Structure and Inhibition of Mouse Leukotriene C4 Synthase

Leukotriene (LT) C₄ synthase (LTC4S) is an integral membrane protein that catalyzes the conjugation reaction between the fatty acid LTA₄ and GSH to form the pro-inflammatory LTC₄, an important mediator of asthma. Mouse models of inflammatory disorders such as asthma are key to improve our understanding of pathogenesis and potential therapeutic targets. Here, we solved the crystal structure of mouse LTC4S in complex with GSH and a product analog, S-hexyl-GSH. Furthermore, we synthesized a nM inhibitor and compared its efficiency and binding mode against the purified mouse and human isoenzymes, along with the enzymes’ steady-state kinetics. Although structural differences near the active site and along the C-terminal α-helix V suggest that the mouse and human LTC4S may function differently in vivo, our data indicate that mouse LTC4S will be a useful tool in future pharmacological research and drug development.     

Cotton Biotechnology

Genetically modified (GM) cotton altered for insect and herbicide resistance released into commercial production in 1996 to 1997 now accounts for the lion's share of cotton acreage in the U.S. The rapid increase in transgenic cotton acreage in such a short period of time attests to the overall success of agricultural biotechnology. Grower satisfaction with transgenic cotton is largely due to several significant benefits, such as lower production costs, streamlined yet flexible management, and a reduced impact on the environment. This review article provides an overview of what has been accomplished thus far, as well as what improved germplasm may lurk on the horizon. A critical assessment of the gene delivery systems in cotton and possible targets for improvement is presented. The performance of the first generation of transgenic cotton plants engineered for insect, disease, or herbicide resistance is evaluated from the perspective of the benefits, the limitations that impact field performance, and management strategies. A few traits that hold future promise for increasing fiber productivity, enhancing and/or increasing the novelty of cotton-based products for the consumer, and improving human health and well-being are presented. Above all, cotton biotechnology offers to greatly enhance breeding programs by introducing novel traits that have eluded more traditional plant improvement methods and therefore will likely play an increasingly important role in the genetic improvement of cotton.     

Seroprevalence and risk factors for Helicobacter pylori infection in Greenlanders

BACKGROUND: In contrast to most populations worldwide, the incidence of gastric cancer increases among Inuit in Greenland. Contributing factors to this increase are unknown, but Helicobacter pylori may be involved. However, little is known regarding the epidemiology of H. pylori in Arctic communities. With the aim of determining age-specific prevalence, risk factors, and association with clinical conditions of H. pylori infection, we carried out a population-based study of H. pylori in Sisimiut, the second biggest town of Greenland. MATERIALS AND METHODS: A population-based sample of 685 persons had serum drawn that was analyzed for H. pylori IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Risk factors analyses were carried out using multivariate logistic regression models. RESULTS: The seroprevalence was lowest among children aged 0-4 years (6%), but increased rapidly thereafter. In persons aged 15-87 years the seroprevalence had stabilized around 58%. Total number of children in household, number of older, but not younger, siblings and narrow age gap to closest older sibling were associated with H. pylori seropositivity. In contrast, number of adults in household and socioeconomic status did not influence serostatus. CONCLUSIONS: The age-specific prevalence pattern in Greenland is intermediate between that of developing and developed countries. The risk factor pattern indicates crowding and older siblings in particular to be key elements in risk of infection.     

Differences in growth,size and sexual dimorphism in skulls of East Greenland and Svalbard polar bears (<Emphasis Type="Italic">Ursus maritimus</Emphasis>)

Size, growth and sexual dimorphism of nine skull traits was studied in 300 East Greenland and 391 Svalbard polar bears (Ursus maritimus). Two traits were significantly larger in bears from East Greenland compared to Svalbard bears, and trait size was smaller after 1960 in five traits. For both localities and both age groups (subadult, adult), mean trait size values were higher in males than females (all: P < 0.05). Gompertz growth models showed trait size increasing with age in seven traits. Depending on the trait, males reached 95% asymptotic trait size at age 3–10, females at age 2–6. The females of both localities matured at approximately the same age, whereas the Svalbard males generally matured years later than their East Greenland peers. The differences found in the present study between the two polar bear subpopulations support the notion that East Greenland and Svalbard polar bears probably should be managed as separate units.     

Restriction of HIV-1 Genotypes in Breast Milk Does Not Account for the Population Transmission Genetic Bottleneck That Occurs following Transmission

Background

Breast milk transmission of HIV-1 remains a major route of pediatric infection. Defining the characteristics of viral variants to which breastfeeding infants are exposed is important for understanding the genetic bottleneck that occurs in the majority of mother-to-child transmissions. The blood-milk epithelial barrier markedly restricts the quantity of HIV-1 in breast milk, even in the absence of antiretroviral drugs. The basis of this restriction and the genetic relationship between breast milk and blood variants are not well established.

Methodology/Principal Findings

We compared 356 HIV-1 subtype C gp160 envelope (env) gene sequences from the plasma and breast milk of 13 breastfeeding women. A trend towards lower viral population diversity and divergence in breast milk was observed, potentially indicative of clonal expansion within the breast. No differences in potential N-linked glycosylation site numbers or in gp160 variable loop amino acid lengths were identified. Genetic compartmentalization was evident in only one out of six subjects in whom contemporaneously obtained samples were studied. However, in samples that were collected 10 or more days apart, six of seven subjects were classified as having compartmentalized viral populations, highlighting the necessity of contemporaneous sampling for genetic compartmentalization studies. We found evidence of CXCR4 co-receptor using viruses in breast milk and blood in nine out of the thirteen subjects, but no evidence of preferential localization of these variants in either tissue.

Conclusions/Significance

Despite marked restriction of HIV-1 quantities in milk, our data indicate intermixing of virus between blood and breast milk. Thus, we found no evidence that a restriction in viral genotype diversity in breast milk accounts for the genetic bottleneck observed following transmission. In addition, our results highlight the rapidity of HIV-1 env evolution and the importance of sample timing in analyses of gene flow.