mi Legal Determinants of Health By feedproxy.google.com Published On :: Mon, 28 Oct 2019 00:00:00 +0000 Full Article
mi Peacemaking in an Era of Global Extremism By feedproxy.google.com Published On :: Mon, 04 Nov 2019 00:00:00 +0000 Full Article
mi Rethinking 'The Economic Consequences of the Peace' By feedproxy.google.com Published On :: Mon, 25 Nov 2019 00:00:00 +0000 Full Article
mi Angola's Business Promise: Evaluating the Progress of Privatization and Other Economic Reforms By feedproxy.google.com Published On :: Tue, 21 Jan 2020 00:00:00 +0000 Full Article
mi Undercurrents: Episode 51 - Preparing for Pandemics, and Gandhi's Chatham House Speech By feedproxy.google.com Published On :: Thu, 30 Apr 2020 00:00:00 +0100 Full Article
mi Undercurrents: Episode 52 - Defining Pandemics, and Mikheil Saakashvili's Ukrainian Comeback By feedproxy.google.com Published On :: Thu, 07 May 2020 00:00:00 +0100 Full Article
mi Proteomic Analysis of Salmonella-modified Membranes Reveals Adaptations to Macrophage Hosts [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Systemic infection and proliferation of intracellular pathogens require the biogenesis of a growth-stimulating compartment. The gastrointestinal pathogen Salmonella enterica commonly forms highly dynamic and extensive tubular membrane compartments built from Salmonella-modified membranes (SMMs) in diverse host cells. Although the general mechanism involved in the formation of replication-permissive compartments of S. enterica is well researched, much less is known regarding specific adaptations to different host cell types. Using an affinity-based proteome approach, we explored the composition of SMMs in murine macrophages. The systematic characterization provides a broader landscape of host players to the maturation of Salmonella-containing compartments and reveals core host elements targeted by Salmonella in macrophages as well as epithelial cells. However, we also identified subtle host specific adaptations. Some of these observations, such as the differential involvement of the COPII system, Rab GTPases 2A, 8B, 11 and ER transport proteins Sec61 and Sec22B may explain cell line-dependent variations in the pathophysiology of Salmonella infections. In summary, our system-wide approach demonstrates a hitherto underappreciated impact of the host cell type in the formation of intracellular compartments by Salmonella. Full Article
mi Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Acute myeloid leukemia (AML) is a clonal disorder arising from hematopoietic myeloid progenitors. Aberrantly activated tyrosine kinases (TK) are involved in leukemogenesis and are associated with poor treatment outcome. Kinase inhibitor (KI) treatment has shown promise in improving patient outcome in AML. However, inhibitor selection for patients is suboptimal. In a preclinical effort to address KI selection, we analyzed a panel of 16 AML cell lines using phosphotyrosine (pY) enrichment-based, label-free phosphoproteomics. The Integrative Inferred Kinase Activity (INKA) algorithm was used to identify hyperphosphorylated, active kinases as candidates for KI treatment, and efficacy of selected KIs was tested. Heterogeneous signaling was observed with between 241 and 2764 phosphopeptides detected per cell line. Of 4853 identified phosphopeptides with 4229 phosphosites, 4459 phosphopeptides (4430 pY) were linked to 3605 class I sites (3525 pY). INKA analysis in single cell lines successfully pinpointed driver kinases (PDGFRA, JAK2, KIT and FLT3) corresponding with activating mutations present in these cell lines. Furthermore, potential receptor tyrosine kinase (RTK) drivers, undetected by standard molecular analyses, were identified in four cell lines (FGFR1 in KG-1 and KG-1a, PDGFRA in Kasumi-3, and FLT3 in MM6). These cell lines proved highly sensitive to specific KIs. Six AML cell lines without a clear RTK driver showed evidence of MAPK1/3 activation, indicative of the presence of activating upstream RAS mutations. Importantly, FLT3 phosphorylation was demonstrated in two clinical AML samples with a FLT3 internal tandem duplication (ITD) mutation. Our data show the potential of pY-phosphoproteomics and INKA analysis to provide insight in AML TK signaling and identify hyperactive kinases as potential targets for treatment in AML cell lines. These results warrant future investigation of clinical samples to further our understanding of TK phosphorylation in relation to clinical response in the individual patient. Full Article
mi Identification of an Unconventional Subpeptidome Bound to the Behcet's Disease-associated HLA-B*51:01 that is Regulated by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Human leukocyte antigen (HLA) B*51:01 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly genetically associated with Behcet's disease (BD). Previous studies have defined two subgroups of HLA-B*51 peptidome containing proline (Pro) or alanine (Ala) at position 2 (P2). Little is known about the unconventional non-Pro/Ala2 HLA-B*51-bound peptides. We aimed to study the features of this novel subpeptidome, and investigate its regulation by ERAP1. CRISPR-Cas9 was used to generate an HLA-ABC-triple knockout HeLa cell line (HeLa.ABC-KO), which was subsequently transduced to express HLA-B*51:01 (HeLa.ABC-KO.B51). ERAP1 was silenced using lentiviral shRNA. Peptides bound to HLA-B*51:01 were eluted and analyzed by mass spectrometry. The characteristics of non-Pro/Ala2, Pro2, and Ala2 peptides and their alteration by ERAP1 silencing were investigated. Effects of ERAP1 silencing on cell surface expression of HLA-B*51:01 were studied using flow cytometry. More than 20% of peptides eluted from HLA-B*51:01 lacked Pro or Ala at P2. This unconventional group of HLA-B*51:01-bound peptides was relatively enriched for 8-mers (with relatively fewer 9-mers) compared with the Pro2 and Ala2 subpeptidomes and had similar N-terminal and C-terminal residue usages to Ala2 peptides (with the exception of the less abundant leucine at position ). Knockdown of ERAP1 increased the percentage of non-Pro/Ala2 from 20% to ~40%, increased the percentage of longer (10-mer and 11-mer) peptides eluted from HLA-B*51:01 complexes, and abrogated the predominance of leucine at P1. Interestingly knockdown of ERAP1 altered the length and N-terminal residue usage of non-Ala2&Pro2 and Ala2 but not the Pro2 peptides. Finally, ERAP1 silencing regulated the expression levels of cell surface HLA-B*51 in a cell-type-dependent manner. In conclusion, we have used a novel methodology to identify an unconventional but surprisingly abundant non-Pro/Ala2 HLA-B*51:01 subpeptidome. It is increased by knockdown of ERAP1, a gene affecting the risk of developing BD. This has implications for theories of disease pathogenesis. Full Article
mi Quantitative Profiling of the Human Substantia Nigra Proteome from Laser-capture Microdissected FFPE Tissue [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Laser-capture microdissection (LCM) allows the visualization and isolation of morphologically distinct subpopulations of cells from heterogeneous tissue specimens. In combination with formalin-fixed and paraffin-embedded (FFPE) tissue it provides a powerful tool for retrospective and clinically relevant studies of tissue proteins in a healthy and diseased context. We first optimized the protocol for efficient LCM analysis of FFPE tissue specimens. The use of SDS containing extraction buffer in combination with the single-pot solid-phase-enhanced sample preparation (SP3) digest method gave the best results regarding protein yield and protein/peptide identifications. Microdissected FFPE human substantia nigra tissue samples (~3,000 cells) were then analyzed, using tandem mass tag (TMT) labeling and LC-MS/MS, resulting in the quantification of >5,600 protein groups. Nigral proteins were classified and analyzed by abundance, showing an enrichment of extracellular exosome and neuron-specific gene ontology (GO) terms among the higher abundance proteins. Comparison of microdissected samples with intact tissue sections, using a label-free shotgun approach, revealed an enrichment of neuronal cell type markers, such as tyrosine hydroxylase and alpha-synuclein, as well as proteins annotated with neuron-specific GO terms. Overall, this study provides a detailed protocol for laser-capture proteomics using FFPE tissue and demonstrates the efficiency of LCM analysis of distinct cell subpopulations for proteomic analysis using low sample amounts. Full Article
