Proteomic profile of acute myeloid leukaemia: A review update

Proteome analysis is a complex and dynamic process that encompasses several analytical platforms that include protein sequencing, structural or expression proteomics, protein modification, sub-cellular protein localization, protein-protein interaction and biological functional proteomics. In fact, expression proteomics is extensively applied in a majority of biomarker detection studies because it provides a detailed overview of differentially expressed proteins in cellular pathways and disease processes. Proteomics are also effective and dynamic in protein-protein interactions and cross-talks between interacting molecules of the cell. Proteomics has evolved into a crucial tool used to investigate the biochemical changes that possibly lead to development of cancer biomarkers. This review draws attention to the progress and advancements in cancer proteomics technology with the aim of simplifying the understanding of the mechanisms underlying the disease and to contribute to detection of biomarkers in addition to the development of novel treatments. Given that proteome is a dynamic entity of cellular functions in health and disease, it is capable of reflecting the immediate environmental state of cells and tissues as shown in this review. The review shows the possibility of elucidating the pathophysiology of acute myeloid leukaemia (AML) through proteome expressions, thus confirming the viability of proteome analysis in profiling AML.

Patterns of long-term settlement and land exploitation in the region of the Nile First Cataract (Egypt)

The First Cataract region (Egypt) has always played a crucial role as a border area and a crossroads for cultures and people living in adjacent landscapes. The region has its central point in the modern city of Aswan, but it extends up to the Kom Ombo Plain in the north and reaches the Bab el-Kalabsha in the south. Its eastern and western limits cannot be defined with the same precision, given that they are located in deserts. This research focused on the landscape analysis of the region intended as a complex entanglement of archaeological evidence in a geographical and natural environment whose changes impacted and, simultaneously, were influenced by human activities. Settlement patterns and land use can give interesting information on how these relationships worked from a diachronic perspective and how they shaped the region’s characteristics. To understand the links between the human presence and its evidence and the landscape of the First Cataract region, the integration of various datasets was needed, from historical and archaeological ones to the remote sensing observation of large areas. An area corresponding to ca. 18.000 km2 has been selected for this research. The chronological framework has been chosen to cover a considerable period, from the beginning of the 5th millennium BCE to the 7th century AD. Multi-temporality and multifunctionality appear as two essential aspects when the archaeological evidence of the First Cataract region is considered in its geographical and topographical setting as a general context for settlement patterns and resource exploitation analyses. A combination of remote sensing data and topographical materials has been integrated with archaeological evidence to obtain information about resource exploitation strategies and settlement adaptation from a diachronic perspective.

An Integrated Framework To Improve The Concept Of Resource Specialisation.

Resource specialisation, although a fundamental component of ecological theory, is employed in disparate ways. Most definitions derive from simple counts of resource species. We build on recent advances in ecophylogenetics and null model analysis to propose a concept of specialisation that comprises affinities among resources as well as their co-occurrence with consumers. In the distance-based specialisation index (DSI), specialisation is measured as relatedness (phylogenetic or otherwise) of resources, scaled by the null expectation of random use of locally available resources. Thus, specialists use significantly clustered sets of resources, whereas generalists use over-dispersed resources. Intermediate species are classed as indiscriminate consumers. The effectiveness of this approach was assessed with differentially restricted null models, applied to a data set of 168 herbivorous insect species and their hosts. Incorporation of plant relatedness and relative abundance greatly improved specialisation measures compared to taxon counts or simpler null models, which overestimate the fraction of specialists, a problem compounded by insufficient sampling effort. This framework disambiguates the concept of specialisation with an explicit measure applicable to any mode of affinity among resource classes, and is also linked to ecological and evolutionary processes. This will enable a more rigorous deployment of ecological specialisation in empirical and theoretical studies.

Platinum Blue Staining Of Cells Grown In Electrospun Scaffolds.

Fibroblast cells grown in electrospun polymer scaffolds were stained with platinum blue, a heavy metal stain, and imaged using scanning electron microscopy. Good contrast on the cells was achieved compared with samples that were gold sputter coated. The cell morphology could be clearly observed, and the cells could be distinguished from the scaffold fibers. Here we optimized the required concentration of platinum blue for imaging cells grown in scaffolds and show that a higher concentration causes platinum aggregation. Overall, platinum blue is a useful stain for imaging cells because of its enhanced contrast using scanning electron microscopy (SEM). In the future it would be useful to investigate cell growth and morphology using three-dimensional imaging methods.

The Prevalence Of The Metabolically Healthy Obese Phenotype In An Aging Population And Its Association With Subclinical Cardiovascular Disease: The Brazilian Study On Healthy Aging.

