A New High-Resolution Map of World Mountains and an Online Tool for Visualizing and Comparing

Answers to the seemingly straightforward questions “what is a mountain?” and “where are the mountains of the world?” are in fact quite complex, and there have been few attempts to map the mountains of the earth in a consistent and rigorous fashion. However, knowing exactly where mountain ecosystems are distributed on the planet is a precursor to conserving them, as called for in Sustainable Development Goals 6 and 15 of the United Nations 2030 Agenda for Sustainable Development. In this article we first compare 3 characterizations of global mountain distributions, including a new, high-resolution (250 m) map of global mountains derived from terrain characteristics. We show how differences in conceptual definition, methodology, and spatial resolution of source data can result in differences in the extent and location of lands classed as mountains. For example, the new 250-m resource documents a larger global mountain extent than previous characterizations, although it excludes plateaus, hilly forelands, and other landforms that are often considered part of mountain areas. We then introduce the Global Mountain Explorer, a new web-based application specifically developed for exploration, visualization, and comparison of these maps. This new open-access tool is an intuitive and versatile resource suitable for a broad range of users and applications

Heparan sulfate expression in the neural crest is essential for mouse cardiogenesis

Impaired heparan sulfate (HS) synthesis in vertebrate development causes complex malformations due to the functional disruption of multiple HS-binding growth factors and morphogens. Here, we report developmental heart defects in mice bearing a targeted disruption of the HS-generating enzyme GlcNAc N-deacetylase/GlcN N-sulfotransferase 1 (NDST1), including ventricular septal defects (VSD), persistent truncus arteriosus (PTA), double outlet right ventricle (DORV), and retroesophageal right subclavian artery (RERSC). These defects closely resemble cardiac anomalies observed in mice made deficient in the cardiogenic regulator fibroblast growth factor 8 (FGF8). Consistent with this, we show that HS-dependent FGF8/FGF-receptor2C assembly and FGF8-dependent ERK-phosphorylation are strongly reduced in NDST1(-/-) embryonic cells and tissues. Moreover, WNT1-Cre/LoxP-mediated conditional targeting of NDST function in neural crest cells (NCCs) revealed that their impaired HS-dependent development contributes strongly to the observed cardiac defects. These findings raise the possibility that defects in HS biosynthesis may contribute to congenital heart defects in humans that represent the most common type of birth defect

Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood

Calibrated Automated Thrombography (CAT) is a versatile and sensitive method for analyzing coagulation reactions culminating in thrombin generation (TG). Here, we present a CAT method for analyzing TG in murine whole blood by adapting the CAT assay used for measuring TG in human plasma. The diagnostically used artificial and physiologic factor XII (FXII) contact activators kaolin, ellagic acid and polyphosphate (polyP) stimulated TG in murine blood in a dose-dependent manner resulting in a gradual increase in endogenous thrombin potential and peak thrombin, with shortened lag times and times to peak. The activated FXII inhibitor rHA-Infestin-4 and direct oral anticoagulants (DOACs) interfered with TG triggered by kaolin, ellagic acid and polyP and TG was completely attenuated in blood of FXII- (F12−/−) and FXI-deficient (F11−/−) mice. Moreover, reconstitution of blood from F12−/− mice with human FXII restored impaired contact-stimulated TG. HEK293 cell-purified polyP also initiated FXII-driven TG in mouse whole blood and addition of the selective inhibitor PPX_112 ablated natural polyP-stimulated TG. In conclusion, the data provide a method for analysis of contact activation-mediated TG in murine whole blood. As the FXII-driven intrinsic pathway of coagulation has emerged as novel target for antithrombotic agents that are validated in mouse thrombosis and bleeding models, our novel assay could expedite therapeutic drug development

Coronary atherosclerosis in diabetes mellitus A population-based autopsy study

AbstractObjectivesThe study was conducted to test the hypothesis that the prevalence of coronary atherosclerosis is greater among diabetic than among nondiabetic individuals and is similar for diabetic individuals without clinical coronary artery disease (CAD) and nondiabetics with clinical CAD.BackgroundPersons with diabetes but without clinical CAD encounter cardiovascular mortality similar to nondiabetic individuals with clinical CAD. This excess mortality is not fully explained. We examined the association between diabetes and coronary atherosclerosis in a geographically defined autopsied population, while capitalizing on the autopsy rate and medical record linkage system available via the Rochester Epidemiology Project, which allows rigorous ascertainment of coronary atherosclerosis, clinical CAD, and diabetes.MethodsUsing two measures, namely a global coronary score and high-grade stenoses, the prevalence of atherosclerosis was analyzed in a cohort of autopsied residents of Rochester, Minnesota, age 30 years or older at death, while stratifying on diabetes, clinical CAD diagnosis, age, and gender.ResultsIn this cohort, diabetes was associated with a higher prevalence of atherosclerosis. Among diabetic decedents without clinical CAD, almost three-fourths had high-grade coronary atherosclerosis and more than half had multivessel disease. Without diabetes, women had less atherosclerosis than men, but this female advantage was lost with diabetes. Among those without clinical CAD, diabetes was associated with a global coronary disease burden and a prevalence of high-grade atherosclerosis similar to that observed among nondiabetic subjects with clinical CAD.ConclusionsThese findings provide mechanistic insights into the excess risk of clinical CAD among diabetic individuals, thereby supporting the need for aggressive prevention of atherosclerosis in all diabetic individuals, irrespective of clinical CAD symptoms

