Proton magnetic resonance spectroscopic imaging of gray and white matter in bipolar-I and schizophrenia.

Background: Glutamine plus glutamate (Glx), as well as N-acetylaspartate compounds, (NAAc), a marker of neuronal viability, are quantified with proton magnetic resonance spectroscopy (H-MRS) and have been reported altered in psychotic disorders. However, few studies have compared these neurometabolites in bipolar disorder and schizophrenia.

Methods: Used H-MRS imaging from an axial supraventricular slab of gray matter (GM; medial-frontal and medial-parietal) and white matter (WM; bilateral-frontal and bilateral-parietal) voxels.

Estimation of the initial viral growth rate and basic reproductive number during acute HIV-1 infection.

During primary infection, the number of HIV-1 particles in plasma increases rapidly, reaches a peak, and then declines until it reaches a set point level. Understanding the kinetics of primary infection, and its effect on the establishment of chronic infection, is important in defining the early pathogenesis of HIV. We studied the viral dynamics of very early HIV-1 infection in 47 subjects identified through plasma donation screening.

Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia.

A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus), but, to date, this period has been logistically difficult to analyze. To probe B-cell responses immediately following HIV-1 transmission, we have determined envelope-specific antibody responses to autologous and consensus Envs in plasma donors from the United States for whom frequent plasma samples were available at time points immediately before, during, and after HIV-1 plasma viral load (VL) ramp-up in acute infection, and we have modeled the antibody effect on the kinetics of plasma viremia.

The effect of early versus delayed challenge after vaccination in controlling SHIV 89.6P infection.

We sought to determine how effectively a CD8+ T cell inducing vaccine controls SHIV-89.6P infection in rhesus macaques at a range of challenge times post-vaccination. To this end, twenty eight Mamu-A*01+ rhesus macaques were given replication incompetent human serotype 5 adenovirus vector expressing SIVmac239 gag DNA and boosted 24 weeks later.

Multiple routes lead to the native state in the energy landscape of the beta-trefoil family.

In general, the energy landscapes of real proteins are sufficiently well designed that the depths of local energetic minima are small compared with the global bias of the native state. Because of the funneled nature of energy landscapes, models that lack energetic frustration have been able to capture the main structural features of the transition states and intermediates found in experimental studies of both small and large proteins. In this study we ask: Are the experimental differences in folding mechanisms among members of a particular structural family due to local topological constraints that deviate from the tertiary fold common to the family? The beta-trefoil structural family members IL-1beta, hisactophilin, and acidic/basic FGFs were chosen to address this question.

Topological frustration and the folding of interleukin-1 beta.

The cytokine, interleukin-1beta (IL-1beta), adopts a beta-trefoil fold. It is known to be much slower folding than similarly sized proteins, despite having a low contact order. Proteins are sufficiently well designed that their folding is not dominated by local energetic traps.

The native energy landscape for interleukin-1beta. Modulation of the population ensemble through native-state topology.

A minimalist Go-model, with no energetic frustration in the native conformation, has been shown to describe accurately the folding pathway of the beta-trefoil protein, interleukin-1beta (IL-1beta). While it appears that these models successfully model transition states and intermediates between the unfolded and native ensembles, it is unclear how accurately they capture smaller, yet biologically relevant, structural changes within the native ensemble after energetic perturbation. Here, we address the following questions.

Quantifying the roughness on the free energy landscape: entropic bottlenecks and protein folding rates.

The prediction of protein folding rates and mechanisms is currently of great interest in the protein folding community. A close comparison between theory and experiment in this area is promising to advance our understanding of the physical-chemical principles governing the folding process. The delicate interplay of entropic and energetic/enthalpic factors in the protein free energy regulates the details of this complex reaction.