Time course of airway remodelling after an acute chlorine gas exposure in mice

Accidental chlorine (Cl₂) gas inhalation is a common cause of acute airway injury. However, little is known about the kinetics of airway injury and repair after Cl₂ exposure. We investigated the time course of airway epithelial damage and repair in mice after a single exposure to a high concentration of Cl₂ gas. Mice were exposed to 800 ppm Cl₂ gas for 5 minutes and studied from 12 hrs to 10 days post-exposure. The acute injury phase after Cl₂ exposure (≤ 24 hrs post-exposure) was characterized by airway epithelial cell apoptosis (increased TUNEL staining) and sloughing, elevated protein in bronchoalveolar lavage fluid, and a modest increase in airway responses to methacholine. The repair phase after Cl₂ exposure was characterized by increased airway epithelial cell proliferation, measured by immunoreactive proliferating cell nuclear antigen (PCNA), with maximal proliferation occurring 5 days after Cl₂ exposure. At 10 days after Cl₂ exposure the airway smooth muscle mass was increased relative to controls, suggestive of airway smooth muscle hyperplasia and there was evidence of airway fibrosis. No increase in goblet cells occurred at any time point. We conclude that a single exposure of mice to Cl₂ gas causes acute changes in lung function, including pulmonary responsiveness to methacholine challenge, associated with airway damage, followed by subsequent repair and airway remodelling.     

Biosynthesis of flaviolin and 5,8-dihydroxy-2,7-dimethoxy-1,4-naphthoquinone.

Tracer experiments indicate a polyketide origin for the production of flaviolin (2,5,7-trihydroxy-1,4-naphthoquinone) by Aspergillus niger and 2,7-dimethoxynaphthazarin (5,8-dihydroxy-2,7-dimethoxy-1,4-naphthoquinone) by Streptomyces no. 12396. With the Streptomycete, a "solid state fermentation" technology was used for the incorporation studies. Radioactivity from shikimic acid was effectively incorporated into flaviolin; this conversion, however, proceeded by way of acetic acid. The latter stages of biosynthesis of 2,7-dimethoxynaphthazarin by the Streptomycete were shown to be as follows: flaviolin leads to mompain leads to 2,7-dimethoxynaphthazarin.     

Biochemical studies on the H-2K mutant B6.C-H-2 bm10

The H-2K glycoprotein from the MHC mutant bm10 was analyzed biochemically to determine where primary structural differences distinguished it from the parental standard molecule, K^b. Comparative peptide maps showed differences in two peptides known to be part of the parental CNBr fragment spanning amino acids 139 to 228. Partial sequence analyses of CNBr fragments and tryptic peptides identified two tightly clustered amino acid substitutions at amino acids 165 (Val to Met) and 173 (Lys to unknown). The substitutions in bm10 represent the most carboxy-terminal substitutions characterized in the K^b molecules of the spontaneous, histogenically active H-2 mutants.     

Membrane insertion of the Escherichia coli MalF protein in cells with impaired secretion machinery

The MalF protein is an integral membrane protein of Escherichia coli containing eight membrane-spanning stretches and a large periplasmic domain of approximately 180 amino acids. We have asked whether this protein is dependent for its membrane insertion on the bacterial secretion machinery specified by the sec genes. Using azide to inhibit the SecA protein and sec mutants to reduce the functioning of the machinery, we have studied the membrane assembly of MalF and beta-galactosidase and alkaline phosphatase fusions to MalF. In no case did we see an effect of reducing sec gene function on the insertion of MalF or fusion proteins. Selection for mutants that would cause internalization of a MalF-beta-galactosidase hybrid protein yielded no mutations in sec genes. Our results suggest that MalF can assemble in the membrane independently of the bacterial secretion machinery.     

Disequilibrium,Adaptation, and the Norse Settlement of Greenland

There is increasing evidence to suggest that arctic cultures and ecosystems have followed non-linear responses to climate change. Norse Scandinavian farmers introduced agriculture to sub-arctic Greenland in the late tenth century, creating synanthropic landscapes and utilising seasonally abundant marine and terrestrial resources. Using a niche-construction framework and data from recent survey work, studies of diet, and regional-scale climate proxies we examine the potential mismatch between this imported agricultural niche and the constraints of the environment from the tenth to the fifteenth centuries. We argue that landscape modification conformed the Norse to a Scandinavian style of agriculture throughout settlement, structuring and limiting the efficacy of seasonal hunting strategies. Recent climate data provide evidence of sustained cooling from the mid thirteenth century and climate variation from the early fifteenth century. Archaeological evidence suggests that the Norse made incremental adjustments to the changing sub-arctic environment, but were limited by cultural adaptations made in past environments.     

