirmed by separately analyzing the CD20-dim and CD20-bright cell fractions from SF3B1-mutated cases as well as by DVL2 knock-out experiments in CLL-like cell models. Altogether, the clinical and biological features that characterize NOTCH1-mutated CLL may also be recapitulated in SF3B1-mutated CLL, contributing to explain the poor prognosis of this CLL subset and providing the rationale for expanding novel agents-based therapies to SF3B1-mutated CLL

Convergent evidences from human and animal studies implicate angiotensin I-converting enzyme activity in cognitive performance in schizophrenia

In schizophrenia (SCZ), higher angiotensin I-converting enzyme (ACE) levels have been reported in patient's blood and cerebrospinal fluid (CSF). Hereby, we propose to explore whether the ACE activity levels are associated to cognitive performance in SCZ. Seventy-two patients with SCZ or schizoaffective disorder diagnosis, and 69 healthy controls (HCs) underwent a cognitive battery with parallel collection of peripheral blood samples to measure ACE activity. Significant higher ACE activity levels were confirmed in the plasma of SCZ patients compared with HCs (Student's t=−5.216; P<0.001). ACE activity significantly correlated to Hopkins delayed recall measures (r=−0.247; P=0.004) and Hopkins total (r=−0.214; P=0.012). Subjects grouped as high ACE activity (above average) had worse performance compared with low ACE activity level group for Hopkins delayed recall measure, even after correction for clinical condition, age, gender and years of education (P=0.029). The adjusted R squared for this final model was 0.343. This result was evident only comparing extreme groups for ACE activity, when splitting the sample in three groups with similar number of subjects. To clarify this finding, we performed an evaluation of the cognitive performance of transgenic mice with three copies of ACE gene in novel object recognition (NOR) test, which showed that such animals presented impairment in NOR (P<0.05) compared with two copies of wild-type animals. The results observed in SCZ patients and animal model suggest both the association of ACE to cognitive deficits in SCZ. This finding may support the evaluation of novel treatment protocols and/or of innovative drugs for specific intervention of cognitive deficits in SCZ envisioning concomitant ACE activity and behavior evaluations

Divergent Biochemical Fractionation, Not Convergent Temperature, Explains Cellulose Oxygen Isotope Enrichment across Latitudes

Recent findings based on the oxygen isotope ratios of tree trunk cellulose indicate that the temperature of biomass production in biomes ranging from boreal to subtropical forests converge to an average leaf temperature of 21.4°C. The above conclusion has been drawn under the assumption that biochemically related isotopic fractionations during cellulose synthesis are not affected by temperature. Here we test the above assumption by heterotrophically generating cellulose at different temperatures and measuring the proportion of carbohydrate oxygen that exchange with water during cellulose synthesis and the average biochemical fractionation associated with this exchange. We observed no variation in the proportion of oxygen that exchange with different temperatures, which averaged 0.42 as it has been observed in other studies. On the other hand, the biochemical oxygen isotope fractionation during cellulose synthesis is affected by temperature and can be described by a 2nd order polynomial equation. The biochemical fractionation changes little between temperatures of 20 and 30°C averaging 26‰ but increases at lower temperatures to values of 31‰. This temperature sensitive biochemical fractionation explains the pattern of cellulose oxygen isotope ratios of aquatic plants encompassing several latitudes. The observed temperature sensitive biochemical fractionation also indicates that divergent biochemical fractionation and not convergent leaf temperature explains the increase in oxygen isotope enrichment of cellulose across several biomes