Microtubule polarity flaws as a treatable driver of neurodegeneration

Microtubule disruption is a common downstream mechanism leading to axonal degeneration in a number of neurological diseases. To date, most studies on this topic have focused on the loss of microtubule mass from the axon, as well as changes in the stability properties of the microtubules and/or their tubulin composition. Here we posit corruption of the normal pattern of microtubule polarity orientation as an underappreciated and yet treatable contributor to axonal degeneration. We include computational modeling to fortify the rigor of our considerations. Our simulations demonstrate that even a small deviation from the usual polarity pattern of axonal microtubules is detrimental to motor-based trafficking of organelles and other intracellular cargo. Additional modeling predicts that axons with such deviations will exhibit significantly reduced speed and reliability of organelle transport, and that localized clusters of wrongly oriented microtubules will result in traffic jams of accumulated organelles

Time preferences and risk aversion: tests on domain differences

The design and evaluation of environmental policy requires the incorporation of time and risk elements as many environmental outcomes extend over long time periods and involve a large degree of uncertainty. Understanding how individuals discount and evaluate risks with respect to environmental outcomes is a prime component in designing effective environmental policy to address issues of environmental sustainability, such as climate change. Our objective in this study is to investigate whether subjects' time preferences and risk aversion across the monetary domain and the environmental domain differ. Crucially, our experimental design is incentivized: in the monetary domain, time preferences and risk aversion are elicited with real monetary payoffs, whereas in the environmental domain, we elicit time preferences and risk aversion using real (bee-friendly) plants. We find that subjects' time preferences are not significantly different across the monetary and environmental domains. In contrast, subjects' risk aversion is significantly different across the two domains. More specifically, subjects (men and women) exhibit a higher degree of risk aversion in the environmental domain relative to the monetary domain. Finally, we corroborate earlier results, which document that women are more risk averse than men in the monetary domain. We show this finding to, also, hold in the environmental domain

Telerobotics : methodology for the development of a through-the-internet robotic teleoperated system

This work presents a methodology for the development of Teleoperated Robotic Systems through the Internet. Initially, it is presented a bibliographical review of the Telerobotic systems that uses Internet as way of control. The methodology is implemented and tested through the development of two systems. The first is a manipulator with two degrees of freedom commanded remotely through the Internet denominated RobWebCam (http://www.graco.unb.br/robwebcam). The second is a system which teleoperates an ABB (Asea Brown Boveri) Industrial Robot of six degrees of freedom denominated RobWebLink (http://webrobot.graco.unb.br). RobWebCam is composed of a manipulator with two degrees of freedom, a video camera, Internet, computers and communication driver between the manipulator and the Unix system; and RobWebLink composed of the same components plus the Industrial Robot. With the use of this technology, it is possible to move far distant positioning objects minimizing transport costs, materials and people; acting in real time in the process that is wanted to be controller. This work demonstrates that the teleoperating via Internet of robotic systems and other equipments is viable, in spite of using rate transmission data with low bandwidth. Possible applications include remote surveillance, control and remote diagnosis and maintenance of machines and equipments

First-principles design and subsequent synthesis of a material to search for the permanent electric dipole moment of the electron

We describe the first-principles design and subsequent synthesis of a new material with the specific functionalities required for a solid-state-based search for the permanent electric dipole moment of the electron. We show computationally that perovskite-structure europium barium titanate should exhibit the required large and pressure-dependent ferroelectric polarization, local magnetic moments, and absence of magnetic ordering even at liquid helium temperature. Subsequent synthesis and characterization of Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ ceramics confirm the predicted desirable properties.Comment: Nature Materials, in pres

Conditional Facilitation of an Aphid Vector, Acyrthosiphon pisum, by the Plant Pathogen, Pea Enation Mosaic Virus

Plant pathogens can induce symptoms that affect the performance of insect herbivores utilizing the same host plant. Previous studies examining the effects of infection of tic bean, Vicia faba L. (Fabales: Fabaceae), by pea enation mosaic virus (PEMV), an important disease of legume crops, indicated there were no changes in the growth and reproductive rate of its primary vector the pea aphid, Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae). Here, we report the results of laboratory experiments investigating how A. pisum responded to PEMV infection of a different host plant, Pisum sativum L., at different stages of symptom development. Aphid growth rate was negatively related to the age of the host plant, but when they were introduced onto older plants with well-developed PEMV symptoms they exhibited a higher growth rate compared to those developing on uninfected plants of the same age. In choice tests using leaf discs A. pisum showed a strong preference for discs from PEMV-infected peas, probably in response to visual cues from the yellowed and mottled infected leaves. When adults were crowded onto leaves using clip-cages they produced more winged progeny on PEMV-infected plants. The results indicate that PEMV produces symptoms in the host plant that can enhance the performance of A. pisum as a vector, modify the production of winged progeny and affect their spatial distribution. The findings provide further evidence that some insect vector/plant pathogen interactions could be regarded as mutualistic rather than commensal when certain conditions regarding the age, stage of infection and species of host plant are met

