Ultralow fouling polyacrylamide on gold surfaces via surface-initiated atom transfer radical polymerization

In this work, polyacrylamide is investigated as an ultralow fouling surface coating to highly resist protein adsorption, cell adhesion, and bacterial attachment. Polyacrylamide was grafted on gold surfaces via surface-initiated atom transfer radical polymerization (ATRP). Protein adsorption from a wide range of biological media, including single protein solutions of fibrinogen, bovine serum albumin, and lysozyme, dilute and undiluted human blood serum, and dilute and undiluted human blood plasma, was studied by surface plasmon resonance (SPR). Dependence of the protein resistance on polyacrylamide film thickness was examined. With the optimal film thickness, the adsorption amount of all three single proteins on polyacrylamide-grafted surfaces was <3 pg/mm(2), close to the detection limit of SPR. The average nonspecific adsorptions from 10% plasma, 10% serum, 100% plasma, and 100% serum onto the polyacrylamide-grafted surfaces were 5, 6.5, 17, and 28 pg/mm(2), respectively, comparable (if not better) than the adsorption levels on poly(ethylene glycol) (PEG) and zwitterionic poly(sulfobetaine methacrylate) surfaces, the best antifouling materials known to date. The polyacrylamide-grafted surfaces were also shown strongly resistant to adhesion from bovine aortic endothelial cells and two bacterial species, Gram-positive Staphylococcus epidermidis ( S. epidermidis ) and Gram-negative Pseudomonas aeruginosa ( P. aeruginosa ). Strong hydrogen bond with water is considered the key attribute for the ultralow fouling properties of polyacrylamide. This is the first work to graft gold surfaces with polyacrylamide brushes via ATRP to achieve ultralow fouling surfaces, demonstrating that polyacrylamide is a promising alternative to traditional PEG-based antifouling materials.     

Deferoxamine Preconditioning of Neural-Like Cells Derived from Human Wharton’s Jelly Mesenchymal Stem Cells as a Strategy to Promote Their Tolerance and Therapeutic Potential: An In Vitro Study

Transplantation of neural-like cells is considered as a promising therapeutic strategy developed for neurodegenerative disease in particular for ischemic stroke. Since cell survival is a major concern following cell implantation, a number of studies have underlined the protective effects of preconditioning with hypoxia or hypoxia mimetic pharmacological agents such as deferoxamine (DFO), induced by activation of hypoxia inducible factor-1 (HIF-1) and its target genes. The present study has investigated the effects of DFO preconditioning on some factors involved in cell survival, angiogenesis, and neurogenesis of neural-like cells derived from human Wharton’s jelly mesenchymal stem cells (HWJ-MSCs) in presence of hydrogen peroxide (H₂O₂). HWJ-MSCs were differentiated toward neural-like cells for 14 days and neural cell markers were identified using immunocytochemistry. HWJ-MSC-derived neural-like cells were then treated with 100 µM DFO, as a known hypoxia mimetic agent for 48 h. mRNA and protein expression of HIF-1 target genes including brain-derived neurotrophic factors (BDNF) and vascular endothelial growth factor (VEGF) significantly increased using RT-PCR and Western blotting which were reversed by HIF-1α inhibitor, while, gene expression of Akt-1, Bcl-2, and Bax did not change significantly but pAkt-1 was up-regulated as compared to poor DFO group. However, addition of H₂O₂ to DFO-treated cells resulted in higher resistance to H₂O₂-induced cell death. Western blotting analysis also showed significant up-regulation of HIF-1α, BDNF, VEGF, and pAkt-1, and decrease of Bax/Bcl-2 ratio as compared to poor DFO. These results may suggest that DFO preconditioning of HWJ-MSC-derived neural-like cells improves their tolerance and therapeutic potential and might be considered as a valuable strategy to improve cell therapy.     

APOA2 ?256T>C polymorphism interacts with saturated fatty acids intake to affect anthropometric and hormonal variables in type 2 diabetic patients

Recent studies have established the interaction between APOA2 −256T>C polymorphism and dietary saturated fatty acids intake in relation to obesity on healthy individuals. In the current study, we investigate the effects of this interaction on anthropometric variables and serum levels of leptin and ghrelin in patients with type 2 diabetes. In this cross-sectional study, 737 patients with type 2 diabetes mellitus (290 males and 447 females) were recruited from diabetes clinics in Tehran. The usual dietary intake of all participants during the last year was obtained by validated semiquantitative food frequency questionnaire. APOA2 genotyping was performed by real-time PCR on genomic DNA. No significant relation was obtained by univariate analysis between anthropometric variables and APOA2 genotypes. However, after adjusting for age, gender, physical activity and total energy intake, we identified a significant interaction between APOA2-saturated fatty acids intake and body mass index (BMI). After adjusting for potential confounders, serum levels of ghrelin in CC genotype patients were significantly higher than T allele carriers (p = 0.03), whereas the case with leptin did not reveal a significant difference. The result of this study confirmed the interaction between APOA2 −256T>C polymorphism and SFAs intake with BMI in type 2 diabetic patients. In fact, homozygous patients for the C allele with high saturated fatty acids intake had higher BMI. The APOA2 −256T>C polymorphism was associated with elevated levels of serum ghrelin.     