mi An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have further evaluated and optimized our recent boosting to amplify signal with isobaric labeling (BASIL) approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of proteins in single cells. This improved BASIL (iBASIL) approach enables reliable quantitative single-cell proteomics analysis with greater proteome coverage by carefully controlling the boosting-to-sample ratio (e.g. in general <100x) and optimizing MS automatic gain control (AGC) and ion injection time settings in MS/MS analysis (e.g. 5E5 and 300 ms, respectively, which is significantly higher than that used in typical bulk analysis). By coupling with a nanodroplet-based single cell preparation (nanoPOTS) platform, iBASIL enabled identification of ~2500 proteins and precise quantification of ~1500 proteins in the analysis of 104 FACS-isolated single cells, with the resulting protein profiles robustly clustering the cells from three different acute myeloid leukemia cell lines. This study highlights the importance of carefully evaluating and optimizing the boosting ratios and MS data acquisition conditions for achieving robust, comprehensive proteomic analysis of single cells. Full Article
mi Proximity Dependent Biotinylation: Key Enzymes and Adaptation to Proteomics Approaches [Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 The study of protein subcellular distribution, their assembly into complexes and the set of proteins with which they interact with is essential to our understanding of fundamental biological processes. Complementary to traditional assays, proximity-dependent biotinylation (PDB) approaches coupled with mass spectrometry (such as BioID or APEX) have emerged as powerful techniques to study proximal protein interactions and the subcellular proteome in the context of living cells and organisms. Since their introduction in 2012, PDB approaches have been used in an increasing number of studies and the enzymes themselves have been subjected to intensive optimization. How these enzymes have been optimized and considerations for their use in proteomics experiments are important questions. Here, we review the structural diversity and mechanisms of the two main classes of PDB enzymes: the biotin protein ligases (BioID) and the peroxidases (APEX). We describe the engineering of these enzymes for PDB and review emerging applications, including the development of PDB for coincidence detection (split-PDB). Lastly, we briefly review enzyme selection and experimental design guidelines and reflect on the labeling chemistries and their implication for data interpretation. Full Article
mi A comprehensive evaluation of a typical plant telomeric G-quadruplex (G4) DNA reveals the dynamics of G4 formation, rearrangement, and unfolding [Plant Biology] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4. Full Article
mi Biochemical and structural insights into how amino acids regulate pyruvate kinase muscle isoform 2 [Enzymology] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes. Full Article
mi Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases. Full Article
mi Atomic force microscopy-based characterization of the interaction of PriA helicase with stalled DNA replication forks [DNA and Chromosomes] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB. Full Article
mi A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC–treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 μm) and nitric oxide (100 μm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 μm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning. Full Article
mi Negative Emissions and Managing Climate Risks Scenarios By feedproxy.google.com Published On :: Thu, 31 Oct 2019 18:15:01 +0000 Research Event 4 July 2019 - 1:30pm to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE This half-day strategic workshop, organized by Chatham House and E3G, brought together key climate experts, policymakers and influential actors, especially in Europe, for a focused and facilitated discussion on the roles, risks and potentials of negative emissions technologies (NETs). An interactive scenario exercise will be conducted, drawing on a climate simulation tool developed by Climate Interactive, to consider the potential roles and risks of different NETs deployments to meet the Paris Agreement targets and to consider the international co-operation required to manage the pathway to net-zero emissions. Participants will explore the political opportunities, discuss different scenarios and risks and identify areas of interventions and collective action.The meeting is part of a series of events being held at Chatham House as part of London Climate Action Week (LCAW). Department/project Energy, Environment and Resources Programme, Bioenergy, Carbon Capture and Storage (BECCS) Full Article
mi Exploring the Looming Water Crisis By feedproxy.google.com Published On :: Tue, 26 Nov 2019 16:12:28 +0000 28 November 2019 Gitika Bhardwaj Editor, Communications & Publishing, Chatham House @GitikaBhardwaj LinkedIn Loïc Fauchon President, World Water Council Loïc Fauchon, president of the World Water Council, speaks to Gitika Bhardwaj about the causes of water scarcity around the world and how best to implement sustainable solutions. GettyImages-686773184.jpg Dry sand and a narrow body of water near the Theewaterskloof Dam in South Africa which has had less than 20 per cent of its normal water capacity during recent water shortages. This dam, about 108km from Cape Town, is the main water source for residents of the city. Photo: Getty Images. One-quarter of humanity faces a looming water crisis, including the prospect of running out of water, which may seem inconceivable when 70 per cent of the Earth’s surface is water. Nevertheless up to 80 per cent of available surface and groundwater is being used every year and water demand globally is projected to increase by 55 per cent by 2050. Why is the world facing a crisis of water scarcity and what is driving the increasing demand for water? The first reason that is causing water stress around the world is the growing human population at the same time as the water supply has remained the same. Given that there are almost one billion more inhabitants on Earth every 15-20 years, this has led to a progressive deficit in the global water supply. The second reason is due to the uneven concentration of the global population. There is not a clear link between the presence of the population in some regions and the presence of water, in other words, water is not where we want it to be every time.For example, there is, what we call, a ‘triangle of thirst’ from southern Spain, to Pakistan, to the Horn of Africa and back again. In this triangle, you have around two billion people in a very water-scarce region.Comparatively, if you go to Russia or Canada, they have more water than they need in terms of the size of their population. So this is another crucial reason we are facing a crisis of water scarcity in some regions of the world – but not everywhere. Climate [change] will be the fruit on the cake. Currently we have global population growth and then later we will have climate change affecting water availability. But at this very moment, however, the problem for water suppliers and for political leaders is the demographic crisis we are facing – not the climate.Water use has grown at more than twice the rate of the human population over the last century in part due to industries, such as agriculture, which account for 70 per cent of global freshwater use. Given that food production will need to grow by up to 70 per cent by 2035 to feed the growing human population, how do we balance the use of water with the need to provide food? There are some solutions. The first is that we need to improve water efficiency in the agricultural sector. We need to have all around the world, but mostly in developing countries, a better capacity to increase the water efficiency of agriculture without increasing the use of industrial chemical products and to move, step-by-step, to an economical system of organic farming. It will take time – it will not be done in one or even five years but more likely over a generation – but it is the best way. Secondly, which could be a faster solution, is that we have to reduce all kind of food waste which represents around 30-40 per cent of all agricultural production. Agriculture is a large sector involving the growing of crops but also livestock. There’s not only waste in terms of consumption but also during the production line, for example, during the transportation of food products. So there is this, sort of, waste cycle which is very important to consider. If you are able to reduce the water waste during the production line by 30-40 per cent, then you use less water, obviously.The third solution is to be able to, step-by-step, change