Current literature has elucidated a new phenotype, metabolically healthy obese (MHO), with risks of cardiovascular disease similar to that of normal weight individuals. Few studies have examined the MHO phenotype in an aging population, especially in association with subclinical CVD. This cross sectional study population consisted of 208 octogenarians and older. Anthropometrics, biochemical, and radiological parameters were measured to assess obesity, metabolic health (assessed by the National Cholesterol Education Program -Adult Treatment Panel (NCEP-ATP III) criteria), and subclinical measures of CVD. The prevalence of MHO was 13.5% (N = 28). No significant association with MHO was noted for age, coronary artery calcium score, cIMT, or hs-CRP > 3 mg/dl (p = NS). Our results suggest that the MHO phenotype exists in the elderly; however, subclinical CVD measures were not different in sub-group analysis suggesting traditional metabolic risk factor algorithms may not be accurate in the very elderly.

H alpha spectropolarimetry of the B[e] supergiant GG Carinae

Aims. We study the geometry of the circumstellar environment of the B[e] supergiant star GG Car. Methods. We present observations acquired using the IAGPOL imaging polarimeter in combination with the Eucalyptus-IFU spectrograph to obtain spectropolarimetric measurements of GG Car across Ha at two epochs. Polarization effects along the emission line are analysed using the Q-U diagram. In particular, the polarization position angle (PA) obtained using the line effect is able to constrain the symmetry axis of the disk/envelope. Results. By analysing the fluxes, GG Car shows an increase in its double-peaked Ha line emission relative to the continuum within the interval of our measurements (similar to 43 days). The depolarization line effect around Ha is evident in the Q-U diagram for both epochs, confirming that light from the system is intrinsically polarized. A rotation of the PA along Ha is also observed, indicating a counter-clockwise rotating disk. The intrinsic PA calculated using the line effect (similar to 85 degrees.) is consistent between our two epochs, suggesting a clearly defined symmetry axis of the disk.

Experimental studies of di-jet survival and surface emission bias in Au plus Au collisions via angular correlations with respect to back-to-back leading hadrons

We report first results from an analysis based on a new multi-hadron correlation technique, exploring jet-medium interactions and di-jet surface emission bias at the BNL Relativistic Heavy Ion Collider (RHIC). Pairs of back-to-back high-transverse-momentum hadrons are used for triggers to study associated hadron distributions. In contrast with two-and three-particle correlations with a single trigger with similar kinematic selections, the associated hadron distribution of both trigger sides reveals no modification in either relative pseudorapidity Delta eta or relative azimuthal angle Delta phi from d + Au to central Au + Au collisions. We determine associated hadron yields and spectra as well as production rates for such correlated back-to-back triggers to gain additional insights on medium properties.

Effects of Varenicline in Adult Smokers: A Multinational, 24-Week, Randomized, Double-Blind, Placebo-Controlled Study

Background: Prevalence rates of smoking are rising in developing countries. Previous trials evaluating the efficacy and tolerability of the smoking-cessation medication varenicline have used largely participants of Caucasian origin. Objective: This study was conducted to evaluate the efficacy and tolerability of varenicline in populations of participants from Latin America, Africa, and the Middle East to investigate potential differences in the therapeutic response to varenicline. Methods: This multinational, randomized, double-blind, placebo-controlled trial was conducted at 42 centers in 11 countries (Latin America: Brazil, Colombia, Costa Rica, Mexico, and Venezuela; Africa: Egypt and South Africa; Middle East: Jordan, Lebanon, Saudi Arabia, and the United Arab Emirates). Participants were male and female smokers aged 18 to 75 years who were motivated to stop smoking; smoked >= 10 cigarettes/d, with no cumulative period of abstinence >3 months in the previous year; and who had no serious or unstable disease within the previous 6 months. Subjects were randomized in a 2:1 ratio to receive varenicline 1 mg or placebo, BID for 12 weeks, with a 12-week nontreatment follow-up. Brief smoking-cessation counseling was provided. The main outcome measures were carbon monoxide confirmed continuous abstinence rate (CAR) at weeks 9 to 12 and weeks 9 to 24. Adverse events (AEs) were recorded for tolerability assessment. Results: Overall, 588 subjects (varenicline, 390; placebo, 198) were randomized and treated. The mean (SD) ages of subjects in the varenicline and placebo groups were 43.1 (10.8) and 43.9 (10.8) years, respectively; 57.7% and 65.7% were male; and the mean (SD) weights were 75.0 (16.0) and 76.7 (16.3) kg (range, 40.0-130.0 and 45.6-126.0 kg). CAR at weeks 9 to 12 was significantly higher with varenicline than with placebo (53.59% vs 18.69%; odds ratio [OR] = 5.76; 95% CI, 3.74-8.88; P < 0.0001), and this rate was maintained during weeks 9 to 24 (39.74% vs 13.13%; OR = 4.78; 95% CI, 2.97-7.68; P < 0.0001). Nausea, headache, and insomnia were the most commonly reported AEs with varenicline and were reported numerically more frequently in the varenicline group compared with the placebo group. Serious AEs (SAEs) were reported in 2.8% of varenicline recipients compared with 1.0% in the placebo group, with 6 subjects reporting psychiatric SAEs compared with none in the placebo group. Conclusion: Based on these data, varenicline was apparently efficacious and generally well tolerated as a smoking-cessation aid in smokers from selected sites in Latin America, Africa, and the Middle East. ClinicalTrials. gov identifier: NCT00594204. (Clin Ther. 2011;33:465-477) (C) 2011 Published by Elsevier HS Journals, Inc.

