Laws of biology: why so few?

Finding fundamental organizing principles is the current intellectual front end of systems biology. From a hydrogen atom to the whole cell level, organisms manage massively parallel and massively interactive processes over several orders of magnitude of size. To manage this scale of informational complexity it is natural to expect organizing principles that determine higher order behavior. Currently, there are only hints of such organizing principles but no absolute evidences. Here, we present an approach as old as Mendel that could help uncover fundamental organizing principles in biology. Our approach essentially consists of identifying constants at various levels and weaving them into a hierarchical chassis. As we identify and organize constants, from pair-wise interactions to networks, our understanding of the fundamental principles in biology will improve, leading to a theory in biology

Worldwide food recall patterns over an eleven month period: A country perspective.

<p>Abstract</p> <p>Background</p> <p>Following the World Health Organization Forum in November 2007, the Beijing Declaration recognized the importance of food safety along with the rights of all individuals to a safe and adequate diet. The aim of this study is to retrospectively analyze the patterns in food alert and recall by countries to identify the principal hazard generators and gatekeepers of food safety in the eleven months leading up to the Declaration.</p> <p>Methods</p> <p>The food recall data set was collected by the Laboratory of the Government Chemist (LGC, UK) over the period from January to November 2007. Statistics were computed with the focus reporting patterns by the 117 countries. The complexity of the recorded interrelations was depicted as a network constructed from structural properties contained in the data. The analysed network properties included degrees, weighted degrees, modularity and <it>k</it>-core decomposition. Network analyses of the reports, based on 'country making report' (<it>detector</it>) and 'country reported on' (<it>transgressor</it>), revealed that the network is organized around a dominant core.</p> <p>Results</p> <p>Ten countries were reported for sixty per cent of all faulty products marketed, with the top 5 countries having received between 100 to 281 reports. Further analysis of the dominant core revealed that out of the top five transgressors three made no reports (in the order China > Turkey > Iran). The top ten detectors account for three quarters of reports with three > 300 (Italy: 406, Germany: 340, United Kingdom: 322).</p> <p>Conclusion</p> <p>Of the 117 countries studied, the vast majority of food reports are made by 10 countries, with EU countries predominating. The majority of the faulty foodstuffs originate in ten countries with four major producers making no reports. This pattern is very distant from that proposed by the Beijing Declaration which urges all countries to take responsibility for the provision of safe and adequate diets for their nationals.</p

Follow-up of internal mammary artery stent with 64-slice CT

We present a case of 81-year-old woman complaining chest pain after minimal efforts who underwent multiple coronary artery bypass grafts (CABGs) during the last 15 years. A significant in-stent re-stenosis was found at ostium of left internal mammary artery (LIMA). A non-invasive CT coronary angiography (CT-CA) was performed after 6-month follow-up. CT-CA is a reliable non-invasive technique for the follow-up of stents in coronary artery bypass grafts

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma

Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on days 1-21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity, and accelerated daratumumab infusions were studied. In part 1 (13 patients), no dose-limiting toxicities were observed, and 16 mg/kg was selected as the R2PD. In part 2 (32 patients), median time since diagnosis was 3.2 years, with a median of 2 prior therapies (range, 1-3 prior therapies), including proteasome inhibitors (91%), alkylating agents (91%), autologous stem cell transplantation (78%), thalidomide (44%), and lenalidomide (34%); 22% of patients were refractory to the last line of therapy. Grade 3 to 4 adverse events (≥5%) included neutropenia, thrombocytopenia, and anemia. In part 2, infusion-related reactions (IRRs) occurred in 18 patients (56%); most were grade ≤2 (grade 3, 6.3%). IRRs predominantly occurred during first infusions and were more common during accelerated infusions. In part 2 (median follow-up of 15.6 months), overall response rate was 81%, with 8 stringent complete responses (25%), 3 complete responses (9%), and 9 very good partial responses (28%). Eighteen-month progression-free and overall survival rates were 72% (95% confidence interval, 51.7-85.0) and 90% (95% confidence interval, 73.1-96.8), respectively. Daratumumab plus lenalidomide/dexamethasone resulted in rapid, deep, durable responses. The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01615029

Long-term vitamin E supplementation fails to reduce lipid peroxidation in people at cardiovascular risk: analysis of underlying factors

BACKGROUND: Antioxidant supplementation with vitamin E had no effect in the prevention of cardiovascular diseases (CVD) in three recent large, randomized clinical trials. In order to reassess critically the role of vitamin E in CVD prevention, it is important to establish whether these results are related to a lack of antioxidant action. METHODS: We examined the in vivo antioxidant effect of vitamin E (300 mg/day for about three years) in 144 participants in the Primary Prevention Project (females and males, aged ≥ 50 y, with at least one major CV risk factor, but no history of CVD). Urinary 8-epi-PGF(2α) (isoprostane F(2α)-III or 15-F(2t)-isoP), a validated biomarker of lipid peroxidation, was measured by mass spectrometry. RESULTS: Urinary excretion of 8-epi-PGF(2α) [pg/mg creatinine, median (range)] was 141 (67–498) in treated and 148 (76–561) in untreated subjects (p = 0.10). Taking into account possible confounding variables, multiple regression analysis confirmed that vitamin E had no significant effect on this biomarker. Levels of 8-epi-PGF(2α) were in the normal range for most subjects, except smokers and those with uncontrolled blood pressure or hyperglycemia. CONCLUSIONS: Prolonged vitamin E supplementation did not reduce lipid peroxidation in subjects with major cardiovascular risk factors. The observation that the rate of lipid peroxidation was near normal in a large proportion of subjects may help explain why vitamin E was not effective as an antioxidant in the PPP study and was ineffective for CVD prevention in large scale trials

