вторник, 19 февраля 2013 г.

Games

Games

Nutrients, Vol. 5, Pages 579-593: Effect of Malnutrition on the Expression of Cytokines Involved in Th1 Cell Differentiation

Posted: 19 Feb 2013 12:00 AM PST

Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response) and the production of cytokines related to the immunological cellular response (Th1 cytokines). We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines). In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21) are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular) response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections.

Sustainability, Vol. 5, Pages 774-778: Corporate Fraud and Internal Control: A Framework for Prevention. By Richard E. Cascarino, Wiley, 2013; 388 Pages. Price £50.00 / €60.00, ISBN 978-1-1183-0156-2

Posted: 19 Feb 2013 12:00 AM PST

The publication Corporate Fraud and Internal Control contains essential guidance for companies to examine and improve their fraud programs: Corporate governance legislation has become increasingly concerned with the ongoing resilience of organizations and, particularly, with their ability to resist corporate fraud from the lowest levels to the upper echelons of executive management. It has become unacceptable for those responsible for corporate governance to claim, "I didn't know". Corporate Fraud and Internal Control focuses on the appropriateness of the design of the system of internal controls in fraud risk mitigation, as well as the mechanisms to ensure effective implementation and monitoring on an ongoing basis. 

Cubed Rally Redline

Posted: 18 Feb 2013 08:43 PM PST

Platform: iOS — Cubed Rally Redline It's not often one can look at a racing game and say "Wow, that appeals to a wide audience!" Cubed Rally Redline is one of those games. Created by No Can Win, this pixel art racing game has more in common with mission-based arcade games like Jetpack Joyride than your average racer. Hit the track, jump a few ponds, dodge some cows, and see how far you can go without crashing. Tagged as: action, arcade, free, game, ios, ipad, iphone, microtransactions, mobile, nocanwin, racing, rating-y, tablet

Microorganisms, Vol. 1, Pages 1-2: Microorganisms—A Forum for Understanding Microbial Life in All Its Forms

Posted: 19 Feb 2013 12:00 AM PST

It is my great pleasure to welcome you to Microorganisms, a new open access journal, which is dedicated to microorganisms in all their forms and via any approach to their study.

Materials, Vol. 6, Pages 565-569: Atlas of Material Damage. By George Wypych, ChemTec Publishing, Year 2012; 310 Pages. Price $325.00, ISBN 978-1-895198-48-5

Posted: 19 Feb 2013 12:00 AM PST

Atlas of Material Damage has 464 microscopic pictures, schematic diagrams, and a few graphs, which show how materials fail, how they are produced to not fail, and how they are designed to perform particular functions to make outstanding products. Findings presented by each illustration are fully explained in the text and labeled.

Sensors, Vol. 13, Pages 2566-2578: Photonic Crystal Biosensor Based on Optical Surface Waves

Posted: 19 Feb 2013 12:00 AM PST

A label-free biosensor device based on registration of photonic crystal surface waves is described. Angular interrogation of the optical surface wave resonance is used to detect changes in the thickness of an adsorbed layer, while an additional simultaneous detection of the critical angle of total internal reflection provides independent data of the liquid refractive index. The abilities of the device are demonstrated by measuring of biotin molecule binding to a streptavidin monolayer, and by measuring association and dissociation kinetics of immunoglobulin G proteins. Additionally, deposition of PSS / PAH polyelectrolytes is recorded in situ resulting calculation of PSS and PAH monolayer thicknesses separately.

