66 research outputs found
Mainstreaming biodiversity: A review of national strategies
Biodiversity is suffering dramatic declines across the globe, threatening the ability of ecosystems to provide the services on which humanity depends. Mainstreaming biodiversity into the plans, strategies and policies of different economic sectors is key to reversing these declines. The importance of this mainstreaming is recognized by the Convention on Biological Diversity (CBD) and its Aichi targets. Individual countries can implement the goals of the CBD through their National Biodiversity Strategies and Action Plans (NBSAPs), which aim to, inter alia, support the mainstreaming of biodiversity into the policies of key economic sectors, such as agriculture, forestry and fisheries. This paper investigates the performance of countries at incorporating biodiversity mainstreaming into their post-2010 NBSAPs. We conduct a large-scale review of 144 NBSAPs against five criteria and calculate a national-level indicator for comparing levels of mainstreaming among countries. Our results show that developing countries, particularly those in Africa, have higher scores, indicating that they have a higher awareness of the importance of biodiversity mainstreaming. Developing nations were also more likely to involve a greater range of stakeholders in the NBSAP development process, whilst developed nations were less likely to give specific details about the monetary contributions of biodiversity to their economies. Overall, our findings suggest that biodiversity mainstreaming remains a challenge across much of the world, but that progress in some areas can provide direction and momentum in the future
Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas
Mycoplasma pneumoniae, responsible for approximately 30% of community-acquired human pneumonia, needs to extract lipids from the host environment for survival and proliferation. Here, we report a comprehensive structural and functional analysis of the previously uncharacterized protein P116 (MPN_213). Single-particle cryo-electron microscopy of P116 reveals a homodimer presenting a previously unseen fold, forming a huge hydrophobic cavity, which is fully accessible to solvent. Lipidomics analysis shows that P116 specifically extracts lipids such as phosphatidylcholine, sphingomyelin and cholesterol. Structures of different conformational states reveal the mechanism by which lipids are extracted. This finding immediately suggests a way to control Mycoplasma infection by interfering with lipid uptake.We thank L. Company and I. Fernández-Vidal for their support during MALS and mass spectroscopy measurements, A. Iborra (Servei de Cultius Cellulars, Anticossos Citometria, UAB) for his assistance with immunizing mice, D. Santos for his assistance in the radioactivity experiment and R. Pérez-Luque and D. Aparicio for their constant support and discussions. J. P. was funded by grants BIO2017-84166-R and PID2021-125632OB-C22 from the ministerio de Ciencia, Innovación y Universidades (MICINN, Spain). I. F. was funded by MICINN-Spain grant PID2021-125632OB-C21. A. S. F. was supported by the Deutsche Forschungsgemeinschaft (FR 1653/14-1 for MS and, FR 1653/6-3 for LS) and the Research Training Group iMOL (GRK 2566/1 for SM)
Impaired high-density lipoprotein function and endothelial barrier stability in severe anaphylaxis
Growing evidence demonstrates the importance of high- and low-density lipoprotein cholesterol in certain immune and allergy-mediated diseases. Objective: This study aimed to evaluate levels of high- and low-density lipoprotein cholesterol and apolipoproteins A1 and B in sera from a cohort of patients presenting with hypersensitivity reactions. We further assessed the function of high-density lipoprotein particles as well as their involvement in the molecular mechanisms of anaphylaxis. Lipid profile determination was performed in paired (acute and baseline) serum samples from 153 patients. Thirty-eight experienced a non-anaphylactic reaction and 115 had an anaphylactic reaction (88 moderate and 27 severe). Lecithin cholesterol acyl transferase activity was assessed in patient sera, and we also evaluated macrophage cholesterol efflux in response to the serum samples. Last, the effect of anaphylactic-derived high-density lipoprotein (HDL) particles on the endothelial barrier was studied. Detailed methods are provided in the Methods section in this article's Online Repository available at www.jacionline.org. Serum samples from severe anaphylactic reactions show statistically significant low levels of HDL cholesterol, low-density lipoprotein cholesterol, and apolipoproteins A1 and B, which points to their possible role as biomarkers. Specifically, HDL particles play a protective role in cardiovascular diseases. Using functional human serum cell assays, we observed impaired capacity of apolipoprotein B-depleted serum to induce macrophage cholesterol efflux in severe anaphylactic reactions. In addition, purified HDL particles from human anaphylactic sera failed to stabilize and maintain the endothelial barrier. These results encourage further research on HDL functions in severe anaphylaxis, which may lead to new diagnostic and therapeutic strategies
