Diapause strategy in the parasitoid Psyllaephagus pistaciae

The processes involved in the induction and termination of diapause in the parasitoid Psyllaephagus pistaciae Ferrière (Hymenoptera: Encyrtidae) were investigated under controlled laboratory conditions. Results indicated that the parasitoid P. pistaciae is able to overwinter successfully as a pupa within the mummified psyllid host Agonoscena pistaciae Burckhardt and Lauterer (Homoptera: Psylloidea), and the parasitoid clearly responded to a short photoperiod by entering diapause. The incidence of diapause increased significantly with decreasing temperature, indicating the existence of an interaction between low temperature and short‐day photoperiod that resulted in a 100% diapause. However, low temperature alone partly stimulated P. pistaciae to enter diapause. The incidence of diapause was likely to be independent from psyllid nymphal instar and the condition of its mother. This investigation showed that the termination of diapause in the overwintering parasitoid pupae and the duration of diapause completion or adult emergence is photoperiod independent, but dependent on temperature. However, chilling treatment was found to be unnecessary for diapause termination in P. pistaciae, although it decreased the duration of diapause maturation. The positive responses of parasitoids to environmental factors appears to act as a basic strategy to induce diapause in the parasitoid P. pistaciae against extreme climatic conditions.     

Biodynamic modeling and simulation of multistage cell mutations

The aim of this study is to present a mathematical computer simulation model for multistage carcinogenesis. The population genetic model is developed based on the reaction diffusion, logistic behavior, and Hollings Type II interactions between normal, benign, and premalignant cells. The simple form of the Fisher-Haldane-Wright equation of the genetic model of tumor suppressor gene and oncogenes is used to describe this type of interaction. Through computer simulation, we observe the behavior, stability, and traveling wave solution of the premalignant stage mutation as well as its survival under natural selection pressure. As a simple case of this model, the interaction between normal and tumor cells with one or two stages of mutations is analyzed.     

Lipid rafts mediate association of LFA-1 and CD3 and formation of the immunological synapse of CTL

Lipid rafts accumulate in the immunological synapse formed by an organized assembly of the TCR/CD3, LFA-1, and signaling molecules. However, the precise role of lipid rafts in the formation of the immunological synapse is unclear. In this study, we show that LFA-1 on CTL is constitutively active and mediates Ag-independent binding of CTL to target cells expressing its ligands. LFA-1 and CD3 on CTL, but not resting T cells, colocalize in lipid rafts. Binding of LFA-1 on CTL to targets initiates the formation of the immunological synapse, which is formed by LFA-1, CD3, and ganglioside GM1 distributed in the periphery of the cell contact site and cholesterol is more widely distributed. The formation of this synapse is Ag independent, but the recognition of Ag by the TCR induces accumulation of tyrosine phosphorylated proteins in the synapse as well as redistribution of the microtubule organization center toward the cell contact site. Our results suggest that LFA-1 recruits lipid rafts and the TCR/CD3 to the synapse, and facilitates efficient and rapid activation of CTL.     

Cerebral cortical representation of external anal sphincter contraction: effect of effort

The external anal sphincter (EAS) plays a critical role in maintaining fecal continence; however, cerebral cortical control of voluntary EAS contraction is not completely understood. Our aims were to determine the cortical areas associated with voluntary EAS contraction and to determine the effect of two levels of sphincter contraction effort on brain activity. Seventeen asymptomatic adults (ages 21-48, 9 male) were studied using functional magnetic resonance imaging (fMRI) to detect brain activity. Studies were done in two stages. In stage 1 (10 subjects, 5 male), anal sphincter pressure was monitored from a catheter-affixed bag. Subjects performed maximal and submaximal EAS contractions during two fMRI scanning sessions consisting of alternating 10-s intervals of sustained contraction and rest. In stage 2 studies, seven subjects (4 male) performed only maximum effort sphincter contractions without a catheter. EAS contraction was associated with multifocal fMRI activity in sensory/motor, anterior cingulate, prefrontal, parietal, occipital, and insular regions. Total cortical activity volume was significantly larger (P < 0.05) for maximal (5,175 +/- 720 microl) compared with submaximal effort contractions (2,558 +/- 306 microl). Similarly, percent fMRI signal change was significantly higher (P < 0.05) for maximal (4.8 +/- 0.1%) compared with submaximal effort contractions (2.2 +/- 0.1%). Cortical region-of-interest analysis showed the incidence of insular activation to be more common in women compared with men. Other cortical regions showed no such gender differences. fMRI activity detected in stage 2 showed similar regions of cortical activation to those of the stage 1 study. Willful contraction of the EAS is associated with multifocal cerebral cortical activity. The volume and intensity of cerebral cortical activation is commensurate with the level of contractile effort.     

Characterization of the cerebral cortical representation of heartburn in GERD patients

Although symptoms arising from the esophagus such as heartburn and pain can at times become challenging clinical problems, esophageal viscerosensation, especially with regard to chemical stimulation in humans, is incompletely understood. Our aims were 1) to characterize and ascertain the reproducibility of cerebral cortical registration of heartburn and 2) to elucidate the differences between these findings and those of esophageal subliminal acid stimulation in asymptomatic controls. We studied 11 gastroesophageal reflux disease (GERD) patients (9 males, 30-55 yr) and 15 healthy controls (8 males, 21-49 yr). Cerebral cortical functional magnetic resonance imaging (fMRI) activity was recorded twice in each subject, during two 5-min intervals of 0.1 N HCl, separated by 5 min of NaCl perfusion. Time from onset of acid perfusion to instant of fMRI signal increase and first report of heartburn averaged 1.60 +/- 0.80 and 1.85 +/- 0.60 min, respectively. Average maximum percent signal increase in the GERD patients (16.3 +/- 3.5%) was significantly greater than that of healthy controls (3.8 +/- 0.9%; P < 0.01). Temporal fMRI signal characteristics during heartburn were significantly different from those of subliminal acid stimulation in controls (P < 0.01). Activated cortical regions included sensory/motor, parieto-occipital, cingulate and prefrontal regions, and the insula. There was 92% concordance between the activated Brodmann areas in repeated studies of GERD patients. Cortical activity associated with perceived and unperceived esophageal acid exposure in GERD patients and healthy controls, respectively, involves multiple brain regions but occurs more rapidly and with greater intensity in GERD patients than the activity in response to subliminal acid exposure in healthy controls. The cortical pain-processing pathway seems to be involved in perception of esophageal acid exposure and could explain the variations encountered in clinical practice defining this sensation.     

