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Improving Identification of In-organello Protein-Protein Interactions Using an Affinity-enrichable, Isotopically Coded, and Mass Spectrometry-cleavable Chemical Crosslinker

By feedproxy.google.com
Published On :: 2020-04-01

Karl A. T. Makepeace
Apr 1, 2020; 19:624-639
Research


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Multi-omic Characterization of the Mode of Action of a Potent New Antimalarial Compound, JPC-3210, Against Plasmodium falciparum [Research]

By feedproxy.google.com
Published On :: 2020-02-01T00:05:30-08:00

The increasing incidence of antimalarial drug resistance to the first-line artemisinin combination therapies underpins an urgent need for new antimalarial drugs, ideally with a novel mode of action. The recently developed 2-aminomethylphenol, JPC-3210, (MMV 892646) is an erythrocytic schizonticide with potent in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum lines, low cytotoxicity, potent in vivo efficacy against murine malaria, and favorable preclinical pharmacokinetics including a lengthy plasma elimination half-life. To investigate the impact of JPC-3210 on biochemical pathways within P. falciparum-infected red blood cells, we have applied a "multi-omics" workflow based on high resolution orbitrap mass spectrometry combined with biochemical approaches. Metabolomics, peptidomics and hemoglobin fractionation analyses revealed a perturbation in hemoglobin metabolism following JPC-3210 exposure. The metabolomics data demonstrated a specific depletion of short hemoglobin-derived peptides, peptidomics analysis revealed a depletion of longer hemoglobin-derived peptides, and the hemoglobin fractionation assay demonstrated decreases in hemoglobin, heme and hemozoin levels. To further elucidate the mechanism responsible for inhibition of hemoglobin metabolism, we used in vitro β-hematin polymerization assays and showed JPC-3210 to be an intermediate inhibitor of β-hematin polymerization, about 10-fold less potent then the quinoline antimalarials, such as chloroquine and mefloquine. Further, quantitative proteomics analysis showed that JPC-3210 treatment results in a distinct proteomic signature compared with other known antimalarials. While JPC-3210 clustered closely with mefloquine in the metabolomics and proteomics analyses, a key differentiating signature for JPC-3210 was the significant enrichment of parasite proteins involved in regulation of translation. These studies revealed that the mode of action for JPC-3210 involves inhibition of the hemoglobin digestion pathway and elevation of regulators of protein translation. Importantly, JPC-3210 demonstrated rapid parasite killing kinetics compared with other quinolones, suggesting that JPC-3210 warrants further investigation as a potentially long acting partner drug for malaria treatment.


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Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer [Research]

By feedproxy.google.com
Published On :: 2020-02-01T00:05:29-08:00

Triple-negative breast cancer (TNBC) is characterized by poor response to therapy and low overall patient survival. Recently, Estrogen Receptor beta (ERβ) has been found to be expressed in a fraction of TNBCs where, because of its oncosuppressive actions on the genome, it represents a potential therapeutic target, provided a better understanding of its actions in these tumors becomes available. To this end, the cell lines Hs 578T, MDA-MB-468 and HCC1806, representing the claudin-low, basal-like 1 and 2 TNBC molecular subtypes respectively, were engineered to express ERβ under the control of a Tetracycline-inducible promoter and used to investigate the effects of this transcription factor on gene activity. The antiproliferative effects of ERβ in these cells were confirmed by multiple functional approaches, including transcriptome profiling and global mapping of receptor binding sites in the genome, that revealed direct negative regulation by ERβ of genes, encoding for key components of cellular pathways associated to TNBC aggressiveness representing novel therapeutic targets such as angiogenesis, invasion, metastasis and cholesterol biosynthesis. Supporting these results, interaction proteomics by immunoprecipitation coupled to nano LC-MS/MS mass spectrometry revealed ERβ association with several potential nuclear protein partners, including key components of regulatory complexes known to control chromatin remodeling, transcriptional and post-transcriptional gene regulation and RNA splicing. Among these, ERβ association with the Polycomb Repressor Complexes 1 and 2 (PRC1/2), known for their central role in gene regulation in cancer cells, was confirmed in all three TNBC subtypes investigated, suggesting its occurrence independently from the cellular context. These results demonstrate a significant impact of ERβ in TNBC genome activity mediated by its cooperation with regulatory multiprotein chromatin remodeling complexes, providing novel ground to devise new strategies for the treatment of these diseases based on ligands affecting the activity of this nuclear receptor or some of its protein partners.


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Improving Identification of In-organello Protein-Protein Interactions Using an Affinity-enrichable, Isotopically Coded, and Mass Spectrometry-cleavable Chemical Crosslinker [Research]

By feedproxy.google.com
Published On :: 2020-04-01T00:05:32-07:00

An experimental and computational approach for identification of protein-protein interactions by ex vivo chemical crosslinking and mass spectrometry (CLMS) has been developed that takes advantage of the specific characteristics of cyanurbiotindipropionylsuccinimide (CBDPS), an affinity-tagged isotopically coded mass spectrometry (MS)-cleavable crosslinking reagent. Utilizing this reagent in combination with a crosslinker-specific data-dependent acquisition strategy based on MS2 scans, and a software pipeline designed for integrating crosslinker-specific mass spectral information led to demonstrated improvements in the application of the CLMS technique, in terms of the detection, acquisition, and identification of crosslinker-modified peptides. This approach was evaluated on intact yeast mitochondria, and the results showed that hundreds of unique protein-protein interactions could be identified on an organelle proteome-wide scale. Both known and previously unknown protein-protein interactions were identified. These interactions were assessed based on their known sub-compartmental localizations. Additionally, the identified crosslinking distance constraints are in good agreement with existing structural models of protein complexes involved in the mitochondrial electron transport chain.


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Blaming China Is a Dangerous Distraction

By feedproxy.google.com
Published On :: Wed, 15 Apr 2020 10:50:59 +0000

15 April 2020

Jim O'Neill

Chair, Chatham House
Chinese officials' initial effort to cover up the coronavirus outbreak was appallingly misguided. But anyone still focusing on China's failings instead of working toward a solution is essentially making the same mistake.

2020-04-15-China-coronavirus-health

Medical staff on their rounds at a quarantine zone in Wuhan, China. Photo by STR/AFP via Getty Images.

As the COVID-19 crisis roars on, so have debates about China’s role in it. Based on what is known, it is clear that some Chinese officials made a major error in late December and early January, when they tried to prevent disclosures of the coronavirus outbreak in Wuhan, even silencing healthcare workers who tried to sound the alarm.

China’s leaders will have to live with these mistakes, even if they succeed in resolving the crisis and adopting adequate measures to prevent a future outbreak. What is less clear is why other countries think it is in their interest to keep referring to China’s initial errors, rather than working toward solutions.

For many governments, naming and shaming China appears to be a ploy to divert attention from their own lack of preparedness. Equally concerning is the growing criticism of the World Health Organization (WHO), not least by Donald Trump who has attacked the organization - and threatens to withdraw US funding - for supposedly failing to hold the Chinese government to account.

Unhelpful and dangerous

At a time when the top global priority should be to organize a comprehensive coordinated response to the dual health and economic crises unleashed by the coronavirus, this blame game is not just unhelpful but dangerous.

Globally and at the country level, we all desperately need to do everything possible to accelerate the development of a safe and effective vaccine, while in the meantime stepping up collective efforts to deploy the diagnostic and therapeutic tools necessary to keep the health crisis under control.

Given there is no other global health organization with the capacity to confront the pandemic, the WHO will remain at the center of the response, whether certain political leaders like it or not.

Having dealt with the WHO to a modest degree during my time as chairman of the UK’s independent Review on Antimicrobial Resistance (AMR), I can say that it is similar to most large, bureaucratic international organizations.

Like the International Monetary Fund (IMF), the World Bank, and the United Nations, it is not especially dynamic or inclined to think outside the box. But rather than sniping at these organizations from the sidelines, we should be working to improve them.

