Revealing evolutionary constraints on proteins through sequence analysis

Statistical analysis of alignments of large numbers of protein sequences has revealed "sectors" of collectively coevolving amino acids in several protein families. Here, we show that selection acting on any functional property of a protein, represented by an additive trait, can give rise to such a sector. As an illustration of a selected trait, we consider the elastic energy of an important conformational change within an elastic network model, and we show that selection acting on this energy leads to correlations among residues. For this concrete example and more generally, we demonstrate that the main signature of functional sectors lies in the small-eigenvalue modes of the covariance matrix of the selected sequences. However, secondary signatures of these functional sectors also exist in the extensively-studied large-eigenvalue modes. Our simple, general model leads us to propose a principled method to identify functional sectors, along with the magnitudes of mutational effects, from sequence data. We further demonstrate the robustness of these functional sectors to various forms of selection, and the robustness of our approach to the identification of multiple selected traits.Comment: 37 pages, 28 figure

Dust continuum and Polarization from Envelope to Cores in Star Formation: A Case Study in the W51 North region

We present the first high-angular resolution (up to 0.7", ~5000 AU) polarization and thermal dust continuum images toward the massive star-forming region W51 North. The observations were carried out with the Submillimeter Array (SMA) in both the subcompact (SMA-SubC) and extended (SMA-Ext) configurations at a wavelength of 870 micron. W51 North is resolved into four cores (SMA1 to SMA4) in the 870 micron continuum image. The associated dust polarization exhibits more complex structures than seen at lower angular resolution. We analyze the inferred morphologies of the plane-of-sky magnetic field (B_bot) in the SMA1 to SMA4 cores and in the envelope using the SMA-Ext and SMA-SubC data. These results are compared with the B_bot archive images obtained from the CSO and JCMT. A correlation between dust intensity gradient position angles (phi_{nabla I}) and magnetic field position angles (phi_B) is found in the CSO, JCMT and both SMA data sets. This correlation is further analyzed quantitatively. A systematically tighter correlation between phi_{nabla I} and phi_B is found in the cores, whereas the correlation decreases in outside-core regions. Magnetic field-to-gravity force ratio (Sigma_B) maps are derived using the newly developed polarization - intensity gradient method by Koch, Tang & Ho 2012. We find that the force ratios tend to be small (Sigma_B <= 0.5) in the cores in all 4 data sets. In regions outside of the cores, the ratios increase or the field is even dominating gravity (Sigma_B > 1). This possibly provides a physical explanation of the tightening correlation between phi_{nabla I} and phi_B in the cores: the more the B field lines are dragged and aligned by gravity, the tighter the correlation is. Finally, we propose a schematic scenario for the magnetic field in W51 North to interpret the four polarization observations at different physical scales.Comment: Accepted for publication in ApJ. 10 pages. 7 figure

The circumstellar disk of AB Aurigae: evidence for envelope accretion at late stages of star formation?

The circumstellar disk of AB Aurigae has garnered strong attention owing to the apparent existence of spirals at a relatively young stage and also the asymmetric disk traced in thermal dust emission. However, the physical conditions of the spirals are still not well understood. The origin of the asymmetric thermal emission is unclear. We observed the disk at 230 GHz (1.3 mm) in both the continuum and the spectral line ^12CO J=2-1 with IRAM 30-m, the Plateau de Bure interferometer, and the Submillimeter Array to sample all spatial scales from 0.37" to about 50". To combine the data obtained from these telescopes, several methods and calibration issues were checked and discussed. The 1.3 mm continuum (dust) emission is resolved into inner disk and outer ring. Molecular gas at high velocities traced by the CO line is detected next to the stellar location. The inclination angle of the disk is found to decrease toward the center. On a larger scale, based on the intensity weighted dispersion and the integrated intensity map of ^12CO J=2-1, four spirals are identified, where two of them are also detected in the near infrared. The total gas mass of the 4 spirals (M_spiral) is 10^-7 < M_spiral < 10^-5 M_sun, which is 3 orders of magnitude smaller than the mass of the gas ring. Surprisingly, the CO gas inside the spiral is apparently counter-rotating with respect to the CO disk, and it only exhibits small radial motion. The wide gap, the warped disk, and the asymmetric dust ring suggest that there is an undetected companion with a mass of 0.03 M_sun at a radius of 45 AU. Although an hypothetical fly-by cannot be ruled out, the most likely explanation of the AB Aurigae system may be inhomogeneous accretion well above or below the main disk plane from the remnant envelope, which can explain both the rotation and large-scale motions detected with the 30-m image.Comment: 17 pages, 13 figures, accepted for publication in A&A journal. Typos are correcte

Co-delivery of human cancer-testis antigens with adjuvant in protein nanoparticles induces higher cell-mediated immune responses.

