Unraveling the Design Principle for Motif Organization in Signaling Networks

Cellular signaling networks display complex architecture. Defining the design principle of this architecture is crucial for our understanding of various biological processes. Using a mathematical model for three-node feed-forward loops, we identify that the organization of motifs in specific manner within the network serves as an important regulator of signal processing. Further, incorporating a systemic stochastic perturbation to the model we could propose a possible design principle, for higher-order organization of motifs into larger networks in order to achieve specific biological output. The design principle was then verified in a large, complex human cancer signaling network. Further analysis permitted us to classify signaling nodes of the network into robust and vulnerable nodes as a result of higher order motif organization. We show that distribution of these nodes within the network at strategic locations then provides for the range of features displayed by the signaling network

Why Are Computational Neuroscience and Systems Biology So Separate?

Despite similar computational approaches, there is surprisingly little interaction between the computational neuroscience and the systems biology research communities. In this review I reconstruct the history of the two disciplines and show that this may explain why they grew up apart. The separation is a pity, as both fields can learn quite a bit from each other. Several examples are given, covering sociological, software technical, and methodological aspects. Systems biology is a better organized community which is very effective at sharing resources, while computational neuroscience has more experience in multiscale modeling and the analysis of information processing by biological systems. Finally, I speculate about how the relationship between the two fields may evolve in the near future

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020

Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Funding Bill & Melinda Gates Foundation

Combined measurement of the Higgs boson mass from the H → γγ and H → ZZ∗ → 4ℓ decay channels with the ATLAS detector using √s = 7, 8, and 13 TeV pp collision data

A measurement of the mass of the Higgs boson combining the H → Z Z ∗ → 4 ℓ and H → γ γ decay channels is presented. The result is based on 140     fb − 1 of proton-proton collision data collected by the ATLAS detector during LHC run 2 at a center-of-mass energy of 13 TeV combined with the run 1 ATLAS mass measurement, performed at center-of-mass energies of 7 and 8 TeV, yielding a Higgs boson mass of 125.11 ± 0.09 ( stat ) ± 0.06 ( syst ) = 125.11 ± 0.11     GeV . This corresponds to a 0.09% precision achieved on this fundamental parameter of the Standard Model of particle physics

Prevalence and awareness about sexually transmitted infections among males in urban slums of Delhi

Background : India is at present facing an emergence of sexually transmitted infections (STIs) and human immunodeficiency virus. Community-based studies on the prevalence of STIs among males are scanty. Aim :(i) To study the prevalence of STIs and (ii) to assess the level of awareness about STIs among males belonging to the reproductive age group residing in an urban slum. Setting and Design :This is a cross-sectional study conducted in selected areas of Delhi, using a camp approach. Materials and Methods : One hundred ninety-six males in the reproductive age group were interviewed regarding their awareness about STIs, past history and present complaints of any symptoms suggestive of an STI. This was followed by a clinical examination. Required samples were also collected for microbiological tests. Statistical Tests : Simple proportions and Chi-square test. Results and Conclusions : As many as 70% of the study participants were unable to mention even one symptom of an STI. About 73.4% of the study participants stated that staying in a monogamous relationship could help prevent STI, while only 39.2% were aware that condoms could afford protection against an STI. As many as 8.7% complained of urethral discharge, while 5.6% complained of itching, 2.5% reported presence of genital ulcer and 1.0% complained of groin swelling. We found a seroprevalence rate of 1.5% for trichomoniasis and 3.6% for syphilis. Thus the overall awareness level about STIs and their prevention was rather low. Poor treatment-seeking behavior was also observed. The actual prevalence rate in the general population might be higher due to the likelihood of presence of an asymptomatic infection. The present study calls for a multipronged approach which also includes targeted interventions and strategies to be adopted in the reproductive health programs for males who have been neglected by the program managers so far