The influence of peripheral afferent signals on the rating of perceived exertion and time to exhaustion during exercise at different intensities

This study determined which peripheral variables would better predict the rating of perceived exertion (RPE) and time to exhaustion (TE) during exercise at different intensities. Ten men performed exercises at first lactate threshold (LT1), second lactate threshold (LT2), 50% of the distance from LT1 to LT2 (TT(50%)), and 25% of the distance from LT2 to maximal power output (TW(25%)). Lactate, catecholamines, potassium, pH, glucose, (V) over dotO(2), VE, HR, respiratory rate (RR) and RPE were measured and plotted against the exercise duration for the slope calculation. Glucose, dopamine, and noradrenaline predicted RPE in TT(50%) (88%), LT2 (64%), and TW(25%) (77%), but no variable predicted RPE in LT1. RPE (55%), RPE+HR (86%), and RPE+RR (92% and 55%) predicted TE in LT1, TT(50%), LT2, and TW(25%), respectively. At intensities from TT(50%) to TW(25%), variables associated with brain activity seem to explain most of the RPE slope, and RPE (+HR and+RR) seems to predict the TE.

Molecular characterization of a miraculin-like gene differentially expressed during coffee development and coffee leaf miner infestation

The characterization of a coffee gene encoding a protein similar to miraculin-like proteins, which are members of the plant Kunitz serine trypsin inhibitor (STI) family of proteinase inhibitors (PIs), is described. PIs are important proteins in plant defence against insects and in the regulation of proteolysis during plant development. This gene has high identity with the Richadella dulcifica taste-modifying protein miraculin and with the tomato protein LeMir; and was named as CoMir (Coffea miraculin). Structural protein modelling indicated that CoMir had structural similarities with the Kunitz STI proteins, but suggested specific folding structures. CoMir was up-regulated after coffee leaf miner (Leucoptera coffella) oviposition in resistant plants of a progeny derived from crosses between C. racemosa (resistant) and C. arabica (susceptible). Interestingly, this gene was down-regulated during coffee leaf miner herbivory in susceptible plants. CoMir expression was up-regulated after abscisic acid application and wounding stress and was prominent during the early stages of flower and fruit development. In situ hybridization revealed that CoMir transcripts accumulated in the anther tissues that display programmed cell death (tapetum, endothecium and stomium) and in the metaxylem vessels of the petals, stigma and leaves. In addition, the recombinant protein CoMir shows inhibitory activity against trypsin. According to the present results CoMir may act in proteolytic regulation during coffee development and in the defence against L. coffeella. The similarity of CoMir with other Kunitz STI proteins and the role of CoMir in plant development and plant stress are discussed.

On the mechanisms of phenothiazine-induced mitochondrial permeability transition: Thiol oxidation, strict Ca(2+) dependence, and cyt c release

Phenothiazines (PTZ) are drugs widely used in the treatment of schizophrenia. Trifluoperazine, a piperazinic PTZ derivative, has been described as inhibitor of the mitochondrial permeability transition (MPT). We reported previously the antioxidant activity of thioridazine at relatively low concentrations associated to the inhibition of the MPT (Brit. J. Pharmacol., 2002;136:136-142). In this study, it was investigated the induction of MPT by PTZ derivatives at concentrations higher than 10 mu M focusing on the molecular mechanism involved. PTZ promoted a dose-response mitochondrial swelling accompanied by mitochondrial transmembrane potential dissipation and calcium release, being thioridazine the most potent derivative. PTZ-induced MPT was partially inhibited by CsA or Mg(2+) and completely abolished by the abstraction of calcium. The oxidation of reduced thiol group of mitochondrial membrane proteins by PTZ was upstream the VIP opening and it was not sufficient to promote the opening of PTP that only occurred when calcium was present in the mitochondrial matrix. EPR experiments using DMPO as spin trapping excluded the participation of reactive oxygen species on the PTZ-induced MPT. Since 117 give rise to cation radicals chemically by the action of peroxidases and cyanide inhibited the PTZ-induced swelling, we propose that VIZ bury in the inner mitochondrial membrane and the chemically generated 117 cation radicals modify specific thiol groups that in the presence of Ca(2+) result in MPT associated to cytochrome c release. These findings contribute for the understanding of mechanisms of MET induction and may have implications for the cell death induced by PTZ. (C) 2010 Elsevier Inc. All rights reserved.