our consumption patterns. Use less meat, all kinds of agricultural products which need a lot of water etc. I think we will be obliged to do this over the next couple of decades, and we will probably have low animal protein diets in the future, which will mean we have to think of different ways to be able to provide food to the increasing global population.There are other industries that are water-intensive that also need to be looked at in terms of their water waste such as the clothing and automobile industries. One piece of paper, for example, takes about 100 litres of water to produce while one litre of milk takes about 1,000 litres of water. Another example is that one cup of coffee takes 150 litres of water – just one cup of coffee – that’s because there is not only the water you are drinking but the water needed to prepare the coffee beans and the water used in the materials that make the coffee cup and so on.So everything consumes water and that’s why humans will be obliged to consume less water over the coming years. More than one in three people globally do not have access to safe drinking water and more than 4 billion people lack adequate sanitation. How can waste water be more efficiently used and do you think global goals to provide everyone with safe and clean drinking water are still realistic? In French, we use a phrase, parent pauvre, which means poor relative. Most of the decisions concerning access to water are not acceptable in the long term. That’s why we at the World Water Council are pushing for the financing of water and sanitation goals [concurrently].For example, if you have a programme for a city to increase access to water for its citizens, they also need a sanitation programme. If we don’t do that, the mismatch that currently exists between water and sanitation will remain. There’s also another important solution which political leaders will be obliged to invest more in which is having more water coming from water reuse. If you produce water from water reuse processes then it means that it will likely have undergone sanitation treatment already which is a win-win solution [for providing safe and clean drinking water].It’s all moving slowly but I’m optimistic concerning the increasing consciousness of people regarding water pollution – for example the pollution of our rivers, seas and oceans – and I think we will move faster in the sanitation area than in the water access area over the next decade.Personally, I do not think that global goals to provide everyone with safe and clean drinking water [are the best solution]. I am more in favour of national and local commitments rather than global commitments. National and local efforts are stronger then [the rhetoric] around global goals where there is no authority to oversee the progress they are making. Only the population of a country or of a city can see if their leaders have done their job regarding providing access to safe and clean water. People queue up to collect water from taps fed by a spring in Newlands in 15 May 2017 in Cape Town, South Africa. South Africa's Western Cape region declared a drought disaster on 22 May 2017 as the province battled its worst water shortages for more than 112 years. Photo: Getty Images. With the depletion of global water supplies, how can governments avoid the politicization of water, as seen in cases such as the Nile River Basin and across the Middle East, to avoid conflicts over water? This is a complicated issue because politicians will always do politics so it will always be difficult to avoid attempts to politicize situations. But the key is dialogue, dialogue and dialogue. That is the only way to solve water conflicts as well as better management of water because, in some regions, some of these conflicts are arising from the mismanagement of water supplies – not because of water scarcity. If you look at Egypt and the US, people are consuming around 800 litres [of water] per day whereas in Europe people are consuming around 200 litres per day. But why is [water consumption] in Egypt, rather than Europe, the same as in the US? Because they have considerable water losses in industries such as agriculture.In addition, in the main cities like Cairo, there is not an adequate range of water networks, so, if in the future those living in Cairo are able to consume less water, they will need less water coming from the Nile River which will make politicization of water by politicians less likely. In the future, social unrest from water shortages is likely, however, I do not think it will ever lead to wars. Countries across the Middle East have invested in modern techniques, such as desalination plants, as an answer to water scarcity, but this can have a negative impact, notably on marine life. In contrast, some of the more ancient techniques, like rainwater harvesting, are being repurposed in cities around the world today. What is your view on these practices and what other solutions are available? There are a lot of solutions and desalination is among them. Currently probably 100 countries in the world are using, or preparing to use, desalination as a solution so it surely is an important solution. But at the same time, reused water is developing fast and is a much cheaper option than desalination. Nevertheless, the price of desalination has been decreasing over the past 20 years and is now less than $1 a cubic metre, whereas 15 years ago, it was $10 a cubic metre.Some of the negative impacts of desalination exist when you are separating the water from the salt, which can lead to disasters, for example, what has happened in the Persian Gulf. When Kuwait, Saudi Arabia, Bahrain and Qatar first used desalination treatments, the temperature of the sea was around 30°C, whereas today, it can be up to 40°C. This increasing sea temperature as a result of the desalination plants has contributed to changes in biodiversity. For example, we are seeing fish disappearing and even the growing population of giant jellyfish – which some desalination plants in Saudi Arabia are dealing with by using shredders which is another type of disaster.Furthermore, in some regions, we need to keep in mind that desalination is not only along the coast but it’s also in the middle of the land too. For example, in the Sahara region, like in Algeria or Morocco, the water coming from the ground is salted so you need to have desalination plants inland and not on the coast. But where they keep the salt inland, that salt mixes with the rain and enters the ground, thereby destroying some of the biodiversity there too. So it must be used prudently. Rainwater harvesting is a technique from centuries ago and I am a great supporter of it as a solution to water scarcity in India, particularly in Rajasthan, and I think it could also be part of the solutions in some places across Africa.That’s why I believe there needs to be an exchange of solutions because something which is successful here could be successful somewhere else. In this way, we need to be able to show a Senegalese farmer a solution which has been implemented elsewhere, such as in India, and show him this can work for you too – it’s sort of like when the Japanese built the Toyota by looking at the British Land Rover.With billions of people threatened by the global water crisis, increased water stress could lead to more ‘Day Zeroes’, a term used in 2018 as Cape Town in South Africa came dangerously close to running out of water. In your view, what will happen if the world doesn’t adequately address the global crisis of water scarcity?The increasing absence of water would mean not only the migration of humans to more water-abundant regions but also the absence of socioeconomic growth of any kind in some places because water scarcity will pose a risk to businesses who will be forced to move to new areas – from small businesses like a hairdresser to factories that are unable to produce any goods or provide any services. So not tackling the water crisis means not being able to tackle our own capacity to prosper by not protecting the environment we depend on.In Cape Town, there was a lack of rain in the city which contributed to the water crisis there but there was also a lack of water management. They knew they could have a lack of rain, and when you have a lack of rain, you have the obligation to prepare a reservoir of water for the year to the next year and so on but that did not happen.There is a French poem from Jean de La Fontaine about a grasshopper and an ant. The grasshopper just spends his time in the summer enjoying life but the ant keeps working hard throughout the summer to save all of his supplies for the winter. In this way, we need to be like the ant, preparing water supplies for today and for tomorrow.In the case of Cape Town, there was also another element, which was that the water supplies were being used by the central government as a tool to isolate the regional governor there who was part of the opposition. So the lack of water management was almost used as a political tool as we discussed earlier.Some say that the water scarcity we are seeing is because of climate change. Yes it is but there is also a lack of water management by humans. If you look at the people living throughout the centuries all the way to antiquity, you see that people around the world prepared reservoirs of water to keep water from the winter to the summer, from the one year to the next, whereas today, we are seeing bad water management. So, in this way, I believe climate change should not be the scapegoat of human error. Full Article
