Effects of transportation, relocation, and acclimation on phenotypes and functional characteristics of peripheral blood lymphocytes in rhesus monkeys (<i>Macaca mulatta</i>)

Nonhuman primates from domestic sources constitute a small, but critical, proportion of animals studied in research laboratories. Many of these nonhuman primates are raised at one facility and subsequently transported/relocated to another facility for research purposes. We examined the effects of transport, relocation, and acclimation on the phenotype and function of peripheral blood mononuclear cells (PBMCs) in a group of rhesus monkeys that were transported by road for approximately 21 hours from one facility to another. Using a panel of human antibodies and a set of standardized human immune assays, we evaluated the phenotype of lymphocyte subsets by flow, mitogen-specific immune responses of PBMCs in vitro, and levels of circulating cytokines and cortisol in plasma at various time points including immediately before transport, immediately upon arrival, and after approximately 30 days of acclimation. Analyses of blood samples revealed that CD3+ T-cell and CD20+ B-cell populations had decreased significantly immediately after relocation but had recovered within 30 days after arrival at the new facility. Similarly, circulating cortisol and cytokine levels in plasma were significantly higher immediately after relocation; and by the 30-day time point, these differences were no longer significant. However, immune assays of PBMCs indicated that mitogen-specific responses for proliferation, interferon γ (IFN-γ), and perforin were significantly higher after relocation and 30 days of acclimation. These findings have implications on the research participation of transported and relocated nonhuman primates in immunologic research studies, suggesting that 30 days is not sufficient to ensure return to baseline immune homeostasis. These data should be considered when planning research studies in order to minimize potential confounding factors associated with relocation and to maximize study validity

Functional Impairment of Central Memory CD4 T Cells Is a Potential Early Prognostic Marker for Changing Viral Load in SHIV-Infected Rhesus Macaques

In HIV infection there is a paucity of literature about the degree of immune dysfunction to potentially correlate and/or predict disease progression relative to CD4+ T cells count or viral load. We assessed functional characteristics of memory T cells subsets as potential prognostic markers for changing viral loads and/or disease progression using the SHIV-infected rhesus macaque model. Relative to long-term non-progressors with low/undetectable viral loads, those with chronic plasma viremia, but clinically healthy, exhibited significantly lower numbers and functional impairment of CD4+ T cells, but not CD8+ T cells, in terms of IL-2 production by central memory subset in response to PMA and ionomycine (PMA+I) stimulation. Highly viremic animals showed impaired cytokine-production by all T cells subsets. These results suggest that functional impairment of CD4+ T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA+I stimulation

Ab initio molecular dynamics using density based energy functionals: application to ground state geometries of some small clusters

The ground state geometries of some small clusters have been obtained via ab initio molecular dynamical simulations by employing density based energy functionals. The approximate kinetic energy functionals that have been employed are the standard Thomas-Fermi $(T_{TF})$ along with the Weizsacker correction $T_W$ and a combination $F(N_e)T_{TF} + T_W$. It is shown that the functional involving $F(N_e)$ gives superior charge densities and bondlengths over the standard functional. Apart from dimers and trimers of Na, Mg, Al, Li, Si, equilibrium geometries for $Li_nAl, n=1,8$ and $Al_{13}$ clusters have also been reported. For all the clusters investigated, the method yields the ground state geometries with the correct symmetries with bondlengths within 5\% when compared with the corresponding results obtained via full orbital based Kohn-Sham method. The method is fast and a promising one to study the ground state geometries of large clusters.Comment: 15 pages, 3 PS figure

Thermodynamics of Na_8 and Na_{20} clusters studied with ab-initio electronic structure methods

We study the thermodynamics of Na_8 and Na_{20} clusters using multiple-histogram methods and an ab initio treatment of the valence electrons within density functional theory. We consider the influence of various electron kinetic-energy functionals and pseudopotentials on the canonical ionic specific heats. The results for all models we consider show qualitative similarities, but also significant temperature shifts from model to model of peaks and other features in the specific-heat curves. The use of phenomenological pseudopotentials shifts the melting peak substantially (~ 50--100 K) when compared to ab-initio results. It is argued that the choice of a good pseudopotential and use of better electronic kinetic-energy functionals has the potential for performing large time scale and large sized thermodynamical simulations on clusters.Comment: LaTeX file and EPS figures. 24 pages, 13 figures. Submitted to Phys. Rev.

