Artificial gravity loading increases the effects of the glutamate transporter inhibitors on the glutamate release and uptake in rat brain nerve terminals

The present study evaluated the effect of artificial gravity loading on transporter-mediated uptake and release of L-glutamate using the inhibitors of glutamate transporters as tools. The competitive nontransportable, DL-threo-beta-benzyloxyaspartate (DL-TBOA), and transportable, DL-threo-beta-hydroxyaspartate (DL-THA), inhibitors were demonstrated to better inhibit the L-[¹⁴C]glutamate uptake under centrifuge-induced hypergravity compared with the normal gravity control. The effect of DL-TBOA on depolarization-induced carrier-mediated L-[¹⁴C]glutamate release also increased after hypergravity loading in Na⁺- and low [Na⁺] NMDG- supplemented media. 10 µM DL-TBOA-induced decrease in L-[¹⁴C]glutamate release in Na⁺ — supplemented medium was 15.2±2.2 % in the control experiments and 26.2±3.9 % after centrifuge-induced loading (P≤0,05) and in low [Na⁺] medium was 37.0±2.5 % and 45.0±3.4 %, respectively.     

Effects of training in procedural justice on perceptions of disciplinary fairness by unionized employees and disciplinary subject matter experts.

A training program, based on procedural justice theory, was developed for teaching supervisors to take effective disciplinary action with employees. Canadian supervisors of unionized employees were randomly assigned to the training (n?=?35) or the control group (n?=?36). Analyses of variance revealed that both supervisory self-efficacy and outcome expectancies were significantly higher in the training than in the control conditions. Following simulated role-play exercises derived from organizational incidents, both unionized employees and disciplinary subject matter experts (managers, union officials, and attorneys) rated the trained supervisors higher on disciplinary fairness behavior than the supervisors in the control group. Self-efficacy was found to mediate the relationship between training and perceptions of disciplinary fairness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Large‐Scale Diffusion Barriers from CVD Grown Graphene

Graphene has been long thought of as a perfect barrier material due to its impermeability to all gases as well as mechanical and chemical durability. Moreover, graphene layers are transparent and conductive, significantly widening the field of potential applications beyond simple barrier coatings. However, it is very challenging to realize such barriers on a macro­scopic scale as immaculate large area films are not available. In this work, a highly effective oxygen gas barrier made from multiple layers of chemical vapor deposited graphene is presented. The individual graphene layers are stacked using a modified polymer‐assisted transfer method, avoiding polymer residue yielding an oxygen‐tight arrangement. A stack of three layers of graphene transmitted 6.9 cm³ m⁻² d⁻¹ of O₂ which corresponds to 1.10 × 10⁻¹⁷ cm³ cm/cm² s (cm Hg) when normalized to thickness and pressure. This is several orders of magnitude better than any macroscale graphene coating reported to date and performs on a level that can compete with most modern coatings while being much thinner and conductive.     

Relationships between storage protein composition,protein content,growing season and flour quality of bread wheat

The storage protein composition from the Glu‐1, Glu‐3 and Gli‐1 loci encoding high and low molecular weight glutenin subunits (HMW‐GS and LMW‐GS) and gliadins, respectively, was determined on 30 wheat (T aestivum L) genotypes from three growing seasons. The gliadins and the LMW‐GS were identified as gliadin/LMW‐GS pairs. All samples were analysed by two one‐dimensional electrophoretic techniques, and selected samples were also subjected to two‐dimensional electrophoretic separation. Different statistical/data‐analytical techniques were evaluated in the study of how the presence or absence of the protein alleles, the protein content and the growing seasons are related to flour quality. The year of growth had a large impact on mixograph peak time. When predicting mixograph peak time from the presence or absence of significant proteins and the year of growth, 70% of the variability in mixograph peak time could be explained, whereas only 49% of the variability could be explained when the year of growth was deleted from the model. Protein had no effect on mixograph peak time as expected, and the well‐known positive effect of HMW‐GS 5 + 10, and the negative effects of 2 + 12 and 6 + 8 was observed. Furthermore, some of the gliadin/LMW‐GS combinations influenced mixograph peak time significantly. The gliadin/LMW‐GS at the combined Gli‐A1, Glu‐A3 loci b; ?? was positively related to mixograph peak time, whereas ??; ?? and a;a was negatively related. Although the LMW‐GS component ?? of the alleles b; ?? and ??; ?? alleles appear similar on one‐dimensional gels, two‐dimensional separation of selected samples may suggest that the ?? components in these alleles are different proteins. Cross‐validated partial least squares regression combined with empirical uncertainty estimates (jack‐knifing) of the parameters estimated in the model, gave similar results to ANOVA in identifying quality related protein alleles. The applicability of the multivariate approach in proteomics is, however, much wider. Copyright © 2004 Society of Chemical Industry     

Dose-Dependent Cytotoxicity of Polypropylene Microplastics (PP-MPs) in Two Freshwater Fishes