IJMS, Vol. 14, Pages 4185-4202: Phenotypic Identification of the Redox Dye Methylene Blue as an Antagonist of Heat Shock Response Gene Expression in Metastatic Melanoma Cells

Posted: 19 Feb 2013 12:00 AM PST

Repurposing approved and abandoned non-oncological drugs is an alternative developmental strategy for the identification of anticancer therapeutics that has recently attracted considerable attention. Due to the essential role of the cellular heat shock response in cytoprotection through the maintenance of proteostasis and suppression of apoptosis, small molecule heat shock response antagonists can be harnessed for targeted induction of cytotoxic effects in cancer cells. Guided by gene expression array analysis and a phenotypic screen interrogating a collection of 3,7-diamino-phenothiazinium derivatives, we have identified the redox-drug methylene blue (MB), used clinically for the infusional treatment of methemoglobinemia, as a negative modulator of heat shock response gene expression in human metastatic melanoma cells. MB-treatment blocked thermal (43 °C) and pharmacological (celastrol, geldanamycin) induction of heat shock response gene expression, suppressing Hsp70 (HSPA1A) and Hsp27 (HSPB1) upregulation at the mRNA and protein level. MB sensitized melanoma cells to the apoptogenic activity of geldanamycin, an Hsp90 antagonist known to induce the counter-regulatory upregulation of Hsp70 expression underlying cancer cell resistance to geldanamycin chemotherapy. Similarly, MB-cotreatment sensitized melanoma cells to other chemotherapeutics (etoposide, doxorubicin). Taken together, these data suggest feasibility of repurposing the non-oncological redox drug MB as a therapeutic heat shock response antagonist for cancer cell chemosensitization.

IJMS, Vol. 14, Pages 4174-4184: Preparation of Chitosan and Water-Soluble Chitosan Microspheres via Spray-Drying Method to Lower Blood Lipids in Rats Fed with High-Fat Diets

Posted: 19 Feb 2013 12:00 AM PST

This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs showed that the microspheres were nearly spherical in shape. The mean size of CTS microspheres was 4.07 μm (varying from 1.50 to 7.21 μm) and of WSC microspheres was 2.00 μm (varying from 0.85 to 3.58 μm). The rats were classified into eight groups (n = 8) and were fed with high-fat diets for two weeks to establish the hyperlipidemic condition and were then treated with CTS microspheres and WSC microspheres, CTS and WSC for four weeks. The results showed that CTS and WSC microspheres reduced blood lipids and plasma viscosity and increased the serum superoxide dismutase (SOD) levels significantly. This study is the first report of the lipid-lowering effects of CTS and WSC microspheres. CTS and WSC microspheres were found to be more effective in improving hyperlipidemia in rats than common CTS and WSC.

IJMS, Vol. 14, Pages 4163-4173: Brain Metastasis in Pancreatic Cancer

Posted: 19 Feb 2013 12:00 AM PST

Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival. Including our own, 12 cases of brain metastases originating from pancreatic cancer were identified. In three patients brain metastases were the first manifestation of pancreatic cancer. All other patients developed brain metastases during their clinical course. In most cases, the disease progressed rapidly and the patients died within weeks or months. However, two patients showed long-term survival. Of note, both patients received resection of the pancreatic cancer as well as curative resection of the metachronous brain metastases. Brain metastases in pancreatic cancer are a rare condition and usually predict a very poor prognosis. However, there is evidence that resection of brain metastases of pancreatic cancer can be immensely beneficial to patient’s survival, even with the chance for cure. Therefore, a surgical approach in metastatic pancreatic cancer should be considered in selective cases.

IJMS, Vol. 14, Pages 4148-4162: The Environmental Pollutant Cadmium Promotes Influenza Virus Replication in MDCK Cells by Altering Their Redox State

