Automated system for analyzing the activity of individual neurons

This paper presents a signal processing system that: (1) provides an efficient and reliable instrument for investigating the activity of neuronal assemblies in the brain; and (2) demonstrates the feasibility of generating the command signals of prostheses using the activity of relevant neurons in disabled subjects. The system operates online, in a fully automated manner and can recognize the transient waveforms of several neurons in extracellular neurophysiological recordings. Optimal algorithms for detection, classification, and resolution of overlapping waveforms are developed and evaluated. Full automation is made possible by an algorithm that can set appropriate decision thresholds and an algorithm that can generate templates on-line. The system is implemented with a fast IBM PC compatible processor board that allows on-line operation

Quality information for quality use of medicines; 2nd International Conference, Kazan, 15-16 October 2010

Kazan hosted Russia's first international conference on medicines that was entirely independent of the pharmaceutical industry, attracting 414 participants from 9 countries and 20 regions of the Russian Federation. The meeting was greeted and endorsed by world leaders in pharmaceutical information, policy and regulation. Delegates discussed the professional and social problems arising from unethical drug promotion, including compromised evidence from clinical trials and consequent impairments in health service delivery. The Conference adopted a resolution prioritizing policy development and health system needs, notably including the development of clinical pharmacology. A website documents conference materials and provides an interface for future collaboration: http://evidenceupdate-tatarstan.ru/confer. © 2011 - IOS Press and the authors. All rights reserved

Zebrafish Mutants calamity and catastrophe Define Critical Pathways of Gene–Nutrient Interactions in Developmental Copper Metabolism

Nutrient availability is an important environmental variable during development that has significant effects on the metabolism, health, and viability of an organism. To understand these interactions for the nutrient copper, we used a chemical genetic screen for zebrafish mutants sensitive to developmental copper deficiency. In this screen, we isolated two mutants that define subtleties of copper metabolism. The first contains a viable hypomorphic allele of atp7a and results in a loss of pigmentation when exposed to mild nutritional copper deficiency. This mutant displays incompletely penetrant skeletal defects affected by developmental copper availability. The second carries an inactivating mutation in the vacuolar ATPase that causes punctate melanocytes and embryonic lethality. This mutant, catastrophe, is sensitive to copper deprivation revealing overlap between ion metabolic pathways. Together, the two mutants illustrate the utility of chemical genetic screens in zebrafish to elucidate the interaction of nutrient availability and genetic polymorphisms in cellular metabolism

Syndromic (phenotypic) diarrhea in early infancy

Syndromic diarrhea (SD), also known as phenotypic diarrhea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN). To date, no epidemiological data are available. The estimated prevalence is approximately 1/300,000–400,000 live births in Western Europe. Ethnic origin does not appear to be associated with SD. Infants are born small for gestational age and present with facial dysmorphism including prominent forehead and cheeks, broad nasal root and hypertelorism. Hairs are woolly, easily removed and poorly pigmented. Severe and persistent diarrhea starts within the first 6 months of life (≤ 1 month in most cases) and is accompanied by severe malabsorption leading to early and relentless protein energy malnutrition with failure to thrive. Liver disease affects about half of patients with extensive fibrosis or cirrhosis. There is currently no specific biochemical profile, though a functional T-cell immune deficiency with defective antibody production was reported. Microscopic analysis of the hair show twisted hair (pili torti), aniso- and poilkilotrichosis, and trichorrhexis nodosa. Histopathological analysis of small intestine biopsy shows non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria, and no specific histological abnormalities involving the epithelium. The etiology remains unknown. The frequent association of the disorder with parental consanguinity and/or affected siblings suggests a genetic origin with an autosomal recessive mode of transmission. Early management consists of total PN. Some infants have a rather milder phenotype with partial PN dependency or require only enteral feeding. Prognosis of this syndrome is poor, but most patients now survive, and about half of the patients may be weaned from PN at adolescence, but experience failure to thrive and final short stature

Lessons from the removal of lead from gasoline for controlling other environmental pollutants: A case study from New Zealand

