An Examination of the Generalizability of Motor Costs

Most approaches to understanding human motor control assume that people maximize their rewards while minimizing their motor efforts. This tradeoff between potential rewards and a sense of effort is quantified with a cost function. While the rewards can change across tasks, our sense of effort is assumed to remain constant and characterize how the nervous system organizes motor control. As such, when a proposed cost function compares well with data it is argued to be the underlying cause of a motor behavior, and not simply a fit to the data. Implicit in this proposition is the assumption that this cost function can then predict new motor behaviors. Here we examined this idea and asked whether an inferred cost function in one setting could explain subject’s behavior in settings that differed dynamically but had identical rewards. We found that the pattern of behavior observed across settings was similar to our predictions of optimal behavior. However, we could not conclude that this behavior was consistent with a conserved sense of effort. These results suggest that the standard forms for quantifying cost may not be sufficient to accurately examine whether or not human motor behavior abides by optimality principles.     

Isolation,Purification and Characterization of Antimicrobial Peptides Produced from <Emphasis Type="Italic">Saccharomyces boulardii</Emphasis>

Saccharomyces boulardii was used for antimicrobial peptides production. Separation process of produced antimicrobial peptides was conducted using ultrafiltration technique through dialysis membranes with porous 10 (MWCO) kDa. The inhibition activity was determined against four bacterial isolates. As a result, higher inhibition zone against Bacillus cereus were 26, 29 and 33 mm after adding 50, 75 and 100 µL of concentrated peptide, respectively. After that, peptide passed through the Sephadex G-50 column to achieve purified peptide using gel filtration. The high activity of purified peptide was confirmed based on the second peak reaching to 37 mm of bacterial inhibition zone while other peaks did not show any inhibition against tested bacteria. Some of the important characteristics of purified bioactive peptide were applied. Antimicrobial peptides stability was studied and found to be stable at pH range from 5 to 7 values studied in addition to its inhibition activity reached to 100%. Regarding thermal stability, it was observed that the peptide was fully activity at a both 60–80 °C for 30 min. Moreover, molecular weight of a peptide was identified using electrophoresis technique with SDS measured at 5792 Dalton.     

Markers of atopic dermatitis,allergic rhinitis and bronchial asthma in pediatric patients: correlation with filaggrin,eosinophil major basic protein and immunoglobulin E

Background

Allergic reactions have been implicated as contributions in a number of atopic disorders, including atopic dermatitis (AD), allergic rhinitis (AR) and bronchial asthma (BA). However, the potential for filaggrin protein, eosinophil major basic protein (MBP) and immunoglobulin E (IgE) to elicit allergic response or to contribute to atopic disorders remains largely unexplored in pediatric patients. This study was undertaken to investigate the status and contribution of filaggrin protein, eosinophil MBP and total IgE in pediatric patients with AD, AR and BA.

Methods

Sera from 395 pediatric patients of AD, AR or BA with varying levels of disease activity according to the disease activity index and 410 age-matched non-atopic healthy controls were evaluated for serum levels of atopic markers, including filaggrin, eosinophil MBP and IgE.

Results

Serum analysis showed that filaggrin levels were remarkably high in pediatric patients with AD, followed by BA and AR, whereas its levels were low in non-atopic pediatric controls. Eosinophil MBP levels in sera of atopic patients were significantly high as compared with their respective controls, but its levels were highest in AR patients, followed by AD and BA. Total IgE in sera of AD patients was markedly high, followed by AR and BA patients, whereas its levels were low in non-atopic pediatric controls. Interestingly, not only was an increased number of subjects positive for filaggrin protein, eosinophil MBP or total IgE, but also their levels were statistically significantly higher among those atopic patients whose disease activity scores were higher as compared with atopic patients with lower disease activity scores.

Conclusions

These findings strongly support a role of filaggrin protein, eosinophil MBP and IgE in the onset of allergic reactions in pediatric patients with AD, AR and BA. The data suggest that filaggrin, eosinophil MBP or IgE might be useful in evaluating the progression of AD, AR or BA and in elucidating the mechanisms involved in the pathogenesis of these pediatric disorders.

     

Favorable outcomes of metformin on coronary microvasculature in experimental diabetic cardiomyopathy

Although metformin is widely prescribed in diabetes, its use with associated cardiac dysfunction remains debatable. In the current study, we investigated the effect of metformin on coronary microvasculature in experimental diabetic cardiomyopathy (DCM) induced by streptozotocin. Administration of metformin after induction of DCM, reversed almost all cardiomyocyte degenerative changes induced by DCM. Metformin diminished the significantly increased (p?<?0.05) collagen deposited in the DCM. In addition metformin had improved the density of the significantly decreased arteriolar (αSMA⁺) and capillary (CD31⁺) coronary microvasculature compared to that of the DCM and non-diabetics (ND) with downregulation of the significantly increased expression (p?<?0.05) of COL-I, III, TGF-β, CTGF, ICAM and VCAM genes. Therefore metformin may be beneficial in limiting the fibrotic and the vascular remodeling occurring in DCM at the genetic as well as the structural levels.     

