Association between Decreased ITGA7 Levels and Increased Muscle α-Synuclein in an MPTP-Induced Mouse Model of Parkinson’s Disease

Parkinson''s disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN), reducing dopaminergic levels in the striatum and affecting motor control. Herein, we investigated the potential relationship between integrin α7 (ITGA7) and α-synuclein (α-syn) in the muscle of methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced mice and C2C12 cells. To characterize the pathology of PD, we examined the expression of tyrosine hydroxylase (TH) in the SN of the midbrain. Compared with the control group, MPTP-treated mice showed a significant decrease in TH expression in the SN, accompanied by a significant decrease in muscle ITGA7 expression. Compared with the control group, α-syn expression was increased in the MPTP group. Furthermore, the pattern of α-syn expression in the MPTP group was similar to the ITGA7 expression pattern in the control group (linear forms). To determine the relationship between ITGA7 and PD, we examined the expression of ITGA7 and α-syn after ITGA7 knockdown using siRNA in C2C12 cells. ITGA7 expression significantly decreased while α-syn expression significantly increased in siRNA-treated C2C12 cells. These results suggest that decreased ITGA7 muscle expression could increase α-syn expression. Moreover, α-syn accumulation, induced by decreased muscle ITGA7, might contribute to PD pathology.     

S100B Protein concentration in milk-formulas for preterm and term infants. Correlation with industrial preparation procedures

Human milk S100B protein possesses important neurotrophic properties. However, in some conditions human milk is substituted by milk formulas. The aims of the present study were: to assess S100B concentrations in milk formulas, to verify any differences in S100B levels between preterm and term infant formulas and to evaluate the impact of industrial preparation at predetermined phases on S100B content. Two different set of samples were tested: (i) commercial preterm (n = 36) and term (n = 36) infant milk formulas; ii) milk preterm (n = 10) and term infant (n = 10) formulas sampled at the following predetermined industrial preparation time points: skimmed cow milk (Time 0); after protein sources supplementation (Time 1); after pasteurization (Time 2); after spray-drying (Time 3). Our results showed that S100B concentration in preterm formulas were higher than in term ones (p < 0.01). In addition, S100B concentrations during industrial preparation showed a significant increase (p < 0.001) at Time 1 followed by a slight decrease (p > 0.05) at Time 2, whereas a significant (p < 0.001) dip was observed at Time 3. In conclusion, S100B showed a sufficient thermostability to resist pasteurization but not spry-drying. New feeding strategies in preterm and term infants are therefore warranted in order to preserve S100B protein during industrial preparation.     

Printed thermochromic displays

Thermochromic displays, which were evaluated in this study, combine printed electronics with the thermochromism phenomenon. Conductive lines printed on the reverse side and thermochromic printing ink printed on the front side of cardboard packaging form a thermochromic display that gives cardboard packaging additional value. Displays were printed on different printing materials, and thermochromic printing ink was deposited in one and two layers. In addition, half of the samples were varnished. The influence of the printing material, the thickness of the thermochromic printing ink layer, the varnish, the high temperature, and light fastness on the display's operability were all evaluated. It was clearly shown that the choice of printing material plays a crucial role in the display's operability. Moreover, high temperature and light fastness also have a significant influence, although the impact is negligible when the display is used at room temperature.     

Need for cognition as a predictor and a moderator of outcome in a tailored letters smoking cessation intervention.

Objective: To analyze whether baseline need for cognition (NFC) was a predictor or a moderator of treatment outcome in a tailored letters intervention for smoking cessation. Design: A total of 1,499 daily smokers were recruited from general medical practices in Germany within a quasi-randomized trial testing the efficacies of two brief interventions for smoking cessation: (a) computer-generated tailored letters and (b) physician-delivered brief counseling versus assessment-only. For this study, we used data from 1,097 daily smokers who were assigned to the tailored letters or the assessment-only condition. Main Outcome Measures: self-reported 6-month prolonged abstinence from tobacco smoking assessed at 12-, 18-, and 24-month follow-ups, and smoking cessation self-efficacy assessed at 6- and 24-month follow-ups. Results: Baseline NFC predicted 6-month prolonged smoking abstinence (p = .01) and smoking cessation self-efficacy (p .05) but on smoking cessation self-efficacy (p = .05). Tailored letters resulted in higher smoking cessation self-efficacy only for persons with higher NFC. Conclusion: Higher levels of NFC are required to increase smoking cessation self-efficacy in computer-tailored interventions for smoking cessation. Considering an individual's NFC might improve the efficacy of written interventions for smoking cessation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selenium-Containing Exopolysaccharides Isolated from the Culture Medium of Lentinula edodes: Structure and Biological Activity

