The Structure Of The Giant Haemoglobin From Glossoscolex Paulistus.

The sequences of all seven polypeptide chains from the giant haemoglobin of the free-living earthworm Glossoscolex paulistus (HbGp) are reported together with the three-dimensional structure of the 3.6 MDa complex which they form. The refinement of the full particle, which has been solved at 3.2 Å resolution, the highest resolution reported to date for a hexagonal bilayer haemoglobin composed of 12 protomers, is reported. This has allowed a more detailed description of the contacts between subunits which are essential for particle stability. Interpretation of features in the electron-density maps suggests the presence of metal-binding sites (probably Zn(2+) and Ca(2+)) and glycosylation sites, some of which have not been reported previously. The former appear to be important for the integrity of the particle. The crystal structure of the isolated d chain (d-HbGp) at 2.1 Å resolution shows different interchain contacts between d monomers compared with those observed in the full particle. Instead of forming trimers, as seen in the complex, the isolated d chains associate to form dimers across a crystallographic twofold axis. These observations eliminate the possibility that trimers form spontaneously in solution as intermediates during the formation of the dodecameric globin cap and contribute to understanding of the possible ways in which the particle self-assembles.711257-127

Projecting Climate Dependent Coastal Flood Risk With a Hybrid Statistical Dynamical Model

ABSTRACT: Numerical models for tides, storm surge, and wave runup have demonstrated ability to accurately define spatially varying flood surfaces. However these models are typically too computationally expensive to dynamically simulate the full parameter space of future oceanographic, atmospheric, and hydrologic conditions that will constructively compound in the nearshore to cause both extreme event and nuisance flooding during the 21st century. A surrogate modeling framework of waves, winds, and tides is developed in this study to efficiently predict spatially varying nearshore and estuarine water levels contingent on any combination of offshore forcing conditions. The surrogate models are coupled with a time-dependent stochastic climate emulator that provides efficient downscaling for hypothetical iterations of offshore conditions. Together, the hybrid statistical-dynamical framework can assess present day and future coastal flood risk, including the chronological characteristics of individual flood and wave-induced dune overtopping events and their changes into the future. The framework is demonstrated at Naval Base Coronado in San Diego, CA, utilizing the regional Coastal Storm Modeling System (CoSMoS; composed of Delft3D and XBeach) as the dynamic simulator and Gaussian process regression as the surrogate modeling tool. Validation of the framework uses both in-situ tide gauge observations within San Diego Bay, and a nearshore cross-shore array deployment of pressure sensors in the open beach surf zone. The framework reveals the relative influence of large-scale climate variability on future coastal flood resilience metrics relevant to the management of an open coast artificial berm, as well as the stochastic nature of future total water levels.This work was funded by the Strategic Environmental Research Development Program (DOD/SERDP RC-2644). Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government. F. J. Mendez, A. Rueda, and L. Cagigal acknowledge the partial funding from the Spanish Ministry of Science and Innovation, project Beach4cast PID2019-107053RB-I00. The authors thank the Scripps Center for Coastal Studies for their efforts to deploy, recover, and process surf zone pressure sensor data used as validation in this study. The authors thank Melisa Menendez for sharing GOW2 hindcast data for Southern California. The authors thank the sea-level rise projection authors for developing and making the sea-level rise projections available, multiple funding agencies for supporting the development of the projections, and the NASA Sea-Level Change Team for developing and hosting the IPCC AR6 Sea-Level Projection Tool

Gravitational waves physics using Fermi coordinates: a new teaching perspective

The detection of gravitational waves is possible thanks to a multidisciplinary approach, involving different disciplines such as astrophysics, physics, engineering and quantum optics. Consequently, it is important today for teachers to introduce the basic features of gravitational waves science in the undergraduate curriculum. The usual approach to gravitational wave physics is based on the use of traceless and transverse coordinates, which do not have a direct physical meaning and, in a teaching perspective, may cause misconceptions. In this paper, using Fermi coordinates, which are simply related to observable quantities, we show that it is possible to introduce a gravitoelectromagnetic analogy that describes the action of gravitational waves on test masses in terms of electric-like and magnetic-like forces. We suggest that this approach could be more suitable when introducing the basic principles of gravitational waves physics to students.Comment: 20 pages, 5 figures, Accepted for publication in the American Journal of Physic

Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan

Odderon Exchange from Elastic Scattering Differences between pp and pp−^{-} Data at 1.96 TeV and from pp Forward Scattering Measurements

We describe an analysis comparing the p¯p elastic cross section as measured by the D0 Collaboration at a center-of-mass energy of 1.96 TeV to that in pp collisions as measured by the TOTEM Collaboration at 2.76, 7, 8, and 13 TeV using a model-independent approach. The TOTEM crosssections, extrapolated to a center-of-mass energy of √s=1.96  TeV, are compared with the D0 measurement in the region of the diffractive minimum and the second maximum of the pp cross section. The two data sets disagree at the 3.4σ level and thus provide evidence for the t-channel exchange of a colorless, C-odd gluonic compound, also known as the odderon. We combine these results with a TOTEM analysis of the same C-odd exchange based on the total cross section and the ratio of the real to imaginary parts of the forward elastic strong interaction scatteringamplitude in pp scattering for which the significance is between 3.4σ and 4.6σ. The combined significance is larger than 5σ and is interpreted as the first observation of the exchange of a colorless, C-odd gluonic compound

Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10−9) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10−4-2.2 × 10−7. Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in genera