Pep19 Has a Positive Effect on Insulin Sensitivity and Ameliorates Both Hepatic and Adipose Tissue Phenotype of Diet-Induced Obese Mice

Peptide DIIADDEPLT (Pep19) has been previously suggested to improve metabolic parameters, without adverse central nervous system effects, in a murine model of diet-induced obesity. Here, we aimed to further evaluate whether Pep19 oral administration has anti-obesogenic effects, in a well-established high-fat diet-induced obesity model. Male Swiss mice, fed either a standard diet (SD) or high-fat diet (HFD), were orally administrated for 30 consecutive days, once a day, with saline vehicle or Pep19 (1 mg/kg). Next, several metabolic, morphological, and behavioral parameters were evaluated. Oral administration of Pep19 attenuated HFD body-weight gain, reduced in approximately 40% the absolute mass of the endocrine pancreas, and improved the relationship between circulating insulin and peripheral insulin sensitivity. Pep19 treatment of HFD-fed mice attenuated liver inflammation, hepatic fat distribution and accumulation, and lowered plasma alanine aminotransferase activity. The inguinal fat depot from the SD group treated with Pep19 showed multilocular brown-fat-like cells and increased mRNA expression of uncoupling protein 1 (UCP1), suggesting browning on inguinal white adipose cells. Morphological analysis of brown adipose tissue (BAT) from HFD mice showed the presence of larger white-like unilocular cells, compared to BAT from SD, Pep19-treated SD or HFD mice. Pep19 treatment produced no alterations in mice behavior. Oral administration of Pep19 ameliorates some metabolic traits altered by diet-induced obesity in a Swiss mice model.     

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated K_i ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification.     

Using the community health assessment to screen for continued driving

This project used the interRAI based, community health assessment (CHA) to develop a model for identifying current elder drivers whose driving behavior should be reviewed. The assessments were completed by independent housing sites in COLLAGE, a non-profit, national senior housing consortium. Secondary analysis of data drawn from older adults in COLLAGE sites in the United States was conducted using a baseline assessment with 8042 subjects and an annual follow-up assessment with 3840 subjects. Logistic regression was used to develop a Driving Review Index (DRI) based on the most useful items from among the many measures available in the CHA assessment. Thirteen items were identified by the logistic regression to predict drivers whose driving behavior was questioned by others. In particular, three variables reference compromised decision-making abilities: general daily decisions, a recent decline in ability to make daily decisions, and ability to manage medications. Two additional measures assess cognitive status: short-term memory problem and a diagnosis of non-Alzheimers dementia. Functional measures reflect restrictions and general frailty, including receiving help in transportation, use of a locomotion appliance, having an unsteady gait, fatigue, and not going out on most days. The final three clinical measures reflect compromised vision, little interest or pleasure in things normally enjoyed, and diarrhea. The DRI focuses the review process on drivers with multiple cognitive and functional problems, including a significant segment of potentially troubled drivers who had not yet been publicly identified by others. There is a need for simple and quickly identified screening tools to identify those older adults whose driving should be reviewed. The DRI, based on the interRAI CHA, fills this void. Assessment at the individual level needs to be part of the backdrop of science as society seeks to target policy to identify high risk drivers instead of simply age-based testing.     

Internal short circuit in Li-ion cells

Effects of internal short circuit (ISCr) on thermal stability of Li-ion cells of various sizes (130-1100 mAh) are investigated using a combination of experimental methods and thermal modeling. Three experimental methods were evaluated: small nail penetration, small indentation, and cell pinch test. The small nail penetration and indentation tests created significant heat sinking to the cell-can or to the nail. Only the cell pinch test provided a reasonable approximation of a high risk ISCr event. ISCr location plays a critical role in the consequences of an ISCr event. ISCr at the edge of the electrode is the worst case because of its limited heat conduction to the cell-can. The effects of cell capacity and state of charge on ISCr are also evaluated through tests and thermal modeling.     

Evolution of supramolecular healable composites: a minireview

Efforts to further extend the range of applications of polymer based materials have resulted in the recent production of healable polymers that can regain their strength after damage. Within this field of healable materials, supramolecular polymers have been subject to extensive investigation. By virtue of their reversible non‐covalent interactions, cracks and fractures in such polymers can be readily and repeatedly healed in order to regain key physical properties. However, many supramolecular polymers are relatively weak and elastomeric in nature, which renders them unsuitable for high strength structural applications. To overcome these deficiencies, preliminary studies have shown that it is possible to reinforce supramolecular polymers with microscale and nanoscale fillers to afford composites that are not only stronger and stiffer compared with the polymers alone but also retain their healing abilities. In this minireview we discuss the evolution of these supramolecular composites and their advantages over more conventional, covalent polymeric materials. © 2014 Society of Chemical Industry     

Selective oxidation of alcohols by combinatorial catalysis

High-throughput synthesis and screening of polyoxometalate (POM) and supported-metal libraries have been developed for the selective aerobic oxidation of alcohols to the corresponding aldehydes/ketones in the liquid phase. Libraries consisting of 96 catalysts were prepared in multi-well reactors and screened for catalytic activity using TLC, GC and NMR detection methods. Promising hits identified in the high-throughput primary screens were successfully scaled up and optimized in conventional laboratory test units. Isolated yields confirm high selectivities of more than 90% with quantitative conversions. Substrates tested include primary and secondary alcohols. Specific results will be presented for hydroxymethyl-substituted heterocycles and bicyclo-octanols.     

Preserved monitoring and control processes in temporal lobe epilepsy.

Objective: The aim of this study was to assess an aspect of metamemory never examined before in patients with temporal lobe epilepsy (TLE): the ability to upgrade the accuracy of one's memory predictions after study. Method: Four lists of different levels of difficulty and relatedness were presented to 15 TLE patients and 15 control participants, who were asked to predict their subsequent recall both before and after studying each list. Results: The results showed clear impairment in recall in TLE patients. However, both TLE patients and controls showed an improvement in accuracy in their poststudy predictions compared with their prestudy predictions, showing that both groups were able to upgrade their metamemory predictions. Unexpectedly, prediction accuracy was overall higher in TLE patients than in controls. Moreover, study time was allocated in both groups taking into account the characteristics of the list. Conclusion: These results confirm and extend findings of Howard et al. (2010) of intact metamemory in TLE patients, and provide further support to the dissociation between memory and metamemory in this clinical population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)