Analytically tractable climate-carbon cycle feedbacks under 21st century anthropogenic forcing

Changes to climate-carbon cycle feedbacks may significantly affect the Earth System’s response to greenhouse gas emissions. These feedbacks are usually analysed from numerical output of complex and arguably opaque Earth System Models (ESMs). Here, we construct a stylized global climate-carbon cycle model, test its output against complex ESMs, and investigate the strengths of its climate-carbon cycle feedbacks analytically. The analytical expressions we obtain aid understanding of carbon-cycle feedbacks and the operation of the carbon cycle. We use our results to analytically study the relative strengths of different climate-carbon cycle feedbacks and how they may change in the future, as well as to compare different feedback formalisms. Simple models such as that developed here also provide "workbenches" for simple but mechanistically based explorations of Earth system processes, such as interactions and feedbacks between the Planetary Boundaries, that are currently too uncertain to be included in complex ESMs

Efficacy of Manipulating Reproduction of Common Ravens to Conserve Sensitive Prey Species: Three Case Studies

Expansion of human enterprise across western North America has resulted in an increase in availability of anthropogenic resource subsidies for generalist species. This has led to increases in generalists’ population numbers across landscapes that were previously less suitable for their current demographic rates. Of particular concern are growing populations of common ravens (Corvus corax; ravens), because predation by ravens is linked to population declines of sensitive species. Ecosystem managers seek management options for mitigating the adverse effects of raven predation where unsustainable predator–prey conflicts exist. We present 3 case studies examining how manipulating reproductive success of ravens influences demographic rates of 2 sensitive prey species. Two case studies examine impacts of removing raven nests or oiling raven eggs on nest survival of greater sage-grouse (Centrocercus urophasianus; sage-grouse) within Wyoming and the Great Basin of California and Nevada, USA, respectively. The third case study uses Mojave desert tortoise (Gopherus agassizii; tortoise) decoys to examine effects of oiling raven eggs on depredation rates of juvenile tortoises in the Mojave Desert in California. Initial trial years from all 3 case studies were consistent in finding improved vital rates associated with the application of strategies for reducing reproductive success of ravens. Specifically, removal of raven nests resulted in increased nest survival of sage-grouse within treatment areas where predation by ravens was the primary cause of nest failure. In addition, nest survival of sage-grouse and survival of juvenile tortoise decoys was higher following a treatment of oiling the eggs of ravens in their nests at 2 sites within the Great Basin and 4 tortoise conservation areas in the Mojave Desert in California. Along with specialized technologies that can make techniques such as egg-oiling more feasible, these findings support these management practices as important tools for managing ravens, especially in areas where breeding ravens have negative impacts on sensitive prey species

Potential feedbacks between loss of biosphere integrity and climate change

Non-technical abstract Individual organisms on land and in the ocean sequester massive amounts of the carbon emitted into the atmosphere by humans. Yet the role of ecosystems as a whole in modulating this uptake of carbon is less clear. Here, we study several different mechanisms by which climate change and ecosystems could interact. We show that climate change could cause changes in ecosystems that reduce their capacity to take up carbon, further accelerating climate change. More research on – and better governance of – interactions between climate change and ecosystems is urgently required. Technical abstract Individual responses of terrestrial and marine species to future climate change will affect the capacity of the land and ocean to store carbon. How system-level changes in the integrity of the biosphere interact with climate change is more uncertain. Here, we explore the consequences of different hypotheses on the interactions between the climate–carbon system and the integrity of the terrestrial and marine biospheres. We investigate mechanisms including impairment of terrestrial ecosystem functioning due to lagged ecosystem responses, permafrost thaw, terrestrial biodiversity loss and impacts of changes in marine biodiversity on the marine biological pump. To investigate climate–biosphere interactions involving complex concepts such as biosphere integrity, we designed and implemented conceptual representations of these climate–biosphere interactions in a stylized climate–carbon model. We find that all four classes of interactions amplify climate change, potentially contributing up to an additional 0.4°C warming across all representative concentration pathway scenarios by the year 2100 and potentially turning the terrestrial biosphere into a net carbon source, although uncertainties are large. The results of this preliminary quantitative study call for more research on – and better integrated governance of – the interactions between climate change and biosphere integrity, the two core ‘planetary boundaries’.The research leading to these results has received funding from the Stordalen Foundation via the Planetary Boundary Research Network (PB.net), the Earth League’s EarthDoc programme, the Leibniz Association (project DOMINOES), European Research Council Synergy project Imbalance-P (grant ERC-2013-SyG-610028), European Research Council Advanced Investigator project ERA (grant ERC-2016-ADG-743080), Deutsche Forschungsgemeinschaft (DFG BE 6485/1-1), Project Grant 2014-589 from the Swedish Research Council Formas and a core grant to the Stockholm Resilience Centre by Mistra