The massive accumulation of plastics over the decades in the aquatic environment has led to the dispersion of plastic components in aquatic ecosystems, invading the food webs. Plastics fragmented into microplastics can be bioaccumulated by fishes via different exposure routes, causing several adverse effects. In the present study, the dose-dependent cytotoxicity of 8–10 μm polypropylene microplastics (PP-MPs), at concentrations of 1 mg/g (low dose) and 10 mg/g dry food (high dose), was evaluated in the liver and gill tissues of two fish species, the zebrafish (Danio rerio) and the freshwater perch (Perca fluviatilis). According to our results, the inclusion of PP-MPs in the feed of D. rerio and P. fluviatilis hampered the cellular function of the gills and hepatic cells by lipid peroxidation, DNA damage, protein ubiquitination, apoptosis, autophagy, and changes in metabolite concentration, providing evidence that the toxicity of PP-MPs is dose dependent. With regard to the individual assays tested in the present study, the biggest impact was observed in DNA damage, which exhibited a maximum increase of 18.34-fold in the liver of D. rerio. The sensitivity of the two fish species studied differed, while no clear tissue specificity in both fish species was observed. The metabolome of both tissues was altered in both treatments, while tryptophan and nicotinic acid exhibited the greatest decrease among all metabolites in all treatments in comparison to the control. The battery of biomarkers used in the present study as well as metabolomic changes could be suggested as early-warning signals for the assessment of the aquatic environment quality against MPs. In addition, our results contribute to the elucidation of the mechanism induced by nanomaterials on tissues of aquatic organisms, since comprehending the magnitude of their impact on aquatic ecosystems is of great importance.     

Partial Reduction in BRCA1 Gene Dose Modulates DNA Replication Stress Level and Thereby Contributes to Sensitivity or Resistance

BRCA1 is a well-known breast cancer risk gene, involved in DNA damage repair via homologous recombination (HR) and replication fork protection. Therapy resistance was linked to loss and amplification of the BRCA1 gene causing inferior survival of breast cancer patients. Most studies have focused on the analysis of complete loss or mutations in functional domains of BRCA1. How mutations in non-functional domains contribute to resistance mechanisms remains elusive and was the focus of this study. Therefore, clones of the breast cancer cell line MCF7 with indels in BRCA1 exon 9 and 14 were generated using CRISPR/Cas9. Clones with successful introduced BRCA1 mutations were evaluated regarding their capacity to perform HR, how they handle DNA replication stress (RS), and the consequences on the sensitivity to MMC, PARP1 inhibition, and ionizing radiation. Unexpectedly, BRCA1 mutations resulted in both increased sensitivity and resistance to exogenous DNA damage, despite a reduction of HR capacity in all clones. Resistance was associated with improved DNA double-strand break repair and reduction in replication stress (RS). Lower RS was accompanied by increased activation and interaction of proteins essential for the S phase-specific DNA damage response consisting of HR proteins, FANCD2, and CHK1.     

Distress-Mediated Remodeling of Cardiac Connexin-43 in a Novel Cell Model for Arrhythmogenic Heart Diseases

Gap junctions and their expression pattern are essential to robust function of intercellular communication and electrical propagation in cardiomyocytes. In healthy myocytes, the main cardiac gap junction protein connexin-43 (Cx43) is located at the intercalated disc providing a clear direction of signal spreading across the cardiac tissue. Dislocation of Cx43 to lateral membranes has been detected in numerous cardiac diseases leading to slowed conduction and high propensity for the development of arrhythmias. At the cellular level, arrhythmogenic diseases are associated with elevated levels of oxidative distress and gap junction remodeling affecting especially the amount and sarcolemmal distribution of Cx43 expression. So far, a mechanistic link between sustained oxidative distress and altered Cx43 expression has not yet been identified. Here, we propose a novel cell model based on murine induced-pluripotent stem cell-derived cardiomyocytes to investigate subcellular signaling pathways linking cardiomyocyte distress with gap junction remodeling. We tested the new hypothesis that chronic distress, induced by rapid pacing, leads to increased reactive oxygen species, which promotes expression of a micro-RNA, miR-1, specific for the control of Cx43. Our data demonstrate that Cx43 expression is highly sensitive to oxidative distress, leading to reduced expression. This effect can be efficiently prevented by the glutathione peroxidase mimetic ebselen. Moreover, Cx43 expression is tightly regulated by miR-1, which is activated by tachypacing-induced oxidative distress. In light of the high arrhythmogenic potential of altered Cx43 expression, we propose miR-1 as a novel target for pharmacological interventions to prevent the maladaptive remodeling processes during chronic distress in the heart.     

Betula alba Bark Extract and Empetrum nigrum Fruit Juice,a Natural Alternative to Niacinamide for Skin Barrier Benefits

The Scandinavian region is home to a unique biome with endemic plant species. The aim of this study was to explore this natural diversity and identify plant extracts providing positive skin barrier effects. Six plant extracts were identified as starting material. Following biochemical screening, two candidates outperformed the rest: Betula alba (BA) and Empetrum nigrum (EN). Quantitative PCR analysis showed that BA and EN upregulated barrier genes, when used individually and in combination. Betula alba increased AQP3 and OCLN protein expression, something niacinamide was incapable of. Additionally, the skin barrier was strengthened, evidenced by inhibition of KLK5 and hyaluronidase and showed strong antioxidant and anti-inflammatory activity through DPPH and COX2 inhibition, respectively. A first split-face clinical study was conducted using the combination of extracts versus placebo. There was a significantly better skin restructuring effect and corneocyte cohesion on the side treated with combined extracts. A second split-face clinical study assessed the combined extracts versus 3% niacinamide. Significant variations in skin hydration and TEWL were observed in favor of the extract treated side. In conclusion, we identified a natural alternative to niacinamide for improving skin barrier health, in Scandinavian plant extracts, which yield strong performance, but at a lower concentration.