MetaPath: identifying differentially abundant metabolic pathways in metagenomic datasets

Enabled by rapid advances in sequencing technology, metagenomic studies aim to characterize entire communities of microbes bypassing the need for culturing individual bacterial members. One major goal of metagenomic studies is to identify specific functional adaptations of microbial communities to their habitats. The functional profile and the abundances for a sample can be estimated by mapping metagenomic sequences to the global metabolic network consisting of thousands of molecular reactions. Here we describe a powerful analytical method (MetaPath) that can identify differentially abundant pathways in metagenomic datasets, relying on a combination of metagenomic sequence data and prior metabolic pathway knowledge. First, we introduce a scoring function for an arbitrary subnetwork and find the max-weight subnetwork in the global network by a greedy search algorithm. Then we compute two p values (p abund and p struct ) using nonparametric approaches to answer two different statistical questions: (1) is this subnetwork differentically abundant? (2) What is the probability of finding such good subnetworks by chance given the data and network structure? Finally, significant metabolic subnetworks are discovered based on these two p values. In order to validate our methods, we have designed a simulated metabolic pathways dataset and show that MetaPath outperforms other commonly used approaches. We also demonstrate the power of our methods in analyzing two publicly available metagenomic datasets, and show that the subnetworks identified by MetaPath provide valuable insights into the biological activities of the microbiome. We have introduced a statistical method for finding significant metabolic subnetworks from metagenomic datasets. Compared with previous methods, results from MetaPath are more robust against noise in the data, and have significantly higher sensitivity and specificity (when tested on simulated datasets). When applied to two publicly available metagenomic datasets, the output of MetaPath is consistent with previous observations and also provides several new insights into the metabolic activity of the gut microbiome. The software is freely available at http://metapath.cbcb.umd.edu .https://doi.org/10.1186/1753-6561-5-S2-S

Diabetes and cardiovascular disease: A statement for healthcare professionals from the American Heart Association

This statement examines the cardiovascular complications of diabetes mellitus and considers opportunities for their prevention. These complications include coronary heart disease (CHD), stroke, peripheral arterial disease, nephropathy, retinopathy, and possibly neuropathy and cardiomyopathy. Because of the aging of the population and an increasing prevalence of obesity and sedentary life habits in the United States, the prevalence of diabetes is increasing. Thus, diabetes must take its place alongside the other major risk factors as important causes of cardiovascular disease (CVD). In fact, from the point of view of cardiovascular medicine, it may be appropriate to say, “diabetes is a cardiovascular disease.

Tamoxifen-elicited uterotrophy: cross-species and cross-ligand analysis of the gene expression program

<p>Abstract</p> <p>Background</p> <p>Tamoxifen (TAM) is a well characterized breast cancer drug and selective estrogen receptor modulator (SERM) which also has been associated with a small increase in risk for uterine cancers. TAM's partial agonist activation of estrogen receptor has been characterized for specific gene promoters but not at the genomic level <it>in vivo</it>.Furthermore, reducing uncertainties associated with cross-species extrapolations of pharmaco- and toxicogenomic data remains a formidable challenge.</p> <p>Results</p> <p>A comparative ligand and species analysis approach was conducted to systematically assess the physiological, morphological and uterine gene expression alterations elicited across time by TAM and ethynylestradiol (EE) in immature ovariectomized Sprague-Dawley rats and C57BL/6 mice. Differential gene expression was evaluated using custom cDNA microarrays, and the data was compared to identify conserved and divergent responses. 902 genes were differentially regulated in all four studies, 398 of which exhibit identical temporal expression patterns.</p> <p>Conclusion</p> <p>Comparative analysis of EE and TAM differentially expressed gene lists suggest TAM regulates no unique uterine genes that are conserved in the rat and mouse. This demonstrates that the partial agonist activities of TAM extend to molecular targets in regulating only a subset of EE-responsive genes. Ligand-conserved, species-divergent expression of carbonic anhydrase 2 was observed in the microarray data and confirmed by real time PCR. The identification of comparable temporal phenotypic responses linked to related gene expression profiles demonstrates that systematic comparative genomic assessments can elucidate important conserved and divergent mechanisms in rodent estrogen signalling during uterine proliferation.</p