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Δευτέρα 10 Απριλίου 2017

Environnement, Risques & Santé


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Environnement, Risques & Santé
 
 
Environnement, Risques & Santé
Volume 16, numéro 2, 2017

Retrouvez le dernier numéro de votre revue Environnement, Risques & Santé

A lire notamment dans ce numéro :

- Éléments de réflexions sur l'hypersensibilité électromagnétique et les intolérances environnementales idiopathiques


- Énergie et intolérances environnementales : électro-hypersensibilité, syndrome éolien, qu'en est-il vraiment ?

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Bonne lecture à tous !

 
    SOMMAIRE :
Éditorial/Editorial
Éléments de réflexions sur l'hypersensibilité électromagnétique et les intolérances environnementales idiopathiques
Anne Perrin
Brèves/News from the Literature
Chaleur et arrêts de grossesse en Californie*
Laurence Nicolle-Mir
Évolution de la vulnérabilité à la chaleur et au froid : revue de la littérature*
Laurence Nicolle-Mir
Mortalité liée à la chaleur au cours de l'été : analyse multi-pays*
Laurence Nicolle-Mir
Pollution atmosphérique et asthme infantile : vaste étude québécoise sur les cas incidents*
Laurence Nicolle-Mir
Exposition des écoliers aux polluants et au bruit du trafic et problèmes comportementaux*
Laurence Nicolle-Mir
Substances toxiques dans l'air ambiant et tumeurs cérébrales de l'enfant : étude californienne*
Laurence Nicolle-Mir
Maladie de Parkinson et expositions environnementales : état des connaissances*
Laurence Nicolle-Mir
Polluants environnementaux et santé de l'enfant : apports des récentes publications*
Laurence Nicolle-Mir
Expositions chimiques et anomalies congénitales : analyse de la littérature*
Laurence Nicolle-Mir
Mortalité dans une communauté italienne alimentée par une eau riche en sélénium inorganique*
Laurence Nicolle-Mir
Consommation de poisson, mercure plasmatique et issues de grossesse dans une cohorte britannique*
Laurence Nicolle-Mir
Sur le Web/On the Web
De Laurence Nicolle-Mir
Synthèse/General Review
Énergie et intolérances environnementales : électro-hypersensibilité, syndrome éolien, qu'en est-il vraiment ?
Monique Bonnet-Belfais, Jacques Lambrozo, Martine Souques, Aleksandra Piotrowski, Paul Tossa
Articles originaux/Original Articles
Comparaison des contaminations et des expositions alimentaires des années 1970, 2000 et 2010
Clarisse Ledoux, Véronique Sirot, Gilles Rivière
L'évaluation de la sécurité chimique dans REACH : principes et premiers retours d'expérience
Pierre Lecoq, Laura Maxim, Cécile Michel, Jean-Ulrich Mullot
Évaluation de l'imprégnation mercurielle chez les nouveau-nés dans la région d'Azzaba (Algérie)
Rachid Djafer, Myriam Megueddem, Barkaham Alamir
Point de vue/Point of View
Convergence NBIC : risques et conditions de possibilité au regard d'autres risques « silencieux »
Jean-Claude André
Portrait/Portrait
Plan « Paris Santé Environnement » et Service parisien de santé environnementale
Georges Salines
Législation/Legislation
De Laurence Nicolle-Mir
Compte rendu de congrès/Congress Review
Society for Risk Analysis, 2016
Pierre-André Cabanes
Ouvrages parus/Recent Publications
Ouvrages parus
Bloc-Notes/Notepad
Bloc-Notes




Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Evaluating impacts of recharging partially treated wastewater on groundwater aquifer in semi-arid region by integration of monitoring program and GIS technique

Abstract

The current study investigates the impact of recharging of partially treated wastewater through an infiltration basin on the groundwater aquifer quality parameters. A monitoring program supported by a geographic information analysis (GIS) tool was used to conduct this study. Groundwater samples from the entire surrounding boreholes located downstream the infiltration basin, in addition to samples from the recharged wastewater coming from the Beit Lahia wastewater treatment (BLWWTP), were monitored and analysed between 2011 and 2014. The analysis was then compared with the available historical data since 2008. Results revealed a groundwater replenishment with the groundwater level increased by 1.0–2.0 m during the study period. It also showed a slight improvement in the groundwater quality parameters, mainly a decrease in TDS, Cl and NO3 levels by 5.5, 17.1 and 20%, respectively, resulting from the relatively better quality of the recharged wastewater. Nevertheless, the level of boron and ammonium in the groundwater wells showed a significant increase over time by 96 and 100%, respectively. Moreover, the infiltration rate was slowed down in time due to the relatively high level of total suspended solid (TSS) in the infiltrated wastewater.



http://ift.tt/2ojvO4z

Synergetic effect of rhamnolipid from Pseudomonas aeruginosa C1501 and phytotoxic metabolite from Lasiodiplodia pseudotheobromae C1136 on Amaranthus hybridus L. and Echinochloa crus-galli weeds

Abstract

Rhamnolipid (Rh) is a biosurfactant produced by the bacterial Pseudomonas aeruginosa. This present study investigates rhizospheric strain C1501 of P. aeruginosa with an accession number KF976394 with the best production of rhamnolipid: a biosurfactant. The partially purified rhamnolipid from strain C1501 and Tween 80 was tested on mycelial growth of wild strain C1136. The enzyme activities involved in biodegradation, as well as necrosis induction on the tested weeds, were performed using scanning electron microscopy. It was observed that the different concentrations of rhamnolipid tested enhanced the dry mycelia weight yield of Lasiodiplodia pseudotheobromae which has been established to be producing a phytotoxic metabolite for killing weeds. It was observed that strain C1136 had a high level of cellulase and xylanase enzyme activities during this study. The scanning electron microscopy showed that the mutant strain of C1136 combined with 0.003% v/v of rhamnolipid enhances biodegradability and a high level of necrosis on the tested weeds compared with that on the untreated weeds. The highest CMCase activities and xylanase activities were obtained on the fourth day from the phytotoxic metabolite produced from the mutant strain of L. pseudotheobromae when combined with 0.003% v/v of rhamnolipid. This study has shown that rhamnolipid can serve as an adjuvant in order to enhance the penetrability of bioherbicide active ingredient for controlling weeds.



http://ift.tt/2oXFNiS

PCDD/F formation during thermal desorption of p,p′-DDT contaminated soil

Abstract

Thermal treatment of polychlorinated biphenyls (PCB) contaminated soil was shown in earlier work to generate polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF). In this study, the PCDD/F were studied arising during the remediation of p,p′-DDT contaminated soil by thermal desorption. Three kinds of soil (sandy, clayey and lateritic soil) were tested to investigate the effect of soil texture on PCDD/F formation. Those soils were artificially polluted with p,p′-DDT, obtaining a concentration level of 100 mg/kg. Thermal desorption experiments were conducted for 10 min at 300 °C in an air atmosphere. The total concentration of PCDD/F generated for three soils were 331, 803 and 865 ng/kg, respectively, and TeCDD and TeCDF were dominant among all PCDD/F congeners. After thermal desorption, the total amount of PCDD/F generated both in soil and in off-gas correlated positively with the amount of DDT added to soil. In addition, a possible pathway of the formation of PCDD/F was presented.



http://ift.tt/2ojx7k2

Proteomic analysis of continuous 900-MHz radiofrequency electromagnetic field exposure in testicular tissue: a rat model of human cell phone exposure

