On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

Prospecting environmental mycobacteria: combined molecular approaches reveal unprecedented diversity

Background: Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods: We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results: PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions: This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in which, as minority members, they would have remained undetected

Evaluation of a student-run smoking cessation clinic for a medically underserved population

<p>Abstract</p> <p>Background</p> <p>Smoking is common among medically underserved populations. Accessible resources to encourage and support smoking cessation among these patients are limited. Volunteer medical student-run free smoking cessation clinics may provide an effective option to help these individuals achieve smoking abstinence. In order to demonstrate the feasibility and cost-effectiveness of a student-run clinic, we analyzed a case series of patients receiving care in a medical student-run Smoking Cessation Clinic (SCC) at the Rochester, Minnesota Salvation Army Good Samaritan Health Clinic (GSHC).</p> <p>Findings</p> <p>Between January 2005 and March 2009, 282 cigarette smokers seeking care at the SCC were analyzed. Student providers at the SCC conducted 1652 weekly individual counseling sessions averaging 18 minutes per encounter. Patients were offered a choice of pharmacotherapies including nicotine replacement therapy (NRT), bupropion, and varenicline for up to 12 weeks. Smoking abstinence was confirmed with exhaled carbon monoxide (CO). Thirty-two patients completed the entire 12-week program (11.3%). At last contact, 94 patients (33.3%) abstained from smoking for ≥ 7 days and 39 patients (13.8%) were continuously abstinent for ≥ 4 weeks. The 7-day point prevalence abstinence rates at last contact were 58.6% for varenicline, 41.2% for bupropion, 33.9% for NRT, and 23.5% for bupropion and NRT. Analyzing missing patients as smoking, the 7-day point prevalence abstinence rates were 7.1%, 8.9%, and 8.2%, at 1 month, 2 months, and 3 months after program enrollment, respectively. No serious adverse drug reactions were recorded.</p> <p>Conclusions</p> <p>Our medical student-run smoking cessation clinic provided an effective and safe experience for medically underserved patients who might not otherwise have access to conventional smoking cessation programs because of high cost, lack of insurance, or other disparities. Similar medical student initiatives focusing on healthy lifestyles may be feasible and beneficial for individuals with limited access to healthcare resources.</p

Mutational Patterns in RNA Secondary Structure Evolution Examined in Three RNA Families

The goal of this work was to study mutational patterns in the evolution of RNA secondary structure. We analyzed bacterial tmRNA, RNaseP and eukaryotic telomerase RNA secondary structures, mapping structural variability onto phylogenetic trees constructed primarily from rRNA sequences. We found that secondary structures evolve both by whole stem insertion/deletion, and by mutations that create or disrupt stem base pairing. We analyzed the evolution of stem lengths and constructed substitution matrices describing the changes responsible for the variation in the RNA stem length. In addition, we used principal component analysis of the stem length data to determine the most variable stems in different families of RNA. This data provides new insights into the evolution of RNA secondary structures and patterns of variation in the lengths of double helical regions of RNA molecules. Our findings will facilitate design of improved mutational models for RNA structure evolution

Towards a science of climate and energy choices

The linked problems of energy sustainability and climate change are among the most complex and daunting facing humanity at the start of the twenty-first century. This joint Nature Energy and Nature Climate Change Collection illustrates how understanding and addressing these problems will require an integrated science of coupled human and natural systems; including technological systems, but also extending well beyond the domain of engineering or even economics. It demonstrates the value of replacing the stylized assumptions about human behaviour that are common in policy analysis, with ones based on data-driven science. We draw from and engage articles in the Collection to identify key contributions to understanding non-technological factors connecting economic activity and greenhouse gas emissions, describe a multi-dimensional space of human action on climate and energy issues, and illustrate key themes, dimensions and contributions towards fundamental understanding and informed decision making

Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT