FunRich proteomics software analysis,let the fun begin!

Protein MS analysis is the preferred method for unbiased protein identification. It is normally applied to a large number of both small‐scale and high‐throughput studies. However, user‐friendly computational tools for protein analysis are still needed. In this issue, Mathivanan and colleagues (Proteomics 2015, 15, 2597–2601) report the development of FunRich software, an open‐access software that facilitates the analysis of proteomics data, providing tools for functional enrichment and interaction network analysis of genes and proteins. FunRich is a reinterpretation of proteomic software, a standalone tool combining ease of use with customizable databases, free access, and graphical representations.     

Guided bone regeneration produced by new mineralized and reticulated collagen membranes in critical-sized rat calvarial defects

The aim of this study was to evaluate the bone regenerative effect of glutaraldehyde (GA) cross-linking on mineralized polyanionic collagen membranes in critical-sized defects on rat calvarias. Bone calvarial defects were induced in Wistar rats, which were then divided into five groups: a sham group; a control group, which received a commercial membrane; and GA, 25GA, and 75GA groups, which received one of three different polyanionic collagen membranes mineralized by 0, 25, or 75 hydroxyapatite cycles and then cross-linked by GA. Bone formation was evaluated based on digital radiography and computerized tomography. Histological analyses were performed 4 and 12 weeks after the surgical procedure to observe bone formation, membrane resorption, and fibrous tissue surrounding the membranes. Measurement of myeloperoxidase activity, tumor necrosis factor alpha, and interleukin 1beta production was performed 24 h after surgery. The percentage of new bone formation in the GA, 25GA, and 75GA groups was higher compared with the control and sham groups. In the GA and 25 GA groups, the membranes were still in place and were contained in a thick fibrous capsule after 12 weeks. No significant difference was found among the groups regarding myeloperoxidase activity and interleukin 1beta levels, although the GA, 25GA, and 75GA groups presented decreased levels of tumor necrosis factor alpha compared with the control group. These new GA cross-linked membranes accelerated bone healing of the calvarium defects and did not induce inflammation. In addition, unlike the control membrane, the experimental membranes were not absorbed during the analyzed period, so they may offer advantages in large bone defects where prolonged membrane barrier functions are desirable.     

A mathematical model of epiphyseal development: hypothesis of growth pattern of the secondary ossification centre

This paper introduces a ‘hypothesis about the growth pattern of the secondary ossification centre (SOC)’, whereby two phases are assumed. First, the formation of cartilage canals as an event essential for the development of the SOC. Second, once the canals are merged in the central zone of the epiphysis, molecular factors are released (primarily Runx2 and MMP9) spreading and causing hypertrophy of adjacent cells. In addition, there are two important molecular factors in the epiphysis: PTHrP and Ihh. The first one inhibits chondrocyte hypertrophy and the second helps the cell proliferation. Between these factors, there is negative feedback, which generates a highly localised and stable pattern over time. From a mathematical point of view, this pattern is similar to the patterns of Turing. The spread of Runx2 hypertrophies the cells from the centre to the periphery of the epiphysis until found with high levels of PTHrP to inhibit hypertrophy. This mechanism produces the epiphyseal bone-plate. Moreover, the hypertrophy is inhibited when the cells sense low shear stress and high pressure levels that maintain the articular cartilage structure. To test this hypothesis, we solve a system of coupled partial differential equations using the finite element method and we have obtained spatio-temporal patterns of the growth process of the SOC. The model is in qualitative agreement with experimental results previously reported by other authors. Thus, we conclude that this model can be used as a methodological basis to present a complete mathematical model of the whole epiphyseal development.     

Simultaneous Accessory Pathway and AV Node Mechanical Block

We report a clinical case of a 22-year-old female referred to our institution due to palpitations and preexcitation. Her ECG suggested a right superior paraseptal accessory pathway (AP), which was localised during the electrophysiological study at the superior paraseptal region in close proximity to the His recordings. Reproducible orthodromic reciprocating tachycardia was induced by atrial pacing with extrastimuli. Cryo-mapping performed in the area of earliest atrial activation was not able to terminate the tachycardia. A second attempt, slightly more posterior, caused mechanical block of the AP, which rendered the tachycardia non-inducible. More pressure with the ablation catheter determined a Wenckebach type supra-hisian AV block, which was transient but reproducible. Given this finding no ablation was done. Simultaneous block to the AP and the atrioventricular node has rarely been reported using radiofrequency energy. However, to our knowledge this phenomenon has not been previously reported in large series using cryo-thermal energy.     

Mutation of SIMPLE in Charcot–Marie–Tooth 1C alters production of exosomes

Charcot–Marie–Tooth (CMT) disease is an inherited neurological disorder. Mutations in the small integral membrane protein of the lysosome/late endosome (SIMPLE) account for the rare autosomal-dominant demyelination in CMT1C patients. Understanding the molecular basis of CMT1C pathogenesis is impeded, in part, by perplexity about the role of SIMPLE, which is expressed in multiple cell types. Here we show that SIMPLE resides within the intraluminal vesicles of multivesicular bodies (MVBs) and inside exosomes, which are nanovesicles secreted extracellularly. Targeting of SIMPLE to exosomes is modulated by positive and negative regulatory motifs. We also find that expression of SIMPLE increases the number of exosomes and secretion of exosome proteins. We engineer a point mutation on the SIMPLE allele and generate a physiological mouse model that expresses CMT1C-mutated SIMPLE at the endogenous level. We find that CMT1C mouse primary embryonic fibroblasts show decreased number of exosomes and reduced secretion of exosome proteins, in part due to improper formation of MVBs. CMT1C patient B cells and CMT1C mouse primary Schwann cells show similar defects. Together the data indicate that SIMPLE regulates the production of exosomes by modulating the formation of MVBs. Dysregulated endosomal trafficking and changes in the landscape of exosome-mediated intercellular communications may place an overwhelming burden on the nervous system and account for CMT1C molecular pathogenesis.     