Structure–activity relationships of dinucleotides: Potent and selective agonists of P2Y receptors
Dinucleoside polyphosphates act as agonists on purinergic P2Y receptors to mediate a variety of cellular processes. Symmetrical, naturally occurring purine dinucleotides are found in most living cells and their actions are generally known. Unsymmetrical purine dinucleotides and all pyrimidine containing dinucleotides, however, are not as common and therefore their actions are not well understood. To carry out a thorough examination of the activities and specificities of these dinucleotides, a robust method of synthesis was developed to allow manipulation of either nucleoside of the dinucleotide as well as the phosphate chain lengths. Adenosine containing dinucleotides exhibit some level of activity on P2Y1 while uridine containing dinucleotides have some level of agonist response on P2Y2 and P2Y6. The length of the linking phosphate chain determines a different specificity; diphosphates are most accurately mimicked by dinucleoside triphosphates and triphosphates most resemble dinucleoside tetraphosphates. The pharmacological activities and relative metabolic stabilities of these dinucleotides are reported with their potential therapeutic applications being discussed
Crystal Structures of T. b. rhodesiense Adenosine Kinase Complexed with Inhibitor and Activator: Implications for Catalysis and Hyperactivation
Recently, we discovered that 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine (compound 1) and its derivatives exhibit specific antitrypanosomal activity toward T. b. rhodesiense, the causative agent of the acute form of HAT. We found that compound 1 would target the parasite adenosine kinase (TbrAK), an important enzyme of the purine salvage pathway, by acting via hyperactivation of the enzyme. This represents a novel and hitherto unexplored strategy for the development of trypanocides. These findings prompted us to investigate the mechanism of action at the molecular level. The present study reports the first three-dimensional crystal structures of TbrAK in complex with the bisubstrate inhibitor AP5A, and in complex with the activator (compound 1). The subsequent structural analysis sheds light on substrate and activator binding, and gives insight into the possible mechanism leading to hyperactivation. Further structure-activity relationships in terms of TbrAK activation properties support the observed binding mode of compound 1 in the crystal structure and may open the field for subsequent optimization of this compound series
Challenges for Sustained Observing and Forecasting Systems in the Mediterranean Sea
The Mediterranean community represented in this paper is the result of more than 30 years of EU and nationally funded coordination, which has led to key contributions in science concepts and operational initiatives. Together with the establishment of operational services, the community has coordinated with universities, research centers, research infrastructures and private companies to implement advanced multi-platform and integrated observing and forecasting systems that facilitate the advancement of operational services, scientific achievements and mission-oriented innovation. Thus, the community can respond to societal challenges and stakeholders needs, developing a variety of fit-for-purpose services such as the Copernicus Marine Service. The combination of state-of-the-art observations and forecasting provides new opportunities for downstream services in response to the needs of the heavily populated Mediterranean coastal areas and to climate change. The challenge over the next decade is to sustain ocean observations within the research community, to monitor the variability at small scales, e.g., the mesoscale/submesoscale, to resolve the sub-basin/seasonal and inter-annual variability in the circulation, and thus establish the decadal variability, understand and correct the model-associated biases and to enhance model-data integration and ensemble forecasting for uncertainty estimation. Better knowledge and understanding of the level of Mediterranean variability will enable a subsequent evaluation of the impacts and mitigation of the effect of human activities and climate change on the biodiversity and the ecosystem, which will support environmental assessments and decisions. Further challenges include extending the science-based added-value products into societal relevant downstream services and engaging with communities to build initiatives that will contribute to the 2030 Agenda and more specifically to SDG14 and the UN's Decade of Ocean Science for sustainable development, by this contributing to bridge the science-policy gap. The Mediterranean observing and forecasting capacity was built on the basis of community best practices in monitoring and modeling, and can serve as a basis for the development of an integrated global ocean observing system
