Signatures of arithmetic simplicity in metabolic network architecture

Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that several of the properties predicted by the artificial chemistry model hold for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity

SpineCor treatment for Juvenile Idiopathic Scoliosis: SOSORT award 2010 winner

<p>Introduction</p> <p>Juvenile idiopathic scoliosis is a condition used to describe patients who are least 4 years of age but younger than 10 when the deformity is first identified. In these patients, the condition is usually progressive and those that are diagnosed at five years or younger have a high chance of progression to a large curve, with additional pulmonary and cardiac complications. The main form of conservative treatment for juvenile scoliosis is the use of a bracing system. This prospective interventional study was conducted to evaluate the effectiveness of the Dynamic SpineCor orthosis for juvenile idiopathic scoliosis as well as to evaluate the stability of the spine after the weaning point.</p> <p>Material and Methods</p> <p>For this study, 150 juvenile patients were treated by the SpineCor orthosis between 1993 and 2009. Of these, 67 patients had a definite outcome and 83 are still actively being treated. To determine the effectiveness of the brace the <b>OUTCOME </b>criteria recommended by the SRS was used.</p> <p>Results</p> <p>The results from our study showed that of the 67 patients with a definite outcome, 32.9% corrected their Cobb angle by at least 5° and 10.5% had a stabilization of their Cobb angle. Within the patients with a definite outcome, 37.3% of patients where recommended for surgery before authorized end of treatment. For this group of patients, surgery was postponed. Looking at the stability of the curves 2 years after the end of the treatment, we found 12.5% of the patients continued their correction without the brace being used and 71.4% remained stable.</p> <p>Discussion</p> <p><b>From our study we can clearly see that the effectiveness of the SpineCor orthosis in obtaining and maintaining the neuromuscular integration of the corrective movement can be achieved effectively for juvenile patients</b>. Over 75% of all patients that finished the treatment had remained stable with a few continuing to correct their Cobb angle after the use of the SpineCor orthosis was discontinued.</p> <p>Conclusion</p> <p>Our conclusion from this study is that the SpineCor orthosis is a very effective method of treatment of juvenile idiopathic scoliosis. The results obtained also indicate that treatment outcomes are better with early bracing. Most encouraging perhaps is the fact that the positive outcome appears to be maintained in the long term, and that surgery can be avoided or at least postponed.</p

Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer

BACKGROUND: Fatty acid binding protein 4 (FABP-4) is a lipid-binding adipokine upregulated in obesity, which may facilitate fatty acid supply for tumor growth and promote insulin resistance and inflammation and may thus play a role in colorectal cancer (CRC) development. We aimed to investigate the association between circulating FABP-4 and CRC and to assess potential causality using a Mendelian randomization (MR) approach. METHODS: The association between pre-diagnostic plasma measurements of FABP-4 and CRC risk was investigated in a nested case-control study in 1324 CRC cases and the same number of matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A two-sample Mendelian randomization study was conducted based on three genetic variants (1 cis, 2 trans) associated with circulating FABP-4 identified in a published genome-wide association study (discovery n = 20,436) and data from 58,131 CRC cases and 67,347 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. RESULTS: In conditional logistic regression models adjusted for potential confounders including body size, the estimated relative risk, RR (95% confidence interval, CI) per one standard deviation, SD (8.9 ng/mL) higher FABP-4 concentration was 1.01 (0.92, 1.12) overall, 0.95 (0.80, 1.13) in men and 1.09 (0.95, 1.25) in women. Genetically determined higher FABP-4 was not associated with colorectal cancer risk (RR per FABP-4 SD was 1.10 (0.95, 1.27) overall, 1.03 (0.84, 1.26) in men and 1.21 (0.98, 1.48) in women). However, in a cis-MR approach, a statistically significant association was observed in women (RR 1.56, 1.09, 2.23) but not overall (RR 1.23, 0.97, 1.57) or in men (0.99, 0.71, 1.37). CONCLUSIONS: Taken together, these analyses provide no support for a causal role of circulating FABP-4 in the development of CRC, although the cis-MR provides some evidence for a positive association in women, which may deserve to be investigated further

Measurement of the t(t)over-bar production cross section in the dilepton channel in pp collisions at √s=8 TeV

