Ion Channels and Transporters as Therapeutic Agents: From Biomolecules to Supramolecular Medicinal Chemistry

Ion channels and transporters typically consist of biomolecules that play key roles in a large variety of physiological and pathological processes. Traditional therapies include many ionchannel blockers, and some activators, although the exact biochemical pathways and mechanisms that regulate ion homeostasis are yet to be fully elucidated. An emerging area of research with great innovative potential in biomedicine pertains the design and development of synthetic ion channels and transporters, which may provide unexplored therapeutic opportunities. However, most studies in this challenging and multidisciplinary area are still at a fundamental level. In this review, we discuss the progress that has been made over the last five years on ion channels and transporters, touching upon biomolecules and synthetic supramolecules that are relevant to biological use. We conclude with the identification of therapeutic opportunities for future exploratio

Prevalence of foodborne pathogens in rural pigs and in derived cold pork meats - preliminary report

The rural breeding of one or two pigs and their domestic slaughtering is a significance reality in the Veneto Region, as a consequence of an ancient tradition still surviving in this countryside. In the eastern part of the Venice Province, about 2,500 rural pigs are bred and slaughtered ever year in the period between November and February. Many data are available on mdustnal breeding and processing, whereas very little is known about the prevalence of foodborne pathogens both in live ammals and in denved food, mainly sausage, salami and cold pork meats

Fichas técnicas sobre as características e potencialidades de uso da madeira de espécies florestais nativas e exóticas.

EVINCI. Resumo 020

Caracterização física, química e anatômica da madeira de Byrsonima orbignyana A. Juss.

EVINCI. Resumo 005

Ganho genético em potencial produtivo do arroz irrigado no Rio Grande do Sul, após o lançamento da cultivar BR-IRGA 409.

Este trabalho teve como objetivo estimar os ganhos genéticos em rendimento de grãos nos últimos 30 anos, ou a partir do lançamento da cultivar BR-IRGA 409, no estado do Rio Grande do Sul, com base no desempenho de cultivares representativas lançadas pela pesquisa

Divergence of the systemic immune response following oral infection with distinct strains of P orphyromonas gingivalis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94514/1/omi12001.pd

Driving up the Electrocatalytic Performance for Carbon Dioxide Conversion through Interface Tuning in Graphene Oxide-Bismuth Oxide Nanocomposites

The integration of graphene oxide (GO) into nanostructured Bi2O3 electrocatalysts for CO2 reduction (CO2RR) brings up remarkable improvements in terms of performance toward formic acid (HCOOH) production. The GO scaffold is able to facilitate electron transfers toward the active Bi2O3 phase, amending for the high metal oxide (MO) intrinsic electric resistance, resulting in activation of the CO2 with smaller overpotential. Herein, the structure of the GO-MO nanocomposite is tailored according to two synthetic protocols, giving rise to two different nanostructures, one featuring reduced GO (rGO) supporting Bi@Bi2O3 core–shell nanoparticles (NP) and the other GO supporting fully oxidized Bi2O3 NP. The two structures differentiate in terms of electrocatalytic behavior, suggesting the importance of constructing a suitable interface between the nanocarbon and the MO, as well as between MO and metal

Caracterização física, química e anatômica da madeira Byrsonima orbignyana.

bitstream/item/37755/1/com-tec167.pd

Insights into Hunter syndrome from the structure of iduronate-2-sulfatase

Hunter syndrome is a rare but devastating childhood disease caused by mutations in the IDS gene encoding iduronate-2-sulfatase, a crucial enzyme in the lysosomal degradation pathway of dermatan sulfate and heparan sulfate. These complex glycosaminoglycans have important roles in cell adhesion, growth, proliferation and repair, and their degradation and recycling in the lysosome is essential for cellular maintenance. A variety of disease-causing mutations have been identified throughout the IDS gene. However, understanding the molecular basis of the disease has been impaired by the lack of structural data. Here, we present the crystal structure of human IDS with a covalently bound sulfate ion in the active site. This structure provides essential insight into multiple mechanisms by which pathogenic mutations interfere with enzyme function, and a compelling explanation for severe Hunter syndrome phenotypes. Understanding the structural consequences of disease-associated mutations will facilitate the identification of patients that may benefit from specific tailored therapies.We acknowledge Diamond Light Source for time on beamline I03 under proposal MX6641. We thank Shire Pharmaceuticals for providing Elaprase (idursulfase) and Tom Terwilliger for helpful advice on multi-crystal averaging. We also thank Alexandre Bonvin for modifying HADDOCK to support the non-standard amino acid FGH (PDB code DDZ). R.J.R. is supported by a Principal Research Fellowship funded by the Wellcome Trust (Grant 082961/Z/07/Z), which also supported C.H.H. and M.D. A.Z. was supported by a Senior Research Fellowship from the British Heart Foundation (PG/09/072/27945). J.E.D. is supported by a Royal Society University Research Fellowship (UF100371). Support received from the US National Institutes of Health (grant P01GM063210 R.J.R.) is gratefully acknowledged. The research was facilitated by a Wellcome Trust Strategic Award (100140) to the Cambridge Institute for Medical Research

Variability of adenoidectomy/tonsillectomy rates among children of the Veneto Region, Italy

<p>Abstract</p> <p>Background</p> <p>Despite national guidelines in 2003 aimed at limiting the recourse to tonsillectomy and/or adenoidectomy (A/T), the latter are among the most frequent pediatric surgeries performed in Italy. Aim of the study is to investigate variability of A/T rates among children of the Veneto Region, Italy.</p> <p>Methods</p> <p>All discharges of Veneto residents with Diagnosis-Related Groups 57–60 and ICD9-CM intervention codes 28.2 (tonsillectomy), 28.3 (adenotonsillectomy), 28.6 (adenoidectomy) were selected in the period 2000–2006 for a descriptive analysis. A multilevel Poisson regression model was applied to estimate Incidence Rate Ratios (IRR) with 95% Confidence Intervals (CI) for A/T surgery among children aged 2–9 years in 2004–2006, while taking into account clustering of interventions within the 21 Local Health Units.</p> <p>Results</p> <p>Through 2000–2006, the overall number of A/T surgeries decreased (-8%); there was a decline of adenoidectomies (-20%) and tonsillectomies (-8%), whereas adenotonsillectomies raised (+18%). Analyses on children aged 2–9 resulted in an overall rate of 14.4 surgeries per 1000 person-years (16.1 among males and 12.5 among females), with a wide heterogeneity across Local Health Units (range 8.1–27.6). At random intercept Poisson regression, while adjusting for sex and age, intervention rates were markedly lower among foreign than among Italian children (IRR = 0.57, CI 0.53–0.61). A/T rates in the 10–40 age group (mainly tonsillectomies) computed for each Local Health Unit and introduced in the regression model accounted for 40% of the variance at Local Health Unit level of pediatric rates (mainly adenoidectomies and adenotonsillectomies).</p> <p>Conclusion</p> <p>A/T rates in the Veneto Region, especially adenoidectomies among children aged 2–9 years, remain high notwithstanding a decrease through 2000–2006. A wide heterogeneity according to nationality and Local Health Units is evident. The propensity to A/T surgery of each Local Health Unit is similar in different age groups and for different surgical indications.</p