mi Maintaining Connections: How Might the UK Remain Engaged in the EU's Climate and Energy Strategies? By feedproxy.google.com Published On :: Thu, 23 Jan 2020 10:35:01 +0000 Invitation Only Research Event 3 March 2020 - 10:30am to 12:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE As the UK leaves the EU and the formal negotiations on the future relationship begins, this workshop will discuss any immediate changes and review the short and medium term impacts of Brexit on the energy sector. The workshop will look to cover:The implications for UK business and system operations of the UK leaving the Internal Energy Market.Current and future investment trends in the UK energy system.The trade of electricity and gas over inter-connectors.The need for the development of a new EU-UK operational framework mechanism.The UK's EU withdrawal agreement and the operation of the Single Electricity Market (SEM) across Ireland. Options for the UK outside of the EU Emissions Trading System (ETS) and the impact on carbon prices.This workshop is part of a programme funded by the UK Energy Research Centre on Brexit and the UK’s Net Zero Energy Policy being run by the University of Warwick and Chatham House.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme Chloé Prendleloup Email Full Article
mi China's 2020: Economic Transition, Sustainability and the Coronavirus By feedproxy.google.com Published On :: Tue, 04 Feb 2020 21:15:01 +0000 Corporate Members Event 10 March 2020 - 12:15pm to 2:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Dr Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham HouseDavid Lubin, Associate Fellow, Global Economy and Finance Programme, Chatham House; Managing Director and Head of Emerging Markets Economics, CitiJinny Yan, Managing Director and Chief China Economist, ICBC StandardChair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House Read all our analysis on the Coronavirus ResponseThe coronavirus outbreak comes at a difficult time for China’s ruling party. A tumultuous 2019 saw the country fighting an economic slowdown coupled with an increasingly hostile international environment. As authorities take assertive steps to contain the virus, the emergency has - at least temporarily - disrupted global trade and supply chains, depressed asset prices and forced multinational businesses to make consequential decisions with limited information. Against this backdrop, panellists reflect on the country’s nascent economic transition from 2020 onward. What has been China’s progress towards a sustainable innovation-led economy so far? To what extent is the ruling party addressing growing concerns over job losses, wealth inequality and a lack of social mobility? And how are foreign investors responding to these developments in China? Members Events Team Email Full Article
mi Privileging Local Food is Flawed Solution to Reduce Emissions By feedproxy.google.com Published On :: Thu, 23 Apr 2020 13:59:11 +0000 23 April 2020 Christophe Bellmann Associate Fellow, Hoffmann Centre for Sustainable Resource Economy LinkedIn The COVID-19 pandemic has brought food security and food imports to the forefront again. Some fear that the crisis could quickly strain global food supply chains as countries adopt new trade restrictions to avoid domestic food shortages. 2020-04-23-Trade-Food-Apples Apples being picked before going into cold storage so they can be bought up until Christmas. Photo by Suzanne Kreiter/The Boston Globe via Getty Images. The pressure of the coronavirus pandemic is adding to a widely held misconception that trade in food products is bad for the environment due to the associated ‘food miles’ – the carbon footprint of agricultural products transported over long distances.This concept, developed by large retailers a decade ago, is often invoked as a rationale for restricting trade and choosing locally-produced food over imports. Consuming local food may seem sensible at first glance as it reduces the carbon footprint of goods and generates local employment. However, this assumption ignores the emissions produced during the production, processing or storage stages which often dwarf transport emissions. Other avenues to address the climate change impact of trade are more promising.Demystifying food emissionsIn the US, for example, food items travel more than 8,000 km on average before reaching the consumer. Yet transport only accounts for 11 per cent of total emissions with 83 per cent – mostly nitrous oxide (N2O) and methane (CH4) emissions – occurring at the production stage.US Department of Agriculture data on energy use in the American food system echoes this finding, showing that processing, packaging, and selling of food represent ten times the energy used to transport food.In practice, it may be preferable from an environmental perspective to consume lamb, onion or dairy products transported by sea because the lower emissions generated at the production stage offset those resulting from transport. Similarly, growing tomatoes under heated greenhouses in Sweden is often more emissions-intensive than importing open-grown ones from Southern Europe.Seasonality also matters. British apples placed in storage for ten months leads to twice the level of emissions as that of South American apples sea-freighted to the UK. And the type of transport is also important as, overall, maritime transport generates 25 to 250 times less emissions than trucks, and air freight generates on average five times more emissions than road transport.Therefore, air-freighted Kenyan beans have a much larger carbon footprint than those produced in the UK, but crossing Europe by truck to import Italian wine might generate more emissions than transatlantic shipments.Finally, one should take into account the last leg of transport. A consumer driving more than 10 km to purchase 1 kg of fresh produce will generate proportionately more greenhouse gas (GHG) emissions than air-freighting 1 kg of produce from Kenya.Shifting consumption towards local foods may reduce GHG emissions in sectors with relatively low emissions intensities but, when non-carbon dioxide emissions are taken into account, this is more often the exception than the rule.Under these circumstances, preventing trade is an inefficient and expensive way of reducing GHG emissions. Bureau et al. for example, calculate that a global tariff maintaining the volume of trade at current levels until 2030 may reduce global carbon dioxide emissions by 3.5 per cent. However, this would be roughly seven times less than the full implementation of the Paris Agreement and cost equivalent to the current GDP of Brazil or 1.8 per cent of world GDP.By preventing an efficient use of resources, such restrictions would also undermine the role of trade in offsetting possible climate-induced production shortfalls in some parts of the world and allowing people to access food when they can’t produce it themselves.Reducing the climate footprint of tradeThis is not to say that nothing should be done to tackle transport emissions. The OECD estimates that international trade-related freight accounted for over 5 per cent of total global fuel emissions with shipping representing roughly half of it, trucks 40 per cent, air 6 per cent and rail 2 per cent. With the projected tripling of freight transport by 2050, emissions from shipping are expected to rise between 50 and 250 per cent.Furthermore, because of their international nature, these emissions are not covered by the Paris Agreement. Instead the two UN agencies regulating these sectors – the International Civil Aviation Organization and the International Maritime Organization – are responsible for reducing these emissions and, so far, significant progress has proven elusive.Regional or bilateral free trade agreements to further stimulate trade could address this problem by exploiting comparative advantages. Impact assessments of those agreements often point towards increases in GHG emissions due to a boost in trade flows. In the future, such agreements could incorporate – or develop in parallel – initiatives to ensure carbon neutrality by connecting carbon markets among contracting parties or by taxing international maritime and air transport emissions.Such initiatives could be combined with providing additional preferences in the form of enhanced market access to low-carbon food and healthier food. The EU, as one of the chief proponents of bilateral and regional trade agreements and a leader in promoting a transition to a low-carbon economy could champion such an approach.This article is part of a series from the Chatham House Global Trade Policy Forum, designed to promote research and policy recommendations on the future of global trade. It is adapted from the research paper, Delivering Sustainable Food and Land Use Systems: The Role of International Trade, authored by Christophe Bellmann, Bernice Lee and Jonathan Hepburn. Full Article