Abstract

Although cell phones have been used worldwide, some adverse and toxic effects were reported for this communication technology apparatus. To analyze in vivo effects of exposure to radiofrequency-electromagnetic field (RF-EMF) on protein expression in rat testicular proteome, 20 Sprague-Dawley rats were exposed to 900 MHz RF-EMF for 0, 1, 2, or 4 h/day for 30 consecutive days. Protein content of rat testes was separated by high-resolution two-dimensional electrophoresis using immobilized pH gradient (pI 4–7, 7 cm) and 12% acrylamide and identified by MALDI-TOF/TOF-MS. Two protein spots were found differentially overexpressed (P < 0.05) in intensity and volume with induction factors 1.7 times greater after RF-EMF exposure. After 4 h of daily exposure for 30 consecutive days, ATP synthase beta subunit (ASBS) and hypoxia up-regulated protein 1 precursor (HYOU1) were found to be significantly up-regulated. These proteins affect signaling pathways in rat testes and spermatogenesis and play a critical role in protein folding and secretion in the endoplasmic reticulum. Our results indicate that exposure to RF-EMF produces increases in testicular proteins in adults that are related to carcinogenic risk and reproductive damage. In light of the widespread practice of men carrying phones in their pockets near their gonads, where exposures can exceed as-tested guidelines, further study of these effects should be a high priority.



http://ift.tt/2oXE65f

Effect of biochar on alleviation of cadmium toxicity in wheat ( Triticum aestivum L.) grown on Cd-contaminated saline soil

Abstract

Soil degradation by salinity and accumulation of trace elements such as cadmium (Cd) in the soils are expected to become one of the most critical issues hindering sustainable production and feeding the increasing population. Biochar (BC) has been known to protect the plants against soil salinity and heavy metal stress. A soil culture study was performed to evaluate the effect of BC on wheat (Triticum aestivum L.) growth, biomass, and reducing Cd and sodium (Na) uptake grown in Cd-contaminated saline soil under ambient conditions. Soil salinity decreased the plant growth, biomass, grain yield, chlorophyll contents, and gas exchange parameters and caused oxidative stress in plants compared with Cd stress alone. Salt stress increased Cd and Na uptake and reduced the potassium (K) and zinc (Zn) uptake by plants. AB-DTPA-extractable Cd and soil electrical conductivity (ECe) increased under salt stress compared to the soil without NaCl stress. Biochar application improved the plant growth and reduced the Cd and Na uptake except in plants treated with higher BC and salt stress (5.0% BC + 50 mM NaCl). Biochar application reduced the oxidative stress in plants and modified the antioxidant enzyme activities, and reduced the bioavailable Cd under salt stress. The positive effects of BC under lower salt stress while the negative effects of BC under higher BC and salt levels indicated that BC doses should be used with great care in higher soil salinity levels simultaneously contaminated with Cd to avoid the negative effects of BC on growth and metal uptake.



http://ift.tt/2ojBwDK

Seasonal assessment of biological indices, bioaccumulation, and bioavailability of heavy metals in sea urchins Paracentrotus lividus from Algerian west coast, applied to environmental monitoring

Abstract

The aim of the present work was to extend our knowledge on the variability of trace metals in sea urchin tissues, focusing on seasonal fluctuations (2010 February for "winter," May for "spring," August for "summer," November for "autumn") in the three different sampling sites of Algerian west coast (Oran Harbor (S1), Ain Defla (S2), and Hadjaj (belonging to Mostaganem City S3)). For this purpose, the bioavailability (metal indices) and bioaccumulation (metal concentrations in soft tissues) of heavy metals (Zn, Cu, Pb, and Cd), the physiological characteristics (e.g., biological indices such as condition index (CI), repletion index (RI), gonad index (GI)), and the biometric parameters (diameter (D) and the height (H)) of sea urchins Paracentrotus lividus were assessed and related to seasons and sites. To investigate the metal bioavailability to sea urchins more precisely, the metal indices were used as a reliable tool in the present work, instead of the metal concentrations only. The interest to standardize metal concentrations with the weight of the urchin test is to overcome the metal burden variations in the soft tissues of urchin related to the seasonal weight changes of the soft body of animal. We evidence that the most contaminated sites were S1 and S2. Furthermore, it should be noted that the bioavailability of metals, corresponding to the values of metal indices, is also more pronounced in S1 and S2 compared to that measured in S3. Thus, a correlation is observed between seasonal metal content in urchin tissues from the three sites and the corresponding metal indices. The high metal concentrations were obtained during the period when RI and CI were highest. So, it appears that the bioaccumulation of metals in sea urchins of the three sites studied is significantly influenced by the reproductive cycle and diet, feeding activity, and physiological state of these organisms. We noticed that the sea urchins from the sites S1 and S2 were small in size. It is probable that these animals, whose internal tissues contained high concentrations of metals, have been exposed to metal pollution, which might have affected both their growth and altered their physiological capacity. This approach is very original and might be used in the monitoring of the quality of coastal waters, and the present work provided a useful data set for Mediterranean monitoring network.