Transcriptome profiling of grapevine seedless segregants during berry development reveals candidate genes associated with berry weight

Indexación: Web of Science; PubMedBackground Berry size is considered as one of the main selection criteria in table grape breeding programs. However, this is a quantitative and polygenic trait, and its genetic determination is still poorly understood. Considering its economic importance, it is relevant to determine its genetic architecture and elucidate the mechanisms involved in its expression. To approach this issue, an RNA-Seq experiment based on Illumina platform was performed (14 libraries), including seedless segregants with contrasting phenotypes for berry weight at fruit setting (FST) and 6–8 mm berries (B68) phenological stages. Results A group of 526 differentially expressed (DE) genes were identified, by comparing seedless segregants with contrasting phenotypes for berry weight: 101 genes from the FST stage and 463 from the B68 stage. Also, we integrated differential expression, principal components analysis (PCA), correlations and network co-expression analyses to characterize the transcriptome profiling observed in segregants with contrasting phenotypes for berry weight. After this, 68 DE genes were selected as candidate genes, and seven candidate genes were validated by real time-PCR, confirming their expression profiles. Conclusions We have carried out the first transcriptome analysis focused on table grape seedless segregants with contrasting phenotypes for berry weight. Our findings contributed to the understanding of the mechanisms involved in berry weight determination. Also, this comparative transcriptome profiling revealed candidate genes for berry weight which could be evaluated as selection tools in table grape breeding programs.http://bmcplantbiol.biomedcentral.com/articles/10.1186/s12870-016-0789-

Role of TGF-β1 haplotypes in the occurrence of myocardial infarction in young Italian patients

<p>Abstract</p> <p>Background</p> <p>Transforming growth factor beta 1 (TGF-β1) gene play an important role in the acute myocardial infarction (AMI), however no investigation has been conducted so far in young AMI patients.</p> <p>In this study, we evaluated the influence of TGF-β1 polymorphisms/haplotypes on the onset and progression of AMI in young Italian population.</p> <p>Methods</p> <p>201 cases and 201 controls were genotyped for three TGF-β1 polymorphisms (G-800A, C-509T and Leu10Pro). The main follow-up end-points (mean follow-up, 107 ± 49 months) were death, myocardial infarction or revascularization procedures.</p> <p>Results</p> <p>Significant risk factors were smoking (p < 10^-4), family history for coronary artery disease (p < 10^-4), hypercholesterolemia (p = 0.001) and hypertension (p = 0.002). The C-509T and Leu10Pro polymorphisms showed significant differences (p = 0.026 and p = 0.004) between cases and controls.</p> <p>The most common haplotypes revealed a possible protective effect (GCT, OR 0.75, 95% CI 0.57–0.99, p = 0.042) and an increased risk of AMI (GTC, OR 1.51, 95% CI 1.13–2.02, p = 0.005), respectively.</p> <p>No statistical differences were observed in genotype distribution in the follow-up study between the two groups: 61 patients with subsequent events (13 deaths) and 108 without events.</p> <p>Conclusion</p> <p>Even though our results need to be further confirmed in larger studies, this is the first study reporting on a possible role of TGFβ1 common haplotypes in the onset of AMI in young patients.</p

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Towards the prediction of essential genes by integration of network topology, cellular localization and biological process information

<p>Abstract</p> <p>Background</p> <p>The identification of essential genes is important for the understanding of the minimal requirements for cellular life and for practical purposes, such as drug design. However, the experimental techniques for essential genes discovery are labor-intensive and time-consuming. Considering these experimental constraints, a computational approach capable of accurately predicting essential genes would be of great value. We therefore present here a machine learning-based computational approach relying on network topological features, cellular localization and biological process information for prediction of essential genes.</p> <p>Results</p> <p>We constructed a decision tree-based meta-classifier and trained it on datasets with individual and grouped attributes-network topological features, cellular compartments and biological processes-to generate various predictors of essential genes. We showed that the predictors with better performances are those generated by datasets with integrated attributes. Using the predictor with all attributes, i.e., network topological features, cellular compartments and biological processes, we obtained the best predictor of essential genes that was then used to classify yeast genes with unknown essentiality status. Finally, we generated decision trees by training the J48 algorithm on datasets with all network topological features, cellular localization and biological process information to discover cellular rules for essentiality. We found that the number of protein physical interactions, the nuclear localization of proteins and the number of regulating transcription factors are the most important factors determining gene essentiality.</p> <p>Conclusion</p> <p>We were able to demonstrate that network topological features, cellular localization and biological process information are reliable predictors of essential genes. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing essentiality.</p