mi Reviewing Antimicrobial Resistance: Where Are We Now and What Needs to Be Done? By feedproxy.google.com Published On :: Fri, 30 Aug 2019 14:55:01 +0000 Research Event 8 October 2019 - 10:30am to 12:00pm RSA House, 8 John Adam Street, London, WC2N 6EZ Event participants Tim Jinks, Head of Drug-Resistant Infections Programme, WellcomeJim O’Neill, Chair, Review on Antimicrobial Resistance; Chair, Chatham HouseHaileyesus Getahun, Director of Global Coordination and Partnership on Antimicrobial Resistance, World Health Organization Juan Lubroth, Chief Veterinary Officer, Food and Agriculture Organization (Videolink)Jyoti Joshi, Head, South Asia, Center for Disease Dynamics, Economics & PolicyEstelle Mbadiwe, Coordinator-Nigeria, Global Antibiotic Resistance PartnershipCharles Clift, Senior Consulting Fellow, Chatham House; Report Author The Review on Antimicrobial Resistance, chaired by Jim O’Neill, was commissioned by former UK prime minister, David Cameron, in July 2014. Supported by the UK government and the Wellcome Trust, the final report of the review was published in May 2016 and has had a global impact in terms of motivating political leaders and decision-makers to take more seriously the threat posed by antimicrobial resistance.Yet there is now a perception that the political momentum to address the issue is waning and needs to be reinvigorated.In a further report produced by Chatham House, the progress of the recommendations of the review is assessed and the key ways to move forward are identified.Panellists at this event, where highlights of the report are presented, provide their assessment of the progress so far and discuss priorities for future action.The report was funded by Wellcome. Department/project Global Health Programme, Antimicrobial Resistance Alexandra Squires McCarthy Programme Coordinator, Global Health Programme +44 (0)207 314 2789 Email Full Article
mi England and Australia Are Failing in Their Commitments to Refugee Health By feedproxy.google.com Published On :: Mon, 09 Sep 2019 12:50:31 +0000 10 September 2019 Alexandra Squires McCarthy Former Programme Coordinator, Global Health Programme Robert Verrecchia Both boast of universal health care but are neglecting the most vulnerable. 2019-09-09-Manus.jpg A room where refugees were once housed on Manus Island, Papua New Guinea. Photo: Getty Images. England and Australia are considered standard-bearers of universal access to health services, with the former’s National Health Service (NHS) recognized as a global brand and the latter’s Medicare seen as a leader in the Asia-Pacific region. However, through the exclusion of migrant and refugee groups, each is failing to deliver true universality in their health services. These exclusions breach both their own national policies and of international commitments they have made.While the marginalization of mobile populations is not a new phenomenon, in recent years there has been a global increase in anti-migrant rhetoric, and such health care exclusions reflect a global trend in which undocumented migrants, refugees and asylum seekers are denied rights.They are also increasingly excluded in the interpretation of phrases such as ‘leave no one behind’ and ‘universal health coverage’, commonly used by UN bodies and member states, despite explicit language in UN declarations that commits countries to include mobile groups.Giving all people – including undocumented migrants and asylum seekers – access to health care is essential not just for the health of the migrant groups but also the public health of the populations that host them. In a world with almost one billion people on the move, failing to take account of such mobility leaves services ill-equipped and will result in missed early and preventative treatment, an increased burden on services and a susceptibility to the spread of infectious disease.EnglandWhile in the three other nations of the UK, the health services are accountable to the devolved government, the central UK government is responsible for the NHS in England, where there are considerably greater restrictions in access.Undocumented migrants and refused asylum seekers are entitled to access all health care services if doctors deem it clinically urgent or immediately necessary to provide it. However, the Home Office’s ‘hostile environment’ policies towards undocumented migrants, implemented aggressively and without training for clinical staff, are leading to the inappropriate denial of urgent and clearly necessary care.One example is the case of Elfreda Spencer, whose treatment for myeloma was delayed for one year, allowing the disease to progress, resulting in her death.In England, these policies, which closely link health care and immigration enforcement, are also deterring people from seeking health care they are entitled to. For example, medical bills received by migrants contain threats to inform immigration enforcement of their details if balances are not cleared in a certain timeframe. Of particular concern, the NGO Maternity Action has demonstrated that such a link to immigration officials results in the deterrence of pregnant women from seeking care during their pregnancy.Almost all leading medical organizations in the United Kingdom have raised concerns about these policies, highlighting the negative impact on public health and the lack of financial justification for their implementation. Many have highlighted that undocument migrants use just and estimated 0.3% of the NHS budget and have pointed to international evidence that suggests that restrictive health care policies may cost the system more.AustraliaIn Australia, all people who seek refuge by boat are held, and have their cases processed offshore in Papua New Guinea (PNG) and Nauru, at a cost of almost A$5 billion between 2013 and 2017. Through this international agreement, in place since 2013, Australia has committed to arrange and pay for the care for the refugees, including health services ‘to a standard of care broadly comparable to that available to the general Australian community under the public health system’.However, the standard of care made available to the refugees is far from comparable to that available to the general population in Australia. Findings against the current care provision contractor on PNG, Pacific International Hospital, which took over in the last year, are particularly damning.For instance, an Australian coroner investigating the 2014 death from a treatable leg infection of an asylum seeker held in PNG concluded that the contractor lacked ‘necessary clinical skills’, and provided ‘inadequate’ care. The coroner’s report, issued in 2018, found the company had also, in other cases, denied care, withheld pain relief, distributed expired medication and had generally poor standards of care, with broken or missing equipment and medication, and services often closed when they were supposed to be open.This has also been reiterated by the Royal Australasian College of Physicians, which has appealed to the Australian government to end its policies of offshore processing immediately, due to health implications for asylum seekers. This echoes concerns of the medical community around the government’s ongoing attempts to repeal the ‘Medivac’ legislation, which enables emergency medical evacuation from PNG and Nauru.Bad policyBoth governments have signed up to UN Sustainable Development Goals commitment to ‘safe and orderly migration’, an essential component of which is access to health care. The vision for this was laid out in a global action plan on promoting the health