Ontogeny of synaptophysin and synaptoporin in the central nervous system

The expression of the synaptic vesicle antigens synaptophysin (SY) and synaptoporin (SO) was studied in the rat striatum, which contains a nearly homogeneous population of GABAergic neurons. In situ hybridization revealed high levels of SY transcripts in the striatal anlage from embryonic day (E) 14 until birth. In contrast. SO hybridization signals were low, and no immunoreactive cell bodies were detected at these stages of development. At E 14, SY-immunoreactivity was restricted to perikarya. In later prenatal stages of development SY-immunoreactivity appeared in puncta (identified as terminals containing immunostained synaptic vesicles), fibers, thick fiber bundles and ‘patches’. In postnatal and adult animals, perikarya of striatal neurons exhibited immunoreaction for SO; ultrastructurally SO antigen was found in the Golgi apparatus and in multivesicular bodies. SO-positive boutons were rare in the striatum. In the neuropil, numerous presynaptic terminals positive for SY were observed. Our data indicate that the expression of synaptic vesicle proteins in GABAergic neurons of the striatum is developmentally regulated. Whereas SY is prevalent during embryonic development, SO is the major synaptic vesicle antigen expressed postnatally by striatal neurons which project to the globus pallidus and the substantia nigra. In contrast synapses of striatal afferents (predominantly from cortex, thalamus and substantia nigra) contain SY

Sampling protein motion and solvent effect during ligand binding.

An exhaustive description of the molecular recognition mechanism between a ligand and its biological target is of great value because it provides the opportunity for an exogenous control of the related process. Very often this aim can be pursued using high resolution structures of the complex in combination with inexpensive computational protocols such as docking algorithms. Unfortunately, in many other cases a number of factors, like protein flexibility or solvent effects, increase the degree of complexity of ligand/protein interaction and these standard techniques are no longer sufficient to describe the binding event. We have experienced and tested these limits in the present study in which we have developed and revealed the mechanism of binding of a new series of potent inhibitors of Adenosine Deaminase. We have first performed a large number of docking calculations, which unfortunately failed to yield reliable results due to the dynamical character of the enzyme and the complex role of the solvent. Thus, we have stepped up the computational strategy using a protocol based on metadynamics. Our approach has allowed dealing with protein motion and solvation during ligand binding and finally identifying the lowest energy binding modes of the most potent compound of the series, 4-decyl-pyrazolo[1,5-a]pyrimidin-7-one

A Distributed IoT Air Quality Measurement System for High-Risk Workplace Safety Enhancement

The safety of an operator working in a hazardous environment is a recurring topic in the technical literature of recent years, especially for high-risk environments such as oil and gas plants, refineries, gas depots, or chemical industries. One of the highest risk factors is constituted by the presence of gaseous substances such as toxic compounds such as carbon monoxide and nitric oxides, particulate matter or indoors, in closed spaces, low oxygen concentration atmospheres, and high concentrations of CO2 that can represent a risk for human health. In this context, there exist many monitoring systems for lots of specific applications where gas detection is required. In this paper, the authors present a distributed sensing system based on commercial sensors aimed at monitoring the presence of toxic compounds generated by a melting furnace with the aim of reliably detecting the insurgence of dangerous conditions for workers. The system is composed of two different sensor nodes and a gas analyzer, and it exploits commercial low-cost commercially available sensors

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Prevalence of Toxoplasma gondii infection in Myocastor coypus in a protected Italian wetland

<p>Abstract</p> <p>Background</p> <p><it>Toxoplasma gondii </it>is the causative agent for a major zoonosis with cosmopolitan distribution. Water has been implicated in outbreaks of toxoplasmosis in recent years. Coypus (<it>Myocastor coypus</it>), commonly nutria, are large semi-aquatic invasive rodents, naturalized throughout European countries, including most wetlands of Central Italy. The habitat of these animals is both terrestrial and aquatic, making them a species highly exposed to the parasite.</p> <p>Findings</p> <p>The occurrence of the infection was evaluated using a modified agglutination test (MAT) in 74 adult coypus from a naturalized population living in a wetland of Central Italy. Nested PCR (n-PCR) assay was carried out on some of them. Positive <it>T. gondii </it>MAT results were found in 44 animals (59·4%), 30 males (68·2%) and 14 females (31·8%). Antibody titers were ranging from 20 to 40960, while 12 out of 23 (52·2%), examined animals, 8 males (66·7%) and 4 females (33·3%), resulted positive to n-PCR. All n-PCR positive animals were seropositive, showing antibody titers ranging from 640 to 40960.</p> <p>Conclusions</p> <p>Our results indicate that examined animals are heavily parasitized with <it>Toxoplasma</it>. This suggests that coypus could be a reservoir of this parasite, because they can be eaten both by scavenger animals and by humans, and that these animals would play a role in maintaining the cycle of <it>T. gondii</it>.</p

Analytical approaches to RNA profiling data for the identification of genes enriched in specific cells

We have recently developed a novel method for the affinity purification of the complete suite of translating mRNA from genetically labeled cell populations. This method permits comprehensive quantitative comparisons of the genes employed by each specific cell type. We provide a detailed description of tools for analysis of data generated with this and related methodologies. An essential question that arises from these data is how to identify those genes that are enriched in each cell type relative to all others. Genes relatively specifically employed by a cell type may contribute to the unique functions of that cell, and thus may become useful targets for development of pharmacological tools for cell-specific manipulations. We describe here a novel statistic, the specificity index, which can be used for comparative quantitative analysis to identify genes enriched in specific cell populations across a large number of profiles. This measure correctly predicts in situ hybridization patterns for many cell types. We apply this measure to a large survey of CNS cell-specific microarray data to identify those genes that are significantly enriched in each population Data and algorithms are available online (www.bactrap.org)