Constrained dansyl derivatives reveal bacterial specificity of highly conserved thymidylate synthases

The elucidation of the structural/functional specificities of highly conserved enzymes remains a challenging area of investigation, and enzymes involved in cellular replication are important targets for functional studies and drug discovery. Thymidylate synthase (TS, ThyA) governs the synthesis of thymidylate for use in DNA synthesis. The present study focused on Lactobacillus casei TS (LcTS) and Escherichia coli TS (EcTS), which exhibit 50 % sequence identity and strong folding similarity. We have successfully designed and validated a chemical model in which linear, but not constrained, dansyl derivatives specifically complement the LcTS active site. Conversely, chemically constrained dansyl derivatives showed up to 1000-fold improved affinity for EcTS relative to the inhibitory activity of linear derivatives. This study demonstrates that the accurate design of small ligands can uncover functional features of highly conserved enzymes.     

Reconceptualizing social influence in counseling: The Elaboration Likelihood Model.

Previous investigations of attitude change in counseling based on S. R. Strong's (see PA, Vol 42:12025) social influence model have yielded mixed and inconclusive results. Such findings resemble the state of attitude change research that until recently existed in social psychology. In this article we introduce a model of attitude change from social psychology, the Elaboration Likelihood Model (ELM) of persuasion, which has served to unify some of the conflicting results in social psychology. The ELM may potentially account for the inconsistent findings within counseling psychology, providing a reconceptualization of the social influence process that builds upon Strong's (1968) theory and subsequent research. We also provide guidelines for the integration of recent social and counseling literatures in regard to the interpersonal influence process as represented by the ELM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Heterogeneous Structural Behavior of E7 from HPV16 Revealed by NMR Spectroscopy

The E7 protein from human papillomavirus (HPV) plays a key role in oncogenesis; for this reason, it is a target of great biomedical interest. To date, no high resolution information is available for the full protein. We present here the NMR characterization of the entire E7 from HPV16, one of the most oncogenic variants of the virus. The protein is very heterogeneous in terms of structural and dynamic properties with a highly flexible N‐terminal module and a more structured C terminus. This opens possibilities for studies of molecular‐level interactions and post‐translational modifications of the protein to unravel functional details that might be linked to its highly oncogenic potential.     

Daily green tea extract supplementation reduces prothrombotic and inflammatory states in dialysis patients

Cardiovascular disease (CVD) remains the most common cause for excess morbidity and mortality in patients with chronic kidney disease (CKD) and end stage renal disease (ESRD) under chronic dialysis. ESRD patients have increased oxidative stress and endothelial dysfunction alongside increased levels of inflammation related proteins, which has prompted the exploration of anti-inflammatory and antioxidant treatments to improve outcomes. As green tea is increasingly well recognized for its antioxidant properties, we probed the effect of consumption of 1 capsule daily of green tea as a commercially available, decaffeinated green tea capsule (1 g, catechin content 68 mg) for 6 months on fibrinogen and inflammation in dialysis patients. Chronic hemodialysis patients (N = 25) were recruited and fibrinogen, FDP-D-dimer, high sensitivity (hs) CRP and the mononuclear cell protein expression of p22^phox, were assessed before, i.e. baseline and after 6 months of ingestion of 1 green tea capsule per day. After 6 months of daily green tea capsule ingestion, dialysis patients showed reduced protein expression of p22^phox (p < 0.0001), reduced hsCPR (p = 0.032) and fibrinogen (p = 0.022) levels and increased FDP-D-dimer (p = 0.0019) compared to their values at baseline. These results document lower oxidative stress and inflammation with green tea capsule ingestion and suggest a likely positive impact of green tea treatment on the atherosclerotic process of ESRD patients under dialysis.     

Measurement of collateral circulation blood flow in anesthetized portal hypertensive rats

