Aging Differentially Affects Multiple Aspects of Vesicle Fusion Kinetics

How fusion pore formation during exocytosis affects the subsequent release of vesicle contents remains incompletely understood. It is unclear if the amount released per vesicle is dependent upon the nature of the developing fusion pore and whether full fusion and transient kiss and run exocytosis are regulated by similar mechanisms. We hypothesise that if consistent relationships exist between these aspects of exocytosis then they will remain constant across any age. Using amperometry in mouse chromaffin cells we measured catecholamine efflux during single exocytotic events at P0, 1 month and 6 months. At all ages we observed full fusion (amperometric spike only), full fusion preceded by fusion pore flickering (pre-spike foot (PSF) signal followed by a spike) and pure “kiss and run” exocytosis (represented by stand alone foot (SAF) signals). We observe age-associated increases in the size of all 3 modes of fusion but these increases occur at different ages. The release probability of PSF signals or full spikes alone doesn't alter across any age in comparison with an age-dependent increase in the incidence of “kiss and run” type events. However, the most striking changes we observe are age-associated changes in the relationship between vesicle size and the membrane bending energy required for exocytosis. Our data illustrates that vesicle size does not regulate release probability, as has been suggested, that membrane elasticity or flexural rigidity change with age and that the mechanisms controlling full fusion may differ from those controlling “kiss and run” fusion

Prion Protein Accumulation In Lipid Rafts of Mouse Aging Brain

The cellular form of the prion protein (PrP(C)) is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrP(C). In old mice, this change favors PrP(C) accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrP(C) translocation into detergent-resistant membranes (DRMs), we looked at PrP(C) compartmentalization in hippocampi from acid sphingomyelinase (ASM) knockout (KO) mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrP(C) in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases

Match running performance and physical capacity profiles of U8 and U10 soccer players

Aim This study aimed to characterize match running performance of very young soccer players and evaluate the relationship between these data and physical capacities and technical skills. Methods Distances covered at different speed thresholds were measured during 31 official matches using GPS technology in U10 (n = 12; age 10.1 ± 0.1 years) and U8 (n = 15; age 7.9 ± 0.1 years) national soccer players. Counter movement jump performance (CMJ), 20 m shuttle running (20 m-SR), linear sprint performance (10, 20, 30 m), shuttle (SHDT) and slalom dribble tests (SLDT) were performed to determine the players physical capacities and technical skills. Results Physical capacities and technical skills were higher in U10 versus U8 players [P 0.05, ES: 0.74). The U10 players covered more total (TD) and high-intensity running distance (HIRD) than their younger counterparts did (P 0.05, ES: 0.99). TD and HIRD covered across the three 15 min periods of match play did not decline (P > 0.05, ES: 0.02–0.55). Very large magnitude correlations were observed between the U8 and U10 players performances during the 20 m-SR versus TD (r = 0.79; P < 0.01) and HIRD (r = 0.82; P < 0.01) covered during match play. Conclusions Data demonstrate differences in match running performance and physical capacity between U8 and U10 players, and large magnitude relationships between match play measures and physical test performances. These findings could be useful to sports science staff working within the academies

Transcript host-RNA signatures to discriminate bacterial and viral infections in febrile children

Abstract: Traditional laboratory markers, such as white blood cell count, C-reactive protein, and procalcitonin, failed to discriminate viral and bacterial infections in children. The lack of an accurate diagnostic test has a negative impact on child’s care, limiting the ability of early diagnosis and appropriate management of children. This, on the one hand, may lead to delayed recognition of sepsis and severe bacterial infections, which still represent the leading causes of child morbidity and mortality. On the other hand, this may lead to overuse of empiric antibiotic therapies, particularly for specific subgroups of patients, such as infants younger than 90 days of life or neutropenic patients. This approach has an adverse effect on costs, antibiotic resistance, and pediatric microbiota. Transcript host-RNA signatures are a new tool used to differentiate viral from bacterial infections by analyzing the transcriptional biosignatures of RNA in host leukocytes. In this systematic review, we evaluate the efficacy and the possible application of this new diagnostic method in febrile children, along with challenges in its implementation. Our review support the growing evidence that the application of these new tools can improve the characterization of the spectrum of bacterial and viral infections and optimize the use of antibiotics in children. Impact: Transcript host RNA signatures may allow to better characterize the spectrum of viral, bacterial, and inflammatory illnesses in febrile children and can be used with traditional diagnostic methods to determine if and when to start antibiotic therapy.This is the first review on the use of transcript RNA signatures in febrile children to distinguish viral from bacterial infections.Our review identified a wide variability of target populations and gold standards used to define sepsis and SBIs, limiting the generalization of our findings

The Data and Information System of the Large Scale Biosphere-Atmosphere Experiment in Amazonia - LBA

The Large-Scale Biosphere-Atmosphere Project in Amazonia (LBA) is an international research study led by Brazil. Investigators include field researchers and modelers from the U.S., South America, and Europe. Beija-flor provides a centralized access point to data sets acquired for and produced by LBA researchers and was developed to support: - Early data exchange among the investigators - Widely diverse data, in both content and format - Data discovery and retrieval, using fielded, free-text, geospatial, and temporal searches Though Beija-flor is a proprietary-based system, its adherence to FGDC metadata standards and the use of XML code allow most of the Beija-flor metadata fields to be understood by other search engines and indexing systems, as well as provide for platform/software-independent creation and maintenance of metadata files

GnRH test for the diagnosis of central precocious puberty: is it time to revisit the protocol ?

The paper discusses relevant issues related to GnRH test for diagnosing central precocious pubert

GnRH test for the diagnosis of central precocious puberty: is it time to revisit the protocol?

The use of a simplified GnRH test with a single dose of LH assessed 30 minutes after GnRH agonist represents a valid alternative to the traditional test required for establishing the diagnosis of central precocious puberty. Although cost optimization and higher facilities for children are important issues, further confirmatory studies with larger populations of children suspected to have central precocious puberty will help confirming the effectiveness of this strategy

METODO INNOVATIVO PER LA PREARMATURA IN AVANZAMENTO ED IL RINFORZO DEL FRONTE CON TUBI IN ACCIAIO AUTOPERFORANTI PER LA COSTRUZIONE DI UNA GALLERIA IN SABBIE INSTABILI SULL'AUTOSTRADA SA-RC

Due nuove gallerie automodali gemelle, lunghe circa mille metri, sono in corso di costruzione per sostituire quelle in esercizio, seriamente compromesse dall'instabilità del terreno ed ormai troppo piccole per il volume di traffico in sviluppo. Il terreno ospitante è un'alternanza caotica di strati variamente ripiegati di sedimenti marini fini, da sabbie a sabbie limose ed argillose, con variabile presenza d'acqua. La totale instabilità del terreno, nel quale non rimangono aperti nemmeno i fori per i consolidamenti ha reso necessario un rinforzo continuo della calotta ed il consolidamento del fronte di scavo. A tale scopo è stato messo a punto un sistema innovativo di consolidamento e rinforzo (Metodo Pelizza 2) che prevede l'impiego sia in corona che al fonte di tubi autoperforanti in acciaio iniettati in corso di perforazione alla pressione di 200 bar con boiacca di cemento lievemente espandente. Nel testo sono forniti dettagli del metodo e dei tempi operativ