Plasma Membrane-Associated Restriction Factors and Their Counteraction by HIV-1 Accessory Proteins.

The plasma membrane is a site of conflict between host defenses and many viruses. One aspect of this conflict is the host's attempt to eliminate infected cells using innate and adaptive cell-mediated immune mechanisms that recognize features of the plasma membrane characteristic of viral infection. Another is the expression of plasma membrane-associated proteins, so-called restriction factors, which inhibit enveloped virions directly. HIV-1 encodes two countermeasures to these host defenses: The membrane-associated accessory proteins Vpu and Nef. In addition to inhibiting cell-mediated immune-surveillance, Vpu and Nef counteract membrane-associated restriction factors. These include BST-2, which traps newly formed virions at the plasma membrane unless counteracted by Vpu, and SERINC5, which decreases the infectivity of virions unless counteracted by Nef. Here we review key features of these two antiviral proteins, and we review Vpu and Nef, which deplete them from the plasma membrane by co-opting specific cellular proteins and pathways of membrane trafficking and protein-degradation. We also discuss other plasma membrane proteins modulated by HIV-1, particularly CD4, which, if not opposed in infected cells by Vpu and Nef, inhibits viral infectivity and increases the sensitivity of the viral envelope glycoprotein to host immunity

An Effective Model for Engaging Faculty and Undergraduate Students in Neuroscience Outreach with Middle Schoolers

Engaging undergraduate students in science outreach events is critical for improving future communication between scientists and community members. Outreach events are opportunities for faculty and undergraduates to utilize active learning strategies to engage non-scientists in scientific questions and principles. Through careful design of outreach events, undergraduate students can practice science communication skills while reaching populations of the public that remain underserved and underrepresented in scientific fields. Here we describe a classroom outreach event designed to give a broad overview of the field of neuroscience to middle school students of all backgrounds by delivering the content in school, during school hours. Through a variety of active learning strategies, middle school students learned about basic structures of the brain and their corresponding functions. Additionally, these students participated in demonstrations during which they generated and tested their own hypotheses and learned about sensory transmission and responses. We designed the lesson to meet the educational goals for middle school students, fulfilling the criteria for the Next Generation Science Standard MS-LS1-8 (NGSS Lead States, 2013). We evaluated the impact of the event on both undergraduate student instructors and middle school participants. Our results demonstrate that these outreach events effectively deliver new content to middle school students while also reinforcing the importance and value of outreach to undergraduate instructors

12 | 2010 | VOLUME 2 VANDERBILT REVIEWS | NEUROSCIENCE

Dopamine (DA) and norepinephrine (NE) have consistently been shown to play a crucial role in cognitive processes. DA and NE share a common synthetic pathway, and have both been implicated in psychiatric disorders such as attention-deficit hyperactivity disorder (ADHD) 1,2 , affective disorders 3 , and schizophrenia DOPAMINE AND NOREPINEPHRINE NEURONS PROJECT TO THE PFC Early studies of both dopamine and norepinephrine focused on the localization of these transmitters in the brain. Using fluorescent histochemistry, as well as electron microscopy, these studies showed that both DA and NE are present in the prefrontal cortex Mechanisms for the Interaction of Dopamine and Norepinephrine in the Prefrontal Cortex: Implications for the Treatment of Cognitive Symptoms of Schizophrenia Peter Vollbrecht Reductions in prefrontal cortical dopamine (DA) levels have been associated with the cognitive symptoms of schizophrenia. When removal of the dopamine innervation to the prefrontal cortex (PFC) was tested in animal models, researchers reported a loss of dendritic spines. Anatomical arrangements in the PFC suggest that dopamine may play a role in the regulation of dendritic architecture. Atypical antipsychotics, but not typical antipsychotics, reverse the loss of dendritic spines seen upon DA denervation. Atypical antipsychotic drugs have also been reported to reduce cognitive symptoms of schizophrenia. Taken together with their ability to reverse spine loss, these data suggest that spine loss may be a pathological correlate to cognitive deficits associated with the prefrontal cortex. The mechanism by which these drugs act to restore DA tone in the PFC remains unclear. Recent data has suggested that norepinephrine (NE) terminals are capable of releasing the NE "precursor" DA. Atypical antipsychotic drugs have a wide target profile, including antagonism of NE autoreceptors. These data suggest that interactions between the DA and NE systems may play a role in treatment for schizophrenia. Although DA and NE have been implicated in disorders involving the prefrontal cortex such as schizophrenia, affective disorders, and attention-deficit hyperactivity disorder (ADHD), the mechanism for interactions between DA and NE has not been widely investigated. Understanding how these systems interact should have a major impact on therapeutic possibilities for disorders arising from disruption of PFC function