of refugees and migrants, agreed by member states at the 2019 World Health Assembly.However, rather than allow national policies to be informed by such international plans and the evidence put forward by leading health professionals and medical organizations, the unsubstantiated framing of migrants as a security risk and economic burden has curtailed migrant and refugee access to health care.The inclusion of migrants and refugees within universal access to health services is not merely a matter of human rights. Despite being framed as a financial burden, ensuring access for all people may reduce costs on health services through prevention of costly later-stage medical complications, increased transmission of infections and inefficient administrative costs of determining eligibility.Thailand provides an example of a middle-income country that recognized this, successfully including all migrants and refugees in its health reforms in 2002. Alongside entitling all residents to join the universal coverage scheme, the country also ensured that services were ‘migrant friendly’, including through the provision of translators. A key justification for the approach was the economic benefit of ensuring a healthy migrant population, including the undocumented population.The denial of quality health services to refugees and undocumented migrants is a poor policy choice. Governments may find it tempting to gain political capital through excluding these groups, but providing adequate access to health services is part of both governments’ commitments made at the national and international levels. Not only are inclusive health services feasible to implement and good for the health of migrants and refugees, in the long term, they are safer for public health and may save money. Full Article
mi Review of Progress on Antimicrobial Resistance By feedproxy.google.com Published On :: Fri, 04 Oct 2019 13:28:22 +0000 8 October 2019 A startling lack of progress on critical recommendations to tackle antimicrobial resistance is highlighted in this new global progress report, as well as opportunities for further action and key obstacles that need to be overcome.Use the Download button to choose either the Research Paper, or the Background and Analysis Paper. Read online Research Paper Background and Analysis Dr Charles Clift Senior Consulting Fellow, Global Health Programme @CliftWorks 2019-10-04-AMR.jpg A PhD student at Melbourne’s Doherty Institute inspects the superbug Staphylcocus epidermidis on an agar plate on 4 September 2018. Photo: Getty Images. The 2016 Review on Antimicrobial Resistance has had a global impact: as an advocacy tool, in raising the profile of antimicrobial resistance (AMR) on the international agenda, and in helping to stimulate a number of new initiatives, in particular relating to the funding of early-stage research.However, there has been very little progress on the review’s central and most expensive recommendations for transforming research and development incentives for antibiotics, vaccines and diagnostics.There have been significant advances in reducing antibiotic use in agriculture, particularly in high-income countries, but there is a long way to go in low- and middle-income countries (LMICs).There has been greater investment in awareness raising but questions remain about its impact and effectiveness in changing behaviour.Proposals to restrict over-the-counter sales of antibiotics, as recommended by the Review, have foundered in the face of poor living conditions and access to healthcare in LMICs.A major reason for the use of antibiotics in LMICs is the prevalence of unhygienic conditions in the community and in healthcare facilities, which contribute to infection and limit the impact of messages about awareness and infection prevention and control.Providing quality healthcare to all and moving towards universal health coverage in LMICs will be crucial in addressing the problems of both adequate access to antibiotics and in restricting over-the-counter sales.A greater emphasis on investments in water, sanitation and housing will be central to reducing reliance on antibiotics in LMICs in the longer term. This agenda should inform the operations of governments and funding agencies such as the International Monetary Fund (IMF) and the World Bank.Investments have been made in improving surveillance of antibiotic use and resistance, particularly for humans, but more effort is required to create surveillance systems that provide data sufficiently accurate to influence policy and action. This applies also to antibiotics and resistant genes circulating in the environment.The emerging innovations in the global governance of AMR need to lead to action rather than more words. Department/project Global Health Programme, Antimicrobial Resistance Full Article
mi Coronavirus: Public Health Emergency or Pandemic – Does Timing Matter? By feedproxy.google.com Published On :: Fri, 01 May 2020 14:48:43 +0000 1 May 2020 Dr Charles Clift Senior Consulting Fellow, Global Health Programme @CliftWorks The World Health Organization (WHO) has been criticized for delaying its announcements of a public health emergency and a pandemic for COVID-19. But could earlier action have influenced the course of events? 2020-05-01-Tedros-WHO-COVID WHO director-general Dr Tedros Adhanom Ghebreyesus at the COVID-19 press briefing on March 11, 2020, the day the coronavirus outbreak was classed as a pandemic. Photo by FABRICE COFFRINI/AFP via Getty Images. The World Health Organization (WHO) declared the spread of COVID-19 to be a Public Health Emergency of International Concern (PHEIC) on January 30 this year and then characterized it as a pandemic on March 11.Declaring a PHEIC is the highest level of alert that WHO is obliged to declare, and is meant to send a powerful signal to countries of the need for urgent action to combat the spread of the disease, mobilize resources to help low- and middle-income countries in this effort and fund research and development on needed treatments, vaccines and diagnostics. It also obligates countries to share information with WHO.Once the PHEIC was declared, the virus continued to spread globally, and WHO began to be asked why it had not yet declared the disease a pandemic. But there is no widely accepted definition of a pandemic, generally it is just considered an epidemic which affects many countries globally.Potentially more deadlyThe term has hitherto been applied almost exclusively to new forms of flu, such as H1N1 in 2009 or Spanish flu in 1918, where the lack of population immunity and absence of a vaccine or effective treatments makes the outbreak potentially much more deadly than seasonal flu (which, although global, is not considered a pandemic).For COVID-19, WHO seemed reluctant to declare a pandemic despite the evidence of global spread. Partly this was because of its influenza origins — WHO’s emergency programme executive director said on March 9 that ‘if this was influenza, we would have called a pandemic ages ago’.He also expressed concern that the word traditionally meant moving — once there was widespread transmission — from trying to contain the disease by testing, isolating the sick and tracing and quarantining their contacts, to a mitigation approach, implying ‘the disease will spread uncontrolled’.WHO’s worry was that the world’s reaction to the word pandemic might be there was now nothing to be done to stop its spread, and so countries would effectively give up trying. WHO wanted to send the message that, unlike flu, it could still be pushed back and the spread slowed down.In announcing the pandemic two days later, WHO’s director-general Dr Tedros Adhanom Ghebreyesus reemphasised this point: ‘We cannot say this loudly enough, or clearly enough, or often enough: all countries can still change the course of this pandemic’ and that WHO was deeply concerned ‘by the alarming levels of inaction’.The evidence suggests that the correct message did in fact get through. On March 13, US president Donald Trump declared a national emergency, referring in passing to WHO’s announcement. On March 12, the UK launched its own strategy to combat the disease. And in the week following WHO’s announcements, at least 16 other countries announced lockdowns of varying rigour including Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Netherlands, Norway, Poland, Portugal, Serbia, Spain and Switzerland. Italy and Greece had both already instituted lockdowns prior to the WHO pandemic announcement.It is not possible to say for sure that WHO’s announcement precipitated these measures because, by then, the evidence of the rapid spread was all around for governments to see. It may be that