Molecular and genetic regulation of fruit ripening

Fleshy fruit undergo a novel developmental program that ends in the irreversible process of ripening and eventual tissue senescence. During this maturation process, fruit undergo numerous physiological, biochemical and structural alterations, making them more attractive to seed dispersal organisms. In addition, advanced or over-ripening and senescence, especially through tissue softening and eventual decay, render fruit susceptible to invasion by opportunistic pathogens. While ripening and senescence are often used interchangeably, the specific metabolic activities of each would suggest that ripening is a distinct process of fleshy fruits that precedes and may predispose the fruit to subsequent senescence.     

Emission analysis of RE3+ (RE = Sm,Dy):B2O3‐TeO2‐Li2O‐AlF3 glasses

This article reports on the optical properties of 0.5% mol of Sm³⁺, Dy³⁺ ion‐doped B₂O₃‐TeO₂‐Li₂O‐AlF₃ (LiAlFBT) glasses. The glass samples were characterized by optical absorption and emission spectra. Judd‐Ofelt theory was applied to analyze the optical absorption spectra and calculate the intensity parameters and radiative properties of the emission transitions. The emission spectra of Sm³⁺ and Dy³⁺:LiAlFBT glasses showed a bright reddish‐orange emission at 598 nm (⁴G_5/2 → ⁶H_7/2) and an intense yellow emission at 574 nm (⁴F_9/2 → ⁶H_13/2), respectively. Full width at half maximum (FWHM), stimulated emission cross section, gain bandwidth and optical gain values were also calculated to extend the applications of the Sm³⁺ and Dy³⁺:LiAlFBT glasses. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis,HPLC Enantioresolution,and X‐ray Analysis of a New Series of C5‐methyl Pyridazines as N‐Formyl Peptide Receptor (FPR) Agonists

The synthesis of three racemates and the corresponding non‐chiral analogues of a C5‐methyl pyridazine series is described here, as well as the isolation of pure enantiomers and their absolute configuration assignment. In order to obtain optically active compounds, direct chromatographic methods of separation by HPLC‐UV were investigated using four chiral stationary phases (CSPs: Lux Amylose‐2, Lux Cellulose‐1, Lux Cellulose‐2 and Lux Cellulose‐3). The best resolution was achieved using amylose tris(5‐chloro‐2‐methylphenylcarbamate) (Lux Amylose‐2), and single enantiomers were isolated on a semipreparative scale with high enantiomeric excess, suitable for biological assays. The absolute configuration of optically active compounds was unequivocally established by X‐ray crystallographic analysis and comparative chiral HPLC‐UV profile. All compounds of the series were tested for formyl peptide receptor (FPR) agonist activity, and four were found to be active, with EC₅₀ values in the micromolar range. Chirality 25:400–408, 2013. © 2013 Wiley Periodicals, Inc.     

Diet Induced Mild Hypercholesterolemia in Pigs: Local and Systemic Inflammation,Effects on Vascular Injury – Rescue by High-Dose Statin Treatment

Objective

The aim of the present study was to comprehensively evaluate systemic and local inflammation as well as progression of vascular inflammation in normal and mechanically injured vessels in a large animal model of mild hypercholesterolemia. Our aim was also to test the effect of high-dose statin treatment on these processes.

Methods

Pigs were kept for 120 days on a standard diet (SD, n=7), high-cholesterol diet (HCD, n=7) or high-cholesterol diet with Atorvastatin starting after 50 days (STATIN, n=7). Left carotid artery balloon injury was conducted in all groups after 60 days of diet treatment. Biochemical analysis together with evaluation of blood and tissue markers of vascular injury and inflammation were performed in all groups at the end of experiment.

Results

HCD compared to SD induced systemic inflammation demonstrated by increased number of circulating monocytes and lymphocytes. HCD compared to SD induced also local inflammation demonstrated by adipocyte hypertrophy and infiltration of T-lymphocytes in abdominal white adipose tissue, activation of hepatic stellate cells with infiltration of T- and B-lymphocytes and macrophages in the liver and increased macrophage content in lung parenchyma. These changes were accompanied by increased Intima/Media thickness, stenosis, matrix deposition and activated T-cell infiltrates in injured but not in uninjured contralateral carotid artery as we previously reported. The treatment with high-dose statin attenuated all aspects of systemic and local inflammation as well as pathological changes in injured carotid artery.

Conclusions

Diet related mild hypercholesterolemia induce systemic and local inflammation in the liver, lung and adipose tissue that coincide with enhanced inflammation of injured vessel but is without deleterious effect on uninjured vessels. High dose statin attenuated systemic and local inflammation and protected injured vessels. However, finding exact role of reduced systemic and remote inflammation in vascular protection requires further studies.     

Biliverdin Protects against Liver Ischemia Reperfusion Injury in Swine

Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs.     

Identifying and quantifying metabolites by scoring peaks of GC-MS data

Background

Metabolomics is one of most recent omics technologies. It has been applied on fields such as food science, nutrition, drug discovery and systems biology. For this, gas chromatography-mass spectrometry (GC-MS) has been largely applied and many computational tools have been developed to support the analysis of metabolomics data. Among them, AMDIS is perhaps the most used tool for identifying and quantifying metabolites. However, AMDIS generates a high number of false-positives and does not have an interface amenable for high-throughput data analysis. Although additional computational tools have been developed for processing AMDIS results and to perform normalisations and statistical analysis of metabolomics data, there is not yet a single free software or package able to reliably identify and quantify metabolites analysed by GC-MS.

Results

Here we introduce a new algorithm, PScore, able to score peaks according to their likelihood of representing metabolites defined in a mass spectral library. We implemented PScore in a R package called MetaBox and evaluated the applicability and potential of MetaBox by comparing its performance against AMDIS results when analysing volatile organic compounds (VOC) from standard mixtures of metabolites and from female and male mice faecal samples. MetaBox reported lower percentages of false positives and false negatives, and was able to report a higher number of potential biomarkers associated to the metabolism of female and male mice.

Conclusions

Identification and quantification of metabolites is among the most critical and time-consuming steps in GC-MS metabolome analysis. Here we present an algorithm implemented in a R package, which allows users to construct flexible pipelines and analyse metabolomics data in a high-throughput manner.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-014-0374-2) contains supplementary material, which is available to authorized users.     

Mononeuritis multiplex as the first presentation of refractory sarcoidosis responsive to etanercept

Background

Several disorders may present with mononeuritis multiplex and the etiological diagnosis can be challenging.

Case presentation

We report a 42 year-old female who presented with severe lower limb neuropathic pain, asymmetric weakness and sensory impairment and was diagnosed with mononeuritis multiplex. Biopsy showed a granulomatous vasculitic process with eosinophils, scarce granulomata and axonal neuropathy and granulomatosis with poliangiitis was assumed. Steroids, cyclophosphamide, alemtuzumab, azathioprine, mycophenolate mofetil and rituximab were used, all with transient and insufficient response. Skin biopsy performed in a further exacerbation allowed sarcoidosis diagnosis. Infliximab and, later, adalimumab induced good clinical and laboratorial response, but neutralizing antibodies developed to both drugs, so etanercept was tried with good clinical response.

Conclusions

To the best of our knowledge, this is the first report of sarcoidosis successfully treated with etanercept. This drug may be considered in refractory sarcoidosis after other TNF-α inhibitors failure, having the advantage of not being associated with neutralizing antibodies development.