Surface Electron-Hole Rich Species Active in the Electrocatalytic Water Oxidation

Iridium and ruthenium and their oxides/hydroxides are the best candidates for the oxygen evolution reaction under harsh acidic conditions owing to the low overpotentials observed for Ru- and Ir-based anodes and the high corrosion resistance of Ir-oxides. Herein, by means of cutting edge operando surface and bulk sensitive X-ray spectroscopy techniques, specifically designed electrode nanofabrication and ab initio DFT calculations, we were able to reveal the electronic structure of the active IrOx centers (i.e., oxidation state) during electrocatalytic oxidation of water in the surface and bulk of high-performance Ir-based catalysts. We found the oxygen evolution reaction is controlled by the formation of empty Ir 5d states in the surface ascribed to the formation of formally IrV species leading to the appearance of electron-deficient oxygen species bound to single iridium atoms (μ1-O and μ1-OH) that are responsible for water activation and oxidation. Oxygen bound to three iridium centers (μ3-O) remains the dominant species in the bulk but do not participate directly in the electrocatalytic reaction, suggesting bulk oxidation is limited. In addition a high coverage of a μ1-OO (peroxo) species during the OER is excluded. Moreover, we provide the first photoelectron spectroscopic evidence in bulk electrolyte that the higher surface-to-bulk ratio in thinner electrodes enhances the material usage involving the precipitation of a significant part of the electrode surface and near-surface active species

Association of Alpha B-Crystallin Genotypes with Oral Cancer Susceptibility, Survival, and Recurrence in Taiwan

BACKGROUND: Alpha B-crystallin (CRYAB) is a protein that functions as "molecular chaperone" in preserving intracellular architecture and cell membrane. Also, CRYAB is highly antiapoptotic. Abnormal CRYAB expression is a prognostic biomarker for oral cancer, while its genomic variations and the association with carcinogenesis have never been studied. METHODOLOGY/FINDING: Therefore, we hypothesized that CRYAB single nucleotide polymorphisms may be associated with oral cancer risk. In this hospital-based study, the association of CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron2 (rs2070894) polymorphisms with oral cancer in a Taiwan population was investigated. In total, 496 oral cancer patients and 992 age- and gender-matched healthy controls were genotyped and analyzed. A significantly different frequency distribution was found in CRYAB C-802G genotypes, but not in A-1215G and intron2 genotypes, between the oral cancer and control groups. The CRYAB C-802G G allele conferred an increased risk of oral cancer (P = 1.49×10(-5)). Patients carrying CG/GG at CRYAB C-802G were of lower 5-year survival and higher recurrence rate than those of CC (P<0.05). CONCLUSION/SIGNIFICANCE: Our results provide the first evidence that the G allele of CRYAB C-802G is correlated with oral cancer risk and this polymorphism may be a useful marker for oral cancer recurrence and survival prediction for clinical reference

Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: An analysis of the phase 3 REACH study

Background: Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH. Methods: Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed. Results: Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P &lt; 0.0001) and to radiographic progression (HR 0.613; P &lt; 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P &lt; 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P &lt; 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P &lt; 0.0001). Conclusions: Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes

An algorithm to assess methodological quality of nutrition and mortality cross-sectional surveys: development and application to surveys conducted in Darfur, Sudan

Background Nutrition and mortality surveys are the main tools whereby evidence on the health status of populations affected by disasters and armed conflict is quantified and monitored over time. Several reviews have consistently revealed a lack of rigor in many surveys. We describe an algorithm for analyzing nutritional and mortality survey reports to identify a comprehensive range of errors that may result in sampling, response, or measurement biases and score quality. We apply the algorithm to surveys conducted in Darfur, Sudan. Methods We developed an algorithm based on internationally agreed upon methods and best practices. Penalties are attributed for a list of errors, and an overall score is built from the summation of penalties accrued by the survey as a whole. To test the algorithm reproducibility, it was independently applied by three raters on 30 randomly selected survey reports. The algorithm was further applied to more than 100 surveys conducted in Darfur, Sudan. Results The Intra Class Correlation coefficient was 0.79 for mortality surveys and 0.78 for nutrition surveys. The overall median quality score and range of about 100 surveys conducted in Darfur were 0.60 (0.12-0.93) and 0.675 (0.23-0.86) for mortality and nutrition surveys, respectively. They varied between the organizations conducting the surveys, with no major trend over time. Conclusion Our study suggests that it is possible to systematically assess quality of surveys and reveals considerable problems with the quality of nutritional and particularly mortality surveys conducted in the Darfur crisis.BioMed Central Open acces