Chemical constituents of Euphorbia marschalliana Boiss

Acetone extract of aerial parts of Euphorbia marschalliana collected from Iran has been subjected to different chromatography techniques for fractionation and purification. The stereo-structures of the myrsinol esters 15-O-acetyl-3-O-propionyl-5-O-butanoyl-7-O-nicotinoylmyrsinol (1) and 15-O-acetyl-3,5-O-dibutanoyl-7-O-nicotinoylmyrsinol (2) have been probed using ROESY spectroscopy and modified for the stereochemistry at C-6, C-12 and C-13. Beta-sitosterol (3), 29-norcycloart-5-ene (4), 5,8-lanostadiene-3beta-ol (5), 3beta,24(S),25-trihydroxycycloartane (6), 3beta,24(R),25-trihydroxycycloartane (7) and 24-methylenecycloartan-3beta-ol (8) were identified for the first time in this plant.     

Inhibitory Effect of Aspergillus fumigatus Extract on matrix metalloproteinases Expression

BACKGROUND: Matrix metalloproteinases (MMPs) play a role in several physiologic and pathologic events. There are some evidence indicating the involvement of MMPs in the pathophysiology of fungal infections. METHODS: Here we study somatic extract of Aspergillus fumigatus. The influence of Aspergillus vs. two other fungal extracts on MMPs production by Fibrosarcoma cell line was investigated using an in vitro cytotoxicity assay, sodium dodecyl sulfate-polyacrylamide and gelatin zymography. RESULTS: Comparative dose-dependent inhibitory effects on MMPs were seen by A. fumigatus extract and compared with some steroidal and non-steroidal drugs. Cytotoxicity analysis of our extract revealed much lower cell death than other examined agents. CONCLUSIONS: Since inhibition of MMPs activity has been employed in modality therapy in such diseases as cancer, this extract might be promising in the preparation of anti-MMP therapeutic derivatives.     

Relevance of the direct pathway of sensitization in corneal transplantation is dictated by the graft bed microenvironment

Corneal grafts were until recently considered entirely devoid of resident APCs, giving rise to the tenet that alloantigen recognition is mediated exclusively by the indirect (host APC-dependent) pathway. The recent discovery of a resident myeloid corneal dendritic cell population that is normally MHC class II(-) but can readily up-regulate class II expression during inflammation led us to hypothesize that under certain conditions the direct pathway of allosensitization becomes operative. To test this, corneal allotransplants were performed in either inflamed (high-risk (HR)) or uninflamed (low-risk (LR)) host beds in mice, and the frequencies of host T cells activated via the direct pathway were determined. We found that directly primed CD4(+) T cells were detected in the HR but not LR setting, and these cells displayed a clear Th1 phenotype by 2 wk after grafting. Moreover, the use of MHC class II knockout donor tissue led to significantly enhanced survival of HR but not LR allografts. Finally, we show that donor corneal APC demonstrate high expression of CD40, CD80, and CD86 costimulatory molecules when derived from HR but not LR grafts. These data are the first to report that a functional donor APC-dependent direct response is elicited in corneal transplant hosts when the graft bed is inflamed and underscore the relevance of the graft microenvironment in dictating the pathway of allosensitization.     

Genetic control of HDL levels and composition in an interspecific mouse cross (CAST/Ei x C57BL/6J)

Strain CAST/Ei (CAST) mice exhibit unusually low levels of high density lipoproteins (HDL) as compared with most other strains of mice, including C57BL/6J (B6). This appears to be due in part to a functional deficiency of lecithin:cholesterol acyltransferase (LCAT). LCAT mRNA expression in CAST mice is normal, but the mice exhibit several characteristics consistent with functional deficiency. First, the activity and mass of LCAT in plasma and in HDL of CAST mice were reduced significantly. Second, the HDL of CAST mice were relatively poor in phospholipids and cholesteryl esters, but rich in free cholesterol and apolipoprotein A-I (apoA-I). Third, the adrenals of CAST mice were depleted of cholesteryl esters, a phenotype similar to that observed in LCAT- and acyl-CoA:cholesterol acyltransferase-deficient mice. Fourth, in common with LCAT-deficient mice, CAST mice contained triglyceride-rich lipoproteins with "panhandle"-like protrusions. To examine the genetic bases of these differences, we studied HDL lipid levels in an intercross between strain CAST and the common laboratory strain B6 on a low fat, chow diet as well as a high fat, atherogenic diet. HDL levels exhibited complex inheritance, as 12 quantitative trait loci with significant or suggestive likelihood of observed data scores were identified. Several of the loci occurred over plausible candidate genes and these were investigated.The results indicate that the functional LCAT deficiency is unlikely to be due to variations of the LCAT gene. Our results suggest that novel genes are likely to be important in the control of HDL metabolism, and they provide evidence of genetic factors influencing the interaction of LCAT with HDL.