Challenges for Sustained Observing and Forecasting Systems in the Mediterranean Sea
The Mediterranean community represented in this paper is the result of more than 30 years of EU and nationally funded coordination, which has led to key contributions in science concepts and operational initiatives. Together with the establishment of operational services, the community has coordinated with universities, research centers, research infrastructures and private companies to implement advanced multi-platform and integrated observing and forecasting systems that facilitate the advancement of operational services, scientific achievements and mission-oriented innovation. Thus, the community can respond to societal challenges and stakeholders needs, developing a variety of fit-for-purpose services such as the Copernicus Marine Service. The combination of state-of-the-art observations and forecasting provides new opportunities for downstream services in response to the needs of the heavily populated Mediterranean coastal areas and to climate change. The challenge over the next decade is to sustain ocean observations within the research community, to monitor the variability at small scales, e.g., the mesoscale/submesoscale, to resolve the sub-basin/seasonal and inter-annual variability in the circulation, and thus establish the decadal variability, understand and correct the model-associated biases and to enhance model-data integration and ensemble forecasting for uncertainty estimation. Better knowledge and understanding of the level of Mediterranean variability will enable a subsequent evaluation of the impacts and mitigation of the effect of human activities and climate change on the biodiversity and the ecosystem, which will support environmental assessments and decisions. Further challenges include extending the science-based added-value products into societal relevant downstream services and engaging with communities to build initiatives that will contribute to the 2030 Agenda and more specifically to SDG14 and the UN's Decade of Ocean Science for sustainable development, by this contributing to bridge the science-policy gap. The Mediterranean observing and forecasting capacity was built on the basis of community best practices in monitoring and modeling, and can serve as a basis for the development of an integrated global ocean observing system
'Big Big' gastrin release by the isolated islets of Langerhans incubated in vitro
The immunoreactive form of gastrin released by the islets and some of the characteristics of this release have been studied. This gastrin released by the islets in the present experiments corresponds to what has been named "Big Big" gastrin in serum of patients with the Zollinger-Ellison syndrome, in normal human serum and in extracts of proximal jejunum. Most of the "Big Big" gastrin released from the islets corresponds to spontaneous release.Peer reviewe
Ecto-enzymatic hydrolysis of diadenosine polyphosphates by cultured adrenomedullary vascular endothelial cells
We investigated the extracellular degradation of diadenosine polyphosphates (ApnA) by cultured adrenomedullary endothelial cells using fluorogenic analogs of ApnA, the di(1,N6-ethenoadenosine) 5',5"'-P1,Pn-polyphosphates [epsilon-(ApnA)]. Kinetic parameters of epsilon-(ApnA) cleavage and effects of pH, ions, and inhibitors were determined by continuous fluorometric assays, using suspensions of endothelial cells grown on Cytodex-1 microspheres. Ecto-enzyme kinetic parameters for epsilon-(Ap3A), epsilon-(Ap4A), and epsilon-(Ap5A) hydrolysis are as follows: Michaelis-Menten constants of 0.39 +/- 0.07, 0.42 +/- 0.09, and 0.37 +/- 0.05 microM respectively, and maximal velocities of 26.1 +/- 6.8, 74.2 +/- 16.4, and 24.4 +/- 3.4 pmol.min-1.10(6) cells-1, respectively. ApnA and guanosine 5',5"'-P1,P4-tetraphosphate behave as competitor substrates of epsilon-(Ap4A) hydrolysis. The ectoenzyme is activated by Mg2+ and Mn2+ and inhibited by Ca2+, F-, adenosine 5'-tetraphosphate, adenosine 5'-O-(3-thiotriphosphate), and suramin. Optimum pH is around 9.0. High-performance liquid chromatography analysis reveals that the ecto-enzyme hydrolyzes epsilon-(ApnA) to give epsilon-adenosine-5'(n-1)-phosphate and epsilon-AMP, which are then further catabolized up to epsilon-adenosine via the membrane-bound nucleotidase system ecto-ATPase, ecto-ADPase (or apyrase), and ecto-5'-nucleotidase. The endothelial ecto-diadenosine polyphosphate hydrolase studied here exhibits different kinetic parameters and sensitivity to ions with respect to the enzyme from the tissue-related neurochromaffin cells. These different properties may be important in the extracellular signaling by ApnA.</jats:p
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