Small Molecule,Non-Peptide p75NTR Ligands Inhibit Aβ-Induced Neurodegeneration and Synaptic Impairment

The p75 neurotrophin receptor (p75^NTR) is expressed by neurons particularly vulnerable in Alzheimer''s disease (AD). We tested the hypothesis that non-peptide, small molecule p75^NTR ligands found to promote survival signaling might prevent Aβ-induced degeneration and synaptic dysfunction. These ligands inhibited Aβ-induced neuritic dystrophy, death of cultured neurons and Aβ-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Aβ-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3β and c-Jun, and tau phosphorylation, and prevented Aβ-induced inactivation of AKT and CREB. Finally, a p75^NTR ligand blocked Aβ-induced hippocampal LTP impairment. These studies support an extensive intersection between p75^NTR signaling and Aβ pathogenic mechanisms, and introduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling pathways, reverse synaptic impairment and inhibit Aβ-induced neuronal dystrophy and death.     

SAR and efficiency evaluation of a 900 MHz waveguide chamber for cell exposure

In this work we present the results of numerical and experimental dosimetry carried out for an in vitro exposure device to irradiate sample groups at 900 MHz. The cells are kept in 8 and 15 ml cell cultures, contained, respectively in T25 and T75 rectangular flasks. The dosimetric assessment of the distribution of the specific absorption rate (SAR) is performed for both the bottom of the flask and the whole volume of the sample to provide results for experiments on either the cell layer or the cell suspension. The irradiating chamber is a rectangular waveguide (WG). Different configurations are considered to assess the optimum orientation and positioning of the cell cultures inside the WG. The system performance is optimal when the electric field is parallel to the sample and the WG is terminated by a matched load. In this condition two 15 or four 8 ml cells cultures can be exposed. The efficiency (ratio between the power absorbed by the sample and the incident power) and the non-uniformity degree (ratio between the standard deviation of SAR values and the average SAR over the sample) are calculated and successfully verified through measurements of the scattering parameters and local temperature increases. In the chosen exposure configuration, the efficiency is 0.40 and the non-uniformity degree is 39% for the 15 ml samples. For the 8 ml samples, the efficiency is 0.19 and a low non-uniformity degree (15%) is found.     

Plasma adrenomedullin concentrations in patients with adrenal pheochromocytoma.

BACKGROUND: The hypotensive peptide adrenomedullin was first isolated in extracts of human pheochromocytoma. There is, however, no information available on the behaviour of circulating adrenomedullin or on the correlation with catecholamines in patients with pheochromocytoma. OBJECTIVES: 1) to investigate whether plasma adrenomedullin levels were changed in 10 patients with pheochromocytoma when compared to 21 healthy subjects and 16 patients with essential hypertension; 2) to determine whether or not adrenomedullin has a counter-regulatory role in catecholamine excess in pheochromocytoma or is responsible for hemodynamic modifications before and after tumour resection; 3) to determine tissue distribution of iradrenomedullin in the pheochromocytoma. METHODS: Plasma adrenomedullin and catecholamine levels were measured in all patients with pheochromocytoma before and four weeks after tumour removal. In the four patients undergoing resection of tumours, plasma levels of adrenomedullin were measured at different time-points during surgery. RESULTS: The mean plasma adrenomedullin concentrations ( SD) in patients with pheochromocytoma (37.9 +/- 6pg/ml) were significantly higher (p<0.0001) than those in normal subjects (13.7 +/- 6.1 pg/mI) and patients with essential hypertension (22.5 +/- 9.lpg/ml). Adrenomedullin levels correlated with plasma noradrenaline (r = 0.516, p = 0.0124). In all patients with pheochromocytoma, plasma adrenomedullin concentrations decreased after removal of tumours (from 37.9 +/- 6 to 10.9 +/- 4.6 pg/ml; p < 0.0001). In the four patients studied during surgery, baseline plasma adrenomedullin and noradrenaline levels were markedly elevated, and increased significantly with tumour manipulation, decreasing 24 hours after operation. Adrenal medulla cells surrounding the pheochromocytoma site stained for ir-adrenomedullin, whereas only isolated cells of pheochromocytoma stained for the peptide. CONCLUSIONS: This study demonstrates that circulating adrenomedullin is increased in pheochromocytoma, and is also correlated with plasma noradrenaline levels. Adrenomedullin may represent an additional biochemical parameter for clinical monitoring of patients with pheochromocytoma.     

