Performance evaluation of the Aptima HIV-1 Quant Dx assay for detection of HIV in infants in Kenya.

Background: Early infant diagnosis (EID) of HIV-1 exposed infants enables timely initiation of antiretroviral therapy (ART), thereby allowing early diagnosis and treatment to slow disease progression and reduce mortality. Turn-around time to results, partially caused by low to medium throughput technology, remains a hindrance to early treatment. A major solution to this challenge is to incorporate high throughput and accurate technologies in the testing process.

Macrophage Migration Inhibitory Factor Regulates U1 Small Nuclear RNP Immune Complex-Mediated Activation of the NLRP3 Inflammasome.

Objective: High-expression alleles of macrophage migration inhibitory factor (MIF) are linked genetically to the severity of systemic lupus erythematosus (SLE). The U1 small nuclear RNP (snRNP) immune complex containing U1 snRNP and anti-U1 snRNP antibodies, which are found in patients with SLE, activates the NLRP3 inflammasome, comprising NLRP3, ASC, and procaspase 1, in human monocytes, leading to the production of interleukin-1β (IL-1β). This study was undertaken to investigate the role of the snRNP immune complex in up-regulating the expression of MIF and its interface with the NLRP3 inflammasome.

Immune Analysis of Radium-223 in Patients With Metastatic Prostate Cancer.

Background: Radium223 (Ra223) delivers high-energy radiation to osteoblastic metastasis of prostate cancer, resulting in irreparable double-stranded DNA damage. The effects of Ra223 on CD8+ T cell subsets in patients with prostate cancer is unknown.

Patients And Methods: Fifteen men with metastatic prostate cancer with clinical indication for Ra223 without any autoimmune or immune deficiency conditions were enrolled.

Depigmenting Effect of Resveratrol Is Dependent on FOXO3a Activation without SIRT1 Activation.

Resveratrol exhibits not only anti-melanogenic property by inhibiting microphthalmia-associated transcription factor (MITF), but also anti-aging property by activating sirtuin-1 (SIRT1). In this study, the relationship between depigmenting effect of resveratrol and SIRT1/forkhead box O (FOXO) 3a activation and was investigated. Resveratrol suppressed melanogenesis by the downregulation of MITF and tyrosinase via ERK pathway.

Oligonol, a lychee fruit-derived low-molecular form of polyphenol mixture, suppresses inflammatory cytokine production from human monocytes.

Monocytes produce high levels of inflammatory cytokines including IL-6 and TNF-α that are involved in autoimmunity, inflammatory diseases, cardiovascular disease and obesity. Therapies targeting IL-6 and TNF-α have been utilized in treating chronic inflammatory diseases. Oligonol is a lychee fruit-derived low-molecular form of polyphenol mixture, typically catechin-type monomers and oligomers of proanthocyanidins, which are produced by an oligomerization process.

Aptima HIV-1 Quant Dx--A fully automated assay for both diagnosis and quantification of HIV-1.

Background: Separate assays are available for diagnosis and viral load (VL) monitoring of HIV-1. Studies have shown that using a single test for both confirmatory diagnosis and VL increases linkage to care.

Objective: To validate a single assay for both diagnosis and VL monitoring of HIV-1 on the fully automated Panther platform.

DNA Methylation Regulates the Differential Expression of CX3CR1 on Human IL-7Rαlow and IL-7Rαhigh Effector Memory CD8+ T Cells with Distinct Migratory Capacities to the Fractalkine.

DNA methylation is an epigenetic mechanism that modulates gene expression in mammalian cells including T cells. Memory T cells are heterogeneous populations. Human effector memory (EM) CD8(+) T cells in peripheral blood contain two cell subsets with distinct traits that express low and high levels of the IL-7Rα.

CSAR data set release 2012: ligands, affinities, complexes, and docking decoys.

A major goal in drug design is the improvement of computational methods for docking and scoring. The Community Structure Activity Resource (CSAR) has collected several data sets from industry and added in-house data sets that may be used for this purpose ( www.csardock.

Self double-stranded (ds)DNA induces IL-1β production from human monocytes by activating NLRP3 inflammasome in the presence of anti-dsDNA antibodies.

The pathogenic hallmark of systemic lupus erythematosus is the autoimmune response against self nuclear Ags, including dsDNA. The increased expression of the proinflammatory cytokine IL-1β has been found in the cutaneous lesion and PBMCs from lupus patients, suggesting a potential involvement of this cytokine in the pathogenesis of lupus. IL-1β is produced primarily by innate immune cells such as monocytes and can promote a Th17 cell response, which is increased in lupus.

Oligosaccharides of hyaluronic acid increased epidermal cell stemness by modulation of integrin expression.

Backgrounds: Hyaluronic acid (HA) is an abundant matrix component and is degraded into polymers of various sizes. These generated fragments appear to have properties that affect wound healing of the skin. In industry, small-sized HA is used as a moisturizing agent but can have biologic effects when it is absorbed through the skin with barrier disruption.

Stem cell recovering effect of copper-free GHK in skin.

The peptide Gly-His-Lys (GHK) is a naturally occurring copper(II)-chelating motifs in human serum and cerebrospinal fluid. In industry, GHK (with or without copper) is used to make hair and skin care products. Copper-GHK plays a physiological role in the process of wound healing and tissue repair by stimulating collagen synthesis in fibroblasts.

Redox status is critical for stemness in skin equivalents.

The skin is constantly exposed to environmental oxidative stress. Skin equivalent (SE) models are three-dimensional systems in which cell-cell or cell-matrix interactions can be investigated. In this study, the effects of vitamin C or plant extracts with high antioxidant activities were tested.

