The pp24 phosphoprotein of Mason-Pfizer monkey virus contributes to viral genome packaging

BACKGROUND: The Gag protein of Mason-Pfizer monkey virus, a betaretrovirus, contains a phosphoprotein that is cleaved into the Np24 protein and the phosphoprotein pp16/18 during virus maturation. Previous studies by Yasuda and Hunter (J. Virology. 1998. 72:4095–4103) have demonstrated that pp16/18 contains a viral late domain required for budding and that the Np24 protein plays a role during the virus life cycle since deletion of this N-terminal domain blocked virus replication. The function of the Np24 domain, however, is not known. RESULTS: Here we identify a region of basic residues (KKPKR) within the Np24 domain that is highly conserved among the phosphoproteins of various betaretroviruses. We show that this KKPKR motif is required for virus replication yet dispensable for procapsid assembly, membrane targeting, budding and release, particle maturation, or viral glycoprotein packaging. Additional experiments indicated that deletion of this motif reduced viral RNA packaging 6–8 fold and affected the transient association of Gag with nuclear pores. CONCLUSION: These results demonstrate that the Np24 domain plays an important role in RNA packaging and is in agreement with evidence that suggests that correct intracellular targeting of Gag to the nuclear compartment is an fundamental step in the retroviral life cycle

The Impact of Experience with a Family Member with Alzheimer's Disease on Views about the Disease across Five Countries

The objective of this paper is to understand how the public's beliefs in five countries may change as more families have direct experience with Alzheimer's disease. The data are derived from a questionnaire survey conducted by telephone (landline and cell) with 2678 randomly selected adults in France, Germany, Poland, Spain, and the United States. The paper analyzes the beliefs and anticipated behavior of those in each country who report having had a family member with Alzheimer's disease versus those who do not. In one or more countries, differences were found between the two groups in their concern about getting Alzheimer's disease, knowledge that the disease is fatal, awareness of certain symptoms, and support for increased public spending. The results suggest that as more people have experience with a family member who has Alzheimer's disease, the public will generally become more concerned about Alzheimer's disease and more likely to recognize that Alzheimer's disease is a fatal disease. The findings suggest that other beliefs may only be affected if there are future major educational campaigns about the disease. The publics in individual countries, with differing cultures and health systems, are likely to respond in different ways as more families have experience with Alzheimer's disease

Human Ubc9 Contributes to Production of Fully Infectious Human Immunodeficiency Virus Type 1 Virions

Ubc9 was identified as a cellular protein that interacts with the Gag protein of Mason-Pfizer monkey virus. We show here that Ubc9 also interacts with the human immunodeficiency virus type 1 (HIV-1) Gag protein and that their interaction is important for virus replication. Gag was found to colocalize with Ubc9 predominantly at perinuclear puncta. While cells in which Ubc9 expression was suppressed with RNA interference produced normal numbers of virions, these particles were 8- to 10-fold less infectious than those produced in the presence of Ubc9. The nature of this defect was assayed for dependence on Ubc9 during viral assembly, trafficking, and Env incorporation. The Gag-mediated assembly of virus particles and protease-mediated processing of Gag and Gag-Pol were unchanged in the absence of Ubc9. However, the stability of the cell-associated Env glycoprotein was decreased and Env incorporation into released virions was altered. Interestingly, overexpression of the Ubc9 trans-dominant-negative mutant C93A, which is a defective E2-SUMO-1 conjugase, suggests that this activity may not be required for interaction with Gag, virion assembly, or infectivity. This finding demonstrates that Ubc9 plays an important role in the production of infectious HIV-1 virions

Damping rates for moving particles in hot QCD

Using a program of perturbative resummation I compute the damping rates for fields at nonzero spatial momentum to leading order in weak coupling in hot $QCD$. Sum rules for spectral densities are used to simplify the calculations. For massless fields the damping rate has an apparent logarithmic divergence in the infrared limit, which is cut off by the screening of static magnetic fields (``magnetic mass''). This demonstrates how at high temperature even perturbative quantities are sensitive to nonperturbative phenomenon.Comment: LaTeX file, 24 pages, BNL-P-1/92 (December, 1992

Coulomb Blockade in a Coupled Nanomechanical Electron Shuttle

We demonstrate single electron shuttling through two coupled nanomechanical pendula. The pendula are realized as nanopillars etched out of the semiconductor substrate. Coulomb blockade is found at room temperature, allowing metrological applications. By controlling the mechanical shuttling frequency we are able to validate the different regimes of electron shuttling

Towards the Theory of Cosmological Phase Transitions

We discuss recent progress (and controversies) in the theory of finite temperature phase transitions. This includes the structure of the effective potential at a finite temperature, the infrared problem in quantum statistics of gauge fields, the theory of formation of critical and subcritical bubbles and the theory of bubble wall propagation.Comment: 50 p

Differential prefrontal and subcortical circuitry engagement during encoding of semantically related words in patients with late‐life depression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109350/1/gps4165.pd

Wildlife Trade and Global Disease Emergence

The global trade in wildlife provides disease transmission mechanisms that not only cause human disease outbreaks but also threaten livestock, international trade, rural livelihoods, native wildlife populations, and the health of ecosystems. Outbreaks resulting from wildlife trade have caused hundreds of billions of dollars of economic damage globally. Rather than attempting to eradicate pathogens or the wild species that may harbor them, a practical approach would include decreasing the contact rate among species, including humans, at the interface created by the wildlife trade. Since wildlife marketing functions as a system of scale-free networks with major hubs, these points provide control opportunities to maximize the effects of regulatory efforts

Arenavirus budding resulting from viral-protein-associated cell membrane curvature

Viral replication occurs within cells, with release (and onward infection) primarily achieved through two alternative mechanisms: lysis, in which virions emerge as the infected cell dies and bursts open; or budding, in which virions emerge gradually from a still living cell by appropriating a small part of the cell membrane. Virus budding is a poorly understood process that challenges current models of vesicle formation. Here, a plausible mechanism for arenavirus budding is presented, building on recent evidence that viral proteins embed in the inner lipid layer of the cell membrane. Experimental results confirm that viral protein is associated with increased membrane curvature, whereas a mathematical model is used to show that localized increases in curvature alone are sufficient to generate viral buds. The magnitude of the protein-induced curvature is calculated from the size of the amphipathic region hypothetically removed from the inner membrane as a result of translation, with a change in membrane stiffness estimated from observed differences in virion deformation as a result of protein depletion. Numerical results are based on experimental data and estimates for three arenaviruses, but the mechanisms described are more broadly applicable. The hypothesized mechanism is shown to be sufficient to generate spontaneous budding that matches well both qualitatively and quantitatively with experimental observations