Divergent evolution of protein conformational dynamics in dihydrofolate reductase.

Molecular evolution is driven by mutations, which may affect the fitness of an organism and are then subject to natural selection or genetic drift. Analysis of primary protein sequences and tertiary structures has yielded valuable insights into the evolution of protein function, but little is known about the evolution of functional mechanisms, protein dynamics and conformational plasticity essential for activity. We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family. Despite structural similarity, Escherichia coli and human DHFRs use different dynamic mechanisms to perform the same function, and human DHFR cannot complement DHFR-deficient E. coli cells. Identification of the primary-sequence determinants of flexibility in DHFRs from several species allowed us to propose a likely scenario for the evolution of functionally important DHFR dynamics following a pattern of divergent evolution that is tuned by cellular environment

The EDGE-CALIFA Survey: Interferometric Observations of 126 Galaxies with CARMA

We present interferometric CO observations, made with the Combined Array for Millimeter-wave Astronomy (CARMA) interferometer, of galaxies from the Extragalactic Database for Galaxy Evolution survey (EDGE). These galaxies are selected from the Calar Alto Legacy Integral Field Area (CALIFA) sample, mapped with optical integral field spectroscopy. EDGE provides good-quality CO data (3σ sensitivity before inclination correction, resolution ∼1.4 kpc) for 126 galaxies, constituting the largest interferometric CO survey of galaxies in the nearby universe. We describe the survey and data characteristics and products, then present initial science results. We find that the exponential scale lengths of the molecular, stellar, and star-forming disks are approximately equal, and galaxies that are more compact in molecular gas than in stars tend to show signs of interaction. We characterize the molecular-to-stellar ratio as a function of Hubble type and stellar mass and present preliminary results on the resolved relations between the molecular gas, stars, and star-formation rate. We then discuss the dependence of the resolved molecular depletion time on stellar surface density, nebular extinction, and gas metallicity. EDGE provides a key data set to address outstanding topics regarding gas and its role in star formation and galaxy evolution, which will be publicly available on completion of the quality assessment.Fil: Bolatto, Alberto. University of Maryland; Estados UnidosFil: Wong, Tony. University of Illinois at Urbana; Estados UnidosFil: Utomo, Dyas. University of California at Berkeley; Estados UnidosFil: Blitz, Leo. University of California at Berkeley; Estados UnidosFil: Vogel, Stuart N.. University of Maryland; Estados UnidosFil: Sánchez, Sebastián F.. Universidad Nacional Autónoma de México; MéxicoFil: Barrera-Ballesteros, Jorge. University Johns Hopkins; Estados UnidosFil: Cao, Yixian. University of Illinois; Estados UnidosFil: Colombo, Dario. Max Planck Institut Fur Radioastronomie; AlemaniaFil: Dannerbauer, Helmut. Universidad de La Laguna; EspañaFil: García-Benito, Rubén. Instituto de Astrofísica de Andalucía; EspañaFil: Herrera-Camus, Rodrigo. Max Planck Institute für Extraterrestrische Physik; AlemaniaFil: Husemann, Bernd. Max-Planck-Institut für Astronomie; AlemaniaFil: Kalinova, Veselina. Max Planck Institut für Radioastronomie; AlemaniaFil: Leroy, Adam K.. Ohio State University; Estados UnidosFil: Leung, Gigi. Max-Planck-Institut für Astronomie; AlemaniaFil: Levy, Rebecca C.. University of Maryland; Estados UnidosFil: Mast, Damian. Observatorio Astronomico de la Universidad Nacional de Cordoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Ostriker, Eve. University of Princeton; Estados UnidosFil: Rosolowsky, Erik. University of Alberta; CanadáFil: Sandstrom, Karin M.. University of California at San Diego; Estados UnidosFil: Teuben, Peter. University of Maryland; Estados UnidosFil: Van De Ven, Glenn. Max-Planck-Institut für Astronomie; AlemaniaFil: Walter, Fabian. Max-Planck-Institut für Astronomie; Alemani