http://ift.tt/2oXxC69

Optimal air quality policies and health: a multi-objective nonlinear approach

Abstract

The use of modelling tools to support decision-makers to plan air quality policies is now quite widespread in Europe. In this paper, the Regional Integrated Assessment Tool (RIAT+), which was designed to support policy-maker decision on optimal emission reduction measures to improve air quality at minimum costs, is applied to the Porto Urban Area (Portugal). In addition to technological measures, some local measures were included in the optimization process. Case study results are presented for a multi-objective approach focused on both NO2 and PM10 control measures, assuming equivalent importance in the optimization process. The optimal set of air quality measures is capable to reduce simultaneously the annual average concentrations values of PM10 and NO2 in 1.7 and 1.0 μg/m3, respectively. This paper illustrates how the tool could be used to prioritize policy objectives and help making informed decisions about reducing air pollution and improving public health.



http://ift.tt/2ojqwpL

Assessing ultraphytoplankton and heterotrophic prokaryote composition by flow cytometry in a Mediterranean lagoon

Abstract

In the eutrophic Ghar El Melh Lagoon (GML, Tunisia), the distribution of heterotrophic prokaryotes, pico- and nanophytoplankton was studied at five stations in November 2012 at the single cell level, along with environmental factors. Flow cytometry analysis of ultraplankton (<10 μm) resolved (i) two heterotrophic prokaryote groups, low and high nucleic acid contents (LNA and HNA, respectively), and (ii) eight to nine ultraphytoplankton groups (cryptophyte-like cells, two nanoeukaryote subgroups, two picoeukaryote subgroups and three Synechococcus-like cells subgroups). Prochlorococcus was not detected. According to redundancy analysis (RDA), a significant difference was found in the distribution of the ultraplankton between stations (F = 2.61, p < 0.05); maximum proliferations of heterotrophic prokaryotes were observed in the inner parts of the lagoon at stations 3, 4 and 5 affected by urban, agricultural and industrial discharges. Ultraphytoplankton concentrations were the highest near the outlet of the lagoon at stations 1 and 2 influenced by freshwater outflow and oligotrophic Mediterranean water inflow, respectively. At station 1, the large ultraphytoplankton concentration derives from the high abundance of cryptophyte-like cells favoured by the freshwater outflow whereas at station 2, the input of oligotrophic Mediterranean water enhanced the abundance of Synechococcus and picoeukaryotes at the expense of nanoeukaryotes. Two trophic regimes were thus differentiated in GML.



http://ift.tt/2oXLa1B

Extended use of grey water for irrigating home gardens in an arid environment

Abstract

The use of treated grey water (GW) for home gardens, peri-urban agriculture and landscaping is becoming popular in many water stressed countries such as Oman. This study aims to investigate the treatment efficacy, health and chemical concerns, cost-benefits and maintenance protocol of a GW treatment system as well as the effect of irrigation with GW on crop yield. Therefore, a decentralized homemade GW treatment system was installed in a newly constructed house in Muscat, Oman and studied over a 2-year period. The treated GW was found to be suitable for irrigation as per Omani standards. GW when mixed with kitchen effluent substituted the use of nutrient supplements for plants and did not show any harmful chemical or biological contamination. The capital cost of the system was around US $980, and the annual operating cost was US $78 with annual income and savings from the system being around US $572 indicating a payback period of nearly 2 years. It was found that the system required simple but regular maintenance particularly cleaning of the top layer of the filter. It can be concluded from this study that such a GW system should be technically, economically and environmentally feasible in Oman. Also, wider acceptance by the general public to the idea of GW reuse will help in mitigating the water shortage problem of the country to some extent.