Italy’s dramatic nationwide lockdown on March 9 reverberated around European capitals and elsewhere.But it is difficult to believe the announcement did not have an effect in stimulating government actions, as was intended by Dr Tedros. Considering the speed with which the virus was spreading from late February, might an earlier pandemic announcement by WHO have stimulated earlier aggressive actions by governments?Declaring a global health emergency — when appropriate — is a key part of WHO’s role in administering the International Health Regulations (IHR). Significantly, negotiations on revisions to the IHR, which had been ongoing in a desultory fashion in WHO since 1995, were accelerated by the experience of the first serious coronavirus outbreak — SARS — in 2002-2003, leading to their final agreement in 2005.Under the IHR, WHO’s director-general decides whether to declare an emergency based on a set of criteria and on the advice of an emergency committee. IHR defines an emergency as an ‘extraordinary event that constitutes a public health risk through the international spread of disease and potentially requires a coordinated international response’.In the case of COVID-19, the committee first met on January 22-23 but were unable to reach consensus on a declaration. Following the director-general’s trip to meet President Xi Jinping in Beijing, the committee reconvened on January 30 and this time advised declaring a PHEIC.But admittedly, public recognition of what a PHEIC means is extremely low. Only six have ever been declared, with the first being the H1N1 flu outbreak which fizzled out quickly, despite possibly causing 280,000 deaths globally. During the H1N1 outbreak, WHO declared a PHEIC in April 2009 and then a pandemic in June, only to rescind both in August as the outbreak was judged to have transitioned to behave like a seasonal flu.WHO was criticized afterwards for prematurely declaring a PHEIC and overreacting. This then may have impacted the delay in declaring the Ebola outbreak in West Africa as a PHEIC in 2014, long after it became a major crisis. WHO’s former legal counsel has suggested the PHEIC — and other aspects of the IHR framework — may not be effective in stimulating appropriate actions by governments and needs to be reconsidered.When the time is right to evaluate lessons about the response, it might be appropriate to consider the relative effectiveness of the PHEIC and pandemic announcements and their optimal timing in stimulating appropriate action by governments. The effectiveness of lockdowns in reducing the overall death toll also needs investigation. Full Article
mi Hepatic monoamine oxidase B is involved in endogenous geranylgeranoic acid synthesis in mammalian liver cells [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:28-07:00 Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from 13C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation. Full Article
mi A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women. Full Article
mi Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by 2H/13C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction. Full Article
mi Myeloid-specific deficiency of pregnane X receptor decreases atherosclerosis in LDL receptor-deficient mice [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXRMyeLDLR–/–) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXRMyeLDLR–/– mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXRMyeLDLR–/– mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management. Full Article
mi The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning. Full Article
mi Membrane domains beyond the reach of microscopy [Commentaries] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Full Article
mi Russia sows new mischief in Trump’s back yard By feedproxy.google.com Published On :: Wed, 15 Jan 2020 12:31:17 +0000 Source The Times URL https://www.thetimes.co.uk/article/russia-sows-new-mischief-in-trumps-back-yard-... Release date 01 December 2019 Expert Dr Christopher Sabatini In the news type Op-ed Hide date on homepage Full Article
mi These Iraqi militias are attacking protesters and getting away with it. Here’s why. By feedproxy.google.com Published On :: Tue, 21 Jan 2020 14:31:50 +0000 Source The Washington Post URL https://www.washingtonpost.com/politics/2019/11/18/these-iraqi-militias-are-atta... Release date 18 November 2019 Expert Dr Renad Mansour In the news type Op-ed Hide date on homepage Full Article
mi Nato Leaders’ Summit 2019: Treaty organisation faces deep divisions at 70 By feedproxy.google.com Published On :: Tue, 21 Jan 2020 14:33:46 +0000 Source The National URL https://www.thenational.ae/world/nato-leaders-summit-2019-treaty-organisation-fa... Release date 02 December 2019 Expert Dr Lindsay Newman In the news type Op-ed Hide date on homepage Full Article
mi China already leads 4 of the 15 U.N. specialized agencies — and is aiming for a 5th By feedproxy.google.com Published On :: Thu, 05 Mar 2020 10:58:21 +0000 Source The Washington Post URL https://www.washingtonpost.com/politics/2020/03/03/china-already-leads-4-15-un-s... Release date 03 March 2020 Expert Courtney J. Fung In the news type Op-ed Hide date on homepage Full Article
mi A Balancing Act for Europe: Stop the Migrants, Support Greece, Assuage Turkey By feedproxy.google.com Published On :: Fri, 06 Mar 2020 16:30:44 +0000 Source The New York Times URL https://www.nytimes.com/2020/03/04/world/europe/europe-migrants-turkey-greece.ht... Release date 04 March 2020 Expert Robin Niblett In the news type Op-ed Hide date on homepage Full Article
mi From Dictator to Demigod By feedproxy.google.com Published On :: Wed, 06 May 2020 17:16:41 +0000 Source Power Corrupts podcast URL https://www.powercorruptspodcast.com/episodes#/from-dictator-to-demigod/ Release date 01 August 2019 Expert Annette Bohr In the news type Op-ed Hide date on homepage Full Article
mi Is COVID-19 an opportunity for more equitable health systems in the Middle East? By feedproxy.google.com Published On :: Wed, 06 May 2020 17:33:00 +0000 Source Euronews URL https://www.euronews.com/2020/04/03/covid-19-pandemic-and-health-systems-in-the-... Release date 03 April 2020 Expert Dr Osman Dar In the news type Op-ed Hide date on homepage Full Article
mi The single CCA-adding enzyme of T. brucei has distinct functions in the cytosol and in mitochondria [RNA] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 tRNAs universally carry a CCA nucleotide triplet at their 3'-ends. In eukaryotes, the CCA is added post-transcriptionally by the CCA-adding enzyme (CAE). The mitochondrion of the parasitic protozoan Trypanosoma brucei lacks tRNA genes and therefore imports all of its tRNAs from the cytosol. This has generated interest in the tRNA modifications and their distribution in this organism, including how CCA is added to tRNAs. Here, using a BLAST search for genes encoding putative CAE proteins in T. brucei, we identified a single ORF, Tb927.9.8780, as a potential candidate. Knockdown of this putative protein, termed TbCAE, resulted in the accumulation of truncated tRNAs, abolished translation, and inhibited both total and mitochondrial CCA-adding activities, indicating that TbCAE is located both in the cytosol and mitochondrion. However, mitochondrially localized tRNAs were much less affected by the TbCAE ablation than the other tRNAs. Complementation assays revealed that the N-terminal 10 amino acids of TbCAE are dispensable for its activity and mitochondrial localization and that deletion of 10 further amino acids abolishes both. A growth arrest caused by the TbCAE knockdown was rescued by the expression of the cytosolic isoform of yeast CAE, even though it was not imported into mitochondria. This finding indicated that the yeast enzyme complements the essential function of TbCAE by adding CCA to the primary tRNA transcripts. Of note, ablation of the mitochondrial TbCAE activity, which likely has a repair function, only marginally affected growth. Full Article
mi Chemical roadblocking of DNA transcription for nascent RNA display [RNA] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Site-specific arrest of RNA polymerases (RNAPs) is fundamental to several technologies that assess RNA structure and function. Current in vitro transcription “roadblocking” approaches inhibit transcription elongation by blocking RNAP with a protein bound to the DNA template. One limitation of protein-mediated transcription roadblocking is that it requires inclusion of a protein factor extrinsic to the minimal in vitro transcription reaction. In this work, we developed a chemical approach for halting transcription by Escherichia coli RNAP. We first established a sequence-independent method for site-specific incorporation of chemical lesions into dsDNA templates by sequential PCR and translesion synthesis. We then show that interrupting the transcribed DNA strand with an internal desthiobiotin-triethylene glycol modification or 1,N6-etheno-2'-deoxyadenosine base efficiently and stably halts Escherichia coli RNAP transcription. By encoding an intrinsic stall site within the template DNA, our chemical transcription roadblocking approach enables display of nascent RNA molecules from RNAP in a minimal in vitro transcription reaction. Full Article