An Assessment of the Representation of Ecosystems in Global Protected Areas Using New Maps of World Climate Regions and World Ecosystems

Representation of ecosystems in protected area networks and conservation strategies is a core principle of global conservation priority setting approaches and a commitment in Aichi Target 11 of the Convention on Biological Diversity. The 2030 Sustainable Development Goals (SDGs) explicitly call for the conservation of terrestrial, freshwater, and marine ecosystems. Accurate ecosystem distribution maps are required to assess representation of ecosystems in protected areas, but standardized, high spatial resolution, and globally comprehensive ecosystem maps have heretofore been lacking. While macroscale global ecoregions maps have been used in global conservation priority setting exercises, they do not identify distinct localized ecosystems at the occurrence (patch) level, and instead describe large ecologically meaningful areas within which additional conservation planning and management are necessary. We describe a new set of maps of globally consistent climate regions and ecosystems at a much finer spatial resolution (250 m) than existing ecological regionalizations. We then describe a global gap analysis of the representation of these ecosystems in protected areas. The new map of terrestrial World Ecosystems was derived from the objective development and integration of 1) global temperature domains, 2) global moisture domains, 3) global landforms, and 4) 2015 global vegetation and land use. These new terrestrial World Ecosystems do not include either freshwater or marine ecosystems, but analog products for the freshwater and marine domains are in development. A total of 431 World Ecosystems were identified, and of these a total of 278 units were natural or semi-natural vegetation/environment combinations, including different kinds of forestlands, shrublands, grasslands, bare areas, and ice/snow regions. The remaining classes were different kinds of croplands and settlements. Of the 278 natural and semi-natural classes, 9 were not represented in global protected areas with a strict biodiversity conservation management objective (IUCN management categories I-IV), and an additional 206 were less than 8.5% protected (half way to the 17% Aichi Target 11 goal). Forty four classes were between 8.5% and 17% protected (more than half way towards the Aichi 17% target), and only 19 classes exceeded the 17% Aichi target. However, when all protected areas (IUCN management categories I-VI plus protected areas with no IUCN designation) were included in a separate global gap analysis, representation of ecosystems increases substantially, with a third of the ecosystems exceeding the 17% Aichi target, and another third between 8.5% and 17%. The overall protection (representation) of global ecosystems in protected areas is considerably less when assessed using only strictly conserved protected areas, and more if all protected areas are included in the analysis. Protected area effectiveness should be included in further evaluations of global ecosystem protection. The ecosystems with the highest representation in protected areas were often bare or sparsely vegetated and found in inhospitable environments (e.g. cold mountains, deserts), and the eight most protected ecosystems were all snow and ice ecosystems. In addition to the global gap analysis of World Ecosystems in protected areas, we report on the representation results for the ecosystems in each biogeographic realm (Neotropical, Nearctic, Afrotropical, Palearctic, Indomalayan, Australasian, and Oceania)

A Global Ecological Classification of Coastal Segment Units to Complement Marine Biodiversity Observation Network Assessments

A new data layer provides Coastal and Marine Ecological Classification Standard (CMECS) labels for global coastal segments at 1 km or shorter resolution. These characteristics are summarized for six US Marine Biodiversity Observation Network (MBON) sites and one MBON Pole to Pole of the Americas site in Argentina. The global coastlines CMECS classifications were produced from a partitioning of a 30 m Landsat-derived shoreline vector that was segmented into 4 million 1 km or shorter segments. Each segment was attributed with values from 10 variables that represent the ecological settings in which the coastline occurs, including properties of the adjacent water, adjacent land, and coastline itself. The 4 million segments were classified into 81,000 coastal segment units (CSUs) as unique combinations of variable classes. We summarize the process to develop the CSUs and derive summary descriptions for the seven MBON case study sites. We discuss the intended application of the new CSU data for research and management in coastal areas

Targeting NETs using dual-active DNase1 variants

Background: Neutrophil Extracellular Traps (NETs) are key mediators of immunothrombotic mechanisms and defective clearance of NETs from the circulation underlies an array of thrombotic, inflammatory, infectious, and autoimmune diseases. Efficient NET degradation depends on the combined activity of two distinct DNases, DNase1 and DNase1-like 3 (DNase1L3) that preferentially digest double-stranded DNA (dsDNA) and chromatin, respectively. Methods: Here, we engineered a dual-active DNase with combined DNase1 and DNase1L3 activities and characterized the enzyme for its NET degrading potential in vitro. Furthermore, we produced a mouse model with transgenic expression of the dual-active DNase and analyzed body fluids of these animals for DNase1 and DNase 1L3 activities. We systematically substituted 20 amino acid stretches in DNase1 that were not conserved among DNase1 and DNase1L3 with homologous DNase1L3 sequences. Results: We found that the ability of DNase1L3 to degrade chromatin is embedded into three discrete areas of the enzyme's core body, not the C-terminal domain as suggested by the state-of-the-art. Further, combined transfer of the aforementioned areas of DNase1L3 to DNase1 generated a dual-active DNase1 enzyme with additional chromatin degrading activity. The dual-active DNase1 mutant was superior to native DNase1 and DNase1L3 in degrading dsDNA and chromatin, respectively. Transgenic expression of the dual-active DNase1 mutant in hepatocytes of mice lacking endogenous DNases revealed that the engineered enzyme was stable in the circulation, released into serum and filtered to the bile but not into the urine. Conclusion: Therefore, the dual-active DNase1 mutant is a promising tool for neutralization of DNA and NETs with potential therapeutic applications for interference with thromboinflammatory disease states