Potential feedbacks between loss of biosphere integrity and climate change

Individual organisms on land and in the ocean sequester massive amounts of the carbon emitted into the atmosphere by humans. Yet the role of ecosystems as a whole in modulating this uptake of carbon is less clear. Here, we study several different mechanisms by which climate change and ecosystems could interact. We show that climate change could cause changes in ecosystems that reduce their capacity to take up carbon, further accelerating climate change. More research on – and better governance of – interactions between climate change and ecosystems is urgently required

Indirect readout: detection of optimized subsequences and calculation of relative binding affinities using different DNA elastic potentials

Essential biological processes require that proteins bind to a set of specific DNA sites with tuned relative affinities. We focus on the indirect readout mechanism and discuss its theoretical description in relation to the present understanding of DNA elasticity on the rigid base pair level. Combining existing parametrizations of elastic potentials for DNA, we derive elastic free energies directly related to competitive binding experiments, and propose a computationally inexpensive local marker for elastically optimized subsequences in protein–DNA co-crystals. We test our approach in an application to the bacteriophage 434 repressor. In agreement with known results we find that indirect readout dominates at the central, non-contacted bases of the binding site. Elastic optimization involves all deformation modes and is mainly due to the adapted equilibrium structure of the operator, while sequence-dependent elasticity plays a minor role. These qualitative observations are robust with respect to current parametrization uncertainties. Predictions for relative affinities mediated by indirect readout depend sensitively on the chosen parametrization. Their quantitative comparison with experimental data allows for a critical evaluation of DNA elastic potentials and of the correspondence between crystal and solution structures. The software written for the presented analysis is included as Supplementary Data

Trajectories of the Earth System in the Anthropocene

This is the final version of the article. Available from National Academy of Sciences via the DOI in this record.We explore the risk that self-reinforcing feedbacks could push the Earth System toward a planetary threshold that, if crossed, could prevent stabilization of the climate at intermediate temperature rises and cause continued warming on a "Hothouse Earth" pathway even as human emissions are reduced. Crossing the threshold would lead to a much higher global average temperature than any interglacial in the past 1.2 million years and to sea levels significantly higher than at any time in the Holocene. We examine the evidence that such a threshold might exist and where it might be. If the threshold is crossed, the resulting trajectory would likely cause serious disruptions to ecosystems, society, and economies. Collective human action is required to steer the Earth System away from a potential threshold and stabilize it in a habitable interglacial-like state. Such action entails stewardship of the entire Earth System-biosphere, climate, and societies-and could include decarbonization of the global economy, enhancement of biosphere carbon sinks, behavioral changes, technological innovations, new governance arrangements, and transformed social values.W.S. and C.P.S. are members of the Anthropocene Working Group. W.S., J.R., K.R., S.E.C., J.F.D., I.F., S.J.L., R.W. and H.J.S. are members of the Planetary Boundaries Research Network PB.net and the Earth League’s EarthDoc Programme supported by the Stordalen Foundation. T.M.L. was supported by a Royal Society Wolfson Research Merit Award and the European Union Framework Programme 7 Project HELIX. C.F. was supported by the Erling– Persson Family Foundation. The participation of D.L. was supported by the Haury Program in Environment and Social Justice and National Science Foundation (USA) Decadal and Regional Climate Prediction using Earth System Models Grant 1243125. S.E.C. was supported in part by Swedish Research Council Formas Grant 2012-742. J.F.D. and R.W. were supported by Leibniz Association Project DOMINOES. S.J.L. receives funding from Formas Grant 2014-589. This paper is a contribution to European Research Council Advanced Grant 2016, Earth Resilience in the Anthropocene Project 743080

Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation

Somatic mutations in the estrogen receptor alpha (ERα) gene (ESR1), especially Y537S and D538G, have been linked to acquired resistance to endocrine therapies. Cell-based studies demonstrated that these mutants confer ERα constitutive activity and antiestrogen resistance and suggest that ligand-binding domain dysfunction leads to endocrine therapy resistance. Here, we integrate biophysical and structural biology data to reveal how these mutations lead to a constitutively active and antiestrogen-resistant ERα. We show that these mutant ERs recruit coactivator in the absence of hormone while their affinities for estrogen agonist (estradiol) and antagonist (4-hydroxytamoxifen) are reduced. Further, they confer antiestrogen resistance by altering the conformational dynamics of the loop connecting Helix 11 and Helix 12 in the ligand-binding domain of ERα, which leads to a stabilized agonist state and an altered antagonist state that resists inhibition

The progress of early phase bone healing using porous granules produced from calcium phosphate cement

<p>Abstract</p> <p>Objective</p> <p>Bone grafting is a vital component in many surgical procedures to facilitate the repair of bone defects or fusions. Autologous bone has been the gold standard to date in spite of associated donor-site morbidity and the limited amount of available donor bone. The aim of this study was to investigate the progress of bone regeneration and material degradation of calcium phosphate granules (CPG) produced from a calcium phosphate self-setting cement powder compared to the use of autologous bone grafting in the treatment of "critical size defects" on load-bearing long bones of minipigs.</p> <p>Methods</p> <p>A critical size defect in the tibial metaphysis of 16 mini-pigs was filled either with autologous cancellous graft or with micro- and macroporous carbonated, apatic calcium phosphate granules (CPG) produced from a calcium phosphate self-setting cement powder. After 6 weeks, the specimens were assessed by X-ray and histological evaluation. The amount of new bone formation was analysed histomorphometrically.</p> <p>Results</p> <p>The semi-quantitative analysis of the radiological results showed a complete osseous bridging of the defect in three cases for the autograft group. In the same group five animals showed a beginning, but still incomplete bridging of the defect, whereas in the CPG group just two animals developed this. All other animals of the CPG group showed only a still discontinuous new bone formation. Altogether, radiologically a better osseous bridging was observed in the autograft group compared to the CPG group.</p> <p>Histomorphometrical analysis after six weeks of healing revealed that the area of new bone was significantly greater in the autograft group concerning the central area of the defect zone (p < 0.001) as well as the cortical defect zone (p < 0.002). All defects showed new bone formation, but only in the autograft group defects regenerated entirely</p> <p>Conclusions</p> <p>Within the limits of the present study it could be demonstrated that autologous cancellous grafts lead to a significantly better bone regeneration compared to the application of calcium phosphate granules (CPG) produced from a calcium phosphate self-setting cement powder after 6 weeks. In the early phase of bone-healing, the sole application of CPG appears to be inferior to the autologous cancellous grafts in an <it>in vivo </it>critical size defect on load-bearing long bones of mini-pigs.</p

Tools and data services registry: a community effort to document bioinformatics resources

Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand. Here we present a community-driven curation effort, supported by ELIXIR—the European infrastructure for biological information—that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners. As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools