ProtQuant: a tool for the label-free quantification of MudPIT proteomics data

<p>Abstract</p> <p>Background</p> <p>Effective and economical methods for quantitative analysis of high throughput mass spectrometry data are essential to meet the goals of directly identifying, characterizing, and quantifying proteins from a particular cell state. Multidimensional Protein Identification Technology (MudPIT) is a common approach used in protein identification. Two types of methods are used to detect differential protein expression in MudPIT experiments: those involving stable isotope labelling and the so-called label-free methods. Label-free methods are based on the relationship between protein abundance and sampling statistics such as peptide count, spectral count, probabilistic peptide identification scores, and sum of peptide Sequest XCorr scores (ΣXCorr). Although a number of label-free methods for protein quantification have been described in the literature, there are few publicly available tools that implement these methods. We describe ProtQuant, a Java-based tool for label-free protein quantification that uses the previously published ΣXCorr method for quantification and includes an improved method for handling missing data.</p> <p>Results</p> <p><it>ProtQuant </it>was designed for ease of use and portability for the bench scientist. It implements the ΣXCorr method for label free protein quantification from MudPIT datasets. <it>ProtQuant </it>has a graphical user interface, accepts multiple file formats, is not limited by the size of the input files, and can process any number of replicates and any number of treatments. In addition,<it>ProtQuant </it>implements a new method for dealing with missing values for peptide scores used for quantification. The new algorithm, called ΣXCorr*, uses "below threshold" peptide scores to provide meaningful non-zero values for missing data points. We demonstrate that ΣXCorr* produces an average reduction in false positive identifications of differential expression of 25% compared to ΣXCorr.</p> <p>Conclusion</p> <p><it>ProtQuant </it>is a tool for protein quantification built for multi-platform use with an intuitive user interface. <it>ProtQuant </it>efficiently and uniquely performs label-free quantification of protein datasets produced with Sequest and provides the user with facilities for data management and analysis. Importantly, <it>ProtQuant </it>is available as a self-installing executable for the Windows environment used by many bench scientists.</p

Rabies Situation in Cambodia

In Cambodia, rabies still elicits fear in the communities. Since 1998 the Institut Pasteur in Cambodia (IPC), Phnom Penh has been the only source of free post-exposure prophylaxis (PEP) and post mortem diagnosis. During 1998–2007, on average ∼12,400 patients received PEP annually at IPC (range 8,907–14,475) and 63 fatal human cases presenting with encephalitis following a dog bite were reported including 73% who tested positive by fluorescent-antibody test on brain samples or/and by reverse-transcriptase polymerase chain reaction on skin, cerebrospinal fluid, or urine. In 2007, 14,475 patients received PEP (100 PEP/100,000 people in Cambodia) including 95% who resided in Phnom Penh city (615 PEP/100,000) or five neighboring provinces. Using a step-by-step probability model, we estimated that 810 human rabies deaths would occur in 2007 (95% confidence interval [CI] 394–1,607); an incidence of 5.8/100,000 (95%CI 2.8–11.5). As a result, despite high attendance at the IPC's PEP center most Cambodians living in peripheral provinces in Cambodia may not have adequate access to PEP. Finally, the model generated one of the highest incidences of rabies worldwide. A national rabies control program is needed to improve surveillance and access to PEP, and to initiate vaccination campaigns in dogs

Enzyme classification with peptide programs: a comparative study

<p>Abstract</p> <p>Background</p> <p>Efficient and accurate prediction of protein function from sequence is one of the standing problems in Biology. The generalised use of sequence alignments for inferring function promotes the propagation of errors, and there are limits to its applicability. Several machine learning methods have been applied to predict protein function, but they lose much of the information encoded by protein sequences because they need to transform them to obtain data of fixed length.</p> <p>Results</p> <p>We have developed a machine learning methodology, called peptide programs (PPs), to deal directly with protein sequences and compared its performance with that of Support Vector Machines (SVMs) and BLAST in detailed enzyme classification tasks. Overall, the PPs and SVMs had a similar performance in terms of Matthews Correlation Coefficient, but the PPs had generally a higher precision. BLAST performed globally better than both methodologies, but the PPs had better results than BLAST and SVMs for the smaller datasets.</p> <p>Conclusion</p> <p>The higher precision of the PPs in comparison to the SVMs suggests that dealing with sequences is advantageous for detailed protein classification, as precision is essential to avoid annotation errors. The fact that the PPs performed better than BLAST for the smaller datasets demonstrates the potential of the methodology, but the drop in performance observed for the larger datasets indicates that further development is required.</p> <p>Possible strategies to address this issue include partitioning the datasets into smaller subsets and training individual PPs for each subset, or training several PPs for each dataset and combining them using a bagging strategy.</p

Associations between severity of obesity in childhood and adolescence, obesity onset and parental BMI: a longitudinal cohort study

