Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival

An unbiased proteomic screen to identify integrin-linked kinase (ILK) interactors revealed rictor as an ILK-binding protein. This finding was interesting because rictor, originally identified as a regulator of cytoskeletal dynamics, is also a component of mammalian target of rapamycin complex 2 (mTORC2), a complex implicated in Akt phosphorylation. These functions overlap with known ILK functions. Coimmunoprecipitation analyses confirmed this interaction, and ILK and rictor colocalized in membrane ruffles and leading edges of cancer cells. Yeast two-hybrid assays showed a direct interaction between the NH(2)- and COOH-terminal domains of rictor and the ILK kinase domain. Depletion of ILK and rictor in breast and prostate cancer cell lines resulted in inhibition of Akt Ser(473) phosphorylation and induction of apoptosis, whereas, in several cell lines, depletion of mTOR increased Akt phosphorylation. Akt and Ser(473)P-Akt were detected in ILK immunoprecipitates and small interfering RNA-mediated depletion of rictor, but not mTOR, inhibited the amount of Ser(473)P-Akt in the ILK complex. Expression of the NH(2)-terminal (1-398 amino acids) rictor domain also resulted in the inhibition of ILK-associated Akt Ser(473) phosphorylation. These data show that rictor regulates the ability of ILK to promote Akt phosphorylation and cancer cell survival.     

Transparent and accurate reporting increases reliability,utility, and impact of your research: reporting guidelines and the EQUATOR Network

Although current electronic methods of scientific publishing offer increased opportunities for publishing all research studies and describing them in sufficient detail, health research literature still suffers from many shortcomings. These shortcomings seriously undermine the value and utility of the literature and waste scarce resources invested in the research. In recent years there have been several positive steps aimed at improving this situation, such as a strengthening of journals' policies on research publication and the wide requirement to register clinical trials.     

Clinical determinants of primary and secondary fatigue in patients with Parkinson’s disease

Clinical and psychosocial factors associated separately with primary and secondary fatigue in Parkinson’s disease (PD) patients have not been thoroughly studied before. The aim of our study was to assess factors associated with different fatigue domains in groups with primary and secondary fatigue in PD separately. We divided 165 non-demented PD patients according to the absence/presence of depression, anxiety and excessive somnolence into groups with primary fatigue (N = 63) and with secondary fatigue (N = 102). Fatigue domains examined using the multidimensional fatigue inventory were associated through multiple linear regression analyses for each group separately with sociodemographic data, disease duration, functional status as assessed by the Unified Parkinson’s Disease Rating Scale, treatment, depression, anxiety, excessive somnolence and sleep quality. Out of the assessed non-motor symptoms, fatigue was the most frequent (77.6 %). The prevalence of fatigue in the secondary fatigue group was significantly higher than in the primary fatigue group. Both fatigue groups differed significantly in factors associated with different fatigue domains. Functional status or other disease-related factors were not associated with primary fatigue. In the secondary fatigue group, we found associations between some fatigue domains and functional status, older age, male gender and higher anxiety scores. To our knowledge, this is the first study to separately describe clinical determinants and psychosocial factors associated with different fatigue domains in primary and secondary fatigue in PD, underlining the importance of distinguishing primary and secondary fatigue in future PD studies and clinical practice.     

Combination of Extrusion and Fermentation with Lactobacillus plantarum and L. uvarum Strains for Improving the Safety Characteristics of Wheat Bran

Processed wheat bran (W) is of great importance for food and feed. Consequently, the biosafety of W should be evaluated and improved with valorisation strategies. This study tested a design combining extrusion (at temperature of 115 and 130 °C; screw speeds of 16, 20, and 25 rpm) and fermentation with Lactobacillus plantarum and L. uvarum strains for the valorisation of W to provide safer food and feed stock. The influence of different treatments on biogenic amine formation, mycotoxin content, and free amino acids, as well as acidity, microbiological parameters, and sugar concentration, were analysed. This research showed that a combination of extrusion and fermentation with selected strains can change several aspects of W characteristics. There was a significant effect of applied treatments on acidity and the microbiological parameters of W, as well as biogenic amines content. The lowest total mycotoxin concentration (29.8 µg/kg) was found in extruded (130 °C; 25 rpm) and fermented with L. uvarum sample. Finally, the combination of the abovementioned treatments can be confirmed as a prospective innovative pre-treatment for W, capable of potentially enhancing their safety characteristics and composition.     

Prevalence and characteristics of noncompliant behaviour and its risk factors in kidney transplant recipients

Noncompliance with therapy is one possible explanation for the observation that long-term graft survival is not sufficiently improved by the development in immunosuppression. The aim of the study was to explore the prevalence, characteristics and risk factors of noncompliance with immunosuppression. A total of 161 adult kidney transplant recipients were interviewed about their self-rated health, social support, education, stress from adverse effects and compliance with the immunosuppression. The prevalence of subclinical noncompliance was 54%. Noncompliant patients declared significantly worse self-rated health, less satisfaction with social support and higher stress from adverse effects. Male gender (OR 7.5, CI 2.4-23.39), high stress from adverse effects (OR 12.27, CI 2.44-61.88), fair self-rated health (OR 4.45, CI 1.04-19.55) and fair satisfaction with social support (OR 4.55, CI 1.08-19.24) were predictors of noncompliance. Standardized detection methods should be developed with the aim of identifying patients who are at risk of noncompliance in order to prevent graft loss.     