Lack of consistency between the trophic interrelationships of five sparid species in two adjacent central Mediterranean coastal lagoons

Both interspecific and intraspecific inter-lagoon differences, between the central Mediterranean coastal lakes of Fogliano and Caprolace, in the trophic patterns of the examined species Diplodus annularis, Diplodus puntazza, Diplodus sargus, Lithognathus mormyrus and Sparus aurata were revealed by means of correspondence analysis. The most evident inter-lagoon qualitative and quantitative diet changes were observed in S. aurata . Feeding similarities among species were synthesized for each lake by means of multidimensional scaling. Trophic interrelationships among sparid fish were different in the two lagoons, as a direct consequence of diet variations in each species. Such differences are interpreted as possibly reflecting differences in the overall structure of the benthic communities. Different feeding models could be identified, each corresponding to a peculiar adaptive strategy for the consumption of lagoon benthic resources. The use of benthophagous fish feeding habits as a tool for the monitoring of the structure and the dynamics of coastal lagoon communities is discussed.     

Preliminary characterization of wine lactobacilli able to degrade arginine

Lactobacillus strains able to degrade arginine were isolated and characterized from a typical red wine. All the strains were gram-positive, catalase-negative and produced both D- and L-lactate from glucose. Strains L2, L3, L4, and L6 were able to produce CO₂ from glucose; however, production of CO₂ from glucose was not observed in strains L1 and L5, suggesting that they belong to the homofermentative wine lactic acid bacteria (LAB) group. All of the lactobacilli were tested for their ability to ferment 49 carbohydrates. The sugar fermentation profile of strain L1 was unique, suggesting that this strain belonged to Lactococcus lactis ssp. cremoris, a non-typical wine LAB. Furthermore, a preliminary typing was performed by using a random amplified polymorphic DNA analysis (RAPD-PCR analysis).     

Growth inhibition by glucose oxidase system of enterotoxic Escherichia coli and Salmonella derby: in vitro studies

The antibacterial effect of different glucose oxidase (GOX)/glucose combinations was studied on two food-poisoning organisms, enterotoxic Escherichia coli PM 015 and Salmonella derby BP 177. Growth of E. coli in nutrient broth (NB) was clearly inhibited by 4.0 mg/ml glucose after 24 h when combined with 2.0 U/ml GOX and after 48 h when combined with 0.5 or 1.0 U/ml GOX. Salmonella derby was more resistant than E. coli, but showed clear growth inhibition only after 48 h when inoculated in tubes where 2 mg glucose/ml and 2 U GOX/ml (or 4 mg glucose/ml and 1 U GOX/ml) were combined. In order to understand if the enzyme effect on microbial growth can be attributed to hydrogen peroxide or to pH decrease as a result of the production of gluconic acid, catalase (CAT) was added to GOX/glucose system. Since CAT decomposes H₂O₂ to H₂O and O₂, the antibacterial effect was ascribed to a pH decrease as a result of gluconic acid in the system.     

A Wandering Mind Does Not Stray Far from Home: The Value of Metacognition in Distant Search

When faced with a problem, how do individuals search for potential solutions? In this article, we explore the cognitive processes that lead to local search (i.e., identifying options closest to existing solutions) and distant search (i.e., identifying options of a qualitatively different nature than existing solutions). We suggest that mind wandering is likely to lead to local search because it operates by spreading activation from initial ideas to closely associated ideas. This reduces the likelihood of accessing a qualitatively different solution. However, instead of getting lost in thought, individuals can also step back and monitor their thoughts from a detached perspective. Such mindful metacognition, we suggest, is likely to lead to distant search because it redistributes activation away from initial ideas to other, less strongly associated, ideas. This hypothesis was confirmed across two studies. Thus, getting lost in thoughts is helpful when one is on the right track and needs only a local search whereas stepping back from thoughts is helpful when one needs distant search to produce a change in perspective.     

Graphical modeling for gene set analysis: A critical appraisal

Current demand for understanding the behavior of groups of related genes, combined with the greater availability of data, has led to an increased focus on statistical methods in gene set analysis. In this paper, we aim to perform a critical appraisal of the methodology based on graphical models developed in Massa et al. ( 2010 ) that uses pathway signaling networks as a starting point to develop statistically sound procedures for gene set analysis. We pay attention to the potential of the methodology with respect to the organizational aspects of dealing with such complex but highly informative starting structures, that is pathways. We focus on three themes: the translation of a biological pathway into a graph suitable for modeling, the role of shrinkage when more genes than samples are obtained, the evaluation of respondence of the statistical models to the biological expectations. To study the impact of shrinkage, two simulation studies will be run. To evaluate the biological expectation we will use data from a network with known behavior that offer the possibility of carrying out a realistic check of respondence of the model to changes in the experimental conditions.