In the current crisis, we all should be doing everything we can to help both the WHO and the IMF to play an effective, leading role in the global response. As I have argued before, the IMF should expand the scope of its annual Article IV assessments to include national public-health systems, given that these are critical determinants in a country’s ability to prevent or at least manage a crisis like the one we are now experiencing.

I have even raised this idea with IMF officials themselves, only to be told that such reporting falls outside their remit because they lack the relevant expertise. That answer was not good enough then, and it definitely isn’t good enough now.

If the IMF lacks the expertise to assess public health systems, it should acquire it. As the COVID-19 crisis makes abundantly clear, there is no useful distinction to be made between health and finance. The two policy domains are deeply interconnected, and should be treated as such.

In thinking about an international response to today’s health and economic emergency, the obvious analogy is the 2008 global financial crisis which started with an unsustainable US housing bubble, fed by foreign savings owing to the lack of domestic savings in the United States.

When the bubble finally burst, many other countries sustained more harm than the US did, just as the COVID-19 pandemic has hit some countries much harder than it hit China.

And yet not many countries around the world sought to single out the US for presiding over a massively destructive housing bubble, even though the scars from that previous crisis are still visible. On the contrary, many welcomed the US economy’s return to sustained growth in recent years, because a strong US economy benefits the rest of the world.

So, rather than applying a double standard and fixating on China’s undoubtedly large errors, we would do better to consider what China can teach us. Specifically, we should be focused on better understanding the technologies and diagnostic techniques that China used to keep its - apparent - death toll so low compared to other countries, and to restart parts of its economy within weeks of the height of the outbreak.

And for our own sakes, we also should be considering what policies China could adopt to put itself back on a path toward 6% annual growth, because the Chinese economy inevitably will play a significant role in the global recovery.

If China’s post-pandemic growth model makes good on its leaders’ efforts in recent years to boost domestic consumption and imports from the rest of the world, we will all be better off.

This article was originally published in Project Syndicate


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A novel NanoBiT-based assay monitors the interaction between lipoprotein lipase and GPIHBP1 in real time

By feedproxy.google.com
Published On :: 2020-04-01

Shwetha K. Shetty
Apr 1, 2020; 61:546-559
Methods


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Episode 44 - The Internet of Police, Camera, Action! (IoPCA!) Pebble, police cameras & Amazon Go

By play.acast.com
Published On :: Fri, 09 Dec 2016 12:20:40 GMT

This week Henry Burrell is in the presenter chair and he has brought puns, sing-songs and tenuous Field of Dreams references. First up is producer Chris to discuss the Fitbit acquisition of fellow wearable maker Pebble and why owners are sad. Then online editor at Techworld Tamlin Magee is discussing the Met Police's decision to upload their body camera footage to the cloud and why this could be problematic (12:00). Finally, fellow online editor Scott Carey runs us through the Amazon Go news and how the retail giant is trying to pull off the technology behind its 'just walk out' shopping experience (24:00).  

See acast.com/privacy for privacy and opt-out information.


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Blaming China Is a Dangerous Distraction

By feedproxy.google.com
Published On :: Wed, 15 Apr 2020 10:50:59 +0000

15 April 2020

Jim O'Neill

Chair, Chatham House
Chinese officials' initial effort to cover up the coronavirus outbreak was appallingly misguided. But anyone still focusing on China's failings instead of working toward a solution is essentially making the same mistake.

2020-04-15-China-coronavirus-health

Medical staff on their rounds at a quarantine zone in Wuhan, China. Photo by STR/AFP via Getty Images.

As the COVID-19 crisis roars on, so have debates about China’s role in it. Based on what is known, it is clear that some Chinese officials made a major error in late December and early January, when they tried to prevent disclosures of the coronavirus outbreak in Wuhan, even silencing healthcare workers who tried to sound the alarm.

China’s leaders will have to live with these mistakes, even if they succeed in resolving the crisis and adopting adequate measures to prevent a future outbreak. What is less clear is why other countries think it is in their interest to keep referring to China’s initial errors, rather than working toward solutions.

For many governments, naming and shaming China appears to be a ploy to divert attention from their own lack of preparedness. Equally concerning is the growing criticism of the World Health Organization (WHO), not least by Donald Trump who has attacked the organization - and threatens to withdraw US funding - for supposedly failing to hold the Chinese government to account.

Unhelpful and dangerous

At a time when the top global priority should be to organize a comprehensive coordinated response to the dual health and economic crises unleashed by the coronavirus, this blame game is not just unhelpful but dangerous.

Globally and at the country level, we all desperately need to do everything possible to accelerate the development of a safe and effective vaccine, while in the meantime stepping up collective efforts to deploy the diagnostic and therapeutic tools necessary to keep the health crisis under control.

Given there is no other global health organization with the capacity to confront the pandemic, the WHO will remain at the center of the response, whether certain political leaders like it or not.

Having dealt with the WHO to a modest degree during my time as chairman of the UK’s independent Review on Antimicrobial Resistance (AMR), I can say that it is similar to most large, bureaucratic international organizations.

Like the International Monetary Fund (IMF), the World Bank, and the United Nations, it is not especially dynamic or inclined to think outside the box. But rather than sniping at these organizations from the sidelines, we should be working to improve them.

In the current crisis, we all should be doing everything we can to help both the WHO and the IMF to play an effective, leading role in the global response. As I have argued before, the IMF should expand the scope of its annual Article IV assessments to include national public-health systems, given that these are critical determinants in a country’s ability to prevent or at least manage a crisis like the one we are now experiencing.

I have even raised this idea with IMF officials themselves, only to be told that such reporting falls outside their remit because they lack the relevant expertise. That answer was not good enough then, and it definitely isn’t good enough now.

If the IMF lacks the expertise to assess public health systems, it should acquire it. As the COVID-19 crisis makes abundantly clear, there is no useful distinction to be made between health and finance. The two policy domains are deeply interconnected, and should be treated as such.

In thinking about an international response to today’s health and economic emergency, the obvious analogy is the 2008 global financial crisis which started with an unsustainable US housing bubble, fed by foreign savings owing to the lack of domestic savings in the United States.

When the bubble finally burst, many other countries sustained more harm than the US did, just as the COVID-19 pandemic has hit some countries much harder than it hit China.

And yet not many countries around the world sought to single out the US for presiding over a massively destructive housing bubble, even though the scars from that previous crisis are still visible. On the contrary, many welcomed the US economy’s return to sustained growth in recent years, because a strong US economy benefits the rest of the world.

So, rather than applying a double standard and fixating on China’s undoubtedly large errors, we would do better to consider what China can teach us. Specifically, we should be focused on better understanding the technologies and diagnostic techniques that China used to keep its - apparent - death toll so low compared to other countries, and to restart parts of its economy within weeks of the height of the outbreak.

And for our own sakes, we also should be considering what policies China could adopt to put itself back on a path toward 6% annual growth, because the Chinese economy inevitably will play a significant role in the global recovery.

If China’s post-pandemic growth model makes good on its leaders’ efforts in recent years to boost domestic consumption and imports from the rest of the world, we will all be better off.

