Over‐Expression of RNA Processing,Heat Shock,and DNA Repair Proteins in Breast Tumor Compared to Normal Tissue

This study identifies the main changes in protein expression in human breast tumors compared to normal breast tissue. Malignant tumors (32) and normal breast tissue samples (23), from formaldehyde‐fixed, paraffin‐embedded specimens are subjected to discovery proteomics using liquid chromatography/tandem mass spectrometry, with spectral counts for quantitation. The dataset contains 1406 proteins. Differential expression is measured using a method that takes advantage of estimates of the percentage of tumor on a slide. This analysis shows that the major classes of proteins over‐expressed by tumors are RNA‐binding, heat shock and DNA repair proteins. RNA‐binding proteins, including heterogeneous nuclear ribonucleoproteins (HNRNPs), SR splice factors (SRSF) and elongation factors form the largest group. Comparison with results from another study demonstrates that the RNA‐binding proteins are associated specifically with malignant transformation, rather than with cell proliferation. HNRNP and SRSF proteins help define splice sites in normal cells. Their over‐expression may dysregulate splicing, which in turn has the potential to promote malignant transformation.     

Role of ultrasonography in diagnosing early rheumatoid arthritis and remission of rheumatoid arthritis - a systematic review of the literature

Introduction

Ultrasonography (US) might have an added value to clinical examination in diagnosing early rheumatoid arthritis (RA) and assessing remission of RA. We aimed to clarify the added value of US in RA in these situations performing a systematic review.

Methods

A systematic literature search was performed for RA, US, diagnosis and remission. Methodological quality was assessed; the wide variability in the design of studies prohibited pooling of results.

Results

Six papers on the added value of US diagnosing early RA were found, in which at least bilateral metacarpophalangeal (MCP), wrists and metatarsophalangeal (MTP) joints were scanned. Compared to clinical examination, US was superior with regard to detecting synovitis and predicting progression to persistent arthritis or RA. Eleven papers on assessing remission were identified, in which at least the wrist and the MCP joints of the dominant hand were scanned. Often US detected inflammation in patients clinically in remission, irrespective of the remission criteria used. Power Doppler signs of synovitis predicted X-ray progression and future flare in patients clinically in remission.

Conclusions

US appears to have added value to clinical examination for diagnosing of RA when scanning at least MCP, wrist and MTP joints, and, when evaluating remission of RA, scanning at least wrist and MCP joints of the dominant hand. For both purposes primarily power Doppler US might be used since its results are less equivocal than those of greyscale US.     

Microsphere embolisation as an alternative for alcohol in percutaneous transluminal septal myocardial ablation

Background

Percutaneous transluminal septal myocardial ablation using microsphere embolisation is a new interventional technique to treat patients with hypertrophic obstructive cardiomyopathy.

Methods and results

In two patients, considered at high risk for myectomy, targeted septal perforators were occluded with microsphere embolisation instead of alcohol ablation to reduce left ventricular outflow gradient. In both cases the left ventricular outflow tract gradient was immediately reduced. No adverse events occurred.

Conclusion

This is the first clinical experience with Embozene® Microspheres in the Netherlands as an alternative for alcohol septal ablation. In both cases it resulted in immediate improvement in the haemodynamics, without any adverse events.     

Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates

Protein O-mannosylation is a post-translational modification essential for correct development of mammals. In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins.     

