1H nuclear magnetic resonance investigation of cobalt(II) substituted carbonic anhydrase

The structure of ClO4 and NO3 adducts of cobalt(II) substituted bovine carbonic anhydrase have been investigated through 1D NOE and 2D 1H nuclear magnetic resonance (NMR) spectroscopy. For the first time two-dimensional NMR techniques are applied to paramagnetic metalloproteins other than iron-containing proteins. Several active site signals have been assigned to specific protons on the grounds of their scalar and dipolar connectivities and T1 values. The experimental dipolar shifts for the protons belonging to noncoordinated residues have allowed the identification of a plausible orientation of the magnetic susceptibility tensor around the cobalt ion as well as of the magnitude and the anisotropy of the principal susceptibility values. In turn, a few more signals have been tentatively assigned on the grounds of their predicted dipolar shifts. The two inhibitor derivatives have a very similar orientation but a different magnitude of the chi tensor, and the protein structure around the active site is highly maintained. The results encourage a more extensive use of the two-dimensional techniques for obtaining selective structural information on the active site of metalloenzymes. With this information at hand, comparisons within homologous series of adducts with various inhibitors and/or mutants of the same enzyme of known structure should be possible using limited sets of NMR data

From regime-building to implementation: Harnessing the UN climate conferences to drive climate action

The gap between the internationally agreed climate objectives and tangible emissions reductions looms large. We explore how the supreme decision-making body of the United Nations Framework Convention on Climate Change (UNFCCC), the Conference of the Parties (COP), could develop to promote more effective climate policy. We argue that promoting implementation of climate action could benefit from focusing more on individual sectoral systems, particularly for mitigation. We consider five key governance functions of international institutions to discuss how the COP and the sessions it convenes could advance implementation of the Paris Agreement: guidance and signal, rules and standards, transparency and accountability, means of implementation, and knowledge and learning. In addition, we consider the role of the COP and its sessions as mega-events of global climate policy. We identify opportunities for promoting sectoral climate action across all five governance functions and for both the COP as a formal body and the COP sessions as conducive events. Harnessing these opportunities would require stronger involvement of national ministries in addition to the ministries of foreign affairs and environment that traditionally run the COP process, as well as stronger involvement of non-Party stakeholders within formal COP processes. This article is categorized under: Policy and Governance > International Policy Framework

The Pediatric Cell Atlas: defining the growth phase of human development at single-cell resolution

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan

Total and Subtypes of Dietary Fat Intake and Its Association with Components of the Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Risk

Background: The effect of dietary fat intake on the metabolic syndrome (MetS) and in turn on cardiovascular disease (CVD) remains unclear in individuals at high CVD risk. Objective: To assess the association between fat intake and MetS components in an adult Mediterranean population at high CVD risk. Design: Baseline assessment of nutritional adequacy in participants (n = 6560, men and women, 55-75 years old, with overweight/obesity and MetS) in the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial. Methods: Assessment of fat intake (total fat, monounsatured fatty acids: MUFA, polyunsaturated fatty acids: PUFA, saturated fatty acids: SFA, trans-fatty acids: trans-FA, linoleic acid, α-linolenic acid, and ω-3 FA) using a validated food frequency questionnaire, and diet quality using 17-item Mediterranean dietary questionnaire and fat quality index (FQI). Results: Participants in the highest quintile of total dietary fat intake showed lower intake of energy, carbohydrates, protein and fiber, but higher intake of PUFA, MUFA, SFA, TFA, LA, ALA and ω-3 FA. Differences in MetS components were found according to fat intake. Odds (5th vs. 1st quintile): hyperglycemia: 1.3-1.6 times higher for total fat, MUFA, SFA and ω-3 FA intake; low high-density lipoprotein cholesterol (HDL-c): 1.2 higher for LA; hypertriglyceridemia: 0.7 lower for SFA and ω-3 FA intake. Conclusions: Dietary fats played different role on MetS components of high CVD risk patients. Dietary fat intake was associated with higher risk of hyperglycemia

Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury: A survey in 66 neurotrauma centers participating in the CENTER-TBI