This article was originally published in Project Syndicate


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Quantitative profiling of protein tyrosine kinases in human cancer cell lines by multiplexed parallel reaction monitoring assays [Technology]

By feedproxy.google.com
Published On :: 2015-09-25T14:31:13-07:00

Protein tyrosine kinases (PTKs) play key roles in cellular signal transduction, cell cycle regulation, cell division, and cell differentiation. Dysregulation of PTK-activated pathways, often by receptor overexpression, gene amplification, or genetic mutation, is a causal factor underlying numerous cancers. In this study, we have developed a parallel reaction monitoring (PRM)-based assay for quantitative profiling of 83 PTKs. The assay detects 308 proteotypic peptides from 54 receptor tyrosine kinases and 29 nonreceptor tyrosine kinases in a single run. Quantitative comparisons were based on the labeled reference peptide method. We implemented the assay in four cell models: 1) a comparison of proliferating versus epidermal growth factor (EGF)-stimulated A431 cells, 2) a comparison of SW480Null (mutant APC) and SW480APC (APC restored) colon tumor cell lines, and 3) a comparison of 10 colorectal cancer cell lines with different genomic abnormalities, and 4) lung cancer cell lines with either susceptibility (11-18) or acquired resistance (11-18R) to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. We observed distinct PTK expression changes that were induced by stimuli, genomic features or drug resistance, which were consistent with previous reports. However, most of the measured expression differences were novel observations. For example, acquired resistance to erlotinib in the 11-18 cell model was associated not only with previously reported upregulation of MET, but also with upregulation of FLK2 and downregulation of LYN and PTK7. Immunoblot analyses and shotgun proteomics data were highly consistent with PRM data. Multiplexed PRM assays provide a targeted, systems-level profiling approach to evaluate cancer-related proteotypes and adaptations. Data are available through Proteome eXchange Accession PXD002706.


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A cross-linking mass spectrometry approach defines protein interactions in yeast mitochondria [Research]

By feedproxy.google.com
Published On :: 2020-04-24T09:36:17-07:00

Protein cross-linking and the analysis of cross-linked peptides by mass spectrometry is currently receiving much attention. Not only is this approach applied to isolated complexes to provide information about spatial arrangements of proteins but it is also increasingly applied to entire cells and their organelles. As in quantitative proteomics, the application of isotopic labelling further makes it possible to monitor quantitative changes in the protein-protein interactions between different states of a system. Here, we cross-linked mitochondria from Saccharomyces cerevisiae grown on either glycerol- or glucose-containing medium to monitor protein-protein interactions under non-fermentative and fermentative conditions. We investigated qualitatively the protein-protein interactions of the 400 most abundant proteins applying stringent data-filtering criteria, i.e. a minimum of two cross-linked peptide spectrum matches and a cut-off in the spectrum scoring of the used search engine. The cross-linker BS3 proved to be equally suited for connecting proteins in all compartments of mitochondria when compared with its water-insoluble but membrane-permeable derivative DSS. We also applied quantitative cross-linking to mitochondria of both the growth conditions using stable-isotope labelled BS3. Significant differences of cross-linked proteins under glycerol and glucose conditions were detected, however, mainly due to the different copy numbers of these proteins in mitochondria under both the conditions. Results obtained from the glycerol condition indicate that the internal NADH:ubiquinone oxidoreductase Ndi1 is part of an electron transport chain supercomplex. We have also detected several hitherto uncharacterized proteins and identified their interaction partners. Among those, Min8 was found to be associated with cytochrome c oxidase. BN-PAGE analyses of min8 mitochondria suggest that Min8 promotes the incorporation of Cox12 into cytochrome c oxidase.


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Peptide-based interaction proteomics [Review]

By feedproxy.google.com
Published On :: 2020-04-28T12:34:32-07:00

Protein-protein interactions are often mediated by short linear motifs (SLiMs) that are located in intrinsically disordered regions (IDRs) of proteins. Interactions mediated by SLiMs are notoriously difficult to study, and many functionally relevant interactions likely remain to be uncovered. Recently, pull-downs with synthetic peptides in combination with quantitative mass spectrometry emerged as a powerful screening approach to study protein-protein interactions mediated by SLiMs. Specifically, arrays of synthetic peptides immobilized on cellulose membranes provide a scalable means to identify the interaction partners of many peptides in parallel. In this minireview we briefly highlight the relevance of SLiMs for protein-protein interactions, outline existing screening technologies, discuss unique advantages of peptide-based interaction screens and provide practical suggestions for setting up such peptide-based screens.


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A nematode sterol C4{alpha}-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity [Research Articles]

By feedproxy.google.com
Published On :: 2020-02-01T00:05:23-08:00

Primitive sterol evolution plays an important role in fossil record interpretation and offers potential therapeutic avenues for human disease resulting from nematode infections. Recognizing that C4-methyl stenol products [8(14)-lophenol] can be synthesized in bacteria while C4-methyl stanol products (dinosterol) can be synthesized in dinoflagellates and preserved as sterane biomarkers in ancient sedimentary rock is key to eukaryotic sterol evolution. In this regard, nematodes have been proposed to convert dietary cholesterol to 8(14)-lophenol by a secondary metabolism pathway that could involve sterol C4 methylation analogous to the C2 methylation of hopanoids (radicle-type mechanism) or C24 methylation of sterols (carbocation-type mechanism). Here, we characterized dichotomous cholesterol metabolic pathways in Caenorhabditis elegans that generate 3-oxo sterol intermediates in separate paths to lophanol (4-methyl stanol) and 8(14)-lophenol (4-methyl stenol). We uncovered alternate C3-sterol oxidation and 7 desaturation steps that regulate sterol flux from which branching metabolite networks arise, while lophanol/8(14)-lophenol formation is shown to be dependent on a sterol C4α-methyltransferse (4-SMT) that requires 3-oxo sterol substrates and catalyzes a newly discovered 3-keto-enol tautomerism mechanism linked to S-adenosyl-l-methionine-dependent methylation. Alignment-specific substrate-binding domains similarly conserved in 4-SMT and 24-SMT enzymes, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of methyl sterols. The combination of these results provides evolutionary leads to sterol diversity and points to cryptic C4-methyl steroidogenic pathways of targeted convergence that mediate lineage-specific adaptations.­­


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A novel NanoBiT-based assay monitors the interaction between lipoprotein lipase and GPIHBP1 in real time [Methods]

By feedproxy.google.com
Published On :: 2020-04-01T00:05:29-07:00

The hydrolysis of triglycerides in triglyceride-rich lipoproteins by LPL is critical for the delivery of triglyceride-derived fatty acids to tissues, including heart, skeletal muscle, and adipose tissues. Physiologically active LPL is normally bound to the endothelial cell protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), which transports LPL across endothelial cells, anchors LPL to the vascular wall, and stabilizes LPL activity. Disruption of LPL-GPIHBP1 binding significantly alters triglyceride metabolism and lipid partitioning. In this study, we modified the NanoLuc® Binary Technology split-luciferase system to develop a novel assay that monitors the binding of LPL to GPIHBP1 on endothelial cells in real time. We validated the specificity and sensitivity of the assay using endothelial lipase and a mutant version of LPL and found that this assay reliably and specifically detected the interaction between LPL and GPIHBP1. We then interrogated various endogenous and exogenous inhibitors of LPL-mediated lipolysis for their ability to disrupt the binding of LPL to GPIHBP1. We found that angiopoietin-like (ANGPTL)4 and ANGPTL3-ANGPTL8 complexes disrupted the interactions of LPL and GPIHBP1, whereas the exogenous LPL blockers we tested (tyloxapol, poloxamer-407, and tetrahydrolipstatin) did not. We also found that chylomicrons could dissociate LPL from GPIHBP1 and found evidence that this dissociation was mediated in part by the fatty acids produced by lipolysis. These results demonstrate the ability of this assay to monitor LPL-GPIHBP1 binding and to probe how various agents influence this important complex.


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Effect of a Sustained Reduction in Plasma Free Fatty Acid Concentration on Intramuscular Long-Chain Fatty Acyl-CoAs and Insulin Action in Type 2 Diabetic Patients

By diabetes.diabetesjournals.org
Published On :: 2005-11-01

Mandeep Bajaj
Nov 1, 2005; 54:3148-3153
Metabolism


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The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion

By diabetes.diabetesjournals.org
Published On :: 2002-12-01

Patrick E. MacDonald
Dec 1, 2002; 51:S434-S442
Section 5: Beta-Cell Stimulus-Secretion Coupling: Hormonal and Pharmacological Modulators


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The dynamics of dissent: when actions are louder than words

By feedproxy.google.com
Published On :: Thu, 02 May 2019 10:01:15 +0000

2 May 2019 , Volume 95, Number 3

In the latest issue a collection of articles explore how international norms are increasingly contested by both state and non-state actors.