Molecular characterization of potentially zoonotic isolates of Giardia duodenalis in horses

Giardia isolates from eight horses from New York State (NY), USA and two horses from Western Australia (WA) were genetically characterized at the SSU-rDNA and triose-phosphate isomerase (TPI) genes. Phylogenetic analysis of the TPI gene provided strong support for the placement of both isolates of Giardia from horses in WA and a single isolate from a horse in NY within the assemblage AI genotype of G. duodenalis. Another two isolates from horses in NY placed within the assemblage All genotype of G. duodenalis. Phylogenetic analysis of the TPI gene also provided strong bootstrap support for the placement of four G. duodenalis isolates from horses in NY into a potentially host-specific sub-assemblage of assemblage BIV. The results of this study are consistent with previous studies showing that assemblages AI and AII of G. duodenalis provide the greatest potential zoonotic risk to humans. Horses may therefore constitute a potential source for human infection of Giardia either directly or via watersheds. (c) 2005 Elsevier B.V. All rights reserved.

A synergistic relationship of elevated low-density lipoprotein cholesterol levels and systolic blood pressure with coronary artery calcification

We sought to evaluate this ""response-to-injury"" hypothesis of atherosclerosis by studying the interaction between systolic blood pressure (SBP) and LDL-cholesterol (LDL-C) in predicting the presence of coronary artery calcification (CAC) in asymptomatic men. We Studied 526 men (46 +/- 7 years of age) referred for electron-beam tomography (EBT) exam. The prevalence of CAC was determined across LDL-C tertiles (low: <115 mg/dl; middle: 115-139 mg/dl high: >= 140 mg/dl) within tertiles of SBP (low: <121 mmHg; middle: 121-130 mmHg; high: >= 131 mmHg). CAC was found in 220 (42%) men. There was no linear trend in the presence of CAC across LDL-C tertiles in the low (p = 0.6 for trend) and middle (p = 0.3 for trend) SBP tertile groups, respectively. In contrast, there was a significant trend for increasing CAC with increasing LDL-C (1st: 44%; 2nd: 49%; 3rd: 83%; p < 0.0001 for trend) in the high SBP tertile group. In multivariate logistic analyses (adjusting for age, smoking, triglyceride levels, HDL-cholesterol levels, body mass index, and fasting glucose levels), the odds ratio for any CAC associated with increasing LDL-C was significantly higher in those with highest SBP levels, whereas no such relationship was observed among men with SBP in the lower two tertiles. An interaction term (LDL-C x SBP) incorporated in the multivariate analyses was statistically significant (p = 0.038). The finding of an interaction between SBP and LDL-C relation to CAC in asymptomatic men support the response-to-injury model of atherogenesis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Relation of Aortic Valve Calcium Detected by Cardiac Computed Tomography to All-Cause Mortality

Aortic valve calcium (AVC) can be quantified on the same computed tomographic scan as coronary artery calcium (CAC). Although CAC is an established predictor of cardiovascular events, limited evidence is available for an independent predictive value for AVC. We studied a cohort of 8,401 asymptomatic subjects (mean age 53 10 years, 69% men), who were free of known coronary heart disease and were undergoing electron beam computed tomography for assessment of subclinical atherosclerosis. The patients were followed for a median of 5 years (range 1 to 7) for the occurrence of mortality from any cause. Multivariate Cox regression models were developed to predict all-cause mortality according to the presence of AVC. A total of 517 patients (6%) had AVC on electron beam computed tomography. During follow-up, 124 patients died (1.5%), for an overall survival rate of 96.1% and 98.7% for those with and without AVC, respectively (hazard ratio 3.39, 95% confidence interval 2.09 to 5.49). After adjustment for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking, and a family history of premature coronary heart disease, AVC remained a significant predictor of mortality (hazard ratio 1.82, 95% confidence interval 1.11 to 2.98). Likelihood ratio chi-square statistics demonstrated that the addition of AVC contributed significantly to the prediction of mortality in a model adjusted for traditional risk factors (chi-square = 5.03, p = 0.03) as well as traditional risk factors plus the presence of CAC (chi-square = 3.58, p = 0.05). In conclusion, AVC was associated with increased all-cause mortality, independent of the traditional risk factors and the presence of CAC. (C) 2010 Published by Elsevier Inc. (Am J Cardiol 2010;106:1787-1791)