Sodium-dependent transport of phosphate in neuronal and related cells

AbstractSodium-dependent phosphate entry into neuronal cells was demonstrated in synaptic plasma membrane vesicles and synaptosomes prepared from rat brains, in PC12 cells and in primary culture of pituitary cells. The extent of the sodium-dependent phosphate transport in the synaptic plasma membrane preparation, at [Na]out=110 mM and [Pi]out=0.1 mM, varied between 0.28 to 1.02 nmol phosphate/mg membrane protein/min. In pituitary cells the value was only about 0.05 nmol Pi/mg protein/min. In PC12 cells the activity increased from 0.0085 to 0.26 nmol Pi/mg protein/min in the transit from undifferentiated to differentiated cells. The dependence of phosphate on sodium concentrations fits a model in which two sodium ions are required to transfer the phosphate into the cells with a K[Na]0.5 of 43 mM. The Km for the phosphate transport in the synaptic plasma membrane preparations was between 0.1 and 0.45 mM. It is concluded that sodium-driven active transport of phosphate is a ubiquitous activity in various types of neuronal cells

Myelin-associated glycoprotein gene mutation causes Pelizaeus-Merzbacher disease-like disorder

Pelizaeus-Merzbacher disease is an X-linked hypomyelinating leukodystrophy. Lossos et al. describe a family with an early-onset Pelizaeus-Merzbacher disease-like phenotype that slowly evolves into complicated hereditary spastic paraplegia, affecting both the CNS and PNS. Exome sequencing reveals a causative homozygous missense mutation in MAG, which encodes myelin associated glycoprotei

Epithelial Neutrophil-Activating Peptide (ENA-78), Acute Coronary Syndrome Prognosis, and Modulatory Effect of Statins

Endothelial inflammation with chemokine involvement contributes to acute coronary syndromes (ACS). We tested the hypothesis that variation in the chemokine gene CXCL5, which encodes epithelial neutrophil-activating peptide (ENA-78), is associated with ACS prognosis. We also investigated whether statin use, a potent modulator of inflammation, modifies CXCL5's association with outcomes and characterized the in vitro effect of atorvastatin on endothelial ENA-78 production. Using a prospective cohort of ACS patients (n = 704) the association of the CXCL5 −156 G>C polymorphism (rs352046) with 3-year all-cause mortality was estimated with hazard ratios (HR). Models were stratified by genotype and race. To characterize the influence of statins on this association, a statin*genotype interaction was tested. To validate ENA-78 as a statin target in inflammation typical of ACS, endothelial cells (HUVECs) were treated with IL-1β and atorvastatin with subsequent quantification of CXCL5 expression and ENA-78 protein concentrations. C/C genotype was associated with a 2.7-fold increase in 3-year all-cause mortality compared to G/G+G/C (95%CI 1.19–5.87; p = 0.017). Statins significantly reduced mortality in G/G individuals only (58% relative risk reduction; p = 0.0009). In HUVECs, atorvastatin dose-dependently decreased IL-1β-stimulated ENA-78 concentrations (p<0.0001). Drug effects persisted over 48 hours (p<0.01). CXCL5 genotype is associated with outcomes after ACS with potential statin modification of this effect. Atorvastatin lowered endothelial ENA-78 production during inflammation typical of ACS. These findings implicate CXCL5/ENA-78 in ACS and the statin response

The Eco-Epidemiology of Pacific Coast Tick Fever in California

Rickettsia philipii (type strain “Rickettsia 364D”), the etiologic agent of Pacific Coast tick fever (PCTF), is transmitted to people by the Pacific Coast tick, Dermacentor occidentalis. Following the first confirmed human case of PCTF in 2008, 13 additional human cases have been reported in California, more than half of which were pediatric cases. The most common features of PCTF are the presence of at least one necrotic lesion known as an eschar (100%), fever (85%), and headache (79%); four case-patients required hospitalization and four had multiple eschars. Findings presented here implicate the nymphal or larval stages of D. occidentalis as the primary vectors of R. philipii to people. Peak transmission risk from ticks to people occurs in late summer. Rickettsia philipii DNA was detected in D. occidentalis ticks from 15 of 37 California counties. Similarly, non-pathogenic Rickettsia rhipicephali DNA was detected in D. occidentalis in 29 of 38 counties with an average prevalence of 12.0% in adult ticks. In total, 5,601 ticks tested from 2009 through 2015 yielded an overall R. philipii infection prevalence of 2.1% in adults, 0.9% in nymphs and a minimum infection prevalence of 0.4% in larval pools. Although most human cases of PCTF have been reported from northern California, acarological surveillance suggests that R. philipii may occur throughout the distribution range of D. occidentalis

Taxation of sugar sweetened beverages and unhealthy foods: a qualitative study of key opinion leaders’ views

Abstract Background Fiscal policies to fight obesity such as taxation of unhealthy foods or sugar-sweetened beverages (SSBs) have gained considerable attention in recent years. Many studies modelling the impact of various magnitudes of taxes on SSB purchasing and their potential effects on various health outcomes have been published; however, legislation and implementation of such taxes have encountered many obstacles in the countries that have implemented them to date. We investigated the perceptions and views of key opinion leaders, policy makers and various other Israeli stakeholders on taxation of SSBs and unhealthy snacks. We also evaluated the challenges and barriers that may be expected for initiating such a policy. Methods A qualitative study based on 39 in-depth interviews with Israeli stakeholders in the fields of health, nutrition, economics, public advocacy and policymaking. Results All stakeholders viewed obesity as a combined societal and personal issue that should be under government responsibility. Only stakeholders from economic sectors thought that taxation of SSBs and unhealthy snacks would reduce their consumption, while the prevailing notion among non-economists was that such a tax would not be acceptable because the higher price would not decrease consumption. Concerns were raised that the tax would mostly affect individuals from low socioeconomic backgrounds. Some of the stakeholders indicated that they would support such a tax only if its revenue would be directed to specific causes such as health-promoting plans. Potential barriers to taxation include: opposition of various sectors, technical and bureaucratic obstacles impeding tax implementation, difficulties in defining which products to tax, and opposition of the treasury to earmark tax revenue for health education. Conclusions Taxation should be a part of a multipronged strategy rather than a sole measure for fighting obesity. Dedicating tax revenues to specific predefined causes should be considered, particularly towards health promotion activities, obesity treatment and prevention, education, and subsidies of healthy food

Climbing atop the Shoulders of Giants: The Impact of Institutions on Cumulative Research

While cumulative knowledge production is central to growth, little empirical research investigates how institutions shape whether existing knowledge can be exploited to create new knowledge. This paper assesses the impact of a specific institution, a biological resource center, whose objective is to certify and disseminate knowledge. We disentangle the marginal impact of this institution on cumulative research from the impact of selection, in which the most important discoveries are endogenously linked to research-enhancing institutions. Exploiting exogenous shifts of biomaterials across institutional settings and employing a difference-in-differences approach, we find that effective institutions amplify the cumulative impact of individual scientific discoveries