A-Kinase Anchoring in Dendritic Cells Is Required for Antigen Presentation

BACKGROUND: Dendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune system. Prostaglandin E(2), cyclic AMP, and protein kinase A (PKA) have all been shown to regulate DC maturation and activity. In other cells, the ability of these molecules to convey their signals has been shown to be dependent on A-kinase anchoring proteins (AKAPs). Here we present evidence for the existence and functional importance of AKAPs in human DC. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and/or western analyses we identify AKAP79, AKAP149, AKAP95, AKAP LBC and Ezrin. We also demonstrate by western analysis that expression of AKAP79, AKAP149 and RII are upregulated with DC differentiation and maturation. We establish the functional importance of PKA anchoring in multiple aspects of DC biology using the anchoring inhibitor peptides Ht31 and AKAP-IS. Incubation of protein or peptide antigen loaded DC with Ht31 or AKAP-IS results in a 30-50% decrease in antigen presentation as measured by IFN-gamma production from antigen specific CD4(+) T cells. Incubation of LPS treated DC with Ht31 results in 80% inhibition of TNF-alpha and IL-10 production. Ht31 slightly decreases the expression of CD18 and CD11a and CD11b, slightly increases the basal expression of CD83, dramatically decreases the LPS stimulated expression of CD40, CD80 and CD83, and significantly increases the expression of the chemokine receptor CCR7. CONCLUSIONS: These experiments represent the first evidence for the functional importance of PKA anchoring in multiple aspects of DC biology

Sparse Representation of Brain Aging: Extracting Covariance Patterns from Structural MRI

An enhanced understanding of how normal aging alters brain structure is urgently needed for the early diagnosis and treatment of age-related mental diseases. Structural magnetic resonance imaging (MRI) is a reliable technique used to detect age-related changes in the human brain. Currently, multivariate pattern analysis (MVPA) enables the exploration of subtle and distributed changes of data obtained from structural MRI images. In this study, a new MVPA approach based on sparse representation has been employed to investigate the anatomical covariance patterns of normal aging. Two groups of participants (group 1∶290 participants; group 2∶56 participants) were evaluated in this study. These two groups were scanned with two 1.5 T MRI machines. In the first group, we obtained the discriminative patterns using a t-test filter and sparse representation step. We were able to distinguish the young from old cohort with a very high accuracy using only a few voxels of the discriminative patterns (group 1∶98.4%; group 2∶96.4%). The experimental results showed that the selected voxels may be categorized into two components according to the two steps in the proposed method. The first component focuses on the precentral and postcentral gyri, and the caudate nucleus, which play an important role in sensorimotor tasks. The strongest volume reduction with age was observed in these clusters. The second component is mainly distributed over the cerebellum, thalamus, and right inferior frontal gyrus. These regions are not only critical nodes of the sensorimotor circuitry but also the cognitive circuitry although their volume shows a relative resilience against aging. Considering the voxels selection procedure, we suggest that the aging of the sensorimotor and cognitive brain regions identified in this study has a covarying relationship with each other

HIV-1 assembly in macrophages

The molecular mechanisms involved in the assembly of newly synthesized Human Immunodeficiency Virus (HIV) particles are poorly understood. Most of the work on HIV-1 assembly has been performed in T cells in which viral particle budding and assembly take place at the plasma membrane. In contrast, few studies have been performed on macrophages, the other major target of HIV-1. Infected macrophages represent a viral reservoir and probably play a key role in HIV-1 physiopathology. Indeed macrophages retain infectious particles for long periods of time, keeping them protected from anti-viral immune response or drug treatments. Here, we present an overview of what is known about HIV-1 assembly in macrophages as compared to T lymphocytes or cell lines

Shoot Feeding as a Nutrient Acquisition Strategy in Free-Living Psylloids

Shoot feeding by sucking insects is accepted as an adaptation to feeding where plant nutrients are most concentrated and/or of higher quality. Psylloids are an important hemipteran taxon, most of which are free-living and comprise many shoot feeding species, whose nutritional ecology has been largely ignored. I conducted a longitudinal study of Ctenarytaina eucalypti (Maskell) and C. bipartita Burckhardt et al. (Aphalaridae) feeding on eucalypts to document how within-plant (ontogenic) variation in nutritional quality, in particular of free amino acids, determines host suitability and hence the distribution and abundance of nymphs. Nymphs were most abundant within developing apical buds but were not more abundant on branchlets of greater vigour (indicated by rate of extension). Nymphs could be found up to two (C. bipartita) to three (C. eucalypti) alternate leaf pairs distant from apical buds but infrequently and in low numbers; they were never found on older, fully expanded leaves. The position of a leaf on a branchlet (indicative of age) determined its nutritional quality. Younger leaves had higher water contents, lower chlorophyll contents and differed in amino acid (essential and non-essential) composition compared to older leaves. The abundance of C. eucalypti nymphs on expanding leaves and in buds was positively correlated with the concentrations of methionine, valine and threonine in E. globulus leaves at the same or comparable position on a branchlet. The abundance of C. bipartita nymphs was positively correlated with foliar leucine concentrations. Shoot feeding by these two psyllids facilitates access to more concentrated, better quality plant nutrients but may not entirely explain the adaptive significance of their behaviour. The humid microclimate created by the architecture of the hosts’ apical buds protects eggs and nymphs from desiccation and is suggested to have had a significant influence on the evolution of host utilisation strategies of psyllids within this genus