mi On the solvability of a class of nonlinear integral equations in the problem of a spread of an epidemic By www.ams.org Published On :: Fri, 10 Apr 2020 08:09 EDT A. G. Sergeev and Kh. A. Khachatryan Trans. Moscow Math. Soc. 80 (2020), 95-111. Abstract, references and article information Full Article
mi Terapia inédita reverte leucemia incurável em bebê de 1 ano By saudeprospera.com.br Published On :: Mon, 30 Oct 2017 20:39:47 +0000 Tratamento genético foi testado em Layla Richards que estava desenganada pelos médicos. Especialistas ressaltam que os resultados são iniciais e podem não ocorrer em outros pacientes. The post Terapia inédita reverte leucemia incurável em bebê de 1 ano appeared first on Saúde Próspera. Full Article Dicas de Saúde
mi Visão embaçada e distorcida nem sempre é miopia: fique atento aos sinais do ceratocone By saudeprospera.com.br Published On :: Tue, 31 Oct 2017 07:37:43 +0000 Aos primeiros sinais de visão embaçada, as hipóteses mais frequentes sempre são miopia, astigmatismo, hipermetropia. Mas esses sintomas podem indicar outra doença ocular chamada ceratocone - uma deformidade progressiva da córnea, que assume o formato... The post Visão embaçada e distorcida nem sempre é miopia: fique atento aos sinais do ceratocone appeared first on Saúde Próspera. Full Article Dicas de Saúde
mi What will an ETF listed under Nasdaq Rule 5704 need to submit to Nasdaq to evidence compliance with the continued listing standards? By feedproxy.google.com Published On :: Publication Date: Apr 10 2020 Funds listed under Nasdaq Rule 5704 are required to submit an annual certification regarding the funds compliance with Rule 6c-11 during the most recent fiscal year. The certification is required within 30 calendar days of a fund’s fiscal year end. The certification can be found here.... Full Article
mi Adult live-streaming site CAM4 leaks millions of emails, private chats By feedproxy.google.com Published On :: Wed, 06 May 2020 10:59:23 +0000 The leak exposed millions of records with full names, emails, user conversations, payment logs, and IP addresses dating back to March. Full Article Data loss Phishing Privacy Security threats adult live streaming anurag sen blackmail breach CAM4 Elasticsearch extortion Granity Entertainment pii porn Safety Detectives
mi Understanding China’s Evolving Role in Global Economic Governance By feedproxy.google.com Published On :: Mon, 04 Nov 2019 13:00:01 +0000 Invitation Only Research Event 21 November 2019 - 4:00pm to 22 November 2019 - 5:00pm The Hague, The Netherlands Draft Agendapdf | 130.1 KB Almost four years since it was established, the China-led Asian Infrastructure Investment Bank (AIIB) has approved 49 projects and proposed 28. The AIIB claims to be more efficient and less bureaucratic than traditional multilateral development banks (MDB’s) which has threatened the existing model of multilateral development finance. At the same time, China’s increased role in previously Western-led economic institutions, such as the WTO and IMF, has raised questions over the future of the international trade order. How will a rising China shape the international institutional order? Where are there opportunities for potential collaboration and what areas pose challenges? And how should other states and international organizations respond?Attendance at this event is by invitation only. Department/project Asia-Pacific Programme, Geopolitics and Governance, Trade, Investment and Economics Lucy Ridout Programme Administrator, Asia-Pacific Programme +44 (0) 207 314 2761 Email Full Article
mi The Belt and Road Initiative: geo-economics and Indo-Pacific security competition By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:58:35 +0000 8 January 2020 , Volume 96, Number 1 Read online Mingjiang Li The Belt and Road Initiative (BRI) has been regarded by international society as a major policy tool in China's geo-economic strategy. Under this policy platform, Beijing has pledged to invest billions of dollars in the infrastructure and industrial sectors across Eurasia and in the Indo-Pacific nations. It is widely believed that such huge amount of investment will inevitably generate significant geostrategic repercussions in these regions. In response to the BRI, the United States and other powers have come up with a ‘free and open Indo-Pacific’ strategy. This article attempts to address the following question: what impact is the BRI likely to have on the security ties between China and the other major players in the Indo-Pacific? The author finds that the BRI may significantly transform China's international security policy and the expansion of Beijing's security influence may further intensify the security competition between China and other major powers in the Indo-Pacific region. The article also proposes a new analytical angle for the study of geo-economics that unpacks the role of economic activities and processes in generating geopolitical intentions and catalysing geopolitical competition. Full Article
mi Understanding the dynamics of the Indo-Pacific: US–China strategic competition, regional actors, and beyond By feedproxy.google.com Published On :: Wed, 08 Jan 2020 21:20:01 +0000 6 November 2019 , Volume 96, Number 1 The first issue of International Affairs in 2020 explores the geopolitics of the 'Indo-Pacific' region. Read online Kai He and Mingjiang Li As a geographical concept, ‘Indo-Pacific’ has existed for decades. As a political and strategic concept, it has since 2010 gradually become established in the foreign policy lexicon of some countries, especially Australia, India, Japan and the United States. However, China seems to be reluctant to identify itself as part of the Indo-Pacific; Chinese leaders believe that the US-led Indo-Pacific strategy aims to contain China's rise. While the battle between the two geographical concepts ‘Indo-Pacific’ and ‘Asia–Pacific’ may be fairly easily settled in the future, US–China strategic competition has just begun. Will the Indo-Pacific become a battlefield for US–China rivalry? How will China cope with the US ‘free and open Indo-Pacific’ (FOIP) strategy? How will other regional actors respond to the US–China strategic competition in the Indo-Pacific? What are the strategic implications of the ‘Indo-Pacific’ concept for regional order transformation? How will the Indo-Pacific be institutionalized, economically, politically and strategically? This article introduces the January 2020 special issue of International Affairs, which aims to address those questions, using both country-specific and regional perspectives. Seven articles focus on the policy responses of major players (Australia, China, India, Indonesia, Japan and ASEAN) to the US FOIP strategy and related US–China rivalry in the region. A further three articles examine the profound implications of Indo-Pacific dynamics for regional institution-building and for geopolitical and geo-economic architecture. Full Article
mi Global Governance: Tackling Economic Nationalism – Japan-UK Partnership Perspectives By feedproxy.google.com Published On :: Tue, 21 Jan 2020 14:15:01 +0000 Invitation Only Research Event 20 February 2020 - 4:30pm to 21 February 2020 - 4:45pm Tokyo, Japan Agendadocx | 223.79 KB Event participants Dr Robin Niblett CMG, Director, Chatham House Toshiro Mutoh, Honorary Chairman, Daiwa Institute of Research; CEO, Tokyo Organising Committee of the Olympic and Paralympic GameJosé Manuel Barroso, Senior Adviser, Chatham House; President of the European Commission (2004-14); Prime Minister of Portugal (2002-04)Akihiko Tanaka, President, National Graduate Institute for Policy Studies This conference will be the fifth in an annual conference series exploring global geopolitical and geoeconomic trends and their respective influences on Japan and the UK.This conference will be held in partnership with the Daiwa Institute of Research.Attendance at this event is by invitation only. Department/project Asia-Pacific Programme, Geopolitics and Governance, Trade, Investment and Economics Lucy Ridout Programme Administrator, Asia-Pacific Programme +44 (0) 207 314 2761 Email Full Article