Jagged1 is necessary for postnatal and adult neurogenesis in the dentate gyrus

Understanding the mechanisms that control the maintenance of neural stem cells is crucial for the study of neurogenesis. In the brain, granule cell neurogenesis occurs during development and adulthood, and the generation of new neurons in the adult subgranular zone of the dentate gyrus contributes to learning. Notch signaling plays an important role during postnatal and adult subgranular zone neurogenesis, and it has been suggested as a potential candidate to couple cell proliferation with stem cell maintenance. Here we show that conditional inactivation of Jagged1 affects neural stem cell maintenance and proliferation during postnatal and adult neurogenesis of the subgranular zone. As a result, granule cell production is severely impaired. Our results provide additional support to the proposal that Notch/Jagged1 activity is required for neural stem cell maintenance during granule cell neurogenesis and suggest a link between maintenance and proliferation of these cells during the early stages of neurogenesis.     

Modification of the detrimental effect of TNF‐α on human endothelial progenitor cells by fasudil and Y27632

Exposure of human endothelial progenitor cells (EPCs) to tumor necrosis factor‐α (TNF‐α) reduced their number and biological activity. Yet, signal transduction events linked to TNF‐α action are still poorly understood. To address this issue, we examined the possible effect of fasudil and Y27632, two inhibitors of Rho kinase pathway, which is involved in endothelial dysfunction, atherosclerosis, and in‐ flammation. Results demonstrated that incubation with fasudil starting from 50 μM but not Y27632 determined a dose‐dependent improvement of EPC number during exposure to TNF‐α (P < 0.05 vs. TNF‐α alone). Analysis of the signal transduction pathway activated by TNF‐α revealed that the increased expression of p‐p38 was not significantly altered by fasudil. Instead, fasudil blocked the TNF‐α induced phosphorylation of Erk1/2 (P < 0.05 vs. TNF‐α) as well as the inhibitor of Erk1/2‐specific phosphorylated form, i.e., PD98059 (P < 0.05 vs. TNF‐α). These results were confirmed by analysis of these kinases by confocal microscopy. Finally, 2D‐DIGE and MALDI‐TOF/TOF analysis of EPCs treated with fasudil revealed increased expression levels of an actin‐related protein and an adenylyl cyclase associated protein and decreased expression levels of proteins related to radical scavenger and nucleotide metabolism. These findings suggest that fasudil positively affects EPC number and that other major signals might take part to this complex pathway. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:351–360, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20345     

Epidemiología de las fungemias en un hospital pediátrico de alta complejidad

BackgroundA retrospective study on the epidemiology of fungaemia due to yeasts of medical importance at the Hospital Nacional de Pediatría Prof. Dr. J. Garrahan, Buenos Aires was conducted between September 2001 and September 2003.ObjectivesTo learn the distribution of yeast species and to evaluate their in vitro antifungal susceptibility profile.MethodsThe minimum inhibitory concentration (MIC) was determined according to the CLSI M27-A2 procedure, and time kill curves against amphotericin B were also performed.Results-ConclusionsThe species isolated were Candida parapsilosis (32.6% of isolates); Candida albicans (26.5%), Candida tropicalis (24.5%), and other yeasts (16.4%). Candida isolates were susceptible to the antifungals evaluated, but amphotericin B-tolerant isolates were detected using time kill curves.     

Effect of conjugated linoleic acid on body fat,tumor necrosis factor alpha and resistin secretion in spontaneously hypertensive rats

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivaties of linoleic acid found mainly in beef and dairy products. CLA has been reported to reduce body fat, as well as to possess anticarcinogenic, antiatherogenic and procatabolic activities in animals. The objective of this study was to evaluate the effect of CLA supplementation to spontaneously hypertensive rats (SHR) on body fat, biochemical parameters of serum related tumor necrosis factor alpha (TNF-α) and resistin secretion. Thirty rats were divided in three groups, the first group of spontaneously hypertensive rats received a standard diet (V-SHR group, n=10), a second group of SHR was fed 1.5% of conjugated linoleic acid (CLA-SHR group, n=10) and the third was the control, non-hypertensive group (KW, n=10) also on a standard diet including 7.5% of sunflower oil during eight weeks.After CLA diet administration, spontaneously hypertensive rats showed a significant reduction in blood pressure, serum glucose, cholesterol and triacylglycerols, together with reduction of index of body fat, pericardic, abdominal and epididymal adipose tissue. These effects were accompanied by a decrease in the secretion of TNF-α and resistin.     

2-Methyl-3-furanyl-4H-1,2,4-triazol-3-ylthioamides: a new class of selective orexin 2 antagonists

A new class of selective orexin 2 antagonist was identified among commercial products. Initial SAR was obtained using commercial derivatives only prior to starting ad hoc medicinal chemistry activities.     

Distribución de la circunferencia de la cintura y de la relación circunferencia de la cintura con respecto a la talla según la categoría del índice de masa corporal en los pacientes atendidos en consultas de endocrinología y nutrición