Trichoderma aureoviride URM 5158 and Trichoderma hamatum URM 6656 are Biocontrol Agents that act against Cassava Root rot through different Mechanisms

Trichoderma has been used to manage a large number of pathogens, but there is a gap in the mechanisms used by these biocontrol agents regarding the physiological response of cassava plants (Manihot esculenta) when it is subjected to cassava root rot. The aims of this study were to investigate the antagonist activity of ten Trichoderma isolates against Fusarium solani on potato dextrose Agar (PDA), to quantify the chitinase production, to select and test in vivo the best isolate from each experiment and to assess the physiological response of cassava to the production of oxidative enzyme complex production (ascorbate peroxidase, catalase, peroxidase and polyphenol oxidase). All Trichoderma isolates have shown competitive capability against F. solani, and Trichoderma hamatum URM 6656 showed the highest inhibition of pathogen growth (88.91%). All isolates have shown chitinase activity, but Trichoderma aureoviride URM 5158 produced the highest amount of chitinase. T. hamatum URM 6656 and T. aureoviride URM 5158 were selected to be applied in vivo. The two Trichoderma strains reduced 64 and 60% of the disease severity in the shoot and 82 and 84% in the root. Cassava plants infected with Trichoderma have shown the highest peroxidase and ascorbate peroxidase production. Our results have indicated that T. aureoviride URM 5158 is an effective biocontrol agent against cassava root rot caused by F. solani, because it presented competitive antagonist capability in vitro, the highest chitinase production, and reduced the cassava root rot severity. The application of T. aureoviride has led to the maximum enzyme activity of reactive oxygen species group in cassava plants.     

Effect of the bidistilled modified water on bovine serum albumin conformation. Fluorescent spectroscopy data

It was shown that bidistilled modified water induces a marked decrease in the intensity of intrinsic fluorescence of bovine serum albumin and increases the binding of this protein to the fluorescent probe 1.8 ANS. These effects can be interpreted as a denaturing action of bidistilled modified water on the protein and a change in its conformational state, which is probably caused by changes in the microenvironment of the protein molecule. In addition, a substantial increase in the intrinsic fluorescence of bidistilled modified water, as compared with that of distilled water, was found.     

Mixed effects models with bivariate and univariate association parameters for longitudinal bivariate binary response data

When two binary responses are measured for each study subject across time, it may be of interest to model how the bivariate associations and marginal univariate risks involving the two responses change across time. To achieve such a goal, marginal models with bivariate log odds ratio and univariate logit components are extended to include random effects for all components. Specifically, separate normal random effects are specified on the log odds ratio scale for bivariate responses and on the logit scale for univariate responses. Assuming conditional independence given the random effects facilitates the modeling of bivariate associations across time with missing at random incomplete data. We fit the model to a dataset for which such structures are feasible: a longitudinal randomized trial of a cardiovascular educational program where the responses of interest are change in hypertension and hypercholestemia status. The proposed model is compared to a naive bivariate model that assumes independence between time points and univariate mixed effects logit models.     

Empirical Bayes estimation of random effects parameters in mixed effects logistic regression models

We extend an approach for estimating random effects parameters under a random intercept and slope logistic regression model to include standard errors, thereby including confidence intervals. The procedure entails numerical integration to yield posterior empirical Bayes (EB) estimates of random effects parameters and their corresponding posterior standard errors. We incorporate an adjustment of the standard error due to Kass and Steffey (KS; 1989, Journal of the American Statistical Association 84, 717-726) to account for the variability in estimating the variance component of the random effects distribution. In assessing health care providers with respect to adult pneumonia mortality, comparisons are made with the penalized quasi-likelihood (PQL) approximation approach of Breslow and Clayton (1993, Journal of the American Statistical Association 88, 9-25) and a Bayesian approach. To make comparisons with an EB method previously reported in the literature, we apply these approaches to crossover trials data previously analyzed with the estimating equations EB approach of Waclawiw and Liang (1994, Statistics in Medicine 13, 541-551). We also perform simulations to compare the proposed KS and PQL approaches. These two approaches lead to EB estimates of random effects parameters with similar asymptotic bias. However, for many clusters with small cluster size, the proposed KS approach does better than the PQL procedures in terms of coverage of nominal 95% confidence intervals for random effects estimates. For large cluster sizes and a few clusters, the PQL approach performs better than the KS adjustment. These simulation results agree somewhat with those of the data analyses.