Read online

Anette Stimmer and Lea Wisken

A profusion of international norms influences state behaviour. Ambiguities and tensions in the normative framework can give rise to contestation. While research on norm contestation has focused on open debates about norms, we identify a second type of norm contestation where norms are contested through particular forms of implementation. We therefore distinguish between contestation through words and actions, that is, discursive and behavioural contestation. Discursive contestation involves debates about the meaning and/or (relative) importance of norms. Behavioural contestation, by contrast, eschews such debates. Instead, different norm understandings become apparent in the different ways in which actors shape the implementation of norms. Despite being a potentially powerful mechanism of challenging and changing norms, behavioural contestation has fallen outside the purview of the literature in part because it frequently remains below the radar. The two forms of contestation overlap when the practices of behavioural contestation are brought to the attention of and discussed by the international community. Thus, discursive and behavioural contestation are not mutually exclusive but can happen at the same time, sequentially or independently of each other. This introduction to a special section of the May 2019 issue of International Affairs, on ‘The dynamics of dissent’, develops the concept of behavioural contestation and outlines triggers and effects of this hitherto under-researched expression of dissent.


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JDF promises 'strong' action against abusive soldiers

By jamaica-gleaner.com
Published On :: Fri, 08 May 2020 13:56:17 -0500

The Jamaica Defence Force (JDF) is promising "strong" action against soldiers found guilty of instructing violators of the national nightly COVID-19 curfew to engage in “corrective measures”. News of the allegations came in an...


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Businesses hope to get some action for Mother’s Day

By jamaica-gleaner.com
Published On :: Sat, 09 May 2020 00:09:50 -0500

Just last year, one could find a variety of deals and promotions for Mother’s Day with ease, but for 2020, the opposite is true. This change could be connected with the coronavirus pandemic and a number of businesses having to close their doors for...


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Delivering Concrete Climate Change Action

By feedproxy.google.com
Published On :: Tue, 14 May 2013 11:06:32 +0000

Conference

Towards 2015

21 October 2013 - 9:30am to 22 October 2013 - 3:30pm

Chatham House, London

Overview

Speakers

Press registration

Sponsors

Media partners

Venue and accommodation

Agenda

Audience profile

Over the past five years, the political conditions for a global agreement on climate change have shifted. There is today growing consensus that responding to a changing climate will require multi-level collaboration and new alliances.

In the run-up to the deadline for a new international climate change agreement in 2015, the 17th Annual Chatham House Conference on Climate Change will focus on workable solutions that will help accelerate global decarbonization.

This conference will ask:

  • What will a global deal in 2015 look like? What are the key components of a shared vision? What elements do developing and developed countries need in order to reach agreement?

  • How can the emerging international climate change regime – comprising voluntary partnerships, formal negotiations and business coalitions – deliver the necessary reductions in greenhouse gas emissions?

  • To what extent will new energy realities affect the politics of climate change?

  • What practical lessons can be learned from existing carbon mitigation and adaptation policies?

  • How can the international community harness progressive leadership?

Registration

  • Michael Anderson

    • Chief Executive Officer

  • The Rt Hon Gregory Barker MP

    • Minister of State for Energy and Climate Change

  • Frances Beinecke

    • President

  • Tim Benton

    • UK Champion for Global Food Security and Professor of Population Ecology

  • Sam Bickersteth

    • Chief Executive

  • Tony De Brum

    • Minister-in-Assistance to the President

  • Giles Dickson

    • VP Environmental Policies and Global Advocacy

  • Reid Detchon

    • Vice President, Energy and Climate

  • Alfred Evans

    • Chief Executive Officer

  • Christiana Figueres

    • Executive Secretary

  • Marcin Korolec

    • Minister of Environment, Poland

  • Kate Hampton

    • Executive Director, Climate Change

  • Cameron Hepburn

    • Professor of environmental economics, Smith School and INET at Oxford Martin School, University of Oxford, and

  • David Hone

    • Climate Change Advisor

  • Pa Ousman Jarju

    • Special Envoy for Climate Change

  • Sir David King

    • Foreign Secretary’s Special Representative for Climate Change

  • Martin Khor

    • Director

  • Johan Kuylenstierna

    • Deputy-Director, Stockholm Environment Institute

  • James Leaton

    • Project Director

  • Bernice Lee

    • Research Director, Energy, Environment and Resources

  • Nick Mabey

    • Chief Executive Officer

  • Amina Mohammed

    • Special Adviser on Post-2015 Development Planning

  • Jennifer Morgan

    • Director of the Climate and Energy Program

  • Admiral Neil Morisetti

    • Foreign Secretary’s Special Representative for Climate Change

  • Mutsuyoshi Nishimura

    • Visiting Research Fellow, Japan Institute of International affairs

  • Dr Atiur Rahman

    • Governor

  • John Schellnhuber

    • Founding Director

  • Todd Stern

    • Special Envoy for Climate Change

  • Kelly Rigg

    • Executive Director

  • Laurence Tubiana

    • Director

  • Fraser Thompson

    • Senior Fellow

  • Dominic Waughray

    • Senior Director and Head of Environmental Initiatives

  • Farhana Yamin

    • Associate Fellow

This conference will be held under the Chatham House Rule. Information for journalists
Press can request a press pass using the form below.

If you are interested in becoming a sponsor for this event, please contact George Woodhams on +44 (0)20 7957 5732 or email gwoodhams@chathamhouse.org.


 

 

 

 

 

 

 

 

 

 

 

 

Venue

Chatham House

conferences@chathamhouse.org

Telephone: +44 (0)20 7957 5729
Fax: +44 (0)20 7957 5710


If you wish to book the venue for your event please phone +44 (0)20 7314 2764


Conference Unit
Chatham House
10 St James's Square
London
SW1Y 4LE
UK


Accommodation

Although we cannot book accommodation for delegates, we have arranged a reduced rate at some nearby hotels, where you can book your own accommodation. Please inform the hotel that you will be attending a conference at Chatham House (The Royal Institute of International Affairs) to qualify for the Institute's reduced rate.

Please note all rates are subject to availability.

Flemings Mayfair
Half Moon Street
Mayfair
London W1Y 7RA
Tel: + 44 (0)20 7499 2964
Fax: + 44 (0)20 7499 1817
Standard Single £190 + VAT

The Cavendish London
81 Jermyn Street
London
SW1U 6JF
Tel: + 44 (0)20 7930 2111
Fax: + 44 (0)20 7839 2125
Standard Single £205 + VAT

To book The Cavendish online

The Stafford London by Kempinski
St James's Place
London
SW1A 1NJ
Tel: 020 7518 1125
Fax: 020 7493 7121
Standard Single £230 +VAT

Monday 21 October 2013

Session One
Bridging the Gap Between Science and Policy
09:00 - 10:10

  • What are the latest findings from climate science and the IPCC? 
  • Is the world on track for global decarbonisation? Is dangerous anthropogenic climate change avoidable?
  • To what extent are future climate risks sufficiently incorporated into policy thinking or investment strategies?

Welcome Address
Bernice Lee, Research Director, Energy, Environment and Resources, Chatham House

Chair
Michael Anderson, Chief Executive Officer, Children’s Investment Fund Foundation  

Keynote Address
Professor Hans Joachim Schellnhuber, Founding Director, Potsdam Institute for Climate Impact Research (PIK)

Speakers
Professor Tim Benton, UK Champion for Global Food Security and Professor of Population Ecology, Leeds University

Sir David King, Foreign Secretary’s Special Representative for Climate Change

Questions and Discussion

10:10 - 10:40   Refreshments

Session Two
Global Deal in 2015: Challenges and Prospects
10:40 - 12:40

  • What will a global deal in 2015 look like? Will there be specific targets or non-binding sets of approaches? What are the building blocks?
  • What is the value and track record of different kind of climate initiatives? For example, how successful are formal agreements compared to voluntary partnerships; climate-driven aid; or business coalitions? 
  • What are the main functions and institutions of the evolving international climate regime? What is the role of the UNFCCC? Is reform an option given the timeframe? What is the role for groupings like the G20 or the G8?

