20 research outputs found

    Selective endocytosis of Ca(2+)-permeable AMPARs by the Alzheimer's disease risk factor CALM bidirectionally controls synaptic plasticity

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    AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission, and the plastic modulation of their surface levels determines synaptic strength. AMPARs of different subunit compositions fulfill distinct roles in synaptic long-term potentiation (LTP) and depression (LTD) to enable learning. Largely unknown endocytic mechanisms mediate the subunit-selective regulation of the surface levels of GluA1-homomeric Ca(2+)-permeable (CP) versus heteromeric Ca(2+)-impermeable (CI) AMPARs. Here, we report that the Alzheimer's disease risk factor CALM controls the surface levels of CP-AMPARs and thereby reciprocally regulates LTP and LTD in vivo to modulate learning. We show that CALM selectively facilitates the endocytosis of ubiquitinated CP-AMPARs via a mechanism that depends on ubiquitin recognition by its ANTH domain but is independent of clathrin. Our data identify CALM and related ANTH domain-containing proteins as the core endocytic machinery that determines the surface levels of CP-AMPARs to bidirectionally control synaptic plasticity and modulate learning in the mammalian brain

    Monitoring the quality of laboraties and the prevalence of resistance to antituberculosis drugs: Italy, 1998-2000

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    In 1998 a network of 20 regional tuberculosis (TB) laboratories (the Italian Multicentre Study on Resistance to Antituberculosis drugs (SMIRA) network) was established in Italy to implement proficiency testing and to monitor the prevalence of drug resistance nationwide. The network managed 30% of all TB cases reported in Italy each year. The aim of the present report is to describe: 1) the accuracy of drug-susceptibility testing in the network; 2) the prevalence of drug resistance for the period 1998-2000. Data were collected from the network laboratories. Sensitivity to streptomycin and ethambutol increased from the first survey (1998-1999) to the second survey (2000) from 87.7 to 91.9%. Specificity, predictive values for resistance and susceptibility, efficiency and reproducibility were consistent in both surveys. In previously untreated cases, the prevalence of multidrug-resistance was the same in both surveys (1.2%), while a slight decrease from the first to the second survey was observed for monoresistance to rifampicin (from 0.8 to 0.4%) and isoniazid (from 2.9 to 2%,). The significant association found between isoniazid resistance and immigration is a useful indicator for both clinicians managing individual tuberculosis cases and public health services planning control strategies

    To degrade or not to degrade:mechanisms and significance of endocytic recycling

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    Basis for nebulized antibiotics: Droplet characterization and in vitro antimicrobial activity versus Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa

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    The aims of this study were to (1) quantify the particle size characteristics of several antibiotics considered suitable for aerosol therapy after aerosolization with the PARI IS/2 nebulizer (Pari GmbH, Sarnberg, Germany) and (2) determine the degree to which in vitro antimicrobial activity of these antibiotics is maintained after nebulization. The aerosolized drugs were tobramycin sulfate, streptomycin, and imipenem, with saline solution as the control. Mean mass aerodynamic diameter of the nebulized drugs was 3.25 mu m for tobramycin, 2.26 mu m for imipenem, and 2.38 mu m for streptomycin. In vitro tests showed that tobramycin and imipenem were unaltered in their bacteriostatic activity against strains of Escherichia coli (American Type Culture Collection [ATCC] 25922) and Staphylococcus aureus (ATCC 29213) as well as against Pseudomonas aeruginosa (ATCC 27853) with minimal inhibitory concentration (MIC) values less than 0.3 mu g/mL. Nebulized streptomycin showed significantly higher MIC values against P. aeruginosa (ATCC 27853). These results suggest that tobramycin and imipenem may be prescribed as an aerosol generated by jet nebulization (PARI IS/2) to treat S. aureus, E. coli, and P. aeruginosa infections without any risk of altering the drugs(1) minimum bacteriostatic activity by the nebulization process. Aerosolization of streptomycin with this nebulizer may not be as effective against P. aeruginosa because it seems to alter the bacteriostatic activity

    Effetti dell'esposizione a piombo inorganico sul Sistema Nervoso Autonomo e sulla variabilità della frequenza cardiaca in lavoratori di una fabbrica di accumulatori

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    Inorganic Lead can cause a toxic effect on Central Nervous System, Peripheral Nervous System and Autonomic Nervous System (ANS). A damage of the ANS can determine an heart rate variability (HRV) reduction. In this study 43 battery workers exposed to inorganic lead with mean PbB = 31.63 microg/dl (DS 14.77 microg/dl) and 35 not exposed subjects underwent to an evaluation of heart rate variability by specific tests. Heart rate variability in the exposed group was, for some tests (lying to standing, lying to standing-standing to lying) reduced compared with not exposed subjects and for other tests (Valsalva manouvre, lying to standing-standing to lying) correlated with PbB and Zinc Protoporphyrin (ZPP), but not with BMI, age and smoking habits. This study, like others conducted on similar populations, suggest an effect of occupational inorganic lead exposure on Autonomic Nervous System and heart rate variabilit
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