HIV Shedding from Male Circumcision Wounds in HIV-Infected Men: A Prospective Cohort Study

BackgroundA randomized trial of voluntary medical male circumcision (MC) of HIV—infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC.ConclusionPenile HIV shedding is significantly reduced after healing of MC wounds. Lower plasma VL is associated with decreased frequency and quantity of HIV shedding from MC wounds. Starting ART prior to MC should be considered to reduce male-to-female HIV transmission risk. Research is needed to assess the time on ART required to decrease shedding, and the acceptability and feasibility of initiating ART at the time of MC.     

Pharmacokinetics of Repeated Sodium Salicylate Administration to Laying Hens: Evidence for Time Dependent Increase in Drug Elimination from Plasma and Eggs

Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs) to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus) salicylate (SA) may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS) to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1^st, 7^th and 14^th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT), minimal plasma concentration (C_min, C_16h) and elimination half-life (T_1/2el) of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (Cl_B) increased. Layers administered with the higher dose showed a decrease only in the T_1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment.     

Activation of p38 Mitogen-Activated Protein Kinase in Gaucher’s Disease

Gaucher’s disease is caused by defects in acid β-glucosidase 1 (GBA1) and has been also proposed as an inflammatory disease. GBA1 cleaves glucosylceramide to form ceramide, an established bioactive lipid, and defects in GBA1 lead to aberrant accumulation in glucosylceramide and insufficient formation of ceramide. We investigated if the pro-inflammatory kinase p38 is activated in Gaucher’s disease, since ceramide has been proposed to suppress p38 activation. Three Gaucher’s disease mouse models were employed, and p38 was found to be activated in lung and liver tissues of all Gaucher’s disease mice. Most interestingly, neuronopathic Gaucher’s disease type mice, but not non-neuronopathic ones, displayed significant activation of p38 and up-regulation of p38-inducible proinflammatory cytokines in brain tissues. In addition, all type of Gaucher’s disease mice also showed increases in serum IL-6. As cellular signalling is believed to represent an in vivo inflammatory phenotype in Gaucher’s disease, activation of p38 and possibly its-associated formation of proinflammatory cytokines were assessed in fibroblasts established from neuronopathic Gaucher’s disease mice. In mouse Gaucher’s disease cells, p38 activation and IL-6 formation by TNF-α treatment were enhanced as compared to those of wild type. Furthermore, human fibroblasts from Gaucher’s disease patients also displayed increases in p38 activation and IL-6 formation as comparison to healthy counterpart. These results raise the potential that proinflammatory responses such as p38 activation and IL-6 formation are augmented in Gaucher’s disease.     

Apolipoprotein E-deficient lipoproteins induce foam cell formation by downregulation of lysosomal hydrolases in macrophages

Apolipoprotein E (apoE) deficiency has been suggested to induce foam cell formation. Using lipoproteins obtained from wild-type mice and apoE-deficient mice expressing apoB-48 but not apoB-100, we studied apoE-deficient lipoprotein-induced changes in lipoprotein catabolism and protein expression in mouse peritoneal macrophages (MPMs). Our data demonstrate that incubation of MPMs with apoE-deficient lipoproteins induced intracellular lipoprotein, cholesteryl ester, and triglyceride accumulation, which was associated with a time-related decline in apoE-deficient lipoprotein degradation in MPMs. Confocal microscopy analysis indicated that the accumulated lipids were localized in lysosomes. ApoE-deficient lipoproteins reduced the protein levels of lysosomal acid lipase, cathepsin B, and cation-dependent mannose 6 phosphate receptor (MPR46). Exogenous apoE reduced apoE-deficient lipoprotein-induced lipid accumulation and attenuated the suppressive effect of apoE-deficient lipoproteins on lysosomal hydrolase and MPR46 expression. Although oxidized lipoproteins also increased lipid contents in MPMs, exogenous apoE could not attenuate oxidized lipoprotein-induced lipid accumulation. Our in vivo studies also showed that feeding apoE-deficient mice a high-fat diet resulted in cholesteryl ester and triglyceride accumulation and reduced lysosomal hydrolase expression in MPMs. These data suggest that apoE-deficient lipoproteins increase cellular lipid contents through pathways different from those activated by oxidized lipoproteins and that reducing lysosomal hydrolases in macrophages might be a mechanism by which apoE-deficient lipoproteins result in intralysosomal lipoprotein accumulation, thereby inducing foam cell formation.     