IntroductionWaist circumference (WC) and the waist-to-height ratio (WHtR) are anthropometric measures widely used in clinical practice to evaluate visceral fat and the consequent cardiovascular risk. However, risk thresholds should be standardized according to body mass index (BMI).ObjectiveTo determine the distribution of WC and WHtR according to the BMI cut-points currently used to describe overweight and obesity.Materials and methodsWC, WHtR and BMI were measured in 3521 adult patients (>18 years) attended in Endocrinology and Nutrition units.ResultsA total of 20.8% (734 patients) were diabetic. Obesity was found in 82.1% of diabetic patients and in 75% of non-diabetic patients. The WC thresholds proposed by the National Institute of Health (102 cm in men, 88 cm in women), Bray (100 cm in men, 90 cm in women) and the International Diabetes Federation (94 cm in men, 80 cm in women) were exceeded by 92.9%, 94.8% and 98.4% of obese men, 96.8%, 95.5% and 99.7% of obese women, 79.1%, 83.1% and 90% of diabetic men and 95.5%, 81.5% and 97.4% of diabetic women, respectively. Thresholds adapted to the degree of obesity (90, 100, 110 and 125 cm in men and 80, 90, 105 and 115 cm in women for normal BMI, overweight, obesity I and obesity greater than I) were exceeded by 58.4% of obese men, 54.2% of obese women, 57.5% of diabetic men and 60.7% of diabetic women. WC was higher in men, and BMI and the WHtR were higher in women. The WC of diabetic women equalled that of men, and WC, WHtR and BMI were higher in diabetic than in non-diabetic women (p<0.001). WC (p<0.005), WHtR (p<0.001) and BMI (p<0.5) were also higher in diabetic than in non-diabetic men.ConclusionWC and WHtR thresholds by BMI discriminated diabetic and obese patients better than single thresholds, and can be represented graphically by the distribution of percentile ranks of WC and WHtR by BMI.ik     

How to predict diffusion of medium-sized molecules in polymer matrices. From atomistic to coarse grain simulations

The normal diffusion regime of many small and medium-sized molecules occurs on a time scale that is too long to be studied by atomistic simulations. Coarse-grained (CG) molecular simulations allow to investigate length and time scales that are orders of magnitude larger compared to classical molecular dynamics simulations, hence providing a valuable approach to span time and length scales where normal diffusion occurs. Here we develop a novel multi-scale method for the prediction of diffusivity in polymer matrices which combines classical and CG molecular simulations. We applied an atomistic-based method in order to parameterize the CG MARTINI force field, providing an extension for the study of diffusion behavior of penetrant molecules in polymer matrices. As a case study, we found the parameters for benzene (as medium sized penetrant molecule whose diffusivity cannot be determined through atomistic models) and Poly (vinyl alcohol) (PVA) as polymer matrix. We validated our extended MARTINI force field determining the self diffusion coefficient of benzene (2.27·10⁻⁹ m² s⁻¹) and the diffusion coefficient of benzene in PVA (0.263·10⁻¹² m² s⁻¹). The obtained diffusion coefficients are in remarkable agreement with experimental data (2.20·10⁻⁹ m² s⁻¹ and 0.25·10⁻¹² m² s⁻¹, respectively). We believe that this method can extend the application range of computational modeling, providing modeling tools to study the diffusion of larger molecules and complex polymeric materials.     

An ecosystem approach to restoration and sustainable management of dry forest in southern Peru

The dry forest of the Peruvian south coast has undergone an almost total process of deforestation. Populations here have increased exponentially through immigration supplying labour to urban coastal development, and demonstrably unsustainable agro-industrial expansion for export markets. Society has become dislocated from local traditions of environmental and resource management whilst still retaining a wealth of Andean agricultural expertise. Indigenous communities still hold on to vestiges of traditional knowledge. Relicts of natural vegetation, traditional agriculture and agrobiodiversity continue to sustain ecosystem services. Moreover, offer livelihood options and resources for restoration. These aspects reflect a long cultural trajectory, including famous extinct cultures such as Nasca, that evolved within an ever-changing riparian and agricultural landscape influenced by external forces and which incorporated important processes of plant domestication and adaptation to climatic oscillation.     

Left-sided infective endocarditis caused by Pseudomonas aeruginosa treated medically

Infective endocarditis due to Pseudomonas aeruginosa is a rare clinical condition, difficult to diagnose and associated with high mortality. Herein we present a case of a 51 years old male without history of intravenous drug use or valvular disease, with past medical history of cholecystectomy in the previous month, who presented to the emergency department with fever, gastrointestinal symptoms, and subsequent signs of distant embolization, positive blood cultures for P. aeruginosa and development of multiple complications of the disease. The clinical presentation of infective endocarditis is nonspecific, leading to delayed diagnosis, and preventing early and effective treatment. Valvular replacement is indicated in fungal or P. aeruginosa endocarditis. This case is notable because of the resolution with amikacin combined with meropenem, in a patient with several complications that contraindicated surgery.     

Species-specificity of nurse plants for the establishment, survivorship, and growth of a columnar cactus

? Premise of the study: Seedling establishment and early survivorship are crucial steps for the regeneration of plant populations because both have long-lasting effects on plant population dynamics. For species recruiting through facilitation, species-specific facilitative effects might affect early fitness, an overlooked aspect in studies of facilitation considering groups of nurse species. ? Methods: We experimentally evaluated the roles of 10 nurse species and open space on the early performance of the columnar cactus Neobuxbaumia mezcalaensis. We measured establishment, survivorship, and growth of individuals over 3 years. Moreover, to study an extended period of the ontogeny of the interaction between this cactus and its nurse plants, we also monitored survivorship and growth rates of individuals between 3 to 12 cm tall during a 3-year period. ? Key results: Neobuxbaumia mezcalaensis performance varied significantly among nurse species, and only six yielded positive effects on early fitness. Densely canopied plants were the best nurses for this cactus. However, even among densely canopied species, some produced negative effects on the early fitness of N. mezcalaensis, indicating that similar nurse plants may elicit either facilitative or interference effects on beneficiary species. ? Conclusions: Our results emphasize the importance of species-specific facilitative interactions in the crucial early stages in the life cycle of N. mezcalaensis and how different nurse species modify the effect of seed-rain and contribute significantly to the population dynamics of the species.