Public preferences for ecological indicators used in Everglades restoration

The Everglades is one of the largest wetland ecosystems in the world covering almost 18,000 square miles from central Florida southward to Florida Bay. Over the 20th century, efforts to drain the Everglades for agriculture and development severely damaged the ecosystem so that today roughly 50% of the historic flow of water through the Everglades has been diverted elsewhere. In an attempt to restore the Everglades, the U.S. Congress authorized the Comprehensive Everglades Restoration Plan (CERP) in 2000, expected to cost over $16 billion and to take several decades to complete. We used the results from a stated preference choice experiment (SPCE) survey of Florida households to estimate the willingness to pay for several ecological attributes related to CERP performance indicators likely to be impacted by Everglades restoration. We also used a latent class model (LCM) to explore preference heterogeneity among respondents. On average, survey respondents were willing to pay for improvements in all of the attributes included in the survey, namely increased populations of wading birds, American alligators, endangered snail kites, and spotted seatrout, and reduced polluted discharges from Lake Okeechobee to the Caloosahatchee and St. Lucie rivers. Willingness to pay was highest for reduced polluted discharges from Lake Okeechobee.Data Availability: All relevant data are available at https://doi.org/10.17605/OSF.IO/9AG7Z.S1 Table. Comparison between the demographics of the survey sample respondents and the Florida population based on 2010 U.S. Census information. https://doi.org/10.1371/journal.pone.0234051.s001S2 Table. Regression results from conditional logit model with willingness to pay estimates. https://doi.org/10.1371/journal.pone.0234051.s002The Everglades Foundationhttp://www.plosone.orghj2020Mammal Research Institut

Quantum state discrimination: a geometric approach

We analyse the problem of finding sets of quantum states that can be deterministically discriminated. From a geometric point of view this problem is equivalent to that of embedding a simplex of points whose distances are maximal with respect to the Bures distance (or trace distance). We derive upper and lower bounds for the trace distance and for the fidelity between two quantum states, which imply bounds for the Bures distance between the unitary orbits of both states. We thus show that when analysing minimal and maximal distances between states of fixed spectra it is sufficient to consider diagonal states only. Hence considering optimal discrimination, given freedom up to unitary orbits, it is sufficient to consider diagonal states. This is illustrated geometrically in terms of Weyl chambers.Comment: 12 pages, 2 figure

Community science for coastal acidification monitoring and research

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Gassett, P. R., O’Brien-Clayton, K., Bastidas, C., Rheuban, J. E., Hunt, C., Turner, E., Liebman, M., Silva, E., Pimenta, A., Grear, J., Motyka, J., McCorkle, D., Stancioff, E., Brady, D., & Strong, A. Community science for coastal acidification monitoring and research. Coastal Management, 49(5), (2021): 510-531, https://doi.org/10.1080/08920753.2021.1947131.Ocean and coastal acidification (OCA) present a unique set of sustainability challenges at the human-ecological interface. Extensive biogeochemical monitoring that can assess local acidification conditions, distinguish multiple drivers of changing carbonate chemistry, and ultimately inform local and regional response strategies is necessary for successful adaptation to OCA. However, the sampling frequency and cost-prohibitive scientific equipment needed to monitor OCA are barriers to implementing the widespread monitoring of dynamic coastal conditions. Here, we demonstrate through a case study that existing community-based water monitoring initiatives can help address these challenges and contribute to OCA science. We document how iterative, sequential outreach, workshop-based training, and coordinated monitoring activities through the Northeast Coastal Acidification Network (a) assessed the capacity of northeastern United States community science programs and (b) engaged community science programs productively with OCA monitoring efforts. Our results (along with the companion manuscript) indicate that community science programs are capable of collecting robust scientific information pertinent to OCA and are positioned to monitor in locations that would critically expand the coverage of current OCA research. Furthermore, engaging community stakeholders in OCA science and outreach enabled a platform for dialogue about OCA among other interrelated environmental concerns and fostered a series of co-benefits relating to public participation in resource and risk management. Activities in support of community science monitoring have an impact not only by increasing local understanding of OCA but also by promoting public education and community participation in potential adaptation measures.AGU Centennial Grant NOAA OAP OFFICE North American Association for Environmental Education Curtis and Edith Munson Foundation Sea Grant programs within the region Senator George J. Mitchell Center for Sustainability Solutions Funding acknowledgment: MIT Sea Grant award NA18OAR4170105 to Bastidas NERACOOS The WestWind foundation (to Rheuban) Woods Hole Sea Grant (NOAA Grant No. NA18OAR4170104

Open-Sourced CIViC Annotation Pipeline to identify and annotate clinically relevant variants using single-molecule molecular inversion probes

PURPOSE: Clinical targeted sequencing panels are important for identifying actionable variants for patients with cancer; however, existing approaches do not provide transparent and rationally designed clinical panels to accommodate the rapidly growing knowledge within oncology. MATERIALS AND METHODS: We used the Clinical Interpretations of Variants in Cancer (CIViC) database to develop an Open-Sourced CIViC Annotation Pipeline (OpenCAP). OpenCAP provides methods to identify variants within the CIViC database, build probes for variant capture, use probes on prospective samples, and link somatic variants to CIViC clinical relevance statements. OpenCAP was tested using a single-molecule molecular inversion probe (smMIP) capture design on 27 cancer samples from 5 tumor types. In total, 2,027 smMIPs were designed to target 111 eligible CIViC variants (61.5 kb of genomic space). RESULTS: When compared with orthogonal sequencing, CIViC smMIP sequencing demonstrated a 95% sensitivity for variant detection (n = 61 of 64 variants). Variant allele frequencies for variants identified on both sequencing platforms were highly concordant (Pearson\u27s CONCLUSION: The OpenCAP design paradigm demonstrates the utility of an open-source and open-access database built on attendant community contributions with peer-reviewed interpretations. Use of a public repository for variant identification, probe development, and variant interpretation provides a transparent approach to build dynamic next-generation sequencing-based oncology panels