Chair
Bernice Lee, Research Director, Energy, Environment and Resources, Chatham House
 
Keynote Addresses
Christiana Figueres, Executive Secretary, United Nations Framework Convention on Climate Change (UNFCCC) (on the record)

Marcin Korolec, Minister of Environment, Poland and President, COP 19, UN Framework Convention on Climate Change (UNFCCC)

Questions and Discussion

Speakers
Nick Mabey, Chief Executive Officer, E3G

Farhana Yamin, Associate Fellow, Chatham House

Laurence Tubiana, Director, The Institute for Sustainable Development and International Relations (IDDRI)

Questions and Discussion

1240 - 14:00   Lunch

Chair
Bernice Lee, Research Director, Energy, Environment and Resources, Chatham House

Keynote Address
Gregory Barker, Minister of State for Energy and Climate Change, United Kingdom (on the record)

Questions and Discussion

Session Three
Climate-Resilient Development: Views from Developing Countries
14:30 - 16:10

  • What are the drivers of domestic climate action in developing countries?
  • What do developing countries need from the international climate regime: e.g. with respect to finance, ‘loss and damage’ and disaster preparedness? 
  • How will the politics among developing countries evolve? Has the G77 been eclipsed by the emergence of BASIC and other developing country alliances?

Chair
Sam Bickersteth, Chief Executive, The Climate and Development Knowledge Network (CDKN)

Keynote Addresses
Dr Atiur Rahman, Governor, Bangladesh Bank

Senator Tony deBrum, Minister-in-Assistance to the President, Republic of Marshall Islands

Questions and Discussion

Speakers
Martin Khor, Director, South Centre

Pa Ousman Jarju, Special Envoy for Climate Change, Republic of the Gambia

Questions and Discussion

16:10 - 16:30    Refreshments

Session Four
Preparing for 2015: The Role of Major Economies
16:30 - 17:30

  • Do countries have clear understandings of how climate risks will reshape their national interests? How will these risks affect other agendas e.g. future economic competitiveness, resource security, public health, foreign policy, or disaster preparedness?
  • How will major countries manage competing domestic priorities when preparing their national positions in the run-up to 2015? What is the evolving trilateral US-China-EU dynamic? Can the EU provide the necessary leadership?
  • Are national investment systems capable of scaling up financing to deliver climate action in key countries like US, EU, China and India?

Chair
Bernice Lee, Research Director, Energy, Environment and Resources, Chatham House

Speakers
David Hone, Climate Change Adviser, Shell

Jennifer Morgan, Director of the Climate and Energy Program, World Resources Institute 

Rear Admiral Neil Morisetti, Foreign Secretary’s Special Representative for Climate Change, United Kingdon

Mutsuyoshi Nishimura,  Visiting Research Fellow, Japan Institute of International affairs and Former Special Adviser to the Cabinet in charge of Climate Change, Japan 

Questions and Discussion

17:30 End of day one and drinks reception hosted by Chatham House


DAY TWO
Tuesday 22 October
09:30 - 15:10

Session Five
The Changing Global Energy Landscape: Implications for Decarbonization
09:30 - 10:45

  • What are the implications of the ‘golden age of gas’? What will growing coal use in many developing economies mean for climate politics?
  • What is the prospect for scaling up renewable investments – given the lessons learned vis-à-vis the scale, speed and cost of low carbon technologies over the past five years?
  • What are the contributions of off-grid, distributive generation and other demand side measures like efficiency?

Chair
David Hone, Climate Change Adviser, Shell

Moderated Panel Discussion
Reid Detchon, Vice President for Energy and Climate, United Nations Foundation

Giles Dickson, Vice President, Environmental Policies & Global Advocacy, Alstom 

Antony Froggatt, Senior Research Fellow, Chatham House

Questions and Discussion

10:45 - 11:15     Refreshments

Session Six
Climate Policy and Finance: The Emerging Toolkit
11:15 - 12:30

  • What is the track record of policies and measures to tackle CO2 emissions – from carbon markets, standards and subsidies removal to taxation? What is the progress on tackling non-CO2 greenhouse gases? 
  • The cost of climate impacts has been escalating. What are the emerging tools (e.g. disaster preparedness, climate-proof aid or insurance) for managing the impacts? 

  • What is the role of public versus private finance for different countries? What is the role of multilateral financing institutions in facilitating the increasingly large finance flows required?

Chair
Cameron Hepburn, Professor of Environmental Economics, Smith School and INET at Oxford Martin School, University of Oxford, and Professorial Research Fellow at the Grantham Research Institute at the LSE

Speakers
Dr Johan Kuylenstierna, Deputy- Director, Stockholm Environment Institute, University of York

Cameron Hepburn, Professor of environmental economics, Smith School and INET at Oxford Martin School, University of Oxford, and Professorial Research Fellow at the Grantham Research Institute at the LSE

James Leaton, Project Director, Carbon Tracker 

Fraser Thompson, Senior Fellow, McKinsey Global Institute

Questions and Discussion

12:30 -13:30    Lunch

13.:30 -14:00

Chair
Bernice Lee, Research Director, Energy, Environment and Resources, Chatham House

Keynote Address
Todd Stern, Special Envoy for Climate Change, United States Department of State

Questions and Discussion

Session Seven
Building the Progressive Conditions for 2015
14:00 - 15:10

  • Can the international community harness progressive leadership – through coalitions of governments, businesses and/or NGOs? 
  • What are the political or mobilisation strategies needed to tackle domestic climate scepticism, build progressive coalitions and neutralise vested interests at different levels? 
  • What are the implications of the post-2015 development discussions for climate change? 

Chair
Dominic Waughray, Senior Director, Head of Environmental Initiatives, World Economic Forum

Moderated Panel Discussion
Frances Beinecke, President, Natural Resources Defense Council 

Alfred Evans, Chief Executive Officer, Climate Change Capital

Kate Hampton, Executive Director, Climate Change, Children's Investment Fund Foundation 

Amina Mohammed, Special Adviser on Post-2015 Development Planning, United Nations

Questions and Discussion

15:10 Close of Conference


© The Royal Institute of International Affairs 2013

This conference will offer a unique opportunity to network with senior officials from businesses, government, NGO's and academic institutions.

Our previous Climate Change conferences saw delegates from companies and institutions such as:

Accenture
AEA Energy & Environment
Agulhas
ArcelorMittal
Association of Asia Pacific Airlines (AAPA)
Atkins Ltd
BASF plc
Bayerngas Norge AS
Beetle Capital
BG Group plc
BHP Billiton
BIRA-IASB
Booz & Co
BP plc
British Council
BT Group plc
Cairn Energy plc
Cambridge Centre for Energy Studies
Cambridge Programme for Sustainable Leadership
Carbon Capture and Storage Association
Carbon Leapfrog
Carbon Trust
Caritas Internationalis
Catholic Fund for Overseas Development (CAFOD)
CH2M Hill
Chamber of Shipping
Chevron Ltd
Chubu Electric Power Co Inc
ClientEarth
Clifford Chance LLP
Climate & Development Knowledge Network (CDKN)
Climate Action Network (CAN)
Climate and Health Council
Climate Secure
Coalition for an International Court for the Environment (ICE Coalition)
Compassion in World Farming (CIWF)
Conocophillips (UK) Ltd
Control Risks
Co-operative Group
Cranfield University
Deloitte Consulting LLP
Department for Business, Innovation & Skills (BIS)
Department for International Development (DFID)
Department of Energy and Climate Change (DECC)
Ecofys UK Ltd
Ecologic Institute
EDF Energy
Energy Charter Secretariat
Energy Technologies Institute
Eni S.p.A
Environment Agency
Environmental Law Foundation (ELF)
Environmental Protection Agency (EPA)
Environmental Resources Management (ERM)
ENWORKS
Ernst & Young
Ethical Investment Research Services Ltd (EIRIS)
European Bank For Reconstruction & Development
European Commission (Directorate General for Enterprise and Industry)
European Parliament
ExxonMobil International Ltd
Fauna & Flora International
FIA Foundation for the Automobile and Society
Finnish Forest Association
Foreign and Commonwealth Office (FCO)
Forestry Commission
Friends of the Earth
Genesis Investment Management LLP
GLG Partners LP
Global CCS Institute
Global Humanitarian Forum
Global Sustainability Institute
Global Witness
Globeleq Ltd
Grantham Research Institute on Climate Change and the Environment, LSE
Greater Manchester Chamber of Commerce
Greenpeace International
Herbert Smith Freehills LLP
HM Treasury
Imperial College London
INPEX Corporation
Institute for Public Policy Research (IPPR)
Institutional Investors Group on Climate Change (IIGCC)
International Association of Oil & Gas Producers
International Council on Mining and Metals
International Finance Corporation (IFC)
International Institute for Environment and Development (IIED)
International Organization for Standardization (ISO)
Japan External Trade Organization (JETRO)
Joseph Rowntree Foundation
JPMorgan
King's College London
KPMG
Kuwait Petroleum Corporation
London Assembly
London Metropolitan University
London School of Economics and Political Science (LSE)
Maersk Group
Massey University
McKinsey & Company
METREX
Ministere des Affaires Etrangeres, France
Ministry of Defence (Development, Concepts and Doctrine Centre)
Ministry of Foreign Affairs, Netherlands
Ministry of Foreign Affairs, Finland
Ministry of Foreign Affairs, Poland
Ministry of Infrastructure and the Environment
Mitsubishi Corporation
National Farmers' Union
National Round Table on the Environment and the Economy
Netherlands Development Finance Company (FMO)
NEXUS Singapore
Office of National Assessments
Ogilvy
Open Society Foundation
Overseas Development Institute (ODI)
Oxford University
Plan UK
PricewaterhouseCoopers LLP
Privy Council Office
Progressio
Quaker Peace and Social Witness
Québec Government Office
Renewable Energy and Energy Efficiency Partnership (REEEP)
Renewable Energy Systems Ltd (RES)
Rolls-Royce International Ltd
RWE Power AG
Save the Children UK
SCA, Svenska Cellulosa Aktiebolaget
School of Oriental and African Studies (SOAS)
Standard Chartered Bank plc
Statoil (UK) Ltd
SustainAbility Ltd
Swedish Defence Research Agency (FOI)
Swiss Agency for Development and Cooperation SDC
Task Consult
Texas A&M University
The 40 Foundation
The Climate Group
The Gold Standard Foundation
The Norwegian Institute for Nature Research
The Open University
The Prince of Wales Corporate Leader Group
The Royal Society
The Saudi Fund For Development
Tokyo Electric Power Company
Total Holdings UK Ltd
UK Chamber of Shipping
UK Collaborative on Development Sciences (UKCDS)
United Nations Environment Programme (UNEP)
University College London (UCL)
University of Cambridge
University of East Anglia (School of Environmental Sciences)
University of Edinburgh
University of Oxford (Department of Politics and International Relations)
US Department of State
USAID
Warwick Business School
WaterAid
World Coal Association
World Coal Institute
World Economic Forum
World Society for the Protection of Animals (WSPA)
World Vision UK
WWF-UK
Xynteo Ltd
Yorkshire Forward


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EU Lays Down Marker for Global Climate Action

By feedproxy.google.com
Published On :: Fri, 24 Oct 2014 13:21:32 +0000

24 October 2014

Antony Froggatt

Senior Research Fellow, Energy, Environment and Resources Programme

Shane Tomlinson

Former Senior Research Fellow, Energy, Environment and Resources
The EU’s climate and energy package represents an important step ahead of a potential global deal next year in Paris. But a disappointing approach to energy efficiency and uncertainty over governance threatens to undermine delivery.

20141024MerkelSchulzClimate.jpg

German Chancellor Angela Merkel talks with European parliament president Martin Schulz during an EU climate summit on 23 October 2014. Photo by Getty Images.

The European Union has reached agreement on its 2030 climate and energy package in preparation for the next major international climate summit in Paris in December 2015. In the agreement member states have signed up to reducing greenhouse gas (GHG) emissions by at least 40% by 2030 – compared to 1990 levels. Currently emissions are approximately 20% below 1990 levels and so the 2030 target represents a continuation of current decarbonization trends, but it is below the rate of reductions required to meet the longer term objective of cutting emission by 80-95% by 2050.

However, the overall 40% reduction will still drive structural changes in Europe’s economy and the energy sector. This could and should be seen as an opportunity for the EU to become a world leader in the innovation of both the new technologies and systems, such as electricity storage, dynamic demand responses and the deployment of electric vehicles, all of which are experiencing a rapid increase in the size of their global markets.

But there are some concerns. The climate and energy package has put forward a collective target to double the current level of renewables so that it will provide at least 27% of energy by 2030. However, the target is binding on the EU as a whole but not on individual member states, which creates uncertainty and is further complicated by a lack of clarity on the enforcement mechanism, which remains vague. To avoid loss of investor and industrial confidence a transparent process needs to be rapidly developed that ensures compliance. 

The EU has also failed to give energy efficiency the priority it deserves, downgrading it to an indicative target (i.e. one that is aspirational only) of a 27% reduction in energy use from business as usual. However, this is equivalent to, at most, a 19% reduction from Europe's pre-recession trajectory. The weaker energy efficiency and renewable energy elements of the package reflects the resistance of a relatively small number of countries to further EU-wide legal commitments, either because they prefer market inducement or due to their reluctance to reform their energy sectors. The package also makes clear that the a reformed Emissions Trading Scheme will be the main instrument to achieve the GHG reduction target and proposes to accelerate the reduction of the cap on maximum permitted emissions. However, this would only kick in after 2021, meaning the scheme will remain relatively ineffective for at least another five years. 

The crisis in Ukraine and the potential implications for security of supply once again highlights the importance of both domestic energy production and common European approaches to energy suppliers. Every 1% of energy saved across the EU reduces gas imports by 2.6%, and a stronger target would do more to reduce dependence on Russian gas imports. The EU’s failure to adopt a more far reaching and binding target on energy efficiency is a missed opportunity given that it is one  of the only approaches that delivers on the three pillars on energy policy, namely environmental protection, competitiveness and security of supply, simultaneously.

It is important to note the progress that the EU has made in both meeting its climate targets over the last decade and the impact that this has had on its other energy policy objectives. Currently, the EU’s 2020 target for reducing GHG emissions by 20% has or is very close to being met, in part due to the economic downturn, but also due to efficiency, renewable energy and changing industrial patterns and technologies. Furthermore, the use of renewable energy is now estimated to save around €30 billion per year in imported energy, improving balance of payments and improving security of supply. Likewise improvements in energy efficiency have been shown since the turn of the century to have contributed to a 1% annual reduction in energy consumption in the EU.

But the EU is not alone in preparing national carbon reduction targets for the UNFCCC conference in Paris 2015. Both China and the US, the world’s first and second largest emitters, are preparing their own emission reduction plans. China announced in September that it would put forward a new target for the peaking of its carbon dioxide emissions as early as possible. It is suggested that this might be as early as in 2025, with the potential for peak coal use coming even earlier in 2020. The US has proposed to set limits on the emissions from new coal-fired power stations and a 30% reduction in US power sector emissions by 2030 (relative to their 2005 baseline), and President Obama is expected to go further with new climate measures next year.