Single atom quantum walk with 1D optical superlattices

A proposal for the implementation of quantum walks using cold atom technology is presented. It consists of one atom trapped in time varying optical superlattices. The required elements are presented in detail including the preparation procedure, the manipulation required for the quantum walk evolution and the final measurement. These procedures can be, in principle, implemented with present technology.Comment: 6 pages, 7 figure

Nef-specific CD45RA+ CD8+ T cells secreting MIP-1β but not IFN-γ are associated with nonprogressive HIV-1 infection

<p>Abstract</p> <p>Background</p> <p>Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease.</p> <p>Results</p> <p>We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gamma^negMIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gamma^negMIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease.</p> <p>Conclusion</p> <p>The novel antigen-specific CD45RA+ IFN-gamma^negMIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.</p

Distinct Genetic Architectures for Male and Female Inflorescence Traits of Maize

We compared the genetic architecture of thirteen maize morphological traits in a large population of recombinant inbred lines. Four traits from the male inflorescence (tassel) and three traits from the female inflorescence (ear) were measured and studied using linkage and genome-wide association analyses and compared to three flowering and three leaf traits previously studied in the same population. Inflorescence loci have larger effects than flowering and leaf loci, and ear effects are larger than tassel effects. Ear trait models also have lower predictive ability than tassel, flowering, or leaf trait models. Pleiotropic loci were identified that control elongation of ear and tassel, consistent with their common developmental origin. For these pleiotropic loci, the ear effects are larger than tassel effects even though the same causal polymorphisms are likely involved. This implies that the observed differences in genetic architecture are not due to distinct features of the underlying polymorphisms. Our results support the hypothesis that genetic architecture is a function of trait stability over evolutionary time, since the traits that changed most during the relatively recent domestication of maize have the largest effects

Developing Outreach Events That Impact Underrepresented Students: Are We Doing It Right?

Many outreach programs share the common goals of serving underrepresented groups in STEM and improving public attitudes toward science. To meet these goals, scientists must find ways to both reach the appropriate audience and communicate the importance of science in meaningful and accessible ways. This requires careful consideration of the outreach method being used. Two common outreach methods include in‐school visits (scientist in the classroom) and science fairs or open houses. Here, we compare the effectiveness of these two outreach methods in meeting the goals of reaching underrepresented students and/or students with less initial interest in science. We have found that in‐school visits reached more underrepresented students and that initial attitudes toward science scores were lower for in‐school visit participants than for open house event participants. Importantly, positive attitudes toward science increased significantly after in‐school outreach events. Taken together, these data suggest that outreach events that are taken out into the community will reach a less enthusiastic but more diverse audience and can have a positive impact on attitudes toward science within these populations. These studies highlight the importance of knowing the goals of your outreach program and choosing the method that is best suited to meeting those goals

A role for MGA2, but not SPT23, in activation of transcription of ERG1 in Saccharomyces cerevisiae

The Saccharomyces cerevisiae MGA2 gene encodes an important regulator of unsaturated fatty acid production, by controlling transcription and mRNA stability of OLE1, the gene encoding the Delta 9 fatty acid desaturase. Lipid composition studies indicated that the mga2 Delta strain contains elevated relative amounts of squalene when compared to wild-type cells. The deletion of the MGA2 homologue SPT23 did not impact squalene levels. To explore the role of MGA2 in the regulation of sterol synthesis, the transcription of the ERG1 gene, which encodes squalene epoxidase, was studied using an ERG1 promoter-lacZ reporter gene construct. We report here that in addition to MGA2\u27s role in regulation of unsaturated fatty acids, MGA2 is required for full basal expression of ERG1. Mga2p was found to be controlled by a novel regulator in its activation of ERG1, as neither unsaturated fatty acids nor cobalt affected ERG1 expression, as had previously been shown for Mga2p\u27s regulation of OLE1. Further, response to miconazole treatment, which inhibits production of ergosterol at a later step in the sterol biosynthetic pathway and results in up-regulation of several genes in ergosterol synthesis, was not affected in the mga2 Delta mutant. In each case, the spr23 Delta mutant strain shows similar ERG1 expression to wild-type cells, while the mga2 Delta/spt23 Delta strain shows reduced ERG1 expression, comparable to the mga2 Delta, suggesting that the role of regulation of ERG1 transcription is unique to Mga2p

Wie die 'Neuen Medien' das Leben und Lernen Erwachsener verändern. Abschlussbericht des Forschungsprojekts "Medienkompetenz im digitalen Zeitalter"

Treumann KP, Baacke D, Haacke K, Vollbrecht R, Hugger K-U. Wie die 'Neuen Medien' das Leben und Lernen Erwachsener verändern. Abschlussbericht des Forschungsprojekts "Medienkompetenz im digitalen Zeitalter". Bielefeld; 2000