This article traces the history of peer review of scientific publications, plotting the development of the process from its inception to its present-day application. We discuss the merits of peer review and its weaknesses, both perceived and real, as well as the practicalities of several major proposed changes to the system. It is our hope that readers will gain a better appreciation of the complexities of the process and, when serving as reviewers themselves, will do so in a manner that will enhance the utility of the exercise. We also propose the development of an international on-line training program for accreditation of potential referees.

Vitamin D deficiency is a risk factor for osteoporosis and other chronic diseases, including type 1 diabetes, hypertension, metabolic syndrome, and ischemic heart disease. Cholesterol and vitamin D share the 7-dehydrocolesterol metabolic pathway. This study evaluated the possible effect of atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Eighty-three patients (52 men and 31 women) with an acute coronary syndrome (75 with acute myocardial infarction and 8 with unstable angina) were included. After diagnosis, patients received atorvastatin as secondary prevention. Serum vitamin D was measured by high-performance liquid chromatography at baseline and at 12 months. Atorvastatin treatment produced a statistically significant decrease in cholesterol and triglyceride levels and an increase in vitamin D levels ( Vitamin D deficiency is a risk factor for osteoporosis and other chronic diseases, including type 1 diabetes, hypertension, metabolic syndrome, and ischemic heart disease. 1 Vitamin D is synthesized in the skin by ultraviolet radiation that acts on 7-dehydrocolesterol, which is hydroxylated into carbon-25 by 25-hydroxyvitamin D-1␣ hydroxylase or CYP27B1, an enzyme located in the mitochondria of the hepatocyte. The resulting metabolite, 25-hydroxyvitamin D, is the best way to measure individual vitamin D levels. 2 Cholesterol and vitamin D share the 7-dehydrocolesterol metabolic pathway. 3 Statins have beneficial effects on morbidity and mortality of patients with acute ischemic heart disease; these may be mediated by vitamin D. These patients have a greater prevalence of vitamin D deficiency and are often treated with statins as secondary prevention. 1 This led us to study the possible effect of atorvastatin on vitamin D levels in this group of patients. Increased levels of vitamin D could explain some of the beneficial effects of atorvastatin at the cardiovascular and bone metabolism levels that are unrelated to cholesterol levels. Methods and ResultsPatients hospitalized for an acute coronary syndrome, defined as high-risk unstable angina, non-ST-elevated myocardial infarction, or ST-elevated myocardial infarction, were eligible for inclusion. Eighty-three patients (52 men and 31 women) with an acute coronary syndrome (75 with acute myocardial infarction and 8 with unstable angina) were included. Patients were recruited at hospital admission. Exclusion criteria were alcoholism, neoplasia, hyperor hypocalcemia, and treatment with phosphocalcium metabolism-modifying drugs. After diagnosis, patients received atorvastatin as secondary prevention. Low (10 to 20 mg) and high (40 to 80 mg) doses were used according to baseline levels of cholesterol and triglycerides and index of vascular risk. Only patients completing follow-up were evaluated. A control group of 73 hypertensive patients (38 men and 35 women) not receiving treatment with statins was included.Blood samples were obtained after 8 or 9 hours of fasting. Total calcium, phosphorus, total cholesterol, and triglycerides were mea...

Patients with heart failure have worse quality of life than the general Spanish population and patients with other chronic diseases. Female sex, being older, comorbidity, advanced symptoms, and recent hospitalization are determinant factors in health-related quality of life in these patients.

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The principal differences in the clinical manifestations of patients with AS from EU and LA were the greater frequency of peripheral arthritis and enthesitis in LA group, the higher percentage of HLA-B27 in EU group, and the form of treatment, with a greater use of NSAID, steroids, and DMARD in the LA group.

BackgroundCrystallin fragments are known to aggregate and cross-link that lead to cataract development. This study has been focused on determination of post-translational modifications (PTMs) of human lens crystallin fragments, and their aggregation properties.MethodsFour crystallin fragments-containing fractions (Fraction I [∼3.5 kDa species], Fraction II [∼3.5–7 kDa species], Fraction III [∼7–10 kDa species] and Fraction IV [>10–18 kDa species]), and water soluble high molecular weight (WS-HMW) protein fraction were isolated from water soluble (WS) protein fraction of human lenses of 50–70 year old-donors. The crystallin fragments of the Fractions I–IV were separated by two-dimensional (2D)-gel electrophoresis followed by analysis of their gel-spots by mass spectrometry. The Fractions I–IV were examined for their molecular mass, particle-diameters, amyloid fibril formation, and for their aggregation by themselves and with WS-HMW proteins.ResultsCrystallin fragments in Fractions I–IV were derived from α-, β- and γ-crystallins, and their 2D-gel separated spots contained multiple crystallins with PTMs such as oxidation, deamidation, methylation and acetylation. Crystallin fragments from all the four fractions exhibited self-aggregated complexes ranging in Mr from 5.5×105 to 1.0×108 Da, with diameters of 10–28 nm, and amyloid fibril-like formation, and aggregation with WS-HMW proteins.ConclusionThe crystallin fragments exhibited several PTMs, and were capable of forming aggregated species by themselves and with WS-HMW proteins, suggesting their potential role in aggregation process during cataract development.General significanceCrystallin fragments play a major role in human cataract development.