An orbital-free molecular dynamics study of melting in K_20, K_55, K_92, K_142, Rb_55 and Cs_55 clusters

The melting-like transition in potasium clusters K_N, with N=20, 55, 92 and 142, is studied by using an orbital-free density-functional constant-energy molecular dynamics simulation method, and compared to previous theoretical results on the melting-like transition in sodium clusters of the same sizes. Melting in potasium and sodium clusters proceeds in a similar way: a surface melting stage develops upon heating before the homogeneous melting temperature is reached. Premelting effects are nevertheless more important and more easily established in potasium clusters, and the transition regions spread over temperature intervals which are wider than in the case of sodium. For all the sizes considered, the percentage melting temperature reduction when passing from Na to K clusters is substantially larger than in the bulk. Once those two materials have been compared for a number of different cluster sizes, we study the melting-like transition in Rb_55 and Cs_55 clusters and make a comparison with the melting behavior of Na_55 and K_55. As the atomic number increases, the height of the specific heat peaks decreases, their width increases, and the melting temperature decreases as in bulk melting, but in a more pronounced way.Comment: LaTeX file. 6 pages with 17 pictures. Final version with minor change

HLA-C and HIV-1: friends or foes?

The major histocompatibility complex class I protein HLA-C plays a crucial role as a molecule capable of sending inhibitory signals to both natural killer (NK) cells and cytotoxic T lymphocytes (CTL) via binding to killer cell Ig-like receptors (KIR). Recently HLA-C has been recognized as a key molecule in the immune control of HIV-1. Expression of HLA-C is modulated by a microRNA binding site. HLA-C alleles that bear substitutions in the microRNA binding site are more expressed at the cell surface and associated with the control of HIV-1 viral load, suggesting a role of HLA-C in the presentation of antigenic peptides to CTLs. This review highlights the role of HLA-C in association with HIV-1 viral load, but also addresses the contradiction of the association between high cell surface expression of an inhibitory molecule and strong cell-mediated immunity. To explore additional mechanisms of control of HIV-1 replication by HLA-C, we address specific features of the molecule, like its tendency to be expressed as open conformer upon cell activation, which endows it with a unique capacity to associate with other cell surface molecules as well as with HIV-1 proteins

Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia

<p>Abstract</p> <p>Background</p> <p>HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood.</p> <p>Methods</p> <p>To study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia. 46 brain regions from two rapidly progressing severely demented patients and 53 regions from 4 HIV+ non-dementia patients were analyzed. Macrophage and CD8+ T cell infiltration of the CNS in relation to HIV was assessed using immuno-histochemical analysis with anti-HIV (P24), anti-CD8 and anti-CD68, anti-S-100A8 and granzyme B antibodies (cellular activation). Statistical analysis was performed with SPSS 12.0 with Student's t test and ANOVA.</p> <p>Results</p> <p>Overall, the patterns of infiltration of macrophages and CD8+ T cells were indiscernible between patients with and without dementia, but the co-localization of macrophages and CD8+ T cells along with HIV P24 antigen in the deeper midline and mesial temporal structures of the brain segregated the two groups. This predilection of infected macrophages and CD8+ T cells to the middle part of the brain was unique to both HAD patients, along with unique nature of provirus gag gene sequences derived from macrophages in the midline and mesial temporal structures.</p> <p>Conclusion</p> <p>Strong predilection of infected macrophages and CD8+ T cells was typical of the deeper midline and mesial temporal structures uniquely in HAD patients, which has some influence on neurocognitive impairment during HIV infection.</p

Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes

BACKGROUND: The entry of human immunodeficiency virus (HIV-1) into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4. METHODOLOGY/PRINCIPAL FINDINGS: We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E(a)) of 269 kJ/mol (64.3 kcal/mol) and an inactivation temperature (T(i)) of 56°C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E(a) of 278 kJ/mol (66.5 kcal/mol), and a T(i) of 52.2°C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules. CONCLUSIONS/SIGNIFICANCE: Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors

A Paper on Green Roof Technology: A Global Trend to Save Environment

Rapid urbanization is the root cause of deteriorating environmental quality. In the twenty first century, under pressure people are exploring different sustainable approaches. Built environment, is the major consumer of energy and a prime contributor to the quality of environment. Technologies like passive techniques, intelligent facade, cool roof, green roof etc. can be used for a sustainable environment. Green roof is one such sustainable approach, which helps us in insulating the buildings and, thereby contributes to energy efficiency of the habitat to different species, reduces the rainwater runoff and leads to better management of the carbon-dioxide cycle. To create an understanding there are different existing rating systems which support appraisal of Green Roof like Leadership in Energy and Environmental Design (LEED) Rating System and Green Rating for Integrated Habitat assessment(GRIHA) rating system. The intent of this paper is to motivate for the integration of Green roof in the GRIHA Green building code. India has resulted in unplanned urban sprawl with increased urban densities and reduction in urban open spaces, and recreational spaces and permanent loss of valuable agricultural land. This paper also includes components, and types of Green Roofs