Significant functional differences in differentiated Conditionally Reprogrammed (CRC)- and Feeder-free Dual SMAD inhibited-expanded human nasal epithelial cells

BackgroundPatient-derived airway cells differentiated at Air Liquid Interface (ALI) are valuable models for Cystic fibrosis (CF) precision therapy. Different culture expansion methods have been established to extend expansion capacity of airway basal cells, while retaining functional airway epithelium physiology. Considerable variation in response to CFTR modulators is observed in cultures even within the same CFTR genotype and despite the use of similar ALI culture techniques. We aimed to address culture expansion method impact on differentiation.MethodsNasal epithelial brushings from 14 individuals (CF=9; non-CF=5) were collected, then equally divided and expanded under conditional reprogramming culture (CRC) and feeder-serum-free “dual-SMAD inhibition” (SMADi) methods. Expanded cells from each culture were differentiated with proprietary PneumaCult?-ALI media. Morphology (Immunofluorescence), global proteomics (LC-MS/MS) and function (barrier integrity, cilia motility, and ion transport) were compared in CRC^ALI and SMADi^ALI under basal and CFTR corrector treated (VX-809) conditions.ResultsNo significant difference in the structural morphology or baseline global proteomics profile were observed. Barrier integrity and cilia motility were significantly different, despite no difference in cell junction morphology or cilia abundance. Epithelial Sodium Channels and Calcium-activated Chloride Channel activity did not differ but CFTR mediated chloride currents were significantly reduced in SMADi^ALI compare to their CRC^ALI counterparts.ConclusionAlteration of cellular physiological function in vitro were more prominent than structural and differentiation potential in airway ALI. Since initial expansion culture conditions significantly influence CFTR activity, this could lead to false conclusions if data from different labs are compared against each other without specific reference ranges.     

Preparation of Cast Metallic Foams with Irregular and Regular Inner Structure

The aim of this paper is to summarize the possibilities of foundry methods for the production of metallic foams. At present, there are a number of production technologies for this interesting material, to which increasing attention has been paid in recent years. What is unique about metallic foams is the combination of their physical and mechanical properties. As part of our research, we designed and verified four main methods of metallic foam production by the foundry technology, whose products are metallic foam castings with regular and irregular arrangements of internal cavities. All these methods use materials and processes commonly used in conventional foundry technologies. The main idea of the research is to highlight such technologies for the production of metallic foams that could be provided by manufacturing companies without the need to introduce changes in production. Moreover, foundry methods for the production of metallic foams have the unique advantage of being able to produce even complex shaped parts and can thus be competitive compared to today’s established technologies, the output of which is usually only a semi-finished product for further processing. This fact was the main motivation for the research.     

An Effect of Oak‐Wood Extract (Robuvit®) on Energy State of Healthy Adults—A Pilot Study

The purpose of our study was to examine the psychological benefits of the treatment with Robuvit® (Horphag Research Ltd.) – polyphenolic extract obtained from the wood of oak Quercus robur – on the healthy elderly individuals using energy subscale scores of the Activation – Deactivation Adjective Check List. Analysis was focused on the comparison of pre‐post treatment effect of Robuvit on symptoms of fatigue. In the total group of volunteers, significant increase of average question scores was found in three of four subscales of feelings (energy, tiredness, and tension) after 4 weeks of Robuvit administration. Effects of extract were observed mainly after stratification of total group of volunteers according to the level of feeling at the pre‐treatment questionnaire. Our results demonstrate positive effect of Robuvit on mental and energy level in healthy human without any unwanted side effects. © 2015 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.     

Synthesis and Effect of the Structure of Bithienyl-Terminated Surfactants for Dielectric Layer Modification in Organic Transistor

A series of bithienyl-terminated surfactants with various alkyl chain lengths (from C8 to C13) and phosphono or chlorodimethylsilyl anchoring groups were synthesized by palladium-catalyzed hydrophosphonation, or platinum-catalyzed hydrosilylation as a key step. Surfactants were tested in pentacene or α-sexithiophene-based organic field-effect transistors (OFETs) for the modification of the dielectric surface. The studied surfactants increased the effective mobility of the α-sexithiophene-based device by up to one order of magnitude. The length of alkyl chain showed to be significant for the pentacene-based device, as the effective mobility only increased in the case of dielectric modification with bithienylundecylphosphonic acid. AFM allowed a better understanding of the morphology of semiconductors on bare SiO₂ and surfaces treated with bithienylundecylphosphonic acid.