The top-antitop quark (t (t) over bar) production cross section is measured in proton-proton collisions at root s = 8 TeV with the CMS experiment at the LHC, using a data sample corresponding to an integrated luminosity of 5.3 fb(-1). The measurement is performed by analysing events with a pair of electrons or muons, or one electron and one muon, and at least two jets, one of which is identified as originating from hadronisation of a bottom quark. The measured cross section is 239 +/- 2 (stat.) +/- 11 (syst.) +/- 6 (lum.) pb, for an assumed top-quark mass of 172.5 GeV, in agreement with the prediction of the standard model

Non-Adherence in Patients on Peritoneal Dialysis: A Systematic Review

Background: It has been increasingly recognized that non-adherence is an important factor that determines the outcome of peritoneal dialysis (PD) therapy. There is therefore a need to establish the levels of non-adherence to different aspects of the PD regimen (dialysis procedures, medications, and dietary/fluid restrictions). Methods: A systematic review of peer-reviewed literature was performed in PubMed, PsycINFO and CINAHL databases using PRISMA guidelines in May 2013. Publications on non-adherence in PD were selected by two reviewers independently according to predefined inclusion and exclusion criteria. Relevant data on patient characteristics, measures, rates and factors associated with non-adherence were extracted. The quality of studies was also evaluated independently by two reviewers according to a revised version of the Effective Public Health Practice Project assessment tool. Results: The search retrieved 204 studies, of which a total of 25 studies met inclusion criteria. Reported rates of nonadherence varied across studies: 2.6 1353% for dialysis exchanges, 3.9 1385% for medication, and 14.4 1367% for diet/fluid restrictions. Methodological differences in measurement and definition of non-adherence underlie the observed variation. Factors associated with non-adherence that showed a degree of consistency were mostly socio-demographical, such as age, employment status, ethnicity, sex, and time period on PD treatment. Conclusion: Non-adherence to different dimensions of the dialysis regimen appears to be prevalent in PD patients. There is a need for further, high-quality research to explore these factors in more detail, with the aim of informing intervention designs to facilitate adherence in this patient populatio

Effects of chronic ascariasis and trichuriasis on cytokine production and gene expression in human blood: a cross-sectional study.

Background Chronic soil-transmitted helminth (STH) infections are associated with effects on systemic immune responses that could be caused by alterations in immune homeostasis. To investigate this, we measured the impact in children of STH infections on cytokine responses and gene expression in unstimulated blood. Methodology/Principal Findings Sixty children were classified as having chronic, light, or no STH infections. Peripheral blood mononuclear cells were cultured in medium for 5 days to measure cytokine accumulation. RNA was isolated from peripheral blood and gene expression analysed using microarrays. Different infection groups were compared for the purpose of analysis: STH infection (combined chronic and light vs. uninfected groups) and chronic STH infection (chronic vs. combined light and uninfected groups). The chronic STH infection effect was associated with elevated production of GM-CSF (P = 0.007), IL-2 (P = 0.03), IL-5 (P = 0.01), and IL-10 (P = 0.01). Data reduction suggested that chronic infections were primarily associated with an immune phenotype characterized by elevated IL-5 and IL-10, typical of a modified Th2-like response. Chronic STH infections were associated with the up-regulation of genes associated with immune homeostasis (IDO, P = 0.03; CCL23, P = 0.008, HRK, P = 0.005), down-regulation of microRNA hsa-let-7d (P = 0.01) and differential regulation of several genes associated with granulocyte-mediated inflammation (IL-8, down-regulated, P = 0.0002; RNASE2, up-regulated, P = 0.009; RNASE3, up-regulated, p = 0.03). Conclusions/Significance Chronic STH infections were associated with a cytokine response indicative of a modified Th2 response. There was evidence that STH infections were associated with a pattern of gene expression suggestive of the induction of homeostatic mechanisms, the differential expression of several inflammatory genes and the down-regulation of microRNA has-let-7d. Effects on immune homeostasis and the development of a modified Th2 immune response during chronic STH infections could explain the systemic immunologic effects that have been associated with these infections such as impaired immune responses to vaccines and the suppression of inflammatory diseases

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO