Analyses of publicly available structural data reveal interesting insights into the impact of the three‐dimensional (3D) structures of protein targets important for discovery of new drugs (e.g., ...G‐protein‐coupled receptors, voltage‐gated ion channels, ligand‐gated ion channels, transporters, and E3 ubiquitin ligases). The Protein Data Bank (PDB) archive currently holds > 155,000 atomic‐level 3D structures of biomolecules experimentally determined using crystallography, nuclear magnetic resonance spectroscopy, and electron microscopy. The PDB was established in 1971 as the first open‐access, digital‐data resource in biology, and is now managed by the Worldwide PDB partnership (wwPDB; wwPDB.org). US PDB operations are the responsibility of the Research Collaboratory for Structural Bioinformatics PDB (RCSB PDB). The RCSB PDB serves millions of RCSB.org users worldwide by delivering PDB data integrated with ∼40 external biodata resources, providing rich structural views of fundamental biology, biomedicine, and energy sciences. Recently published work showed that the PDB archival holdings facilitated discovery of ∼90% of the 210 new drugs approved by the US Food and Drug Administration 2010–2016. We review user‐driven development of RCSB PDB services, examine growth of the PDB archive in terms of size and complexity, and present examples and opportunities for structure‐guided drug discovery for challenging targets (e.g., integral membrane proteins).
Two illustrations integrate current knowledge about severe acute respiratory syndrome (SARS) coronaviruses and their life cycle. They have been widely used in education and outreach through free ...distribution as part of a coronavirus-related resource at Protein Data Bank (PDB)-101, the education portal of the RCSB PDB. Scientific sources for creation of the illustrations and examples of dissemination and response are presented.
The Research Collaboratory for Structural Bioinformatics (RCSB) Molecule of the Month series provides a curated introduction to the 3-D biomolecular structures available in the Protein Data Bank ...archive and the tools that are available at the RCSB website for accessing and exploring them. A variety of educational materials, such as articles, videos, posters, hands-on activities, lesson plans, and curricula, build on this series for use in a variety of educational settings as a general introduction to key topics, such as enzyme action, protein synthesis, and viruses. The series and associated educational materials are freely available at www.rcsb.org.
Conservation efforts should target the few remaining areas of the world that represent outstanding examples of ecological integrity and aim to restore ecological integrity to a much broader area of ...the world with intact habitat and minimal species loss while this is still possible. There have been many assessments of “intactness” in recent years but most of these use measures of anthropogenic impact at a site, rather than faunal intactness or ecological integrity. This paper makes the first assessment of faunal intactness for the global terrestrial land surface and assesses how many ecoregions have sites that could qualify as Key Biodiversity Areas (KBAs – sites contributing significantly to the global persistence of biodiversity) based on their outstanding ecological integrity (under KBA Criterion C). Three datasets are combined on species loss at sites to create a new spatially explicit map of numbers of species extirpated. Based on this map it is estimated that no more than 2.9% of the land surface can be considered to be faunally intact. Additionally, using habitat/density distribution data for 15 large mammals we also make an initial assessment of areas where mammal densities are reduced, showing a further decrease in surface area to 2.8% of the land surface that could be considered functionally intact. Only 11% of the functionally intact areas that were identified are included within existing protected areas, and only 4% within existing KBAs triggered by other criteria. Our findings show that the number of ecoregions that could qualify as Criterion C KBAs could potentially increase land area up to 20% if their faunal composition was restored with the reintroduction of 1–5 species. Hence, if all necessary requirements are met in order to reintroduce species and regain faunal integrity, this will increase ecological integrity across much of the area where human impacts are low (human footprint ≤4). Focusing restoration efforts in these areas could significantly increase the area of the planet with full ecological integrity.
Abstract
The Wallacea biogeographic region of Sulawesi, the Moluccas and Lesser Sunda is globally renowned for exceptional endemism, but is currently emerging as a development frontier in Indonesia. ...We assessed patterns and drivers of forest loss and fragmentation across the region, and used dynamic deforestation models to project future deforestation to 2053. Up to 10 231 km
2
was deforested between 2000 and 2018, and a further 49 570 km
2
is expected to be lost by 2053, with annual deforestation rates ranging between 0.09% and 2.17% in different sub-regions (average: 1.23%). Key biodiversity areas (priority sites for endemic and threatened biodiversity) are particularly vulnerable to deforestation if they are small, coastal and unprotected. Sub-regional variation in deforestation patterns and drivers must be acknowledged if conservation interventions are to be targeted and effective. We provide a valuable baseline from which to monitor Wallacea’s new development course, as Indonesia undergoes profound policy changes that will provide both challenges and opportunities for environmental governance and conservation.