Functional genomics reveals serine synthesis is essential in PHGDH-amplified breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation[superscript 1, 2]. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes[superscript 3]. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.Susan G. Komen Breast Cancer Foundation (Fellowship)Life Sciences Research Foundation (Fellowship)W. M. Keck FoundationDavid H. Koch Cancer Research FundAlexander and Margaret Stewart TrustNational Institutes of Health (U.S.) (Grant CA103866

Landscape Mapping of Functional Proteins in Insulin Signal Transduction and Insulin Resistance: A Network-Based Protein-Protein Interaction Analysis

The type 2 diabetes has increased rapidly in recent years throughout the world. The insulin signal transduction mechanism gets disrupted sometimes and it's known as insulin-resistance. It is one of the primary causes associated with type-2 diabetes. The signaling mechanisms involved several proteins that include 7 major functional proteins such as INS, INSR, IRS1, IRS2, PIK3CA, Akt2, and GLUT4. Using these 7 principal proteins, multiple sequences alignment has been created. The scores between sequences also have been developed. We have constructed a phylogenetic tree and modified it with node and distance. Besides, we have generated sequence logos and ultimately developed the protein-protein interaction network. The small insulin signal transduction protein arrangement shows complex network between the functional proteins

Polysaccharides from Agaricus bisporus and Agaricus brasiliensis show similarities in their structures and their immunomodulatory effects on human monocytic THP-1 cells

<p>Abstract</p> <p>Background</p> <p>Mushroom polysaccharides have traditionally been used for the prevention and treatment of a multitude of disorders like infectious illnesses, cancers and various autoimmune diseases. Crude mushroom extracts have been tested without detailed chemical analyses of its polysaccharide content. For the present study we decided to chemically determine the carbohydrate composition of semi-purified extracts from 2 closely related and well known basidiomycete species, i.e. <it>Agaricus bisporus </it>and <it>A. brasiliensis </it>and to study their effects on the innate immune system, in particular on the <it>in vitro </it>induction of pro-inflammatory cytokines, using THP-1 cells.</p> <p>Methods</p> <p>Mushroom polysaccharide extracts were prepared by hot water extraction and precipitation with ethanol. Their composition was analyzed by GC-MS and NMR spectroscopy. PMA activated THP-1 cells were treated with the extracts under different conditions and the production of pro-inflammatory cytokines was evaluated by qPCR.</p> <p>Results</p> <p>Semi-purified polysaccharide extracts of <it>A. bisporus </it>and <it>A. brasiliensis </it>(= <it>blazei</it>) were found to contain (1→6),(1→4)-linked α-glucan, (1→6)-linked β-glucan, and mannogalactan. Their proportions were determined by integration of ¹H-NMR signs, and were considerably different for the two species. <it>A. brasiliensis </it>showed a higher content of β-glucan, while <it>A. bisporus </it>presented mannogalactan as its main polysaccharide. The extracts induced a comparable increase of transcription of the pro-inflammatory cytokine genes IL-1β and TNF-α as well as of COX-2 in PMA differentiated THP-1 cells. Pro-inflammatory effects of bacterial LPS in this assay could be reduced significantly by the simultaneous addition of <it>A. brasiliensis </it>extract.</p> <p>Conclusions</p> <p>The polysaccharide preparations from the closely related species <it>A. bisporus </it>and <it>A. brasiliensis </it>show major differences in composition: <it>A. bisporus </it>shows high mannogalactan content whereas <it>A. brasiliensis </it>has mostly β-glucan. Semi-purified polysaccharide extracts from both <it>Agaricus </it>species stimulated the production of pro-inflammatory cytokines and enzymes, while the polysaccharide extract of <it>A. brasiliensis </it>reduced synthesis of these cytokines induced by LPS, suggesting programmable immunomodulation.</p

A High-Temporal Resolution Technology for Dynamic Proteomic Analysis Based on 35S Labeling

As more and more research efforts have been attracted to dynamic or differential proteomics, a method with high temporal resolution and high throughput is required. In present study, a 35S in vivo Labeling Analysis for Dynamic Proteomics (SiLAD) was designed and tested by analyzing the dynamic proteome changes in the highly synchronized A549 cells, as well as in the rat liver 2/3 partial hepatectomy surgery. The results validated that SiLAD technique, in combination with 2-Dimensional Electrophoresis, provided a highly sensitivity method to illustrate the non-disturbed endogenous proteins dynamic changes with a good temporal resolution and high signal/noise ratio. A significant number of differential proteins can be discovered or re-categorized by this technique. Another unique feature of SiLAD is its capability of quantifying the rate of protein expression, which reflects the cellular physiological turn points more effectively. Finally, the prescribed SiLAD proteome snapshot pattern could be potentially used as an exclusive symbol for characterizing each stage in well regulated biological processes