Posted: 19 Feb 2013 12:00 AM PST

Cadmium (Cd) is a toxic heavy metal that is considered an environmental contaminant. Several sources of human exposure to Cd, including employment in primary metal industries, production of certain batteries, foods, soil and cigarette smoke, are known. Its inhalation has been related to different respiratory diseases and toxic effects, among which alterations of the physiological redox state in individuals exposed to the metal have been described. Host-cell redox changes characteristic of oxidative stress facilitate the progression of viral infection through different mechanisms. In this paper, we have demonstrated that pre-treatment with CdCl2 of MDCK cells increased influenza virus replication in a dose-dependent manner. This phenomenon was related to increased viral protein expression (about 40% compared with untreated cells). The concentration of CdCl2, able to raise the virus titer, also induced oxidative stress. The addition of two antioxidants, a glutathione (GSH) derivative or the GSH precursor, N-acetyl-L-cysteine, to Cd pre-treated and infected cells restored the intracellular redox state and significantly inhibited viral replication. In conclusion, our data demonstrate that Cd-induced oxidative stress directly increases the ability of influenza virus to replicate in the host-cell, thus suggesting that exposure to heavy metals, such as this, could be a risk factor for individuals exposed to a greater extent to the contaminant, resulting in increased severity of virus-induced respiratory diseases.

Assassin’s Creed III: Tyranny of King Washington dev demo

Posted: 19 Feb 2013 01:50 AM PST

Assassin's Creed III's episodic DLC explores a rather intriguing concept: What if George Washington had established himself as a king rather than

IJMS, Vol. 14, Pages 4135-4147: 5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH)

Posted: 19 Feb 2013 12:00 AM PST

We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH). A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

IJMS, Vol. 14, Pages 4121-4134: Polymorphisms in XPD and ERCC1 Associated with Colorectal Cancer Outcome

Posted: 19 Feb 2013 12:00 AM PST

Using the comprehensive approach to selecting polymorphisms to date, we sought to examine whether recurrence in colorectal cancer was associated with inherited variation in three genes involved in DNA repair and cell proliferation. Three polymorphisms, which are excision repair cross-complementation 1 (ERCC1), xeroderma pigmentosum group D (XPD) and epidermal growth factor receptor (EGFR), were assessed in 257 postoperative stage II/III CRC patients with 5-fluorouracial chemotherapy in Taiwan. In addition, the correlations between genetic polymorphisms and patients’ clinicopathological features were investigated. Genotypes of XPD codon751 A/A and ERCC1 codon118 T/T were associated with regional recurrence in a statistically significant way (p = 0.018). Patients who carried XPD AA and ERCC1 TT genotypes demonstrated a significantly greater regional recurrence risk (OR = 5.625, 95% CI, 1.557–20.32). Inherited variation in XPD and ERCC1 was associated with outcome in patients with colorectal cancer in Taiwan. As the significant association of single-nucleotide polymorphisms has not been studied previously in colorectal cancer, these findings suggest novel sites of variation, in part explaining the range of treatment responses seen in this disease.

Molecules, Vol. 18, Pages 2376-2385: Free Radical Scavenging Activity of Kielmeyera variabilis (Clusiaceae)

Posted: 19 Feb 2013 12:00 AM PST

As part of our ongoing research on antioxidant agents from Brazilian flora, we screened the free radical scavenging activity of two extracts and eight fractions of Kielmeyera variabilis (Clusiaceae) using DPPH· (2,2-diphenyl-1-picrylhydrazyl-hydrate) and ABTS·+ [2,2'-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid)] colorimetric assays. The ethyl acetate and n-butanol fractions of the leaves of K. variabilis displayed the strongest activity (IC50 of 3.5 ± 0.3 and 4.4 ± 0.2 μg mL−1 for DPPH· and 6.6 ± 0.4 and 3.1 ± 0.1 μg mL−1 for ABTS·+, respectively). Chromatographic fractionation of the most potent fractions led to identification of three flavonols with previously described antioxidant activity, quercitrin (1), quercetin-3-O-b-glucoside (3), and quercetin-3-O-b-galactoside (4), and of one biflavone, podocarpusflavone A (2). This is the first time that the presence of these flavonoids in Kielmeyera variabilis has been reported.

