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Search Results: 1 - 10 of 214177 matches for " Jaime L. Wetzel "
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Transcriptional and Post-Transcriptional Regulation of SPAST, the Gene Most Frequently Mutated in Hereditary Spastic Paraplegia
Brian J. Henson, Wan Zhu, Kelsey Hardaway, Jaime L. Wetzel, Mihaela Stefan, Kathryn M. Albers, Robert D. Nicholls
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036505
Abstract: Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ~70–80% of cases, with additional cases being recessive or X-linked. The most common type of HSP is SPG4 with mutations in the SPAST gene, encoding spastin, which occurs in 40% of dominantly inherited cases and in ~10% of sporadic cases. Both loss-of-function and dominant-negative mutation mechanisms have been described for SPG4, suggesting that precise or stoichiometric levels of spastin are necessary for biological function. Therefore, we hypothesized that regulatory mechanisms controlling expression of SPAST are important determinants of spastin biology, and if altered, could contribute to the development and progression of the disease. To examine the transcriptional and post-transcriptional regulation of SPAST, we used molecular phylogenetic methods to identify conserved sequences for putative transcription factor binding sites and miRNA targeting motifs in the SPAST promoter and 3′-UTR, respectively. By a variety of molecular methods, we demonstrate that SPAST transcription is positively regulated by NRF1 and SOX11. Furthermore, we show that miR-96 and miR-182 negatively regulate SPAST by effects on mRNA stability and protein level. These transcriptional and miRNA regulatory mechanisms provide new functional targets for mutation screening and therapeutic targeting in HSP.
Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis
Volker Fensterl,Jaime L. Wetzel,Srividya Ramachandran,Tomoaki Ogino,Stephen A. Stohlman,Cornelia C. Bergmann,Michael S. Diamond,Herbert W. Virgin,Ganes C. Sen
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002712
Abstract: Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2?/?) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1?/? mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2?/? mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2?/? mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2?/? mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2?/? mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2?/? mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2?/? mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.
What Does Clustering Tell Us About the Buildup of the Red Sequence?
Jeremy L. Tinker,Andrew R. Wetzel
Physics , 2009, DOI: 10.1088/0004-637X/719/1/88
Abstract: We analyze the clustering of red and blue galaxies from four samples spanning a redshift range of 0.4
Galaxy evolution in groups and clusters: star formation rates, red sequence fractions, and the persistent bimodality
Andrew R. Wetzel,Jeremy L. Tinker,Charlie Conroy
Physics , 2011, DOI: 10.1111/j.1365-2966.2012.21188.x
Abstract: Using galaxy group/cluster catalogs created from the Sloan Digital Sky Survey Data Release 7, we examine in detail the specific star formation rate (SSFR) distribution of satellite galaxies and its dependence on stellar mass, host halo mass, and halo-centric radius. All galaxies, regardless of central-satellite designation, exhibit a similar bimodal SSFR distribution, with a strong break at SSFR ~ 10^-11 yr^-1 and the same high SSFR peak; in no regime is there ever an excess of galaxies in the `green valley'. Satellite galaxies are simply more likely to lie on the quenched (`red sequence') side of the SSFR distribution. Furthermore, the satellite quenched fraction excess above the field galaxy value is nearly independent of galaxy stellar mass. An enhanced quenched fraction for satellites persists in groups with halo masses down to 3 x 10^11 Msol and increases strongly with halo mass and toward halo center. We find no detectable quenching enhancement for galaxies beyond ~2R_vir around massive clusters once these galaxies have been decomposed into centrals and satellites. These trends imply that (1) galaxies experience no significant environmental effects until they cross within ~R_vir of a more massive host halo, (2) after this, star formation in active satellites continues to evolve in the same manner as active central galaxies for several Gyrs, and (3) once begun, satellite star formation quenching occurs rapidly. These results place strong constraints on satellite-specific quenching mechanisms, as we will discuss further in companion papers.
Transforma??o do contrato psicológico no contexto da privatiza??o: estudo de casos
Wetzel, Ursula;
Revista de Administra??o Contemporanea , 2001, DOI: 10.1590/S1415-65552001000500012
Abstract: this study describes the transformation of the psychological contract in two service companies privatized in the years of 1997 and 1998. data were collected through 42 in-depth interviews in two states in the south and one state in southeast brazil. interviews occured in all hierarchical levels, including 2 human resources top managers, 17 middle managers and 23 white and blue collar employees. according to rousseau (1996)'s model, four stages of the transformation process were identified: (1) challenging of the old contract; (2) preparation for change; (3) new contract generation; and (4) living in the new contract. according to the study, transformation of the psychological contract requires not only understanding those aspects related to explicit or implicit promises, but also aspects external to the contract such as trust, changes in the firm's external environment (competition, labor market), and changes in the internal environment (organizational culture, technology).
Die Soldatenmütter Sankt Petersburg The Soldiers’ Mothers of St. Petersburg
Frauke Wetzel
querelles-net , 2001,
Abstract: Eine wachsende Zahl von Frauen in Ru land schafft es, gegen die tragende Rolle des Milit rs zu rebellieren. Sie leisten Widerstand gegen die undemokratischen Streitkr fte, in denen Wehrdienstleistende mi handelt und gefoltert werden. Eva Maria Hinterhuber, selbst für einige Zeit Mitarbeiterin der Soldatenmütter Sankt Petersburg, schreibt in ihrer nun ver ffentlichten Diplomarbeit über eine Gruppe von Widerst ndigen, ihre Rolle im Transformationsproze und ihre Bedeutung für das Entstehen einer Zivilgesellschaft in Ru land. An increasing number of women is successfully rebelling against the Russian army. They try to resist an undemocratic military force where soldiers are ill-treated and tortured. Eva Maria Hinterhuber, a former employee at the St. Peterburg Soldiers’ Mothers, writes in her recently published thesis about one group of opposers, their role in the process of transformation and their importance for the development of a civil society in Russia.