The purpose of the study was to compare the effects of deamidation alone, truncation alone, or both truncation and deamidation on structural and functional properties of human lens alphaA-crystallin. Specifically, the study investigated whether deamidation of one or two sites in alphaA-crystallin (i.e., alphaA-N101D, alphaA-N123D, alphaA-N101/123D) and/or truncation of the N-terminal domain (residues 1-63) or C-terminal extension (residues 140-173) affected the structural and functional properties relative to wild-type (WT) alphaA. Human WT-alphaA and human deamidated alphaA (alphaA-N101D, alphaA-N123D, alphaA-N101/123D) were used as templates to generate the following eight N-terminal domain (residues 1-63) deleted or C-terminal extension (residues 140-173) deleted alphaA mutants and deamidated plus N-terminal domain or C-terminal extension deleted mutants: (i) alphaA-NT (NT, N-terminal domain deleted), (ii) alphaA-N101D-NT, (iii) alphaA-N123D-NT, (iv) alphaA-N101/123D-NT, (v) alphaA-CT (CT, C-terminal extension deleted), (vi) alphaA-N101D-CT, (vii) alphaA-N123D-CT, and (viii) alphaA-N101/123D-CT. All of the proteins were purified and their structural and functional (chaperone activity) properties determined. The desired deletions in the alphaA-crystallin mutants were confirmed by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometric analysis. Relative to WT-alphaA homomers, the mutant proteins exhibited major structural and functional changes. The maximum decrease in chaperone activity in homomers occurred on deamidation of N123 residue, but it was substantially restored after N- or C-terminal truncations in this mutant protein. Far-UV circular dichroism (CD) spectral analyses generally showed an increase in the beta-contents in alphaA mutants with deletions of N-terminal domain or C-terminal extension and also with deamidation plus above N- or C-terminal deletions. Intrinsic tryptophan (Trp) and total fluorescence spectral studies suggested altered microenvironments in the alphaA mutant proteins. Similarly, the ANS (8-anilino-1-naphthalenesulfate) binding showed generally increased fluorescence with blue shift on deletion of the N-terminal domain in the deamidated mutant proteins, but opposite effects were observed on deletion of the C-terminal extension. Molecular mass, polydispersity of homomers, and the rate of subunit exchange with WT-alphaB-crystallin increased on deletion of the C-terminal extension in the deamidated alphaA mutants, but on N-terminal domain deletion these values showed variable results based on the deamidation site. In summary, the data suggested that the deamidation alone showed greater effect on chaperone activity than the deletion of N-terminal domain or C-terminal extension of alphaA-crystallin. The N123 residue of alphaA-crystallin plays a crucial role in maintaining its chaperone function. However, both the N-terminal domain and C-terminal extension are also important for the chaperone activity of alphaA-crystallin because the activity was partia...

New insights into the intrarenal renin-angiotensin system (RAS) have modified our traditional view of the system. However, many finer details of this network of peptides and associated peptidases remain unclear. We hypothesized that a computational systems biology approach, applied to peptidomic data, could help to unravel the network of enzymatic conversions. We built and refined a Bayesian network model and a dynamic systems model starting from a skeleton created with established elements of the RAS and further developed it with archived MALDI-TOF mass spectra from experiments conducted in mouse podocytes exposed to exogenous angiotensin (Ang) substrates. The model-building process suggested previously unrecognized steps, three of which were confirmed in vitro, including the conversion of Ang(2-10) to Ang(2-7) by neprilysin (NEP), and Ang(1-9) to Ang(2-9) and Ang(1-7) to Ang(2-7) by aminopeptidase A (APA). These data suggest a wider role of NEP and APA in glomerular formation of bioactive Ang peptides and/or shunting their formation. Other steps were also suggested by the model and supporting evidence for those steps was evaluated using model-comparison methods. Our results demonstrate that systems biology methods applied to peptidomic data are effective in identifying novel steps in the Ang peptide processing network, and these findings improve our understanding of the glomerular RAS.