Nanoparticles have attracted considerable interest as cancer vaccine delivery vehicles for inducing sufficient CD8+ T cell-mediated immune responses to overcome the low immunogenicity of the tumor microenvironment. Our studies described here are the first to examine the effects of clinically-tested human cancer-testis (CT) peptide epitopes within a synthetic nanoparticle. Specifically, we focused on two significant clinical CT targets, the HLA-A2 restricted epitopes of NY-ESO-1 and MAGE-A3, using a viral-mimetic packaging strategy. Our data shows that simultaneous delivery of a NY-ESO-1 epitope (SLLMWITQV) and CpG using the E2 subunit assembly of pyruvate dehydrogenase (E2 nanoparticle), resulted in a 25-fold increase in specific IFN-γ secretion in HLA-A2 transgenic mice. This translated to a 15-fold increase in lytic activity toward target cancer cells expressing the antigen. Immunization with a MAGE-A3 epitope (FLWGPRALV) delivered with CpG in E2 nanoparticles yielded an increase in specific IFN-γ secretion and cell lysis by 6-fold and 9-fold, respectively. Furthermore, combined delivery of NY-ESO-1 and MAGE-A3 antigens in E2 nanoparticles yielded an additive effect that increased lytic activity towards cells bearing NY-ESO-1+ and MAGE-A3+. Our investigations demonstrate that formulation of CT antigens within a nanoparticle can significantly enhance antigen-specific cell-mediated responses, and the combination of the two antigens in a vaccine can preserve the increased individual responses that are observed for each antigen alone

Web-based Seminar - New Source of Qualitative Study: Data Collection during the Pandemic of COVID-19

Objective- This article aims to discuss the authors’ own experience using a web-based seminar (webinar) as a new data collection method for a qualitative descriptive study on factors influencing digital banking adoption among potential users in Malaysia (Digital Banking Study).   Design - This will be the first study to gather information from industry players and public perception towards digital banking service using webinars, with evidence compared to the study’s quantitative results.  Findings – Data derived from webinar sessions are consistent with the quantitative results, and the potential of its uses as a new research tool was discussed in detail. Policy Implications- The findings showed several practical implications that are potentially useful for researchers, academics, and business analysts to consider adopting webinar data as a new qualitative data collection method. Originality - This study documents the supporting evidence of the potential use of webinars as a useful tool to collect quality observation data

Managerial Risk Perceptions of Corporate Social Responsibility Disclosure : Evidence from the Forestry Sector in China

Understanding how managers perceive risks in the decision-making process of corporate social responsibility (CSR) disclosure is vital, especially in sectors with high social and environmental demands on sustainability. The main aim of this study was to explore the impact of managerial risk perceptions and influencing factors on CSR disclosure in the forestry sector of China and to improve the sustainable development of forestry. Utilizing survey data of 214 managers from Chinese forestry enterprises, we analyzed how manager backgrounds, including six variables (gender, age, education level, degree major, number of years working as a manager, and work experience) related to the managers’ risk perceptions of CSR disclosure via a two-stage model. The analyses of the two-stage model revealed that the influence factors differ in the two stages of risk perception. According to our results, influencing factors were not the same at various stages of the CSR reporting process. This requires decision makers to take practical driving factors into account and select managers with different characteristics to carry out the CSR disclosure of forestry enterprises

Circumbinary Ring, Circumstellar disks and accretion in the binary system UY Aurigae

