Effect of Metformin on T2D-Induced MAM Ca2+ Uncoupling and Contractile Dysfunction in an Early Mouse Model of Diabetic HFpEF

Diabetic cardiomyopathy (DCM) is a leading complication in type 2 diabetes patients. Recently, we have shown that the reticulum-mitochondria Ca²⁺ uncoupling is an early and reversible trigger of the cardiac dysfunction in a diet-induced mouse model of DCM. Metformin is a first-line antidiabetic drug with recognized cardioprotective effect in myocardial infarction. Whether metformin could prevent the progression of DCM remains not well understood. We therefore investigated the effect of a chronic 6-week metformin treatment on the reticulum-mitochondria Ca²⁺ coupling and the cardiac function in our high-fat high-sucrose diet (HFHSD) mouse model of DCM. Although metformin rescued the glycemic regulation in the HFHSD mice, it did not preserve the reticulum-mitochondria Ca²⁺ coupling either structurally or functionally. Metformin also did not prevent the progression towards cardiac dysfunction, i.e., cardiac hypertrophy and strain dysfunction. In summary, despite its cardioprotective role, metformin is not sufficient to delay the progression to early DCM.     

Proteolytic Cleavage of Bioactive Peptides and Protease-Activated Receptors in Acute and Post-Colitis

The protease activity in inflammatory bowel disease (IBD) and irritable bowel syndrome has been studied extensively using synthetic fluorogenic substrates targeting specific sets of proteases. We explored activities in colonic tissue from a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model by investigating the cleavage of bioactive peptides. Pure trypsin- and elastase-like proteases on the one hand and colonic tissue from rats with TNBS-induced colitis in the acute or post-inflammatory phase on the other, were incubated with relevant peptides to identify their cleavage pattern by mass spectrometry. An increased cleavage of several peptides was observed in the colon from acute colitis rats. The tethered ligand (TL) sequences of peptides mimicking the N-terminus of protease-activated receptors (PAR) 1 and 4 were significantly unmasked by acute colitis samples and these cleavages were positively correlated with thrombin activity. Increased cleavage of β-endorphin and disarming of the TL-sequence of the PAR3-based peptide were observed in acute colitis and linked to chymotrypsin-like activity. Increased processing of the enkephalins points to the involvement of proteases with specificities different from trypsin- or chymotrypsin-like enzymes. In conclusion, our results suggest thrombin, chymotrypsin-like proteases and a set of proteases with different specificities as potential therapeutic targets in IBD.     

Sulfonated polybutadiene ionomer‐templated nanocopper composites

New composites based on nanosize particles provide a promising route to the fabrication of novel materials for advanced technology applications in the 21st century. To prepare desired materials, it is important to control the composition and distribution of nanoclusters within the bulk or surface coating of nanostructured materials. To achieve this aim, we developed a novel method of preparing nanocopper–ionomer thermoplastic composite material with sulfonated cis‐1,4‐polybutadiene random ionomer as a matrix and a capping polymer in organic solvent. The effect of sonication on stabilized nanocopper colloid was studied. The self‐assembled composite film was characterized by ultraviolet–visible spectroscopy, transmission electron microscopy, ¹H‐NMR, and thermogravimetric analysis. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 3180–3184, 2002     

Effect of Drying Methods on the Quality Characteristics of Fenugreek (Trigonella foenum-graecum) Greens

Different drying methods were investigated for efficient dehydration of fenugreek (Trigonella foenum-graecum) greens for optimal retention of color and its constituents. Accordingly, hot air (HA, 40°C, 58–63% RH), low humidity air (LHA, 40°C and 28–30% RH), and radiofrequency (RF, 40°C, 56–60% RH) were explored for efficient drying of fenugreek greens. The three single-layer drying models (Exponential, Page, and Modified Page) tested showed excellent fit (R² = 0.92–0.99) for all three drying methods. The time required for drying with LHA and RF was less (～27%), as compared to HA drying. LHA-dried fenugreek had superior green color and a more porous and uniform structure than those obtained from RF and HA drying. Aqueous methanolic (60:40) extract of fenugreek greens dehydrated by LHA exhibited the highest radical scavenging activity. Dehydrated fenugreek greens showed good consumer acceptance as well as shelf life.     

An evaluation of polygraphers' judgments: A review from a decision theoretic perspective.

Reexamined data from 7 field studies to estimate the discriminability of the control questions technique (CQT) in real-life situations. A signal detection model was applied, and an attempt was made to derive the value system of the polygraphers who participated. It was demonstrated that under an assumption of rationality, the examiners tended to value the detection of guilty suspects highly, even in the presence of a high risk of falsely classifying innocent suspects as deceptive. An index of usefulness of the CQT-based evaluation system was defined, and the CQT's range of usefulness was examined as a function of operating costs, possible payoff ratios, and prior probabilities of guilt. It is unlikely that the CQT method of lie detection would be useful for determining guilt in a court of law or even for preemployment screening, although it might be useful for police investigative procedures. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The web from a complex adaptive systems perspective

The web continues to grow at a phenomenal rate, and the amount of information on the web is overwhelming. Finding the relevant information remains a big challenge. Due to its wide distribution, its openness and high dynamics, the web is a complex system, for which we have to imagine mechanisms of content maintaining, filtering and organizing that are able to deal with its evolving dynamics and distribution. Integrating mechanisms of self-organization of the web content is an attractive perspective, to match with these requirements. Self-organized complex systems can be programmed using situated multi-agent systems with a coupling between the agents' social organization and spatial organization. This paper explores the web from a complex adaptive system (CAS) perspective. It reviews some characteristic behaviors of CASs and shows how the web exhibits similar behaviors. We propose a model and a prototype of a system that addresses the dynamic web content organization, adopting the CAS vision and using the multi-agent paradigm.     

Enzyme monolayer-functionalized field-effect transistors for biosensor applications

A gate surface of an ion-selective field-effect transistor was modified with a monolayer enzyme array that stimulates biocatalytic reactions that control the gate potential. Stepwise assemblage of the biocatalytic layer included primary silanization of the Al₂O₃-gate with 3-aminopropyltriethoxysilane, subsequent activation of the amino groups with glutaric dialdehyde and the covalent attachment of the enzyme to the functionalized gate surface. Urease, glucose oxidase, acetylcholine esterase and α-chymotrypsin were used to organize the biocatalytic matrices onto the chip gate. The resulting enzyme-based field-effect transistors, ENFETs, demonstrated capability to sense urea, glucose, acetylcholine and N-acetyl- -tyrosine ethyl ester, respectively. The mechanism of the biosensing involves the alteration of the pH in the sensing layer by the biocatalytic reactions and the detection of the pH change by the ENFET. The major advantage of the enzyme-thin-layered FET devices as biosensors is the fast response-time (several tens of seconds) of these bioelectronic devices. This advantage over traditional thick-polymer-based ENFETs results from the low diffusion barrier for the substrate penetration to the biocatalytic active sites and minute isolation of the pH-sensitive gate surface from the bulk solution.