Dietary and Physical Activity Correlates of Long-Term Weight Loss

Covariations in body mass index (BMI), physical activity, macronutrient intake, and the frequency of consumption of specific foods were examined among 82 men and 75 women participating in a behavioral weight loss program over a period of 18 months. Results of repeated measures analyses of covariance showed that BMI change was inversely related to change in physical activity and change in frequency of vegetable consumption. BMI change was positively related to change in calorie intake from fat and change in frequency of consumption of beef, hot dogs, and sweets. Change in fat calories predicted BMI change better than change in total calories. In addition, change in the frequency of consumption of specific foods accounted for a larger percentage of the variance in BMI change than did change in macronutrients (10.4% vs. 5.2%). No differences were found between predictors of weight loss vs. weight maintenance.     

Effects of storage and the presence of a beef microflora on the thermal resistance of Salmonella Typhimurium DT104 in beef and broth systems

AIMS: To investigate the effects of storage and the presence of a beef microflora on the thermal resistance of Salmonella serotype Typhimurium DT104 on beef surfaces and in a broth system during subsequent heat treatments after extended low-temperature storage (4 degrees C for 14 days) or mild temperature abuse (10 degrees C for 7 days). METHODS AND RESULTS: Surviving Salm. Typhimurium DT104 cells were estimated after heating in a water bath (55 degrees C) by plating beef and broth samples on tryptone soya agar and overlaying with xylose-lysine-deoxycholate agar. In beef and broth systems, D(55) values for Salm. Typhimurium DT104 stored at 4 degrees C or 10 degrees C in the presence or absence of a beef microflora were significantly lower (P < 0.01) than the D values for this organism heat-treated immediately after inoculation. In beef systems, the D(55) values were significantly lower (P < 0.05) in the presence of a beef microflora than the D(55) values obtained in 'pure' culture under all temperature/storage combinations. However, in broth systems, there was no significant difference between the D(55) values obtained in 'pure' culture and the D(55) values obtained from systems containing beef microflora. CONCLUSIONS: Storage of Salm. Typhimurium DT104 significantly reduced the thermal resistance of the pathogen in beef and broth systems. In the presence of high numbers of a Gram-negative beef microflora, the heat sensitivity of the pathogen was further increased on beef surfaces but not in broth. SIGNIFICANCE AND IMPACT OF THE STUDY: Studies investigating the survival of Salm. Typhimurium DT104 in different food systems will help define safe food preservation processes and will aid in the elimination this pathogen from the food production environments.     

Downregulation of the CCK-B receptor in pancreatic cancer cells blocks proliferation and promotes apoptosis

Gastrin stimulates the growth of pancreatic cancer cells through the activation of the cholecystokinin-B receptor (CCK-BR), which has been found to be overexpressed in pancreatic cancer. In this study, we proposed that the CCK-BR drives growth of pancreatic cancer; hence, interruption of CCK-BR activity could potentially be an ideal target for cancer therapeutics. The effect of CCK-BR downregulation in the human pancreatic adenocarcinoma cells was examined by utilizing specific CCK-BR-targeted RNA interference reagents. The CCK-BR receptor expression was both transiently and stably downregulated by transfection with selective CCK-BR small-interfering RNA or short-hairpin RNA, respectively, and the effects on cell growth and apoptosis were assessed. CCK-BR downregulation resulted in reduced cancer cell proliferation, decreased DNA synthesis, and cell cycle arrest as demonstrated by an inhibition of G(1) to S phase progression. Furthermore, CCK-BR downregulation increased caspase-3 activity, TUNEL-positive cells, and decreased X-linked inhibitor of apoptosis protein expression, suggesting apoptotic activity. Pancreatic cancer cell mobility was decreased when the CCK-BR was downregulated, as assessed by a migration assay. These results show the importance of the CCK-BR in regulation of growth and apoptosis in pancreatic cancer. Strategies to decrease the CCK-BR expression and activity may be beneficial for the development of new methods to improve the treatment for patients with pancreatic cancer.