Pattern analysis in a benthic bacteria-nutrient system
Daniel Wetzel
Mathematics , 2014,
Abstract: We study pattern formation in a reaction-diffusion system for a benthic bacteria-nutrient model in a marine sediment, which originally contains some spatially varying coefficients and with these shows some layering of patterns. Using the Landau reduction for the system with homogeneous coefficients, we locally analyze Turing bifurcations in 1D and 2D. Moreover, we use the software pde2path to compute the corresponding branches globally and find a number of snaking branches of patterns over patterns. This shows that spatially varying patterns are not necessarily due to spatially varying coefficients. We find a type of hexagon patches on a homogeneous background with no prior mention in the literature. We show the first numerically calculated solution-branch, which connects two different types of hexagons in parameter space. We call states on this branch rectangles. We check numerically, if the stability changes for hexagons and stripes, which are continued homogeneously into the third dimension. We find that stripes and one type of hexagons have the same stable range over bounded 2D and 3D domains, while the other type of hexagons becomes unstable earlier. Here we find a snaking branch of solutions, which are spatial connects between hexagonal prisms and a genuine 3D pattern (balls).
Factors Influencing the Emergence and Spread of HIV Drug Resistance Arising from Rollout of Antiretroviral Pre-Exposure Prophylaxis (PrEP)
Ume L. Abbas,Gregory Hood,Arthur W. Wetzel,John W. Mellors
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018165
Abstract: The potential for emergence and spread of HIV drug resistance from rollout of antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is an important public health concern. We investigated determinants of HIV drug resistance prevalence after PrEP implementation through mathematical modeling.
Transient Receptor Potential Channels Encode Volatile Chemicals Sensed by Rat Trigeminal Ganglion Neurons
Matthias Lübbert, Jessica Kyereme, Nicole Sch?bel, Leopoldo Beltrán, Christian Horst Wetzel, Hanns Hatt
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077998
Abstract: Primary sensory afferents of the dorsal root and trigeminal ganglia constantly transmit sensory information depicting the individual’s physical and chemical environment to higher brain regions. Beyond the typical trigeminal stimuli (e.g. irritants), environmental stimuli comprise a plethora of volatile chemicals with olfactory components (odorants). In spite of a complete loss of their sense of smell, anosmic patients may retain the ability to roughly discriminate between different volatile compounds. While the detailed mechanisms remain elusive, sensory structures belonging to the trigeminal system seem to be responsible for this phenomenon. In order to gain a better understanding of the mechanisms underlying the activation of the trigeminal system by volatile chemicals, we investigated odorant-induced membrane potential changes in cultured rat trigeminal neurons induced by the odorants vanillin, heliotropyl acetone, helional, and geraniol. We observed the dose-dependent depolarization of trigeminal neurons upon application of these substances occurring in a stimulus-specific manner and could show that distinct neuronal populations respond to different odorants. Using specific antagonists, we found evidence that TRPA1, TRPM8, and/or TRPV1 contribute to the activation. In order to further test this hypothesis, we used recombinantly expressed rat and human variants of these channels to investigate whether they are indeed activated by the odorants tested. We additionally found that the odorants dose-dependently inhibit two-pore potassium channels TASK1 and TASK3 heterologously expressed In Xenopus laevis oocytes. We suggest that the capability of various odorants to activate different TRP channels and to inhibit potassium channels causes neuronal depolarization and activation of distinct subpopulations of trigeminal sensory neurons, forming the basis for a specific representation of volatile chemicals in the trigeminal ganglia.
Toxicity of Deepwater Horizon Source Oil and the Chemical Dispersant, Corexit? 9500, to Coral Larvae
Gretchen Goodbody-Gringley, Dana L. Wetzel, Daniel Gillon, Erin Pulster, Allison Miller, Kim B. Ritchie
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0045574
Abstract: Acute catastrophic events can cause significant damage to marine environments in a short time period and may have devastating long-term impacts. In April 2010 the BP-operated Deepwater Horizon (DWH) offshore oil rig exploded, releasing an estimated 760 million liters of crude oil into the Gulf of Mexico. This study examines the potential effects of oil spill exposure on coral larvae of the Florida Keys. Larvae of the brooding coral, Porites astreoides, and the broadcast spawning coral, Montastraea faveolata, were exposed to multiple concentrations of BP Horizon source oil (crude, weathered and WAF), oil in combination with the dispersant Corexit? 9500 (CEWAF), and dispersant alone, and analyzed for behavior, settlement, and survival. Settlement and survival of P. astreoides and M. faveolata larvae decreased with increasing concentrations of WAF, CEWAF and Corexit? 9500, however the degree of the response varied by species and solution. P. astreoides larvae experienced decreased settlement and survival following exposure to 0.62 ppm source oil, while M. faveolata larvae were negatively impacted by 0.65, 1.34 and 1.5 ppm, suggesting that P. astreoides larvae may be more tolerant to WAF exposure than M. faveolata larvae. Exposure to medium and high concentrations of CEWAF (4.28/18.56 and 30.99/35.76 ppm) and dispersant Corexit? 9500 (50 and 100 ppm), significantly decreased larval settlement and survival for both species. Furthermore, exposure to Corexit? 9500 resulted in settlement failure and complete larval mortality after exposure to 50 and 100 ppm for M. faveolata and 100 ppm for P. astreoides. These results indicate that exposure of coral larvae to oil spill related contaminants, particularly the dispersant Corexit? 9500, has the potential to negatively impact coral settlement and survival, thereby affecting the resilience and recovery of coral reefs following exposure to oil and dispersants.
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