Genomic mining of prokaryotic repressors for orthogonal logic gates

Genetic circuits perform computational operations based on interactions between freely diffusing molecules within a cell. When transcription factors are combined to build a circuit, unintended interactions can disrupt its function. Here, we apply 'part mining' to build a library of 73 TetR-family repressors gleaned from prokaryotic genomes. The operators of a subset were determined using an in vitro method, and this information was used to build synthetic promoters. The promoters and repressors were screened for cross-reactions. Of these, 16 were identified that both strongly repress their cognate promoter (5- to 207-fold) and exhibit minimal interactions with other promoters. Each repressor-promoter pair was converted to a NOT gate and characterized. Used as a set of 16 NOT/NOR gates, there are >10[superscript 54] circuits that could be built by changing the pattern of input and output promoters. This represents a large set of compatible gates that can be used to construct user-defined circuits.United States. Air Force Office of Scientific Research (Award FA9550-11-C-0028)American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship (32 CFR 168a)United States. Defense Advanced Research Projects Agency. Chronical of Lineage Indicative of Origins (N66001-12-C-4016)United States. Office of Naval Research (N00014-13-1-0074)National Institutes of Health (U.S.) (GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (SA5284-11210

Computer-Based Screening of Functional Conformers of Proteins

A long-standing goal in biology is to establish the link between function, structure, and dynamics of proteins. Considering that protein function at the molecular level is understood by the ability of proteins to bind to other molecules, the limited structural data of proteins in association with other bio-molecules represents a major hurdle to understanding protein function at the structural level. Recent reports show that protein function can be linked to protein structure and dynamics through network centrality analysis, suggesting that the structures of proteins bound to natural ligands may be inferred computationally. In the present work, a new method is described to discriminate protein conformations relevant to the specific recognition of a ligand. The method relies on a scoring system that matches critical residues with central residues in different structures of a given protein. Central residues are the most traversed residues with the same frequency in networks derived from protein structures. We tested our method in a set of 24 different proteins and more than 260,000 structures of these in the absence of a ligand or bound to it. To illustrate the usefulness of our method in the study of the structure/dynamics/function relationship of proteins, we analyzed mutants of the yeast TATA-binding protein with impaired DNA binding. Our results indicate that critical residues for an interaction are preferentially found as central residues of protein structures in complex with a ligand. Thus, our scoring system effectively distinguishes protein conformations relevant to the function of interest

Course and prognosis of recovery for chronic non-specific low back pain: design, therapy program and baseline data of a prospective cohort study

Background: There has been increasing focus on factors predicting the development of chronic musculoskeletal disorders. For patients already experiencing chronic non-specific low back pain it is also relevant to investigate which prognostic factors predict recovery. We present the design of a cohort study that aims to determine the course and prognostic factors for recovery in patients with chronic non-specific low back pain. Methods/Design. All participating patients were recruited (Jan 2003-Dec 2008) from the same rehabilitation centre and were evaluated by means of (postal) questionnaires and physical examinations at baseline, during the 2-month therapy program, and at 5 and 12 months after start of therapy. The therapy protocol at the rehabilitation centre used a bio-psychosocial approach to stimulate patients to adopt adequate (movement) behaviour aimed at physical and functional recovery. The program is part of regular care and consists of 16 sessions of 3 hours each, over an 8-week period (in total 48 hours), followed by a 3-month self-management program. The primary outcomes are low back pain intensity, disability, quality of life, patient's global perceived effect of recovery, and participation in work. Baseline characteristics include information on socio-demographics, low back pain, employment status, and additional clinical items status such as fatigue, duration of activities, and fear of kinesiophobia. Prognostic variables are determined for recovery at short-term (5 months) and long-term (12 months) follow-up after start of therapy. Discussion. In a routine clinical setting it is important to provide patients suffering from chronic non-specific low back pain with adequate information about the prognosis of their complaint

Candida glabrata : a review of its features and resistance

Candida species belong to the normal microbiota of the oral cavity and gastrointestinal and vaginal tracts, and are responsible for several clinical manifestations, from mucocutaneous overgrowth to bloodstream infections. Once believed to be non-pathogenic, Candida glabrata was rapidly blamable for many human diseases. Year after year, these pathological circumstances are more recurrent and problematic to treat, especially when patients reveal any level of immunosuppression. These difficulties arise from the capacity of C. glabrata to form biofilms and also from its high resistance to traditional antifungal therapies. Thus, this review intends to present an excerpt of the biology, epidemiology, and pathology of C. glabrata, and detail an approach to its resistance mechanisms based on studies carried out up to the present.The authors are grateful to strategic project PTDC/SAU-MIC/119069/2010 for the financial support to the research center and for Celia F. Rodrigues' grant