<p>Abstract</p> <p>Background</p> <p>It took over two decades to achieve the removal of leaded gasoline in this country. This was despite international evidence and original research conducted in New Zealand on the harm to child cognitive function and behaviour from lead exposure.</p> <p>Objective</p> <p>To identify lessons from the New Zealand experience of removing leaded gasoline that are potentially relevant to the control of other environmental pollutants.</p> <p>Discussion</p> <p>From the available documentation, we suggest a number of reasons for the slow policy response to the leaded gasoline hazard. These include: (1) industry power in the form of successful lobbying by the lead additive supplier, Associated Octel; (2) the absence of the precautionary principle as part of risk management policy; and (3) weak policymaking machinery that included: (a) the poor use of health research evidence (from both NZ and internationally), as well as limited use of expertise in academic and non-governmental organisations; (b) lack of personnel competent in addressing technically complex issues; and (c) diffusion of responsibility among government agencies.</p> <p>Conclusion</p> <p>There is a need for a stronger precautionary approach by policymakers when considering environmental pollutants. Politicians, officials and health workers need to strengthen policymaking processes and effectively counter the industry tactics used to delay regulatory responses.</p

Genome-Wide Analysis of Human Disease Alleles Reveals That Their Locations Are Correlated in Paralogous Proteins

The millions of mutations and polymorphisms that occur in human populations are potential predictors of disease, of our reactions to drugs, of predisposition to microbial infections, and of age-related conditions such as impaired brain and cardiovascular functions. However, predicting the phenotypic consequences and eventual clinical significance of a sequence variant is not an easy task. Computational approaches have found perturbation of conserved amino acids to be a useful criterion for identifying variants likely to have phenotypic consequences. To our knowledge, however, no study to date has explored the potential of variants that occur at homologous positions within paralogous human proteins as a means of identifying polymorphisms with likely phenotypic consequences. In order to investigate the potential of this approach, we have assembled a unique collection of known disease-causing variants from OMIM and the Human Genome Mutation Database (HGMD) and used them to identify and characterize pairs of sequence variants that occur at homologous positions within paralogous human proteins. Our analyses demonstrate that the locations of variants are correlated in paralogous proteins. Moreover, if one member of a variant-pair is disease-causing, its partner is likely to be disease-causing as well. Thus, information about variant-pairs can be used to identify potentially disease-causing variants, extend existing procedures for polymorphism prioritization, and provide a suite of candidates for further diagnostic and therapeutic purposes

Tau association with synaptic vesicles causes presynaptic dysfunction

Tau is implicated in more than 20 neurodegenerative diseases, including Alzheimer's disease. Under pathological conditions, Tau dissociates from axonal microtubules and missorts to pre- and postsynaptic terminals. Patients suffer from early synaptic dysfunction prior to Tau aggregate formation, but the underlying mechanism is unclear. Here we show that pathogenic Tau binds to synaptic vesicles via its N-terminal domain and interferes with presynaptic functions, including synaptic vesicle mobility and release rate, lowering neurotransmission in fly and rat neurons. Pathological Tau mutants lacking the vesicle binding domain still localize to the presynaptic compartment but do not impair synaptic function in fly neurons. Moreover, an exogenously applied membrane-permeable peptide that competes for Tau-vesicle binding suppresses Tau-induced synaptic toxicity in rat neurons. Our work uncovers a presynaptic role of Tau that may be part of the early pathology in various Tauopathies and could be exploited therapeutically.status: publishe

Antioxidant intervention of smoking-induced lung tumor in mice by vitamin E and quercetin

<p>Abstract</p> <p>Background</p> <p>Epidemiological and in vitro studies suggest that antioxidants such as quercetin and vitamin E (VE) can prevent lung tumor caused by smoking; however, there is limited evidence from animal studies.</p> <p>Methods</p> <p>In the present study, Swiss mouse was used to examine the potential of quercetin and VE for prevention lung tumor induced by smoking.</p> <p>Results</p> <p>Our results suggest that the incidence of lung tumor and tumor multiplicity were 43.5% and 1.00 ± 0.29 in smoking group; Quercetin has limited effects on lung tumor prevention in this in vivo model, as measured by assays for free radical scavenging, reduction of smoke-induced DNA damage and inhibition of apoptosis. On the other hand, vitamin E drastically decreased the incidence of lung tumor and tumor multiplicity which were 17.0% and 0.32 ± 0.16, respectively (p < 0.05); and demonstrated prominent antioxidant effects, reduction of DNA damage and decreased cell apoptosis (p < 0.05). Combined treatment with quercetin and VE in this animal model did not demonstrate any effect greater than that due to vitamin E alone. In addition, gender differences in the occurrence of smoke induced-lung tumor and antioxidant intervention were also observed.</p> <p>Conclusion</p> <p>We conclude that VE might prevent lung tumor induced by smoking in Swiss mice.</p