The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), funded by the United States National Science Foundation, National Institutes of Health, and Department of ...Energy, supports structural biologists and Protein Data Bank (PDB) data users around the world. The RCSB PDB, a founding member of the Worldwide Protein Data Bank (wwPDB) partnership, serves as the US data center for the global PDB archive housing experimentally-determined three-dimensional (3D) structure data for biological macromolecules. As the wwPDB-designated Archive Keeper, RCSB PDB is also responsible for the security of PDB data and weekly update of the archive. RCSB PDB serves tens of thousands of data depositors (using macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, and micro-electron diffraction) annually working on all permanently inhabited continents. RCSB PDB makes PDB data available from its research-focused web portal at no charge and without usage restrictions to many millions of PDB data consumers around the globe. It also provides educators, students, and the general public with an introduction to the PDB and related training materials through its outreach and education-focused web portal. This review article describes growth of the PDB, examines evolution of experimental methods for structure determination viewed through the lens of the PDB archive, and provides a detailed accounting of PDB archival holdings and their utilization by researchers, educators, and students worldwide.
Abstract The Asian tapir Tapirus indicus is the only tapir species in Southeast Asia. It is declining across its range and is categorized as Endangered on the IUCN Red List. The forests of Sumatra ...are critical to Asian tapir conservation as they contain some of the last remaining populations of the species, yet conservation efforts are hindered by a lack of information on habitat suitability. We collated camera-trap data from nine landscapes across 69,500 km 2 of Sumatran rainforest to help predict suitable habitat for Asian tapirs on the island. Predictions from Bayesian occupancy models demonstrated that tapir occupancy was greatest in forests below 600 m elevation and exclusively in forests with high aboveground biomass. Forests around the Barisan Mountains on the west of Sumatra provide the most suitable habitat for the species. Only 36% of the most critical habitat (i.e. 80th percentile of predicted occupancy values, or above) for tapirs is formally protected for conservation, with much of the remainder found in forests allocated to watershed protection (35%) or logging (23%). We highlight several key areas in Sumatra where tapir conservation could be bolstered, such as by leveraging existing conservation efforts for other charismatic flagships species on the island.
Various global-scale proposals exist to reduce the loss of biological diversity. These include the Half-Earth and Whole-Earth visions that respectively seek to set aside half the planet for wildlife ...conservation or to diversify conservation practices fundamentally and change the economic systems that determine environmental harm. Here we assess these visions in the specific context of Bornean orangutans Pongo pygmaeus and their conservation. Using an expert-led process we explored three scenarios over a 10-year time frame: continuation of Current Conditions, a Half-Earth approach and a Whole-Earth approach. In addition, we examined a 100-year population recovery scenario assuming 0% offtake of Bornean orangutans. Current Conditions were predicted to result in a population c. 73% of its current size by 2032. Half-Earth was judged comparatively easy to achieve and predicted to result in an orangutan population of c. 87% of its current size by 2032. Whole-Earth was anticipated to lead to greater forest loss and ape killing, resulting in a prediction of c. 44% of the current orangutan population for 2032. Finally, under the recovery scenario, populations could be c. 148% of their current size by 2122. Although we acknowledge uncertainties in all of these predictions, we conclude that the Half-Earth and Whole-Earth visions operate along different timelines, with the implementation of Whole-Earth requiring too much time to benefit orangutans. None of the theorized proposals provided a complete solution, so drawing elements from each will be required. We provide recommendations for equitable outcomes.
Knowledge about the structure and function of biomolecules continues to grow exponentially, enabling us to “see” structural snapshots of biomolecular interactions and functional assemblies. At ...PDB-101, the educational portal of the RCSB Protein Data Bank, we have taken a storytelling approach to make this body of knowledge accessible and comprehensible to a wide community of students, educators, and the general public. For over 20 years, the Molecule of the Month series has utilized a traditional illustrated storytelling approach that is regularly adapted for classroom instruction. Similar visual and interactive storytelling approaches are used to present topical subjects at PDB-101 and full curricular materials and case studies for building a detailed narrative around topics of particular interest. This emphasis on storytelling led to the Video Challenge for High School students, now in its 8th year. In this Article, we will present some of the lessons we have learned for teaching and communicating structural biology using the PDB archive of biomolecular structures.
Oxidative stress occurs through an imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defense mechanisms of cells. The eye is particularly exposed to oxidative ...stress because of its permanent exposure to light and due to several structures having high metabolic activities. The anterior part of the eye is highly exposed to ultraviolet (UV) radiation and possesses a complex antioxidant defense system to protect the retina from UV radiation. The posterior part of the eye exhibits high metabolic rates and oxygen consumption leading subsequently to a high production rate of ROS. Furthermore, inflammation, aging, genetic factors, and environmental pollution, are all elements promoting ROS generation and impairing antioxidant defense mechanisms and thereby representing risk factors leading to oxidative stress. An abnormal redox status was shown to be involved in the pathophysiology of various ocular diseases in the anterior and posterior segment of the eye. In this review, we aim to summarize the mechanisms of oxidative stress in ocular diseases to provide an updated understanding on the pathogenesis of common diseases affecting the ocular surface, the lens, the retina, and the optic nerve. Moreover, we discuss potential therapeutic approaches aimed at reducing oxidative stress in this context.
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