http://ift.tt/2ojzbIJ

Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations

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Publication date: Available online 9 April 2017
Source:Brain and Development
Author(s): Naoko Kurahashi, Noriko Miyake, Seiji Mizuno, Eriko Koshimizu, Hirokazu Kurahashi, Keitaro Yamada, Jun Natsume, Yusuke Aoki, Miho Nakamura, Hiroko Taniai, Yuki Maki, Chihiro Abe-Hatano, Naomichi Matsumoto, Koichi Maruyama
BackgroundThe characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations (KABUK1) have not yet been well documented. This is the first review to explore this.Materials & methodsWe enrolled 14 patients with KABUK1, whose median age was 13.6years (range=4.1–21.3years). Their medical records from October 1981 to May 2016 were retrospectively analyzed.ResultsEpilepsy was present in 5 (36%) patients. Four of these patients presented with nonsense mutations and one with missense mutations. None presented with brain abnormalities. Four patients presented with annual or monthly focal seizures, of which three evolved to bilateral convulsive seizures. Median onset age of focal epilepsy was 11.8years (range=9.5–12.8years). One presented with monthly myoclonic seizures from age 11.2, whose mother with no other KABUK1 features, had focal epilepsy. The cumulative incidence of epilepsy related to KABUK1 up until age 13 was 45%. Interictal electroencephalogram revealed focal paroxysmal epileptiform discharges (in frontal, central, and parietal regions) in three patients, diffuse high-voltage spike-and-waves in one patient, and normal sleep record in one patient. Myoclonic seizures were rapidly controlled by levetiracetam. In contrast, focal seizures were not controlled in the early period of antiepileptic therapy.ConclusionThis long-term follow-up of patients with KABUK1 revealed a higher prevalence of epilepsy than previously reported. The age of epilepsy onset and rate of focal seizures evolving to bilateral convulsive seizures in KABUK1 were also higher than previously reported in patients with clinically diagnosed Kabuki syndrome. Although seizure outcome is reported to be favorable in Kabuki syndrome, focal seizures in patients with KABUK1 were not immediately responsive to medication.



http://ift.tt/2opFgpg

Immuno-informatics based approaches to identify CD8+ T cell epitopes within the Leishmania donovani 3-ectonucleotidase in cured visceral leishmaniasis subjects

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Publication date: Available online 1 April 2017
Source:Microbes and Infection
Author(s): Vijaya Mahantesh, Ajay Amit, Manas R. Dikhit, Ashish K. Singh, T. Venkateshwaran, V.N.R. Das, Pradeep Das, Sanjiva Bimal
Leishmaniases are vector-borne diseases for which no vaccine exists. These diseases are caused by the Leishmania species complex. Activation of the CD8+ T cell is crucial for protection against intracellular pathogens, and peptide antigens are attractive strategies for the precise activation of CD8+ T in vaccine development against intracellular infections. The traditional approach to mine the epitopes is an arduous task. However, with the advent of immunoinformatics, in silico epitope prediction tools are available to expedite epitope identification. In this study, we employ different immunoinformatics tools to predict CD8+ T cell specific 9 mer epitopes presented by HLA-A*02 and HLA-B40 within the highly conserved 3′-ectonucleotidase of Leishmania donovani. We identify five promiscuous epitopes, which have no homologs in humans, theoretically cover 85% of the world's population and are highly conserved (100%) among Leishmania species. Presentation of selected peptides was confirmed by T2 cell line based HLA-stabilization assay, and three of them were found to be strong binders. The in vitro peptide stimulation of peripheral blood mononuclear cells (PBMC) from cured HLA-A02+ visceral leishmaniasis (VL) subjects produced significantly higher IFN-γ, IL-2 and IL-12 compared to no peptide control healthy subjects. Further, CD8+ cells from treated VL subjects produced significantly higher intracellular IFN-γ, lymphocyte proliferation and cytotoxic activity against selected peptides from the PBMCs of treated HLA-A02+ VL subjects. Thus, the CD8+ T cell specific epitopes shown in this study will speed up the development of polytope vaccines for leishmaniasis.