AIMS: The aim of this study was to develop a technique to measure collateral blood flow in portal hypertensive rats. METHODS: Morphological techniques included inspection, casts and angiographies of portosystemic shunts. The main hemodynamic measurements were splenorenal shunt blood flow (transit time ultrasound method), percentage of portosystemic shunts and regional blood flows (microsphere method). In study 1, a model of esophageal varices was developed by ligating the splenorenal shunt. In study 2, morphological studies of the splenorenal shunt were performed in rats with portal vein ligation. In study 3, the relationship between splenorenal shunt blood flow with percentage of portosystemic shunts was evaluated in dimethylnitrosamine cirrhosis. In study 4, secondary biliary, CCl4 and dimethylnitrosamine cirrhosis were compared. In study 5, rats with portal vein ligation received acute administration of octreotide. In study 6, rats with dimethylnitrosamine cirrhosis received acute administration of vapreotide. RESULTS: Blood flow of para-esophageal varices could not be measured. SRS blood flow was correlated with the mesenteric percentage of portosystemic shunts (r = 0.74, P < 0.05), splenic percentage of portosystemic shunts (r = 0.54, P < 0.05) and estimated portosystemic blood flow (r = 0.91, P < 0.01). Splenorenal shunt blood flow was 6 to 12 times higher in portal hypertensive rats, e.g., in portal vein ligated rats: 2.8 +/- 2.7 vs 0.3 +/- 0.1 mL.min-1 in sham rats (P < 0.01), and was similar in the different cirrhosis models but was higher in portal vein ligated rats than in cirrhotic rats (1.2 +/- 0.7 vs 0.6 +/- 0.6 mL.min-1.100 g-1, P = 0.05). Octreotide significantly decreased splenorenal shunt blood flow: -23 +/- 20% (P < 0.01) vs -6 +/- 8% (not significant) in placebo rats. The variation of splenorenal shunt blood flow after vapreotide was significant but not that of the splenic percentage of portosystemic shunts compared to placebo. CONCLUSIONS: The splenorenal shunt is the main portosystemic shunt in rats. The measurement of splenorenal shunt blood flow is easy, accurate and reproducible and should replace the traditional measurement of the percentage of portosystemic shunts in pharmacological studies.     

Doppler echocardiographic assessment of left ventricular diastolic function in myotonic dystrophy

To determine the increased production and release of vascular endothelial growth factor (VEGF) from the retina in the eye with non-angiogenic retinal detachment in which relative blood supply disturbance may be present, the concentration of VEGF in subretinal fluid and vitreous fluid collected from the eyes was investigated by enzyme linked immunospecific assay. The average concentration of VEGF was 0.5 +/- 1.1 ng/ml (mean +/- standard deviation) in nine samples of vitreous fluid collected from proliferative retinal detachment, and was 1.2 +/- 1.2 ng/ml in eleven samples of subretinal fluid from rhegmatogenous retinal detachment. The concentration of VEGF in six samples of vitreous fluid from angiogenic diabetic eyes (5.0 +/- 2.8 ng/ml) was significantly higher than in the samples from eyes with retinal detachment. The results suggest that the relative ischemic insult to the detached retina increases the release of VEGF into the vitreous cavity and subretinal space. The increased concentration of VEGF does not induce remarkable angiogenesis since the concentration is lower than the biological threshold, or the effect is modulated by inhibitors.     

Apoptosis and liver fibrosis: antifibrotic strategies

Hepatic fibrosis is a frequent response of the liver and is similar to parenchymal wound healing in other tissues. Apoptosis has been described in different models of liver fibrosis. Hepatic stellate cells are the main source of extracellular matrix. At present, one can speculate that inhibition of apoptosis is responsible for activation and proliferation of hepatic stellate cells. Thus, the inhibition of hepatic stellate cell apoptosis could be a target for antifibrotic strategies. Until now, no drugs have been clearly shown to be effective in reducing specifically the development of hepatic fibrosis. However, serious candidates are presently under studies in clinical trials, including especially alpha interferon and phosphatidylcholine.     

Characterization of the impact of network topology on the performance of single-radio wireless mesh networks

Stub Wireless Mesh Networks (WMNs) are used to extend Internet access. The use of multiple channels improves the capacity of WMN but significant challenges arise when nodes are limited to a single-radio interface to form the WMN. In particular, the assignment of mesh nodes to channels results on the creation of multiple sub-networks, one per channel, where individual capacity may depend on the sub-network topologies This paper identifies the relevant topological characteristics of the sub-networks resultant from the channel assignment process and studies, through simulation, the impact and relative importance of those characteristics on the maximal throughput enabled by the stub WMN. The number of nodes in the gateways neighborhood and the hidden node problem in the gateways neighborhood were identified as the characteristics having the highest impact on the WMN throughput.     

Diffuse vascular ectasia of the antrum, duodenum, and jejunum in a patient with nodular regenerative hyperplasia. Lack of response to portosystemic shunt or gastrectomy

The case is reported of a 70 year old man who presented with severe anaemia because of chronic gastrointestinal blood loss. This loss was ascribed to vascular ectasia resembling the gastric antral vascular ectasia syndrome but extended to include the antrum, the duodenum, the jejunum, and, possibly, the cardiac area. This condition was associated with portal hypertension as a result of nodular regenerative hyperplasia. Consecutive treatments including sucralfate, prostaglandin E2, propranolol, organic nitrates, pentoxyphilline, corticosteroids, endoscopic sclerotherapy, portosystemic shunt, total gastrectomy, proved ineffective.