immunocytochemical localization of urokinase-type plasminogen activator in lewis lung carcinoma

The invasively growing and metasizing Lewis lung carcinoma consistently contained urokinase-type plasminogen activator (u-PA) enzyme activity. When investigated immunocytochemically with antibodies against u-PA, different parts of individual tumors showed a pronounced heterogeneity in staining intensity. Strong staining was found in areas with invasive growth and degradation of surrounding normal tissue, while other areas were completely devoid of staining. Immunoreactivity occurred both with a perinuclear cytoplasmic localization in tumor cells and associated with apparently extracellular material. SDS PAGE of tumor extracts, under both reducing and nonreducing conditions, followed by immunoblotting, showed only one immunocytochemically stainable band with an electrophoretic mobility corresponding to that of purified proenzyme to u-PA, while no two-chain u-PA was detected. This indicates that the major part of the activator in Lewis lung carcinoma is present as one-chain pro-u-PA.     

Post-construction avian mortality monitoring at Project West Wind

Abstract

Post-construction avifauna investigations were undertaken at Project West Wind, Meridian Energy Limited's 62-turbine wind farm on the Wellington south coast. These investigations were required in accordance with the resource consent conditions to quantify the level of avian mortalities occurring at the wind farm, particularly in regard to New Zealand falcon (Falco novaeseelandiae), kākā (Nestor meridionalis) and kererū (Hemiphaga novaeseelandiae). This is the first comprehensive study at a New Zealand operating wind farm. The methods included three field components necessary to calculate annual estimates of mortalities across the wind farm site: routine turbine searches; carcass detection trials; and carcass removal trials. Results from years 1 and 2 of a three-year programme are presented. To date, mortalities have been recorded for 17 taxa at 18 of the 24 study turbines. There have been no recorded mortalities of falcon, kākā or kererū. Australasian harrier (Circus approximans) has been the species for which the most mortalities have been recorded. Overall estimated annual mortality rates for years 1 and 2 were calculated to be approximately six and five birds per turbine respectively.     

Genetic architecture of survival and fitness-related traits in two populations of Atlantic salmon

The additive genetic effects of traits can be used to predict evolutionary trajectories, such as responses to selection. Non-additive genetic and maternal environmental effects can also change evolutionary trajectories and influence phenotypes, but these effects have received less attention by researchers. We partitioned the phenotypic variance of survival and fitness-related traits into additive genetic, non-additive genetic and maternal environmental effects using a full-factorial breeding design within two allopatric populations of Atlantic salmon (Salmo salar). Maternal environmental effects were large at early life stages, but decreased during development, with non-additive genetic effects being most significant at later juvenile stages (alevin and fry). Non-additive genetic effects were also, on average, larger than additive genetic effects. The populations, generally, did not differ in the trait values or inferred genetic architecture of the traits. Any differences between the populations for trait values could be explained by maternal environmental effects. We discuss whether the similarities in architectures of these populations is the result of natural selection across a common juvenile environment.     

Leptin activation of mTOR pathway in intestinal epithelial cell triggers lipid droplet formation,cytokine production and increased cell proliferation

Accumulating evidence suggests that obesity and enhanced inflammatory reactions are predisposing conditions for developing colon cancer. Obesity is associated with high levels of circulating leptin. Leptin is an adipocytokine that is secreted by adipose tissue and modulates immune response and inflammation. Lipid droplets (LD) are organelles involved in lipid metabolism and production of inflammatory mediators, and increased numbers of LD were observed in human colon cancer. Leptin induces the formation of LD in macrophages in a PI3K/mTOR pathway-dependent manner. Moreover, the mTOR is a serine/threonine kinase that plays a key role in cellular growth and is frequently altered in tumors. We therefore investigated the role of leptin in the modulation of mTOR pathway and regulation of lipid metabolism and inflammatory phenotype in intestinal epithelial cells (IEC-6 cells). We show that leptin promotes a dose- and time-dependent enhancement of LD formation. The biogenesis of LD was accompanied by enhanced CXCL1/CINC-1, CCL2/MCP-1 and TGF-β production and increased COX-2 expression in these cells. We demonstrated that leptin-induced increased phosphorylation of STAT3 and AKT and a dose and time-dependent mTORC activation with enhanced phosphorilation of the downstream protein P70S6K protein. Pre-treatment with rapamycin significantly inhibited leptin effects in LD formation, COX-2 and TGF-β production in IEC-6 cells. Moreover, leptin was able to stimulate the proliferation of epithelial cells on a mTOR-dependent manner. We conclude that leptin regulates lipid metabolism, cytokine production and proliferation of intestinal cells through a mechanism largely dependent on activation of the mTOR pathway, thus suggesting that leptin-induced mTOR activation may contribute to the obesity-related enhanced susceptibility to colon carcinoma.     

Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection

Glycans play important roles in host-microbe interactions. Tissue-specific expression patterns of the blood group glycosyltransferase β-1,4-N-acetylgalactosaminyltransferase 2 (B4galnt2) are variable in wild mouse populations, and loss of B4galnt2 expression is associated with altered intestinal microbiota. We hypothesized that variation in B4galnt2 expression alters susceptibility to intestinal pathogens. To test this, we challenged mice genetically engineered to express different B4galnt2 tissue-specific patterns with a Salmonella Typhimurium infection model. We found B4galnt2 intestinal expression was strongly associated with bacterial community composition and increased Salmonella susceptibility as evidenced by increased intestinal inflammatory cytokines and infiltrating immune cells. Fecal transfer experiments demonstrated a crucial role of the B4galnt2-dependent microbiota in conferring susceptibility to intestinal inflammation, while epithelial B4galnt2 expression facilitated epithelial invasion of S. Typhimurium. These data support a critical role for B4galnt2 in gastrointestinal infections. We speculate that B4galnt2-specific differences in host susceptibility to intestinal pathogens underlie the strong signatures of balancing selection observed at the B4galnt2 locus in wild mouse populations.     

Selected anthropometric variables and aerobic fitness as predictors of cardiovascular disease risk in children

The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children.     

Systemic and Mucosal Immune Reactivity upon Mycobacterium avium ssp. paratuberculosis Infection in Mice

Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne''s disease, an inflammatory bowel disorder of ruminants. Due to the similar pathology, MAP was also suggested to cause Crohn''s disease (CD). Despite of intensive research, this question is still not settled, possibly due to the lack of versatile mouse models. The aim of this study was to identify basic immunologic mechanisms in response to MAP infection. Immune compromised C57BL/6 Rag2 ^−/− mice were infected with MAP intraperitoneally. Such chronically infected mice were then reconstituted with CD4⁺ and CD8⁺ T cells 28 days after infection. A systemic inflammatory response, detected as enlargement of the spleen and granuloma formation in the liver, was observed in mice infected and reconstituted with CD4⁺ T cells. Whereby inflammation in infected and CD4⁺CD45RB^hi T cell reconstituted animals was always higher than in the other groups. Reconstitution of infected animals with CD8⁺ T cells did not result in any inflammatory signs. Interestingly, various markers of inflammation were strongly up-regulated in the colon of infected mice reconstituted with CD4⁺CD45RB^lo/int T cells. We propose, the usual non-colitogenic CD4⁺CD45RB^lo/int T cells were converted into inflammatory T cells by the interaction with MAP. However, the power of such cells might be not sufficient for a fully established inflammatory response in the colon. Nevertheless, our model system appears to mirror aspects of an inflammatory bowel disease (IBD) like CD and Johne''s diseases. Thus, it will provide an experimental platform on which further knowledge on IBD and the involvement of MAP in the induction of CD could be acquired.     

Nuclear factor-kappa B localization and function within intrauterine tissues from term and preterm labor and cultured fetal membranes

Background  

The objective of this study was to quantify the nuclear localization and DNA binding activity of p65, the major transactivating nuclear factor-kappa B (NF-kappaB) subunit, in full-thickness fetal membranes (FM) and myometrium in the absence or presence of term or preterm labor.     

Automated Flight Test and System Identification for Rotary Wing Small Aerial Platform Using Frequency Responses Analysis

This paper proposes an autopilot system that can be used to control the small scale rotorcraft during the flight test for linear-frequency-domain system identification. The input frequency-sweep is generated automatically as part of the autopilot control command. Therefore the bandwidth coverage and consistency of the frequency-sweep are guaranteed to produce high quality data for system identification. Beside that, we can set the safety parameters during the flight test （maximum roll/pitch value, minimum altitude, etc.） so the safety of the whole flight test is guaranteed. This autopilot system is validated using hardware in the loop simulator for hover flight condition.