Objective: To explore the relationship between severity of obesity at age 7 and age 15, age at onset of obesity, and parental body mass index (BMI) in obese children and adolescents. Design: Longitudinal cohort study.Subjects:Obese children (n231) and their parents (n462) from the Swedish National Childhood Obesity Centre. Methods: Multivariate regression analyses were applied with severity of obesity (BMI standard deviation score (BMI SDS)) and onset of obesity as dependent variables. The effect of parental BMI was evaluated and in the final models adjusted for gender, parental education, age at onset of obesity, severity of obesity at age 7 and obesity treatment. Results: For severity of obesity at age 7, a positive correlation with maternal BMI was indicated (P<0.05). Severity of obesity at this age also showed a strong negative correlation with the age at onset of obesity. Severity of obesity at age 15 was significantly correlated with both maternal and paternal BMI (P≥0.01). In addition, BMI SDS at age 15 differed by gender (higher for boys) and was positively correlated with severity of obesity at age 7 and negatively correlated with treatment. Also, a negative correlation was indicated at this age for parental education. No correlation with age at onset was found at age 15. For age at onset of obesity there was no relevant correlation with parental BMI. Children within the highest tertile of the BMI SDS range were more likely to have two obese parents. Conclusion: The impact of parental BMI on the severity of obesity in children is strengthened as the child grows into adolescence, whereas the age at onset is probably of less importance than previously thought. The influence of parental relative weight primarily affects the severity of childhood obesity and not the timing. © 2011 Macmillan Publishers Limited All rights reserved.link_to_subscribed_fulltex

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Survey of Activated FLT3 Signaling in Leukemia

Activating mutations of FMS-like tyrosine kinase-3 (FLT3) are found in approximately 30% of patients with acute myeloid leukemia (AML). FLT3 is therefore an attractive drug target. However, the molecular mechanisms by which FLT3 mutations lead to cell transformation in AML remain unclear. To develop a better understanding of FLT3 signaling as well as its downstream effectors, we performed detailed phosphoproteomic analysis of FLT3 signaling in human leukemia cells. We identified over 1000 tyrosine phosphorylation sites from about 750 proteins in both AML (wild type and mutant FLT3) and B cell acute lymphoblastic leukemia (normal and amplification of FLT3) cell lines. Furthermore, using stable isotope labeling by amino acids in cell culture (SILAC), we were able to quantified over 400 phosphorylation sites (pTyr, pSer, and pThr) that were responsive to FLT3 inhibition in FLT3 driven human leukemia cell lines. We also extended this phosphoproteomic analysis on bone marrow from primary AML patient samples, and identify over 200 tyrosine and 800 serine/threonine phosphorylation sites in vivo. This study showed that oncogenic FLT3 regulates proteins involving diverse cellular processes and affects multiple signaling pathways in human leukemia that we previously appreciated, such as Fc epsilon RI-mediated signaling, BCR, and CD40 signaling pathways. It provides a valuable resource for investigation of oncogenic FLT3 signaling in human leukemia

Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice

10.1038/srep03754Scientific Reports4

Rationally designed transition metal hydroxide nanosheet arrays on graphene for artificial CO2 reduction

The performance of transition metal hydroxides, as cocatalysts for CO2 photoreduction, is significantly limited by their inherent weaknesses of poor conductivity and stacked structure. Herein, we report the rational assembly of a series of transition metal hydroxides on graphene to act as a cocatalyst ensemble for efficient CO2 photoreduction. In particular, with the Ru-dye as visible light photosensitizer, hierarchical Ni(OH)2 nanosheet arrays-graphene (Ni(OH)2-GR) composites exhibit superior photoactivity and selectivity, which remarkably surpass other counterparts and most of analogous hybrid photocatalyst system. The origin of such superior performance of Ni(OH)2-GR is attributed to its appropriate synergy on the enhanced adsorption of CO2, increased active sites for CO2 reduction and improved charge carriers separation/transfer. This work is anticipated to spur rationally designing efficient earth-abundant transition metal hydroxides-based cocatalysts on graphene and other two-dimension platforms for artificial reduction of CO2 to solar chemicals and fuels

Alzheimer's Disease: a Review of its Visual System Neuropathology. Optical Coherence Tomography-a Potential Role As a Study Tool in Vivo

Alzheimer's disease (AD) is a prevalent, long-term progressive degenerative disorder with great social impact. It is currently thought that, in addition to neurodegeneration, vascular changes also play a role in the pathophysiology of the disease. Visual symptoms are frequent and are an early clinical manifestation; a number of psychophysiologic changes occur in visual function, including visual field defects, abnormal contrast sensitivity, abnormalities in color vision, depth perception deficits, and motion detection abnormalities. These visual changes were initially believed to be solely due to neurodegeneration in the posterior visual pathway. However, evidence from pathology studies in both animal models of AD and humans has demonstrated that neurodegeneration also takes place in the anterior visual pathway, with involvement of the retinal ganglion cells' (RGCs) dendrites, somata, and axons in the optic nerve. These studies additionally showed that patients with AD have changes in retinal and choroidal microvasculature. Pathology findings have been corroborated in in-vivo assessment of the retina and optic nerve head (ONH), as well as the retinal and choroidal vasculature. Optical coherence tomography (OCT) in particular has shown great utility in the assessment of these changes, and it may become a useful tool for early detection and monitoring disease progression in AD. The authors make a review of the current understanding of retinal and choroidal pathological changes in patients with AD, with particular focus on in-vivo evidence of retinal and choroidal neurodegenerative and microvascular changes using OCT technology.info:eu-repo/semantics/publishedVersio