http://ift.tt/2ohTjNi

Vitamin D receptor expression and hepcidin levels in the protection or severity of leprosy: a systematic review

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Publication date: Available online 16 March 2017
Source:Microbes and Infection
Author(s): Ana Laura Grossi de Oliveira, Ana Thereza Chaves, Cristiane Alves Silva Menezes, Nathalia Sernizon Guimarães, Lilian Lacerda Bueno, Ricardo Toshio Fujiwara, Manoel Otávio da Costa Rocha
Leprosy is a chronic infectious disease whose disequilibrium in the host's genetic, immunological and clinical mechanisms leads to distinct manifestations defining the type of immunological response. This review focuses its attention on the influence of the Vitamin D Receptor and hepcidin expressions that can suggest the protection or severity of leprosy.



http://ift.tt/2oXQgYL

3-Amino 1,8-naphthalimide, a structural analog of the anti-cholera drug virstatin inhibits chemically-biased swimming and swarming motility in vibrios

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Publication date: Available online 6 April 2017
Source:Microbes and Infection
Author(s): Hongxia Wang, Anisia J. Silva, Jorge A. Benitez
A screen for inhibitors of Vibrio cholerae motility identified the compound 3-amino 1,8-naphthalimide (3-A18NI), a structural analog of the cholera drug virstatin. Similar to virstatin, 3-A18NI diminished cholera toxin production. In contrast, 3-A18NI impeded swimming and/or swarming motility of V. cholerae and V. parahemolyticus suggesting that it could target the chemotaxis pathway shared by the polar and lateral flagellar system of vibrios. 3-A18NI did not inhibit the expression of V. cholerae major flagellin FlaA or the assembly of its polar flagellum. Finally, 3-A18NI enhanced V. cholerae colonization mimicking the phenotype of chemotaxis mutants that exhibit counterclockwise-biased flagellum rotation.



http://ift.tt/2oi19GN

Population and function analysis of cultivable bacteria associated with spores of arbuscular mycorrhizal fungus Gigaspora margarita.

Related Articles

Population and function analysis of cultivable bacteria associated with spores of arbuscular mycorrhizal fungus Gigaspora margarita.

3 Biotech. 2017 May;7(1):8

Authors: Long L, Lin Q, Yao Q, Zhu H

Abstract
This study was aimed to investigate the diversity and function of bacterial population associated with Gigaspora margarita spores. The fungus was propagated in sterilized sand/soil pots using alfalfa (Medicago sativa), grain sorghum (Sorghum bicolor), or maize (Zea mays) as host plants, or in sterilized vermiculite pots using alfalfa as host plants, respectively. Bacteria were isolated from the new-formed spores using diluted plate method, and typical bacterial isolates were identified according to 16S rRNA gene phylogenetic analysis. Total 43 bacterial isolates affiliated to three phyla and 23 genera were obtained. The spore-associated bacterial communities were obviously different among the four source spores, suggesting that plant species or substrates could influence the bacterial population. Bacillus and Streptomyces were most frequently associated with the fungal spores. Function analysis of these bacteria by plate tests, it was found that about 30.2% isolates stimulated the spore germination, five out of seven tested isolates improved the hyphal growth, total 57.5% of the tested isolates solubilized phosphorus at different levels, 15% isolates degraded chitin, and a few isolates suppressed the growth of Escherichia coli or Staphylococcus aureus. In pot experiment, three bacterial isolates (belonging to Curtobacterium, Ensifer, or Bacillus, respectively) displayed improvement effect on alfalfa growth and/or the colonization of roots by G. margarita.