Recent exo-planetary surveys reveal that planets can orbit and survive around binary stars. This suggests that some fraction of young binary systems which possess massive circumbinary disks (CB) may be in the midst of planet formation. However, there are very few CB disks detected. We revisit one of the known CB disks, the UY Aurigae system, and probe 13CO 2-1, C18O 2-1, SO 5(6)-4(5) and 12CO 3-2 line emission and the thermal dust continuum. Our new results confirm the existence of the CB disk. In addition, the circumstellar (CS) disks are clearly resolved in dust continuum at 1.4 mm. The spectral indices between the wavelengths of 0.85 mm and 6 cm are found to be surprisingly low, being 1.6 for both CS disks. The deprojected separation of the binary is 1.26" based on our 1.4 mm continuum data. This is 0.07" (10 AU) larger than in earlier studies. Combining the fact of the variation of UY Aur B in $R$ band, we propose that the CS disk of an undetected companion UY Aur Bb obscures UY Aur Ba. A very complex kinematical pattern inside the CB disk is observed due to a mixing of Keplerian rotation of the CB disk, the infall and outflow gas. The streaming gas accreting from the CB ring toward the CS disks and possible outflows are also identified and resolved. The SO emission is found to be at the bases of the streaming shocks. Our results suggest that the UY Aur system is undergoing an active accretion phase from the CB disk to the CS disks. The UY Aur B might also be a binary system, making the UY Aur a triple system.Comment: 14 pages, 11 figures; accepted for publication in Ap

Estimating the Richness of a Population When the Maximum Number of Classes Is Fixed: A Nonparametric Solution to an Archaeological Problem

Background: Estimating assemblage species or class richness from samples remains a challenging, but essential, goal. Though a variety of statistical tools for estimating species or class richness have been developed, they are all singly-bounded: assuming only a lower bound of species or classes. Nevertheless there are numerous situations, particularly in the cultural realm, where the maximum number of classes is fixed. For this reason, a new method is needed to estimate richness when both upper and lower bounds are known. Methodology/Principal Findings: Here, we introduce a new method for estimating class richness: doubly-bounded confidence intervals (both lower and upper bounds are known). We specifically illustrate our new method using the Chao1 estimator, rarefaction, and extrapolation, although any estimator of asymptotic richness can be used in our method. Using a case study of Clovis stone tools from the North American Lower Great Lakes region, we demonstrate that singly-bounded richness estimators can yield confidence intervals with upper bound estimates larger than the possible maximum number of classes, while our new method provides estimates that make empirical sense. Conclusions/Significance: Application of the new method for constructing doubly-bound richness estimates of Clovis stone tools permitted conclusions to be drawn that were not otherwise possible with singly-bounded richness estimates, namely, that Lower Great Lakes Clovis Paleoindians utilized a settlement pattern that was probably more logistical in nature than residential. However, our new method is not limited to archaeological applications. It can be applied to any set of data for which there is a fixed maximum number of classes, whether that be site occupancy models, commercial products (e.g. athletic shoes), or census information (e.g. nationality, religion, age, race)

Impact of multimorbidity count on all-cause mortality and glycaemic outcomes in people with type 2 diabetes: a systematic review protocol

Introduction: Type 2 diabetes (T2D) is a leading health priority worldwide. Multimorbidity (MM) is a term describing the co-occurrence of two or more chronic diseases or conditions. The majority of people living with T2D have MM. The relationship between MM and mortality and glycaemia in people with T2D is not clear. Methods and analysis: Medline, Embase, Cumulative Index of Nursing and Allied Health Complete, The Cochrane Library, and SCOPUS will be searched with a prespecified search strategy. The searches will be limited to quantitative empirical studies in English with no restriction on publication date. One reviewer will perform title screening and two review authors will independently screen the abstract and full texts using Covidence software, with disagreements adjudicated by a third reviewer. Data will be extracted using a using a Population, Exposure, Comparator and Outcomes framework. Two reviewers will independently extract data and undertake the risk of bias (quality) assessment. Disagreements will be resolved by consensus. A narrative synthesis of the results will be conducted and meta-analysis considered if appropriate. Quality appraisal will be undertaken using the Newcastle-Ottawa quality assessment scale and the quality of the cumulative evidence of the included studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. This protocol was prepared in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines to ensure the quality of our review. Ethics and dissemination: This review will synthesise the existing evidence about the impact of MM on mortality and glycaemic outcomes in people living with T2D and increase our understanding of this subject and will inform future practice and policy. Findings will be disseminated via conference presentations, social media and peer-reviewed publication