Structural genomics: keeping up with expanding knowledge of the protein universe

Structural characterization of the protein universe is the main mission of Structural Genomics (SG) programs. However, progress in gene sequencing technology, set in motion in the 1990s, has resulted in rapid expansion of protein sequence space--a twelvefold increase in the past seven years. For the SG field, this creates new challenges and necessitates a re-assessment of its strategies. Nevertheless, despite the growth of sequence space, at present nearly half of the content of the Swiss-Prot database and over 40% of Pfam protein families can be structurally modeled based on structures determined so far, with SG projects making an increasingly significant contribution. The SG contribution of new Pfam structures nearly doubled from 27.2% in 2003 to 51.6% in 2006.     

Microbiota in Wheat Roots,Rhizosphere and Soil in Crops Grown in Organic and Other Production Systems

Culturable microbial communities and diseases were compared in organic, integrated and conventional systems of winter wheat production and monoculture. Particular emphasis was placed on the density and diversity of cereal pathogens and their potential antagonists, and on the association of the active microbial populations with the health and productivity of wheat. In roots, rhizoplane and rhizosphere, fungi tended to be most abundant in the integrated system or monoculture, and bacteria in the organic system. The dominant fungal groups (with individual frequency >5%) included root pathogens (Fusarium, Gibberella, Haematonectria and Ilyonectria) and known pathogen antagonists (Acremonium strictum, Clonostachys, Chaetomium, Gliocladium and Trichoderma spp.). The 50 subdominant species (with individual frequency 1–5%) included the pathogens Alternaria, Cladosporium (leaf spot), Gaeumannomyces graminis (take‐all), Glomerella graminicola (anthracnose), Oculimacula yallundae (eyespot), Phoma spp. (leaf spots), and Pythium and Rhizoctonia (root rot). The 40 subrecedent species (with individual frequency <1%) included minor pathogens (Botrytis, Coniothyrium, Leptosphaeria). Antagonists in roots, rhizoplane and rhizosphere were most frequent in the organic system and least frequent in monoculture, suggesting that these systems had the most and least disease‐suppressive habitats, respectively. The other two systems were intermediate, with microbial communities suggesting that the conventional system produced a slightly more suppressive environment than the integrated system. The highest grain yield, in the integrated system, was associated with high abundance of fungi, including fungal pathogens, lowest abundance of Arthrobacter, Pseudomonas and Streptomyces in roots, rhizoplane and soil, and relatively high stem‐base and leaf disease severity. The lowest grain yields, in the organic system and monoculture, were associated with less abundant fungi and more abundant Pseudomonas. There is no clear indication that yields were affected by diseases.     

Biochemical isolation and purification of ovulation-inducing factor (OIF) in seminal plasma of llamas

Background  

The objective of the present study was to isolate and purify the protein fraction(s) of llama seminal plasma responsible for the ovulation-inducing effect of the ejaculate.     

Tocopherol content and activities of tyrosine aminotransferase and cystine lyase in Arabidopsis under stress conditions

Tocopherols are presumed to be important antioxidants and scavengers of lipid radicals and reactive oxygen species in plants. Age is known to be a condition under which oxidative stress increases. In leaves of aging Arabidopsis thaliana plants, the content of alpha-tocopherol as well as of gamma-tocopherol increased significantly. The activity of tyrosine aminotransferase, which supplies the biosynthetic pathway with 4-hydroxyphenylpyruvate, was increased as well. On the other hand, coronatine, a phytotoxin mimicking octadecanoids and leading to symptoms of senescence, caused a moderate increase in alpha-tocopherol as well as some enhancement of gamma-tocopherol.