A Precision Measurement of the Lambda_c Baryon Mass

The $\Lambda_c^+$ baryon mass is measured using $\Lambda_c^+\to\Lambda K^0_S K^+$ and $\Lambda_c^+\to\Sigma^0 K^0_S K^+$ decays reconstructed in 232 fb$^{-1}$ of data collected with the BaBar detector at the PEP-II asymmetric-energy $e^+e^-$ storage ring. The $\Lambda_c^+$ mass is measured to be $2286.46\pm0.14\mathrm{MeV}/c^2$. The dominant systematic uncertainties arise from the amount of material in the tracking volume and from the magnetic field strength.Comment: 14 pages, 8 postscript figures, submitted to Phys. Rev.

Measurement of branching fractions and resonance contributions for B-0 ->(D)over-bar(0)K(+)pi(-) and search for B-0 ->(DK+)-K-0 pi(-) decays

Using 226x10(6) Upsilon(4S)-> B (B) over bar events collected with the BABAR detector at the PEP-II e(+)e(-) storage ring at the Stanford Linear Accelerator Center, we measure the branching fraction for B-0->(D) over bar (0)K(+)pi(-), excluding B-0-> D*-K+, to be B(B-0->(0)K(+)pi(-))=(88 +/- 15 +/- 9)x10(-6). We observe B-0->(D) over bar K-0(*)(892)(0) and B-0-> D-2(*)(2460)K--(+) contributions. The ratio of branching fractions B(B-0-> D*-K+)/B(B-0-> D(*-)pi(+))=(7.76 +/- 0.34 +/- 0.29)% is measured separately. The branching fraction for the suppressed mode B-0-> D(0)K(+)pi(-) is B(B-0-> D(0)K(+)pi(-))< 19x10(-6) at the 90% confidence level

Measurements of branching fractions and dalitz distributions for B-0 ->(DK0)-K-(*)+/-pi(-/+) decays

We present measurments of the branching fractions for the three-body decays B-0 -> D((*) -/+)K(0)pi(+/-) and their resonant submodes B0 -> D(*)K-/+*(+/-) usinga sample of approximately 88 x 10(6) B (B) over bar pairs collected by the BABER detector at the SLAC PEP-II assymetric energy storage ring. We measure: B(B-0-> D(-/+)K(0)pi(+/-)) = (4.9 +/- 0.7(stat) +/- 0.5(syst)) x 10(-4), B(B-0 -> D*(-/+)K(0)pi(+/-)) = (3.0 +/- 0.7(stat) +/- 0.3(syst)) x 10(-4), B(B-0 -> D-/+K*(+/-)) = (4.6 +/- 0.6(stat) +/- 0.5(syst)) x 10(-4), B(B-0 -> D*K-/+*(+/-) = (3.2 +/- 0.6(stat) +/- 0.3(syst)) x 10(-4). From these measurements we determine the fractions of resonant events to be f(B0 -> D+/-K*(-/+)) = 0.63 +/- 0.08(stat) +/- 0.04(syst) and f(B-0 -> D*K-/+*(+/-)) = 0.72 +/- 0.14(stat) +/- 0.05(syst)

Measurements of branching fractions and CP-violating asymmetries in B meson decays to charmless two-body states containing a K-0

We present measurements of branching fractions and CP-violating asymmetries in decays of B mesons to two-body final states containing a K-0. The results are based on a data sample of approximately 88x10(6) Y(4S)-->B (B) over bar decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We measure B(B+-->K(0)pi(+))=(22.3+/-1.7+/-1.1)x10(-6), B(B-0-->K(0)pi(0))=(11.4+/-1.7+/-0.8)x10(-6), B(B+-->(K) over bar K-0(+))K-0(K) over bar (0))K(0)pi(+))=-0.05+/-0.08+/-0.01 and A(CP)(B-0-->K(0)pi(0))=0.03+/-0.36+/-0.11

Search for radiative penguin decays B+->rho(+)gamma, B-0 ->rho(0)gamma, and B-0 ->omega gamma

A search for the decays B-->rho(770)gamma and B-0-->omega(782)gamma is performed on a sample of 211x10(6) Y(4S)-->B (B) over bar events collected by the BABAR detector at the SLAC PEP-II asymmetric-energy e(+)e(-) storage ring. No evidence for the decays is seen. We set the following limits on the individual branching fractions: B(B+-->rho(+)gamma)rho(0)gamma)omegagamma)(rho/omega)gamma]<1.2x10(-6), from which we determine a constraint on the ratio of Cabibbo-Kobayashi-Maskawa matrix elements |V-td|/|V-ts|