In the year ahead all countries that are party to the UNFCCC are expected to put on the table their national carbon abatement plans for 2030.  Some will be conditional upon further international assistance and commitments. The package agreed by Europe has scope to respond to increased efforts by other countries. This could include increasing the EU’s own domestic target (currently framed as ‘at least 40%’) or through international offsets and climate finance. How the EU responds to other countries efforts will be a test of its global leadership on climate issues.

To comment on this article, please contact Chatham House Feedback 


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Flow pushes passion for action for team members

By jamaica-gleaner.com
Published On :: Mon, 09 Mar 2020 00:15:16 -0500

With passion, motivation and determination to go against what is deemed as conventional in today’s society, Flow hosted a staff summit ahead of the International Womens’ Day under the theme ‘Passion for Action’, which supports a collective will to...


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Adverse drug reactions

By feeds.bmj.com
Published On :: Tue, 06 Nov 2018 15:53:33 +0000

Clinical trials for regulatory approval are designed to test efficacy, but new drugs might have adverse reactions - reactions those trials aren’t designed to spot. To talk about those adverse reactions - how to spot them, how to report them and what to do about them, we're joined by Robin Ferner, from the West Midlands Centre for Adverse Drug...


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Evidence for 5'AMP-Activated Protein Kinase Mediation of the Effect of Muscle Contraction on Glucose Transport

By diabetes.diabetesjournals.org
Published On :: 1998-08-01

Tatsuya Hayashi
Aug 1, 1998; 47:1369-1373
Rapid Publications


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Insulin Action, Diabetogenes, and the Cause of Type II Diabetes

By diabetes.diabetesjournals.org
Published On :: 1994-08-01

C. Ronald Kahn
Aug 1, 1994; 43:1066-1085
Banting Lecture


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Skeletal Muscle Triglyceride Levels Are Inversely Related to Insulin Action

By diabetes.diabetesjournals.org
Published On :: 1997-06-01

D A Pan
Jun 1, 1997; 46:983-988
Original Article


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Physical activity: a (mobile) call to action

By feeds.bmj.com
Published On :: Tuesday, January 28, 2020 - 14:40


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The Novel Adipokine Gremlin 1 Antagonizes Insulin Action and Is Increased in Type 2 Diabetes and NAFLD/NASH

By diabetes.diabetesjournals.org
Published On :: 2020-02-20T11:55:30-08:00

The BMP2/4 antagonist and novel adipokine Gremlin 1 is highly expressed in human adipose cells and increased in hypertrophic obesity. As a secreted antagonist, it inhibits the effect of BMP2/4 on adipose precursor cell commitment/differentiation. We examined mRNA levels of Gremlin 1 in key target tissues for insulin and also measured tissue and serum levels in several carefully phenotyped human cohorts. Gremlin 1 expression was high in adipose tissue, higher in visceral than in subcutaneous tissue, increased in obesity, and further increased in type 2 diabetes (T2D). A similar high expression was seen in liver biopsies, but expression was considerably lower in skeletal muscles. Serum levels were increased in obesity but most prominently in T2D. Transcriptional activation in both adipose tissue and liver as well as serum levels were strongly associated with markers of insulin resistance in vivo (euglycemic clamps and HOMA of insulin resistance), and the presence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We also found Gremlin 1 to antagonize insulin signaling and action in human primary adipocytes, skeletal muscle, and liver cells. Thus, Gremlin 1 is a novel secreted insulin antagonist and biomarker as well as a potential therapeutic target in obesity and its complications T2D and NAFLD/NASH.


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A Single Bout of One-Legged Exercise to Local Exhaustion Decreases Insulin Action in Nonexercised Muscle Leading to Decreased Whole-Body Insulin Action

By diabetes.diabetesjournals.org
Published On :: 2020-03-20T11:50:28-07:00

A single bout of exercise enhances insulin action in the exercised muscle. However, not all human studies find that this translates into increased whole-body insulin action, suggesting that insulin action in rested muscle or other organs may be decreased by exercise. To investigate this, eight healthy men underwent a euglycemic-hyperinsulinemic clamp on 2 separate days: one day with prior one-legged knee-extensor exercise to local exhaustion (~2.5 h) and another day without exercise. Whole-body glucose disposal was ~18% lower on the exercise day as compared with the resting day due to decreased (~37%) insulin-stimulated glucose uptake in the nonexercised muscle. Insulin signaling at the level of Akt2 was impaired in the nonexercised muscle on the exercise day, suggesting that decreased insulin action in nonexercised muscle may reduce GLUT4 translocation in response to insulin. Thus, the effect of a single bout of exercise on whole-body insulin action depends on the balance between local effects increasing and systemic effects decreasing insulin action. Physiologically, this mechanism may serve to direct glucose into the muscles in need of glycogen replenishment. For insulin-treated patients, this complex relationship may explain the difficulties in predicting the adequate insulin dose for maintaining glucose homeostasis following physical activity.


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Vitamin C in Human Health and Disease: Effects, Mechanisms of Action, and New Guidance on Intake

By jnm.snmjournals.org
Published On :: 2020-04-01T06:00:28-07:00


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Climate Action in 2020: Time to Focus on Forests

By feedproxy.google.com
Published On :: Tue, 14 Jan 2020 09:26:46 +0000

14 January 2020

Alison Hoare

Senior Research Fellow, Energy, Environment and Resources Programme
More ambitious policies to reduce deforestation are key to effective climate policy, but to succeed, they require three big changes in approach.

2020-01-14-ReforestBrazil.jpg

Mahogany tree seedlings being taken to be planted out in the Amazon. Photo: Getty Images.

December’s UN climate talks held in Madrid were aptly titled ‘Time for Action’. While little progress was made at the conference in establishing an international framework that would help to instigate this, there is still much scope for action in 2020. The need for this has become all too apparent as the impacts of climate change are increasingly seen around the world.

One of the key areas where progress can be made in 2020 is in increasing the ambition of nationally determined contributions (NDCs), these being governments’ plans to take action in response to climate change. To date, 184 countries have submitted NDCs, yet the commitments that have been made fall far short of what is needed to avert catastrophic climate change.

In 2020, however, many countries will be revising their NDCs, presenting an important opportunity to shift momentum; to date 79 countries have announced that they will be enhancing the ambition of their NDCs.

The forest sector is one area where more ambitious targets are likely to be set, and indeed, at the Climate Action Summit in September 2019, more than 20 countries made new commitments for the conservation, reforestation and restoration of their forests.

This will be essential. As is well documented, reducing deforestation is critical to reducing carbon emissions, while healthy and diverse forests are vital for adapting and increasing resilience to climate change.

However, while it is important that ambitious targets are set, this is relatively easy; the bigger challenge lies in ensuring that these are achievable.

This is all too apparent from experience thus far. In 2014, the New York Declaration on Forests set the goal to halve forest loss by 2020, and to end it by 2030. In addition, it included the goal to restore 150 million hectares of degraded landscapes and forestlands by 2020, and a further 200 million hectares by 2030.

The declaration has been endorsed by over 50 countries, as well as business and civil society organizations, yet the 2020 goals are far from being reached – in the six years since the declaration was launched, it has been found that forest loss increased rather than declined, and only about 27 million hectares of land have been restored.

What then is needed to ensure that the commitments being made by governments in their NDCs will actually be met? Three big changes are required.

Firstly, a shift in perspective is needed in many countries to a more forest-sensitive approach to development, one that gives adequate recognition to the full range of values provided by forests, rather than primarily focusing on their role as a global carbon sink. These include their importance for local and national economies, for livelihoods and the well-being of forest-dependent peoples, and for biodiversity and the regulation of local climate and water systems.

The focus on nature-based solutions at the international level offers potential to support this shift. However, it is critical that these are not seen as ‘niche’ approaches, and that countries identify what nature-based solutions mean for them, and how forests and tree-rich landscapes can best be integrated into their development strategies.

