Chemical sensing by nonequilibrium cooperative receptors

Cooperativity arising from local interactions in equilibrium receptor systems provides gain, but does not increase sensory performance, as measured by the signal-to-noise ratio (SNR) due to a fundamental tradeoff between gain and intrinsic noise. Here we allow sensing to be a nonequilibrium process and show that energy dissipation cannot circumvent the fundamental tradeoff, so that SNR is still optimal for independent receptors. For systems requiring high gain, nonequilibrium 2D-coupled receptors maximize SNR, revealing a new design principle for biological sensors

Conserved microRNA targeting reveals preexisting gene dosage sensitivities that shaped amniote sex chromosome evolution

Mammalian X and Y Chromosomes evolved from an ordinary autosomal pair. Genetic decay of the Y led to X Chromosome inactivation (XCI) in females, but some Y-linked genes were retained during the course of sex chromosome evolution, and many X-linked genes did not become subject to XCI. We reconstructed gene-by-gene dosage sensitivities on the ancestral autosomes through phylogenetic analysis of microRNA (miRNA) target sites and compared these preexisting characteristics to the current status of Y-linked and X-linked genes in mammals. Preexisting heterogeneities in dosage sensitivity, manifesting as differences in the extent of miRNA-mediated repression, predicted either the retention of a Y homolog or the acquisition of XCI following Y gene decay. Analogous heterogeneities among avian Z-linked genes predicted either the retention of a W homolog or gene-specific dosage compensation following W gene decay. Genome-wide analyses of human copy number variation indicate that these heterogeneities consisted of sensitivity to both increases and decreases in dosage. We propose a model of XY/ZW evolution incorporating such preexisting dosage sensitivities in determining the evolutionary fates of individual genes. Our findings thus provide a more complete view of the role of dosage sensitivity in shaping the mammalian and avian sex chromosomes and reveal an important role for post-transcriptional regulatory sequences (miRNA target sites) in sex chromosome evolution

Completing the nuclear reaction puzzle of the nucleosynthesis of 92Mo

One of the greatest questions for modern physics to address is how elements heavier than iron are created in extreme, astrophysical environments. A particularly challenging part of that question is the creation of the so-called p-nuclei, which are believed to be mainly produced in some types of supernovae. The lack of needed nuclear data presents an obstacle in nailing down the precise site and astrophysical conditions. In this work, we present for the first time measurements on the nuclear level density and average strength function of $^{92}$Mo. State-of-the-art p-process calculations systematically underestimate the observed solar abundance of this isotope. Our data provide stringent constraints on the $^{91}$Nb$(p,{\gamma})^{92}$Mo reaction rate, which is the last unmeasured reaction in the nucleosynthesis puzzle of $^{92}$Mo. Based on our results, we conclude that the $^{92}$Mo abundance anomaly is not due to the nuclear physics input to astrophysical model calculations.Comment: Submitted to PR

3D facial phenotyping by biometric sibling matching used in contemporary genomic methodologies

The analysis of contemporary genomic data typically operates on one-dimensional phenotypic measurements (e.g. standing height). Here we report on a data-driven, family-informed strategy to facial phenotyping that searches for biologically relevant traits and reduces multivariate 3D facial shape variability into amendable univariate measurements, while preserving its structurally complex nature. We performed a biometric identification of siblings in a sample of 424 children, defining 1,048 sib-shared facial traits. Subsequent quantification and analyses in an independent European cohort (n = 8,246) demonstrated significant heritability for a subset of traits (0.17–0.53) and highlighted 218 genome-wide significant loci (38 also study-wide) associated with facial variation shared by siblings. These loci showed preferential enrichment for active chromatin marks in cranial neural crest cells and embryonic craniofacial tissues and several regions harbor putative craniofacial genes, thereby enhancing our knowledge on the genetic architecture of normal-range facial variation

Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations

Facial morphology is highly variable, both within and among human populations, and a sizable portion of this variation is attributable to genetics. Previous genome scans have revealed more than 100 genetic loci associated with different aspects of normal-range facial variation. Most of these loci have been detected in Europeans, with few studies focusing on other ancestral groups. Consequently, the degree to which facial traits share a common genetic basis across diverse sets of humans remains largely unknown. We therefore investigated the genetic basis of facial morphology in an East African cohort. We applied an open-ended data-driven phenotyping approach to a sample of 2,595 3D facial images collected on Tanzanian children. This approach segments the face into hierarchically arranged, multivariate features that capture the shape variation after adjusting for age, sex, height, weight, facial size and population stratification. Genome scans of these multivariate shape phenotypes revealed significant (p < 2.5 × 10−8) signals at 20 loci, which were enriched for active chromatin elements in human cranial neural crest cells and embryonic craniofacial tissue, consistent with an early developmental origin of the facial variation. Two of these associations were in highly conserved regions showing craniofacial-specific enhancer activity during embryological development (5q31.1 and 12q21.31). Six of the 20 loci surpassed a stricter threshold accounting for multiple phenotypes with study-wide significance (p < 6.25 × 10−10). Cross-population comparisons indicated 10 association signals were shared with Europeans (seven sharing the same associated SNP), and facilitated fine-mapping of causal variants at previously reported loci. Taken together, these results may point to both shared and population-specific components to the genetic architecture of facial variation

betabeta decay of 75Ni^75Ni and the systematics of the low-lying level structure of neutron-rich odd-AA Cu isotopes

International audienceBackground: Detailed spectroscopy of neutron-rich odd-A Cu isotopes is of great importance for studying the shell evolution in the region of Ni78. While there is experimental information on excited states in Cu69−73,77,79 isotopes, the information concerning Cu75 is very limited. Purpose: Experimentally observed single-particle, core-coupling, and proton-hole intruder states in Cu75, will complete the systematics of these states in the chain of isotopes. Method: Excited states in Cu75 were populated in the β decay of Ni75 isotopes. The Ni nuclei were produced by the in-flight fission of U238 projectiles, and were separated, identified, and implanted in a highly segmented Si detector array for the detection of the β-decay electrons. The β-delayed γ rays were detected in a HPGe cluster array. Monte Carlo shell model calculations were performed using the A3DA interaction built on the pfg9/2d5/2 model space for both neutrons and protons. Results: A level scheme of Cu75 was built up to ≈4 MeV by performing a γ-γ coincidence analysis. The excited states below 2 MeV were interpreted based on the systematics of neutron-rich odd-A Cu isotopes and the results of the shell model calculations. Conclusions: The evolution of the single-particle, core-coupling, and proton-hole intruder states in the chain of neutron-rich odd-A Cu isotopes is discussed in the present work, in connection with the newly observed level structure of Cu75

Search for lepton-number violating B+ -> X(-)l(+)l '(+) decays

We report on a search for eleven lepton-number violating processes B+ -> X(-)l(+)l'(+) with X- = K-, pi(-), rho(-), K*(-), or D- and l(+)/l'(+) = e(+) or mu(+), using a sample of 471 +/- 3 million B (B) over bar events collected with the BABAR detector at the PEP-II e(+)e(-) collider at the SLAC National Accelerator Laboratory. We find no evidence for any of these modes and place 90% confidence level upper limits on their branching fractions in the range (1.5-26) x 10(-7)

Magnetic resonance imaging, magnetic resonance arthrography and ultrasonography for assessing rotator cuff tears in people with shoulder pain for whom surgery is being considered