In continuation of our research on the influence of selenium incorporation on the biosynthesis, structure, and immunomodulatory and antioxidant activities of polysaccharides of fungal origin, we have isolated from a post-culture medium of Lentinula edodes a selenium (Se)-containing exopolysaccharide fraction composed mainly of a highly branched 1-6-α-mannoprotein of molecular weight 4.5 × 10⁶ Da, with 15% protein component. The structure of this fraction resembled mannoproteins isolated from yeast and other mushroom cultures, but it was characterized by a significantly higher molecular weight. X-ray absorption fine structure spectral analysis in the near edge region (XANES) suggested that selenium in the Se-exopolysaccharide structure was present mainly at the IV oxidation state. The simulation analysis in the EXAFS region suggested the presence of two oxygen atoms in the region surrounding the selenium. On the grounds of our previous studies, we hypothesized that selenium-enriched exopolysaccharides would possess higher biological activity than the non-Se-enriched reference fraction. To perform structure–activity studies, we conducted the same tests of biological activity as for previously obtained mycelial Se-polyglucans. The Se-enriched exopolysaccharide fraction significantly enhanced cell viability when incubated with normal (human umbilical vein endothelial cells (HUVEC)) cells (but this effect was absent for malignant human cervical HeLa cells) and this fraction also protected the cells from oxidative stress conditions. The results of tests on the proliferation of human peripheral blood mononuclear cells suggested a selective immunosuppressive activity, like previously tested Se-polyglucans isolated from L. edodes mycelium. The Se-exopolysaccharide fraction, in concentrations of 10–100 µg/mL, inhibited human T lymphocyte proliferation induced by mitogens, without significant effects on B lymphocytes. As with previously obtained Se-polyglucans, in the currently tested Se-polymannans, the selenium content increased the biological activity. However, the activity of selenium exopolysaccharides in all tests was significantly lower than that of previously tested mycelial isolates, most likely due to a different mode of selenium binding and its higher degree of oxidation.     

Discovery of the First Highly Selective Antagonist of the GluK3 Kainate Receptor Subtype

Kainate receptors belong to the family of glutamate receptors ion channels, which are responsible for the majority of rapid excitatory synaptic transmission in the central nervous system. The therapeutic potential of kainate receptors is still poorly understood, which is also due to the lack of potent and subunit-selective pharmacological tools. In search of selective ligands for the GluK3 kainate receptor subtype, a series of quinoxaline-2,3-dione analogues was synthesized and pharmacologically characterized at selected recombinant ionotropic glutamate receptors. Among them, compound 28 was found to be a competitive GluK3 antagonist with submicromolar affinity and unprecedented high binding selectivity, showing a 400-fold preference for GluK3 over other homomeric receptors GluK1, GluK2, GluK5 and GluA2. Furthermore, in functional assays performed for selected metabotropic glutamate receptor subtypes, 28 did not show agonist or antagonist activity. The molecular determinants underlying the observed affinity profile of 28 were analyzed using molecular docking and molecular dynamics simulations performed for individual GluK1 and GluK3 ligand-binding domains.     

Nuestra culpa: Collective guilt and shame as predictors of reparation for historical wrongdoing.

Three studies examined the hypothesis that collective guilt and shame have different consequences for reparation. In 2 longitudinal studies, the ingroup was nonindigenous Chileans (Study 1: N = 124/120, lag = 8 weeks; Study 2: N = 247/137, lag = 6 months), and the outgroup was Chile's largest indigenous group, the Mapuche. In both studies, it was found that collective guilt predicted reparation attitudes longitudinally. Collective shame had only cross-sectional associations with reparation and no direct longitudinal effects. In Study 2, collective shame moderated the longitudinal effects of collective guilt such that the effects of guilt were stronger for low-shame respondents. In Study 3 (N = 193 nonindigenous Chileans), the cross-sectional relationships among guilt, shame, and reparation attitudes were replicated. The relationship between shame and reparation attitudes was mediated by a desire to improve the ingroup's reputation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of Processing on Anti-nutritional Factors of Red Kidney Bean (Phaseolus vulgaris) Grains

The effect of different processing methods (soaking in water or solutions of sodium bicarbonate, citric acid, soaking plus cooking, and germination) on anti-nutritional factors (phytic acid, total polyphenols, tannins, and hydrocyanic acid) of red kidney bean was studied. The anti-nutritional factors were reduced significantly (P < 0.001) with processing techniques. Cyanide contents were most effectively (25%) reduced by cooking after soaking in sodium bicarbonate solution, followed by germination. The most drastic effect was noted on tannin contents. Cooking after soaking in either citric acid or sodium bicarbonate solutions almost eliminated it. However, simple soaking in water did not result in any reduction in tannin contents. Reduction in total polyphenols was 78.7% with cooking after soaking in sodium bicarbonate solution. Phytic acid contents were reduced only with germination treatment (42.6%), while the other treatments did not bring about any large reduction.     

Synthesis of Uronic Acid 1-Azasugars as Putative Inhibitors of α-Iduronidase, β-Glucuronidase and Heparanase**

1-Azasugar analogues of l -iduronic acid (l -IdoA) and d -glucuronic acid (d -GlcA) and their corresponding enantiomers have been synthesized as potential pharmacological chaperones for mucopolysaccharidosis I (MPS I), a lysosomal storage disease caused by mutations in the gene encoding α-iduronidase (IDUA). The compounds were efficiently synthesized in nine or ten steps from d - or l -arabinose, and the structures were confirmed by X-ray crystallographic analysis of key intermediates. All compounds were inactive against IDUA, although l -IdoA-configured 8 moderately inhibited β-glucuronidase (β-GLU). The d -GlcA-configured 9 was a potent inhibitor of β-GLU and a moderate inhibitor of the endo-β-glucuronidase heparanase. Co-crystallization of 9 with heparanase revealed that the endocyclic nitrogen of 9 forms close interactions with both the catalytic acid and catalytic nucleophile.