Micelle‐enhanced spectrofluorimetric method for determination of lacidipine in tablet form; application to content uniformity testing

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of lacidipine (LCP) in tablets. The proposed method is based on the investigation of the fluorescence spectral behavior of LCP in both sodium dodecyl sulphate (SDS) and the tween‐80 micellar system. In aqueous solutions of acetate buffer (pH 4.5), the fluorescence intensities of LCP were greatly enhanced (ca. 2.4 and 4.3 folds) in the presence of either SDS or tween‐80, respectively. The fluorescence intensity was measured at 444 nm after excitation at 277 nm using either SDS or tween‐80 as a surfactant. The fluorescence–concentration plots were rectilinear over the ranges of 50.0–500.0 ng/ml and 5.0–200.0 ng/ml with lower detection limits of 5.11 and 2.06 ng/ml and lower quantification limits of 17 and 6.87 ng/ml using SDS and tween‐80, respectively. The method was successfully applied to the analysis of LCP in commercial tablets and the results were in good agreement with those obtained with the comparison method. Furthermore, content uniformity testing of pharmaceutical tablets was also conducted. Copyright © 2014 John Wiley & Sons, Ltd.     

Analysis of G6PD enzyme deficiency in Saudi population

The evolutionary conservation of a housekeeping gene such as G6PD is greater than that of tissue-specific genes, presumably because the latter may require more specific adaptation to the physiology of individual organisms. The abundance of distinct mutation sites and their clinical manifestations make G6PD ideal for structure-function analysis. Therefore, it is of interest to screen of G6PD deficiency in the blood donors in Kingdom of Saudi Arabia. We report the mean and variation of enzyme activity in a huge set of Suadi to non-Saudi population with reference to the entire population. The sequence level conservation of G6PD among distant species is demonstrated using phylogenetic trees. These observations have implications in the sequence-structure-function understanding of G6PD with reference to its association to several human diseases.     

Involvement of myosin Vb in glutamate receptor trafficking

Myosin V motors mediate cargo transport; however, the identity of neuronal molecules transported by these proteins remains unknown. Here we show that myosin Vb is expressed in several neuronal populations and associates with the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptor subunit GluR1. In developing hippocampal neurons, expression of the tail domain of myosin Vb, but not myosin Va, enhanced GluR1 accumulation in the soma and reduced its surface expression. These changes were accompanied by reduced GluR1 clustering and diminished frequency of excitatory but not inhibitory synaptic currents. Similar effects were observed upon expression of full-length myosin Vb lacking a C-terminal region required for binding to the small GTPase Rab11. In contrast, mutant myosin Vb did not change the localization of several other neurotransmitter receptors, including the glutamate receptor subunit NR1. These results reveal a novel mechanism for the transport of a specific glutamate receptor subunit in neurons mediated by a member of the myosin V family.     

Biotechnological Process for Production of β-Dipeptides from Cyanophycin on a Technical Scale and Its Optimization

A triphasic process was developed for the production of β dipeptides from cyanophycin (CGP) on a large scale. Phase I comprises an optimized acid extraction method for technical isolation of CGP from biomass. It yielded highly purified CGP consisting of aspartate, arginine, and a little lysine. Phase II comprises the fermentative production of an extracellular CGPase (CphE_al) from Pseudomonas alcaligenes strain DIP1 on a 500-liter scale in mineral salts medium, with citrate as the sole carbon source and CGP as an inductor. During optimization, it was shown that 2 g liter⁻¹ citrate, pH 6.5, and 37°C are ideal parameters for CphE_al production. Maximum enzyme yields were obtained after induction in the presence of 50 mg liter⁻¹ CGP or CGP dipeptides for 5 or 3 h, respectively. Aspartate at a concentration of 4 g liter⁻¹ induced CphE_al production with only about 30% efficiency in comparison to that with CGP. CphE_al was purified utilizing its affinity for the substrate and its specific binding to CGP. CphE_al turned out to be a serine protease with maximum activity at 50°C and at pH 7 to 8.5. Phase III comprises degradation of CGP to β-aspartate-arginine and β-aspartate-lysine dipeptides with a purity of over 99% (by thin-layer chromatography and high-performance liquid chromatography), employing a crude CphE_al preparation. Optimum degradation parameters were 100 g liter⁻¹ CGP, 10 g liter⁻¹ crude CphE_al powder, and 4 h of incubation at 50°C. The overall efficiency of phase III was 91%, while 78% (wt/wt) of the used CphE_al powder with sustained activity toward CGP was recovered. The optimized process was performed with industrial materials and equipment and is applicable to any desired scale.     

Modulation of Activation-Induced Cytidine Deaminase by Curcumin in Helicobacter pylori-Infected Gastric Epithelial Cells

Background: Anomalous expression of activation‐induced cytidine deaminase (AID) in Helicobacter pylori‐infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)‐κB activation by H. pylori and hence, inhibition of NF‐κB pathway can downregulate the expression of AID. Curcumin, a spice‐derived polyphenol, is known for its anti‐inflammatory activity via NF‐κB inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF‐κB inhibitory activity in H. pylori‐infected gastric epithelial cells. Materials and Methods: MKN‐28 or MKN‐45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co‐culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme‐linked immunosorbent assay was performed to evaluate the anti‐adhesion activity of curcumin. Real‐time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF‐κB, inhibitors of NF‐κB (IκB), and IκB kinase (IKK) complex regulation with or without curcumin. Results: The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (≤10 μmol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF‐κB activation inhibitor (SN‐50) and proteasome inhibitor (MG‐132) also downregulated the mRNA expression of AID. Moreover, curcumin (≤10 μmol/L) has suppressed H. pylori‐induced NF‐κB activation via inhibition of IKK activation and IκB degradation. Conclusion: Nonbactericidal concentrations of curcumin downregulated H. pylori‐induced AID expression in gastric epithelial cells, probably via the inhibition of NF‐κB pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori‐related gastric carcinogenesis.