Background: No definitive evidence exists on how intracranial hypertension should be treated in patients with traumatic brain injury (TBI). It is therefore likely that centers and practitioners individually balance potential benefits and risks of different intracranial pressure (ICP) management strategies, resulting in practice variation. The aim of this study was to examine variation in monitoring and treatment policies for intracranial hypertension in patients with TBI. Methods: A 29-item survey on ICP monitoring and treatment was developed based on literature and expert opinion, and pilot-tested in 16 centers. The questionnaire was sent to 68 neurotrauma centers participating in the Collaborative European Neurotrauma Effectiveness Research (CENTER-TBI) study. Results: The survey was completed by 66 centers (97% response rate). Centers were mainly academic hospitals (n = 60, 91%) and designated level I trauma centers (n = 44, 67%). The Brain Trauma Foundation guidelines were used in 49 (74%) centers. Approximately ninety percent of the participants (n = 58) indicated placing an ICP monitor in patients with severe TBI and computed tomography abnormalities. There was no consensus on other indications or on peri-insertion precautions. We found wide variation in the use of first- and second-tier treatments for elevated ICP. Approximately half of the centers were classified as having a relatively aggressive approach to ICP monitoring and treatment (n = 32, 48%), whereas the others were considered more conservative (n = 34, 52%). Conclusions: Substantial variation was found regarding monitoring and treatment policies in patients with traumatic brain injury and intracranial hypertension. The results of this survey indicate a lack of consensus between European neurotrauma centers and provide an opportunity and necessity for comparative effectiveness research

Prospecting and dispersal: their eco-evolutionary dynamics and implications for population patterns

Dispersal is not a blind process, and evidence is accumulating that individual dispersal strategies are informed in most, if not all, organisms. The acquisition and use of information are traits that may evolve across space and time as a function of the balance between costs and benefits of informed dispersal. If information is available, individuals can potentially use it in making better decisions, thereby increasing their fitness. However, prospecting for and using information probably entail costs that may constrain the evolution of informed dispersal, potentially with population-level consequences. By using individual-based, spatially explicit simulations, we detected clear coevolutionary dynamics between prospecting and dispersal movement strategies that differed in sign and magnitude depending on their respective costs. More specifically, we found that informed dispersal strategies evolve when the costs of information acquisition during prospecting are low but only if there are mortality costs associated with dispersal movements. That is, selection favours informed dispersal strategies when the acquisition and use processes themselves were not too expensive. When non-informed dispersal strategies evolve, they do so jointly with the evolution of long dispersal distance because this maximizes the sampling area. In some cases, selection produces dispersal rules different from those that would be ‘optimal’ (i.e. the best possible population performance—in our context quantitatively measured as population density and patch occupancy—among all possible individual movement rules) for the population. That is, on the one hand, informed dispersal strategies led to population performance below its highest possible level. On the other hand, un- and poorly informed individuals nearly optimized population performance, both in terms of density and patch occupancy.Peer reviewe

From regime-building to implementation: Harnessing the UN climate conferences to drive climate action

The gap between the internationally agreed climate objectives and tangible emissions reductions looms large. We explore how the supreme decision-making body of the United Nations Framework Convention on Climate Change (UNFCCC), the Conference of the Parties (COP), could develop to promote more effective climate policy. We argue that promoting implementation of climate action could benefit from focusing more on individual sectoral systems, particularly for mitigation. We consider five key governance functions of international institutions to discuss how the COP and the sessions it convenes could advance implementation of the Paris Agreement: guidance and signal, rules and standards, transparency and accountability, means of implementation, and knowledge and learning. In addition, we consider the role of the COP and its sessions as mega-events of global climate policy. We identify opportunities for promoting sectoral climate action across all five governance functions and for both the COP as a formal body and the COP sessions as conducive events. Harnessing these opportunities would require stronger involvement of national ministries in addition to the ministries of foreign affairs and environment that traditionally run the COP process, as well as stronger involvement of non-Party stakeholders within formal COP processes. This article is categorized under: Policy and Governance > International Policy Framework

From regime-building to implementation : harnessing the UN climate conferences to drive climate action

The gap between the internationally agreed climate objectives and tangible emissions reductions looms large. We explore how the supreme decision-making body of the United Nations Framework Convention on Climate Change (UNFCCC), the Conference of the Parties (COP), could develop to promote more effective climate policy. We argue that promoting implementation of climate action could benefit from focusing more on individual sectoral systems, particularly for mitigation. We consider five key governance functions of international institutions to discuss how the COP and the sessions it convenes could advance implementation of the Paris Agreement: guidance and signal, rules and standards, transparency and accountability, means of implementation, and knowledge and learning. In addition, we consider the role of the COP and its sessions as mega-events of global climate policy. We identify opportunities for promoting sectoral climate action across all five governance functions and for both the COP as a formal body and the COP sessions as conducive events. Harnessing these opportunities would require stronger involvement of national ministries in addition to the ministries of foreign affairs and environment that traditionally run the COP process, as well as stronger involvement of non-Party stakeholders within formal COP processes