Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells

The intestinal epithelium serves as a barrier to the intestinal flora. In response to pathogens, intestinal epithelial cells (IEC) secrete proinflammatory cytokines. To aid in defense against bacteria, IEC also secrete antimicrobial peptides, termed defensins. The aim of our studies was to understand the role of TLR signaling in regulation of beta-defensin expression by IEC. The effect of LPS and peptidoglycan on beta-defensin-2 expression was examined in IEC lines constitutively or transgenically expressing TLRs. Regulation of beta-defensin-2 was assessed using promoter-reporter constructs of the human beta-defensin-2 gene. LPS and peptidoglycan stimulated beta-defensin-2 promoter activation in a TLR4- and TLR2-dependent manner, respectively. A mutation in the NF-kappaB or AP-1 site within the beta-defensin-2 promoter abrogated this response. In addition, inhibition of Jun kinase prevents up-regulation of beta-defensin-2 protein expression in response to LPS. IEC respond to pathogen-associated molecular patterns with expression of the antimicrobial peptide beta-defensin-2. This mechanism may protect the intestinal epithelium from pathogen invasion and from potential invaders among the commensal flora.     

Regional assignment of human liver-type 6-phosphofructokinase to chromosome 21q22.3 by using somatic cell hybrids and a monoclonal anti-L antibody

Summary The three structural loci encoding human phosphofructokinase, a key regulatory enzyme of glycolysis, are located on separate chromosomes. The gene coding for the liver-type subunit PFKL has previously been assigned to chromosome 21. We have used a subunit- and human-specific monoclonal antibody to liver PFK to detect the expression of human PFKL in hamster x human hybrid cell lines. A cell line carrying an 8;21 translocation which contains all of chromosome 21 except the band 21q22.3 was negative for the expression of PFKL whereas cell lines carrying the reciprocal 8;21 translocation were positive. In addition, a cell line with a ring chromosome 21 containing a breakpoint which excluded the distal part of the q22.3 band was negative for expression of PFKL. These results indicate that human PFKL is located on chromosome 21q22.3.     

Metabolic studies with neurospora: Action of 5-bromo- and 5-nitrouracils

Summary There is no growth inhibition of Neurospora crassa even in presence of high levels of 5-bromouracil. Although there is no significant change in the DNA and RNA contents, the analogue is utilized by the organism, a part of it being incorporated in DNA. There is an increase in total folate and citrovorum factor activities with 5-bromouracil.5-Nitrouracil causes a significant growth inhibition at higher concentration which is accompanied by a decrease in pteroylglutamic acid and citrovorum factor levels in the organism.Pteroylglutamic acid and thymidine cause a partial reversal of growth inhibition by 5-nitrouracil and complete reversal when the two metabolites are added simultaneously.     

Experimental Sociality and Gestational Surrogacy in the Indian ART Clinic

Abstract

This article marks experimental modes of sociality in a transnational Indian assisted reproductive technology (ART) clinic as a contact zone between elite doctors, gestational surrogates, and transnational commissioning parents. It examines efforts within one ART clinic to separate social relationships from reproductive bodies in its surrogacy arrangements as well as novel social formations occurring both because of and despite these efforts. Draft regulative legislation in India marks a shift in the distribution of risk among actors in the clinic that parallels a shift in medical practice away from a technique of caring for the body to producing bodies as instruments of contracted service. The clinic provides an opportunity to observe forms of sociality that emerge as experiments with modernities, with different relationships to the body and the social meaning of medicalized biological reproduction, and with understanding the role of the market and altruism in the practice of gestational surrogacy.     

CeleST: Computer Vision Software for Quantitative Analysis of C. elegans Swim Behavior Reveals Novel Features of Locomotion

In the effort to define genes and specific neuronal circuits that control behavior and plasticity, the capacity for high-precision automated analysis of behavior is essential. We report on comprehensive computer vision software for analysis of swimming locomotion of C. elegans, a simple animal model initially developed to facilitate elaboration of genetic influences on behavior. C. elegans swim test software CeleST tracks swimming of multiple animals, measures 10 novel parameters of swim behavior that can fully report dynamic changes in posture and speed, and generates data in several analysis formats, complete with statistics. Our measures of swim locomotion utilize a deformable model approach and a novel mathematical analysis of curvature maps that enable even irregular patterns and dynamic changes to be scored without need for thresholding or dropping outlier swimmers from study. Operation of CeleST is mostly automated and only requires minimal investigator interventions, such as the selection of videotaped swim trials and choice of data output format. Data can be analyzed from the level of the single animal to populations of thousands. We document how the CeleST program reveals unexpected preferences for specific swim “gaits” in wild-type C. elegans, uncovers previously unknown mutant phenotypes, efficiently tracks changes in aging populations, and distinguishes “graceful” from poor aging. The sensitivity, dynamic range, and comprehensive nature of CeleST measures elevate swim locomotion analysis to a new level of ease, economy, and detail that enables behavioral plasticity resulting from genetic, cellular, or experience manipulation to be analyzed in ways not previously possible.

This is a PLOS Computational Biology Software Article

     

p53 expression in leukoplakia and carcinoma of the tongue

There is growing interest in assessing multistep carcinogenesis and predicting its course using different molecular markers. TP53 is a tumor suppressor gene and appears to be one of the molecular targets of tobacco-related carcinogens in oral cancer. The present study evaluated the role of p53 expression in patients with leukoplakia and carcinoma of the tongue. p53 expression was studied by immunohistochemistry. All patients with leukoplakia of the tongue were male tobacco users. Nuclear staining of p53 was observed in 79% of those patients. Fifty percent, 25% and 4% of the patients expressed 1+, 2+ and 3+ nuclear staining, respectively. When leukoplakia patients were graded according to histopathology, 67% had hyperplasia and 33% had dysplasia. Nuclear p53 accumulation was 88% in hyperplasia and 62% in dysplasia. In patients with tongue cancer, nuclear accumulation of p53 was seen in only 19% of the tumors, with a staining intensity of 1+ in 13%, 2+ in 2% and 3+ in 4% of the tumors. The prevalence of nuclear p53 positivity (79%) was significantly higher in patients with leukoplakia than in patients with tongue cancer (19%; chi2 = 34.32, r = -0.45, df = 1, p = 0.0001; odds ratio (OR) = 16.66, 95% CI, 5.25-52.86). Therefore, leukoplakia patients who show p53 expression have a higher risk of developing tongue cancer than those who do not show p53 expression. As the percentage of positivity of nuclear p53 was very low, none of the clinicopathological parameters or disease status showed any significant association with it. The interesting finding is that none of the female cancer patients showed nuclear p53 expression. Therefore, p53 accumulation is believed to be an early event in neoplastic progression of the tongue.     

p38 MAP kinase inhibitors. Part 5: discovery of an orally bio-available and highly efficacious compound based on the 7-amino-naphthyridone scaffold

A new sub-class of p38 inhibitors represented by 7-amino-naphthyridone have been discovered. Benchmark compound 16 potently inhibited p38 in vitro, was functionally active, and displayed excellent pharmacokinetic profiles in two animal species. Compound 16 reduced inflammation in animal disease models at EC(50) doses as low as 0.2mpk.