An Automated and Intelligent Medical Decision Support System for Brain MRI Scans Classification

A wide interest has been observed in the medical health care applications that interpret neuroimaging scans by machine learning systems. This research proposes an intelligent, automatic, accurate, and robust classification technique to classify the human brain magnetic resonance image (MRI) as normal or abnormal, to cater down the human error during identifying the diseases in brain MRIs. In this study, fast discrete wavelet transform (DWT), principal component analysis (PCA), and least squares support vector machine (LS-SVM) are used as basic components. Firstly, fast DWT is employed to extract the salient features of brain MRI, followed by PCA, which reduces the dimensions of the features. These reduced feature vectors also shrink the memory storage consumption by 99.5%. At last, an advanced classification technique based on LS-SVM is applied to brain MR image classification using reduced features. For improving the efficiency, LS-SVM is used with non-linear radial basis function (RBF) kernel. The proposed algorithm intelligently determines the optimized values of the hyper-parameters of the RBF kernel and also applied k-fold stratified cross validation to enhance the generalization of the system. The method was tested by 340 patients’ benchmark datasets of T1-weighted and T2-weighted scans. From the analysis of experimental results and performance comparisons, it is observed that the proposed medical decision support system outperformed all other modern classifiers and achieves 100% accuracy rate (specificity/sensitivity 100%/100%). Furthermore, in terms of computation time, the proposed technique is significantly faster than the recent well-known methods, and it improves the efficiency by 71%, 3%, and 4% on feature extraction stage, feature reduction stage, and classification stage, respectively. These results indicate that the proposed well-trained machine learning system has the potential to make accurate predictions about brain abnormalities from the individual subjects, therefore, it can be used as a significant tool in clinical practice.     

Adaptive control of movement deceleration during saccades

As you read this text, your eyes make saccades that guide your fovea from one word to the next. Accuracy of these movements require the brain to monitor and learn from visual errors. A current model suggests that learning is supported by two different adaptive processes, one fast (high error sensitivity, low retention), and the other slow (low error sensitivity, high retention). Here, we searched for signatures of these hypothesized processes and found that following experience of a visual error, there was an adaptive change in the motor commands of the subsequent saccade. Surprisingly, this adaptation was not uniformly expressed throughout the movement. Rather, after experience of a single error, the adaptive response in the subsequent trial was limited to the deceleration period. After repeated exposure to the same error, the acceleration period commands also adapted, and exhibited resistance to forgetting during set-breaks. In contrast, the deceleration period commands adapted more rapidly, but suffered from poor retention during these same breaks. State-space models suggested that acceleration and deceleration periods were supported by a shared adaptive state which re-aimed the saccade, as well as two separate processes which resembled a two-state model: one that learned slowly and contributed primarily via acceleration period commands, and another that learned rapidly but contributed primarily via deceleration period commands.     

A fluorescence-based reporter substrate for monitoring RNA editing in trypanosomatid pathogens

RNA editing regulates mitochondrial gene expression in trypanosomatid pathogens by creating functional mRNAs. It is catalyzed by a multi-protein complex (the editosome), and is found to be essential in both insect stage and mammalian blood stream form of Trypanosoma brucei. This particular form of RNA editing is unique to trypanosomatids, and thus provides a suitable drug target in trypanosomatid pathogens. Here, we demonstrate the feasibility of a rapid and sensitive fluorescence-based reporter assay to monitor RNA editing based on ribozyme activity. We could validate our new assay using previously identified inhibitors against the essential RNA editing ligase. The principle advantages of this assay are: (i) the use of non-radioactively labeled materials, (ii) sensitivity afforded by fluorescence instrumentation applicable to high-throughput screening of chemical inhibitors against the essential editosome and (iii) a rapid and convenient ‘mix and measure’ type of assay in low volume with a high signal to noise ratio. This assay should enhance rapid identification and characterization of the editosome inhibitors primarily based on the overall composition of the editosomes from T. brucei. These inhibitors could also be tested against the editosomes from the closely related pathogens including T. cruzi and Leishmania species.