Molecules, Vol. 18, Pages 2328-2375: Techniques for Analysis of Plant Phenolic Compounds

Posted: 19 Feb 2013 12:00 AM PST

Phenolic compounds are well-known phytochemicals found in all plants. They consist of simple phenols, benzoic and cinnamic acid, coumarins, tannins, lignins, lignans and flavonoids. Substantial developments in research focused on the extraction, identification and quantification of phenolic compounds as medicinal and/or dietary molecules have occurred over the last 25 years. Organic solvent extraction is the main method used to extract phenolics. Chemical procedures are used to detect the presence of total phenolics, while spectrophotometric and chromatographic techniques are utilized to identify and quantify individual phenolic compounds. This review addresses the application of different methodologies utilized in the analysis of phenolic compounds in plant-based products, including recent technical developments in the quantification of phenolics.

Metal Gear Solid - Videos and Trailers

Posted: 19 Feb 2013 12:04 AM PST

Cutting People Up In Metal Gear Rising: Revengeance

PS4 price: Sony reportedly considering £300

Posted: 19 Feb 2013 12:40 AM PST

Sony is reportedly considering a UK PlayStation 4 price of about £300.That's according to Murad Ahmed, technology reporter for UK broadsheet The Times,

Molecules, Vol. 18, Pages 2307-2327: 3-Substituted Prolines: From Synthesis to Structural Applications, from Peptides to Foldamers

Posted: 19 Feb 2013 12:00 AM PST

Among the twenty natural proteinogenic amino acids, proline is unique as its secondary amine forms a tertiary amide when incorporated into biopolymers, thus preventing hydrogen bond formation. Despite the lack of hydrogen bonds and thanks to conformational restriction of flexibility linked to the pyrrolidine ring, proline is able to stabilize peptide secondary structures such as b-turns or polyproline helices. These unique conformational properties have aroused a great interest in the development of proline analogues. Among them, proline chimeras are tools combining the proline restriction of flexibility together with the information brought by natural amino acids side chains. This review will focus on the chemical syntheses of 3-substituted proline chimeras of potential use for peptide syntheses and as potential use as tools for SAR studies of biologically active peptides and the development of secondary structure mimetics. Their influence on peptide structure will be briefly described.

Molecules, Vol. 18, Pages 2297-2306: Neglschisandrins E–F: Two New Lignans and Related Cytotoxic Lignans from Schisandra neglecta

Posted: 19 Feb 2013 12:00 AM PST

Phytochemical investigation of an ethanolic extract of stems of Schisandra neglecta led to the isolation and identification of two new dibenzocyclooctadiene lignans, designated neglschisandrins E (1) and F (2), and thirteen known lignans. All structures and stereochemistries were determined by spectroscopic methods, including 2D-NMR techniques. The isolates were evaluated for in vitro cytotoxic activity. Among them, compounds 2–6 exhibited moderate to weak cytotoxicity against the human colorectal carcinoma HCT-8 cell line with EC50 values of 7.33~19.8 μg/mL. In addition, compounds 2–4 also exhibited marginal cytotoxicity against the human lung carcinoma A549 cell line with EC50 values of 11.8~15.0 μg/mL.

Toxins, Vol. 5, Pages 363-375: On The Role of Natural Killer Cells in Neurodegenerative Diseases

Posted: 19 Feb 2013 12:00 AM PST

Natural killer (NK) cells exert important immunoregulatory functions by releasing several inflammatory molecules, such as IFN-γ and members of chemokines, which include CCL3/MIP-1α and CCL4/MIP-1β. These cells also express heptahelical receptors, which are coupled to heterotrimeric G proteins that guide them into inflamed and injured tissues. NK cells have been shown to recognize and destroy transformed cells and virally-infected cells, but their roles in neurodegenerative diseases have not been examined in detail. In this review, I will summarize the effects of NK cells in two neurodegenerative diseases, namely multiple sclerosis and globoid cell leukodystrophy. It is hoped that the knowledge obtained from these diseases may facilitate building rational protocols for treating these and other neurodegenerative or autoimmune diseases using NK cells and drugs that activate them as therapeutic tools.
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