Epigenetic deregulation of the COX pathway in cancer

Inflammation is a major cause of cancer and may condition its progression. The deregulation of the cyclooxygenase (COX) pathway is implicated in several pathophysiological processes, including inflammation and cancer. Although, its targeting with nonsteroidal antiinflammatory drugs (NSAIDs) and COX-2 selective inhibitors has been investigated for years with promising results at both preventive and therapeutic levels, undesirable side effects and the limited understanding of the regulation and functionalities of the COX pathway compromise a more extensive application of these drugs. Epigenetics is bringing additional levels of complexity to the understanding of basic biological and pathological processes. The deregulation of signaling and biosynthetic pathways by epigenetic mechanisms may account for new molecular targets in cancer therapeutics. Genes of the COX pathway are seldom mutated in neoplastic cells, but a large proportion of them show aberrant expression in different types of cancer. A growing body of evidence indicates that epigenetic alterations play a critical role in the deregulation of the genes of the COX pathway. This review summarizes the current knowledge on the contribution of epigenetic processes to the deregulation of the COX pathway in cancer, getting insights into how these alterations may be relevant for the clinical management of patients.     

Bioremediation of naphthalene in water by Sphingomonas paucimobilis using new biodegradable surfactants based on poly (ɛ-caprolactone)

New amphiphilic block surfactants ABA based on a central segment of polycaprolactone with different molecular composition were evaluated in the bioremediation of naphthalene in water by Sphingomonas paucimobilis and compared with sodium dodecyl sulphate as reference surfactant (SDS). Also the biodegradation of the new surfactants by bacteria, S. paucimobilis and a mixture of bacteria (Pseudomonas aureginosa, Bacillus subtilis, Bacillus amyloliquefaciens and Bacillus megaterium) was studied by indirect impedance technique and carbon dioxide determination. All the bacteria biodegraded in solution and micellar phase the central segment of PCL with mineralization rates in the range of 0.024–0.036 mg of CO₂ per day.S. paucimobilis biodegraded naphthalene in the presence of the new surfactants and GC analysis demonstrated that conversion to products started immediately after inoculum. In all the experiments, except for SDS, at 140 h of incubation time, the remaining naphthalene concentration was about 10% of the initial concentration. In contrast, the production of CO₂ was delayed 4–7 days and values around 75% of naphthalene mineralization degree were achieved in three weeks. The addition of PCL-surfactants, in solution and in micellar phase, not interfered in the naphthalene mineralization. These results have shown promising potential of these biodegradable PCL-surfactants in surfactant-enhanced remediation (SER) technology for removing residual organics from contaminated groundwater and soils.     

Different properties of ACPA and IgM-RF derived from a large dataset: further evidence of two distinct autoantibody systems

Introduction  

The aim of this study was to examine seroconversion and the relationship with age and inflammation of autoantibodies in a large group of patients attending an outpatient rheumatology clinic.     

Use of methotrexate therapy is not associated with decreased prevalence of metabolic syndrome

With great interest, we read the article by Toms and colleagues [1] in the previous issue of Arthritis Research & Therapy, in which they assessed prevalences of metabolic syndrome (MetS) in rheumatoid arthritis (RA) patients. Moreover, they identified demographic and clinical factors that may be associated with MetS. Toms and colleagues found prevalences of up to 45% of MetS and demonstrated older age and health status (health assessment questionnaire) to be associated with MetS irrespectively of the definition used. Of most interest, an association between methotrexate (MTX) use and decreased presence of MetS was observed in patients more than 60 years of age. The investigators hypothesized that this may be attributed to a drug-specific effect (and not to an anti-inflammatory effect) either by changing levels of adenosine, which is known to interact with glucose and lipid metabolism, or by an indirect effect mediated through concomitant folic acid administration, thereby decreasing homocysteine levels.Recently, we also examined the prevalence of MetS in (a subgroup of) RA patients in the CARRÉ investigation, a prospective cohort study on prevalent and incident cardiovascular disease and its underlying cardiovascular risk factors [2]. The findings of Toms and colleagues stimulated us to perform additional analyses in our total study population (n = 353).The prevalences of MetS were 35% and 25% (Table ​(Table1)1) according to criteria of National Cholesterol Education Program (NCEP) 2004 and NCEP 2001, respectively. In multivariate backward regression analyses, we found significant associations between body mass index, pulse rate, creatinine levels, hypothyroidism and diabetes mellitus and the presence of MetS independently of the criteria used (Table ​(Table2).2). However, an independent association between single use of MTX or use of MTX in combination with other disease-modifying antirheumatic drugs, on the one hand, and a decreased prevalence of MetS, on the other hand, could not be demonstrated (even in the subgroup of patients over the age of 60).

Table 1

Characteristics of the study population

Effect of a Short Contact Time With Lees on Volatile Composition of Airen and Macabeo Wines

Volatile compounds were analyzed in Airen and Macabeo wines at the end of the alcoholic fermentation and after a short time contact with wine lees. The concentration of 34 analyzed compounds, with the exception of hexyl acetate, linalool, ß-ionone and farnesol, increased significantly after contact with lees in Airen wines. Esters and terpenic compounds decreased significantly in Macabeo wines after contact with lees. The contact with lees could be considered as favourable in Airen wines to improve the aroma quality.