Background Shoulder pain is a very common symptom. Disorders of the rotator cuff tendons due to wear or tear are among the most common causes of shoulder pain and disability. Magnetic resonance imaging (MRI), magnetic resonance arthrography (MRA) and ultrasound (US) are increasingly being used to assess the presence and size of rotator cuff tears to assist in planning surgical treatment. It is not known whether one imaging method is superior to any of the others.Objectives To compare the diagnostic test accuracy of MRI, MRA and US for detecting any rotator cuff tears (i.e. partial or full thickness) in people with suspected rotator cuff tears for whom surgery is being considered.Search methods We searched the Cochrane Register of Diagnostic Test Accuracy Studies, MEDLINE, EMBASE, and LILACS from inception to February 2011. We also searched trial registers, conference proceedings and reference lists of articles to identify additional studies. No language or publication restrictions were applied.Selection criteria We included all prospective diagnostic accuracy studies that assessed MRI, MRA or US against arthroscopy or open surgery as the reference standard, in people suspected of having a partial or full thickness rotator cuff tear. We excluded studies that selected a healthy control group, or participants who had been previously diagnosed with other specific causes of shoulder pain such as osteoarthritis or rheumatoid arthritis. Studies with an excessively long period (a year or longer) between the index and reference tests were also excluded.Data collection and analysis Two review authors independently extracted data on study characteristics and results of included studies, and performed quality assessment according to QUADAS criteria. Our unit of analysis was the shoulder. for each test, estimates of sensitivity and specificity from each study were plotted in ROC space and forest plots were constructed for visual examination of variation in test accuracy. Meta-analyses were performed using the bivariate model to produce summary estimates of sensitivity and specificity. We were unable to formally investigate potential sources of heterogeneity because of the small number of studies.Main results We included 20 studies of people with suspected rotator cuff tears (1147 shoulders), of which six evaluated MRI and US (252 shoulders), or MRA and US (127 shoulders) in the same people. Many studies had design flaws, with the potential for bias, thus limiting the reliability of their findings. Overall, the methodological quality of the studies was judged to be low or unclear. for each test, we observed considerable heterogeneity in study results, especially between studies that evaluated US for the detection of full thickness tears and studies that evaluated MRA for the detection of partial thickness tears. the criteria for a positive diagnostic test (index tests and reference standard) varied between studies.Meta-analyses were not possible for studies that assessed MRA for detection of any rotator cuff tears or partial thickness tears. We found no statistically significant differences in sensitivity or specificity between MRI and US for detecting any rotator cuff tears (P = 0.13), or for detecting partial thickness tears (P = 1.0). Similarly, for the comparison between MRI, MRA and US for detecting full thickness tears, there was no statistically significant difference in diagnostic performance (P = 0.7). for any rotator cuff tears, the summary sensitivity and specificity were 98% (95% CI 92% to 99%) and 79% (95% CI 68% to 87%) respectively for MRI (6 studies, 347 shoulders), and 91% (95% CI 83% to 95%) and 85% (95% CI 74% to 92%) respectively for US (13 studies, 854 shoulders). for full thickness tears, the summary sensitivity and specificity were 94% (95% CI 85% to 98%) and 93% (95% CI 83% to 97%) respectively for MRI (7 studies, 368 shoulders); 94% (95% CI 80% to 98%) and 92% (95% CI 83% to 97%) respectively for MRA (3 studies, 183 shoulders); and 92% (95% CI 82% to 96%) and 93% (95% CI 81% to 97%) respectively for US (10 studies, 729 shoulders).Because few studies were direct head-to-head comparisons, we could not perform meta-analyses restricted to these studies. the test comparisons for each of the three classifications of the target condition were therefore based on indirect comparisons which may be prone to bias due to confounding.Authors' conclusions MRI, MRA and US have good diagnostic accuracy and any of these tests could equally be used for detection of full thickness tears in people with shoulder pain for whom surgery is being considered. the diagnostic performance of MRI and US may be similar for detection of any rotator cuff tears. However, both MRI and US may have poor sensitivity for detecting partial thickness tears, and the sensitivity of US may be much lower than that of MRI. the strength of evidence for all test comparisons is limited because most studies were small, heterogeneous and methodologically flawed, and there were few comparative studies. Well designed studies that directly compare MRI, MRA and US for detection of rotator cuff tears are needed.Universidade Federal de São Paulo, BrazilParker Institute, DenmarkOak FoundationTeesside University, UKUniversidade Federal de São Paulo, Dept Orthopaed & Traumatol, BR-04038032 São Paulo, BrazilMonash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Monash Dept Clin Epidemiol,Cabrini Hosp, Malvern, AustraliaUniv Birmingham, Birmingham, W Midlands, EnglandUniv Teesside, Hlth & Social Care Inst, Middlesbrough, Cleveland, EnglandUniversidade Federal de São Paulo, Dept Orthopaed & Traumatol, BR-04038032 São Paulo, BrazilWeb of Scienc