Chronic CRH depletion from GABAergic, long-range projection neurons in the extended amygdala reduces dopamine release and increases anxiety

The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release.Fil: Dedic, Nina. Max Planck Institute Of Psychiatry; AlemaniaFil: Kühne, Claudia. Max Planck Institute Of Psychiatry; AlemaniaFil: Jakovcevski, Mira. Max Planck Institute Of Psychiatry; AlemaniaFil: Hartmann, Jakob. Max Planck Institute Of Psychiatry; AlemaniaFil: Genewsky, Andreas J.. Max Planck Institut Of Psychiatry; AlemaniaFil: Gomes, Karina S.. Max Planck Institute Of Psychiatry; AlemaniaFil: Anderzhanova, Elmira. Max Planck Institute Of Psychiatry; AlemaniaFil: Pöhlmann, Max L.. Max Planck Institute Of Psychiatry; AlemaniaFil: Chang, Simon. Max Planck Institute Of Psychiatry; AlemaniaFil: Kolarz, Adam. Max Planck Institute Of Psychiatry; AlemaniaFil: Vogl, Annette M.. Max Planck Institute Of Psychiatry; AlemaniaFil: Dine, Julien. Max Planck Institute Of Psychiatry; AlemaniaFil: Metzger, Michael W.. Max Planck Institute of Psychiatry; ArmeniaFil: Schmid, Bianca. Max Planck Institute Of Psychiatry; AlemaniaFil: Almada, Rafael C.. Max Planck Institute Of Psychiatry; AlemaniaFil: Ressler, Kerry J.. Harvard Medical School; Estados UnidosFil: Wotjak, Carsten T.. Max Planck Institute Of Psychiatry; AlemaniaFil: Grinevich, Valery. University of Heidelberg; AlemaniaFil: Chen, Alon. Max Planck Institute Of Psychiatry; AlemaniaFil: Schmidt, Mathias V.. Institute Of Developmental Genetics, Helmholtz Zentrum; AlemaniaFil: Wurst, Wolfgang. German Center for Neurodegenerative Diseases; AlemaniaFil: Refojo, Damian. Max Planck Institute Of Psychiatry; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Deussing, Jan M.. Max Planck Institute Of Psychiatry; Alemani

Doha agreement meeting on terminology and definitions in groin pain in athletes.

BACKGROUND: Heterogeneous taxonomy of groin injuries in athletes adds confusion to this complicated area. AIM: The 'Doha agreement meeting on terminology and definitions in groin pain in athletes' was convened to attempt to resolve this problem. Our aim was to agree on a standard terminology, along with accompanying definitions. METHODS: A one-day agreement meeting was held on 4 November 2014. Twenty-four international experts from 14 different countries participated. Systematic reviews were performed to give an up-to-date synthesis of the current evidence on major topics concerning groin pain in athletes. All members participated in a Delphi questionnaire prior to the meeting. RESULTS: Unanimous agreement was reached on the following terminology. The classification system has three major subheadings of groin pain in athletes: 1. Defined clinical entities for groin pain: Adductor-related, iliopsoas-related, inguinal-related and pubic-related groin pain. 2. Hip-related groin pain. 3. Other causes of groin pain in athletes. The definitions are included in this paper. CONCLUSIONS: The Doha agreement meeting on terminology and definitions in groin pain in athletes reached a consensus on a clinically based taxonomy using three major categories. These definitions and terminology are based on history and physical examination to categorise athletes, making it simple and suitable for both clinical practice and research

A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2

Background: As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus, whether from infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure antibody-based protection to SARS-CoV-2, ideally with rapid turnaround and without the need for laboratory-based testing. Methods: We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibody (NAb) from whole blood, with a result that can be determined by eye or quantitatively on a small instrument. We compared our lateral flow test with the gold-standard microneutralisation assay, using samples from convalescent and vaccinated donors, as well as immunised macaques. Findings: We show a high correlation between our lateral flow test with conventional neutralisation and that this test is applicable with animal samples. We also show that this assay is readily adaptable to test for protection to newly emerging SARS-CoV-2 variants, including the beta variant which revealed a marked reduction in NAb activity. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (specificity 100% and sensitivity 96% at a microneutralisation cutoff of 1:40) and that fingerprick whole blood samples are sufficient for this test. Interpretation: Taken together, the COVID-19 NAb-testTM device described here provides a rapid readout of NAb based protection to SARS-CoV-2 at the point of care