PMID: 28391471 [PubMed - in process]



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Scholar : These new articles for Addiction Research & Theory are available online

Taylor & Francis Online - The new journals and reference work platform for Taylor & Francis
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Original Article

Do sensation seeking and aggression traits moderate the association between peer influence and alcohol outcomes among young Swiss men?
Véronique S. Grazioli, Gerhard Gmel, Meichun Mohler-Kuo, Jean-Bernard Daeppen, Nicolas Bertholet & Joseph Studer
Pages: 1-11 | DOI: 10.1080/16066359.2017.1310847


The Opiate Epidemic. Click here for the Free Access Article Collection: http://ift.tt/2cHzs7g.
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Scholar : These new articles for Voice and Speech Review are available online

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Book Review

Watching TV with a linguist
Diane Robinson
Pages: 1-3 | DOI: 10.1080/23268263.2017.1305155


Communication Research Reports Editorial Notes - Editor interviews and free access articles.

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Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.



Bivalent O-glycoside mimetics with S/disulfide/Se substitutions and aromatic core: synthesis, molecular modeling and inhibitory activity on biomedically relevant lectins in assays of increasing physiological relevance

Publication date: Available online 9 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Herbert Kaltner, Tamás Szabó, Krisztina Fehér, Sabine André, Sára Balla, Joachim C. Manning, László Szilágyi, Hans-Joachim Gabius
The emerging significance of recognition of cellular glycans by lectins for diverse aspects of pathophysiology is a strong incentive for considering development of bioactive and non-hydrolyzable glycoside derivatives, for example by introducing S/Se atoms and the disulfide group instead of oxygen into the glycosidic linkage. We report the synthesis of 12 bivalent thio-, disulfido- and selenoglycosides attached to benzene/naphthalene cores. They present galactose, for blocking a plant toxin, or lactose, the canonical ligand of adhesion/growth-regulatory galectins. Modeling reveals unrestrained flexibility and inter-headgroup distances too small to bridge two sites in the same lectin. Inhibitory activity was first detected by solid-phase assays using a surface-presented glycoprotein, with relative activity enhancements per sugar unit relative to free cognate sugar up to nearly 10fold. Inhibitory activity was also seen on lectin binding to surfaces of human carcinoma cells. In order to proceed to characterize this capacity in the tissue context monitoring of lectin binding in the presence of inhibitors was extended to sections of three types of murine organs as models. This procedure proved to be well-suited to determine relative activity levels of the glycocompounds to block binding of the toxin and different human galectins to natural glycoconjugates at different sites in sections. The results on most effective inhibition by two naphthalene-based disulfides and a selenide raise the perspective for broad applicability of the histochemical assay in testing glycoclusters that target biomedically relevant lectins.

Graphical abstract

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http://ift.tt/2oWHVaQ

Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex

Publication date: Available online 9 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Arun K. Ghosh, Margherita Brindisi, Prasanth R. Nyalapatla, Jun Takayama, Jean-Rene Ella-Menye, Sofiya Yashchuk, Johnson Agniswamy, Yuan-Fang Wang, Manabu Aoki, Masayuki Amano, Irene T. Weber, Hiroaki Mitsuya
Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme Ki of 0.025 nM and antiviral IC50 of 69 nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33 Å resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27 Å resolution. These structures revealed important molecular insight into the inhibitor–HIV-1 protease interactions in the active site.

Graphical abstract

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http://ift.tt/2nxdjwv

A hypothesis for mechanism for brain edema due to glycine

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Publication date: Available online 9 April 2017
Source:Medical Hypotheses
Author(s): Suchita J. Mehta, Andrea Roche Recinos, Subodh J. Saggi, Man S. Oh
Death following the use the glycine distension solution in transurethral prostatectomy (TURP) or hysteroscopic surgery has been attributed to the toxic effect of glycine on the brain through the glycine receptors and hyperammonemia, contending that glycine-associated hyponatremia is isosmotic and therefore would not cause brain edema. Here we propose a hypothesis that the mechanism of brain edema and death is actually osmotic brain edema caused by selective diffusion of glycine into the brain while sodium cannot diffuse out of the brain a despite favorable concentration gradient because of the absence of sodium transporter on the cerebral capillaries needed for the exit of sodium from the brain. The mechanism for unidirectional diffusion of solutes into the brain in glycine-associated hyponatremia is explained.



http://ift.tt/2oXwDjL

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