U1-small nuclear ribonucleoprotein activates the NLRP3 inflammasome in human monocytes.

The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is a caspase-1-containing cytosolic protein complex that is essential for processing and secretion of IL-1β. The U1-small nuclear ribonucleoprotein (U1-snRNP) that includes U1-small nuclear RNA is a highly conserved intranuclear molecular complex involved in splicing pre-mRNA. Abs against this self nuclear molecule are characteristically found in autoimmune diseases like systemic lupus erythematosus, suggesting a potential role of U1-snRNP in autoimmunity.

The relationship of cytomegalovirus (CMV) infection with circulatory IFN-α levels and IL-7 receptor α expression on CD8+ T cells in human aging.

The IL-7 receptor alpha (IL-7Rα) is the high affinity receptor for IL-7 which is essential for T cell homeostasis. We recently reported an age-associated expansion of human effector memory (EM) CD8(+) T cells expressing IL-7Rα low (IL-7Rα(low)), which could be detrimental to hosts by occupying "immunological space". We investigated the potential mechanisms for this phenomenon, focusing on cytomegalovirus (CMV) infection and INF-α.

Novel anti-inflammatory peptides as cosmeceutical peptides.

Ultraviolet (UV) radiation induced inflammation plays an important role in the aging of human skin. Prostaglandin (PG) E(2) is the primary mediator of UVB induced photoinflammation. We screened an internal library for dipeptides that inhibited UVB induced PGE(2) synthesis but showed no cytotoxicity toward human keratinocytes.

Age-associated alteration in naive and memory Th17 cell response in humans.

Th17 cells produce IL-17 that plays an important role in host defense. However, little is known about whether aging affects human Th17 cells. Here we demonstrated that healthy elderly people (age ≥ 65) had a decreased frequency of IL-17-producing cells in memory CD4(+) T cells compared to healthy young people (age ≤ 40) while both groups had similar frequencies of IFN-γ-producing cells in the same memory cell subset as measured by flow cytometry.

Structure of grouper iridovirus purine nucleoside phosphorylase.

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of purine ribonucleosides to the corresponding free bases and ribose 1-phosphate. The crystal structure of grouper iridovirus PNP (givPNP), corresponding to the first PNP gene to be found in a virus, was determined at 2.4 A resolution.

Copper-GHK increases integrin expression and p63 positivity by keratinocytes.

Glycyl-L-histidyl-L-lysyl (GHK) possesses a high affinity for copper(II) ions, with which it spontaneously forms a complex (copper-GHK). It is well known that copper-GHK plays a physiological role in the process of wound healing and tissue repair by stimulating collagen synthesis in fibroblasts. This study was conducted to investigate the effects of copper-GHK on keratinocytes.

A novel function for the N-terminal nucleophile hydrolase fold demonstrated by the structure of an archaeal inosine monophosphate cyclohydrolase.

Inosine 5'-monophosphate (IMP) cyclohydrolase catalyzes the cyclization of 5-formaminoimidazole-4-carboxamide ribonucleotide (FAICAR) to IMP in the final step of de novo purine biosynthesis. Two major types of this enzyme have been discovered to date: PurH in Bacteria and Eukarya and PurO in Archaea. The structure of the MTH1020 gene product from Methanothermobacter thermoautotrophicus was previously solved without functional annotation but shows high amino acid sequence similarity to other PurOs.

Structural insights into the mechanism of the PLP synthase holoenzyme from Thermotoga maritima.

Pyridoxal 5'-phosphate (PLP) is the biologically active form of vitamin B6 and is an important cofactor for several of the enzymes involved in the metabolism of amine-containing natural products such as amino acids and amino sugars. The PLP synthase holoenzyme consists of two subunits: YaaD catalyzes the condensation of ribulose 5-phosphate, glyceraldehyde-3-phosphate, and ammonia, and YaaE catalyzes the production of ammonia from glutamine. Here we describe the structure of the PLP synthase complex (YaaD-YaaE) from Thermotoga maritima at 2.

Crystallization and preliminary crystallographic analysis of endo-1,3-beta-glucanase from Arthrobacter sp.

Endo-1,3-beta-glucanases hydrolyze internal 1,3-beta-glucosyl linkages. The endo-1,3-beta-glucanase from Arthrobacter sp. was crystallized by the hanging-drop vapour-diffusion method.

Structural analysis of threonine 342 mutants of soybean beta-amylase: role of a conformational change of the inner loop in the catalytic mechanism.

Two different conformations of the inner loop (residues 340-346) have been found in the soybean beta-amylase structures. In the "product form", the Thr 342 residue creates hydrogen bonds with Glu 186 (catalytic acid) and with the glucose residues at subsites -1 and +1, whereas most of those interactions are lost in the "apo form". To elucidate the relationship between the structural states of the inner loop and the catalytic mechanism, Thr 342 was mutated to Val, Ser, and Ala, respectively, and their crystal structures complexed with maltose were determined together with that of the apo enzyme at 1.

Crystallization and preliminary crystallographic analysis of monodehydroascorbate radical reductase from cucumber.

Monodehydroascorbate (MDA) radical reductase (EC 1.6.5.

The roles of Glu186 and Glu380 in the catalytic reaction of soybean beta-amylase.

It has previously been suggested that the glutamic acid residues Glu186 and Glu380 of soybean beta-amylase play critical roles as a general acid and a general base catalyst, respectively. In order to confirm the roles of Glu186 and Glu380, each residue was mutated to a glutamine residue and the crystal structures of the substrate (E186Q/maltopentaose) and product (E380Q/maltose) complexes were determined at resolutions of 1.6 Angstrom and 1.