Fundamental to achieving this will be further improvements in governance, and this is the second change that is required. Legal and institutional reforms are needed in many countries as well as significant investments in human and technical resources. This will enable processes to be strengthened, or put in place, so that equitable strategies can be developed and implemented – strategies that reflect a balance of the needs and priorities of the full range of stakeholders, including local and global, rural and urban, women and men, young and old.

Financing will of course be critical for this, and the least developed countries in particular will be hindered in the actions they can take without additional finance. This is the third area of change that is needed, and it is to be hoped that the international community will make better progress on this in 2020. Forest and land-use options are often described as a cost-effective means of tackling climate change, as is noted in the Santiago Call for Action on Forests for example.

This is not to say that these will be easy or cheap – as Chatham House has documented, experience of forest governance reform has shown that it takes significant funding and time to bring about deep-rooted change. However, the huge potential benefits that can result, for the citizens of forest-rich countries as well as for the planet, mean that forests and sustainable land-use are a good investment.


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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.


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Shaping a Narrative of "Crisis" at Border, Trump Administration Takes Muscular Action

By www.migrationpolicy.org
Published On :: Tue, 18 Dec 2018 16:06:51 -0500

The Trump administration took sweeping action in 2018 to slow legal immigration, make life harder for some immigrants already in the United States, rebuff would-be asylum seekers, and reduce refugee resettlement. Shaping a narrative of crisis at the border, the administration significantly changed the U.S. asylum system, deployed troops and tear gas, and separated families—yet Central American migrants continued to arrive.


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The First 100 Days: Summary of Major Immigration Actions Taken by the Trump Administration

By www.migrationpolicy.org
Published On :: Mon, 24 Apr 2017 17:24:00 -0400

During his first 100 days in office, President Trump has taken a sweeping set of actions on immigration, ranging from imposing a travel ban to cutting refugee admissions, "extreme" vetting, and fortifying immigration enforcement at the border and in the U.S. interior. This fact sheet examines the major immigration actions taken to date, legal challenges, and related policy and personnel developments.


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Targeted Enforcement: Projecting the Effects of Executive Action on Deportations

By www.migrationpolicy.org
Published On :: Thu, 23 Jul 2015 16:15:50 -0400

Marking the release of an MPI report, this briefing explores the effects of recent revisions in DHS immigration enforcement priorities on deportations within the U.S. interior.


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Despite Flurry of Actions, Trump Administration Faces Constraints in Achieving Its Immigration Agenda

By www.migrationpolicy.org
Published On :: Wed, 24 Apr 2019 10:39:18 -0400

Though it has achieved success in some areas, the Trump administration’s many efforts to stiffen immigration enforcement in the U.S. interior and at the Southwest border are being consistently stymied by court injunctions, existing laws and settlements, state and local resistance, congressional pushback, and migration pressures that are beyond the government’s ability to swiftly address, as this article explores.


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Pathways to Quality Inpatient Management of Hyperglycemia and Diabetes: A Call to Action

By care.diabetesjournals.org
Published On :: 2013-07-01

Boris Draznin
Jul 1, 2013; 36:1807-1814
Perspectives in Care


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Insulinotropic Action of Glucagonlike Peptide-I-(7-37) in Diabetic and Nondiabetic Subjects

By care.diabetesjournals.org
Published On :: 1992-02-01

David M Nathan
Feb 1, 1992; 15:270-276
Short Report


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Vasodilatory Actions of Glucagon-Like Peptide 1 Are Preserved in Skeletal and Cardiac Muscle Microvasculature but Not in Conduit Artery in Obese Humans With Vascular Insulin Resistance

By care.diabetesjournals.org
Published On :: 2020-02-20T11:55:30-08:00

OBJECTIVE

Obesity is associated with microvascular insulin resistance, which is characterized by impaired insulin-mediated microvascular recruitment. Glucagon-like peptide 1 (GLP-1) recruits skeletal and cardiac muscle microvasculature, and this action is preserved in insulin-resistant rodents. We aimed to examine whether GLP-1 recruits microvasculature and improves the action of insulin in obese humans.

RESEARCH DESIGN AND METHODS

Fifteen obese adults received intravenous infusion of either saline or GLP-1 (1.2 pmol/kg/min) for 150 min with or without a euglycemic insulin clamp (1 mU/kg/min) superimposed over the last 120 min. Skeletal and cardiac muscle microvascular blood volume (MBV), flow velocity and blood flow, brachial artery diameter and blood flow, and pulse wave velocity (PWV) were determined.

 RESULTS

Insulin failed to change MBV or flow in either skeletal or cardiac muscle, confirming the presence of microvascular insulin resistance. GLP-1 infusion alone increased MBV by ~30% and ~40% in skeletal and cardiac muscle, respectively, with no change in flow velocity, leading to a significant increase in microvascular blood flow in both skeletal and cardiac muscle. Superimposition of insulin to GLP-1 infusion did not further increase MBV or flow in either skeletal or cardiac muscle but raised the steady-state glucose infusion rate by ~20%. Insulin, GLP-1, and GLP-1 + insulin infusion did not alter brachial artery diameter and blood flow or PWV. The vasodilatory actions of GLP-1 are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.

 CONCLUSIONS

In obese humans with microvascular insulin resistance, GLP-1’s vasodilatory actions are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.


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Africa Deepens its Approach to Migration Governance, But Are Policies Translating to Action?

By www.migrationpolicy.org
Published On :: Thu, 02 Apr 2020 11:41:21 -0400

While migration once was a lower-priority topic for African governments, the last decade has seen a deepening in governance. Policymakers have integrated migration into their national development strategies and mainstreamed it across policy domains such as health and education. The actions are promising on paper, yet questions remain about the extent to which they will translate to more effective migration management.


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A World of Insults, a World of Reactions

By www.washingtonpost.com
Published On :: Mon, 17 Jul 2006 00:00:00 EDT

You don't have to be a sports fan to know that something extraordinary happened in the World Cup soccer final last week. Ten minutes from the climactic end -- with his country's hopes, the championship and his place in the history books at stake -- French captain Zinedine Zidane violently...


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Are We Judging Actions, Or the People Behind Them?

By www.washingtonpost.com
Published On :: Mon, 21 May 2007 00:00:00 EDT

Like lunar and solar eclipses, there are some Washington phenomena that are so common they ought to have distinct names. Here is one: A public figure comes to be hated by large numbers of people. But the person cannot be prosecuted or punished, perhaps because his behavior did not involve a crime so...


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'Attraction Effect' Helps Voters Pick From the Pack

By www.washingtonpost.com
Published On :: Mon, 21 Jan 2008 00:00:00 EST

Some years ago, a political scientist conducted an interesting experiment that speaks to the fractured race for the Republican presidential nomination, which now has six candidates, five issues, and four potential front-runners.


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Hillary Clinton and the Action Bias

By www.washingtonpost.com
Published On :: Mon, 31 Mar 2008 00:00:00 EDT

On Oct. 10, 2002, Hillary Rodham Clinton stood in the Senate to explain why she was authorizing President Bush to use force against Iraq: "In balancing the risks of action versus inaction, I think New Yorkers who have gone through the fires of hell may be more attuned to the risk of not acting. I...


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Beyond Transactional Deals: Building Lasting Migration Partnerships in the Mediterranean

By www.migrationpolicy.org
Published On :: Mon, 13 Nov 2017 15:59:04 -0500

Since the 2015–16 refugee crisis, European policymakers have eagerly sought cooperation with origin and transit countries in the hopes of stemming unauthorized migration to Europe. This approach is neither new, nor without its limitations. By examining the evolution of two longstanding Mediterranean partnerships—between Spain and Morocco, and Italy and Tunisia—this report offers insights on what has and has not worked.


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5 Secrets to Increase Your Sexual Satisfaction: Tips From a Sex Therapist

By feedproxy.google.com
Published On :: Wed, 15 Apr 2020 14:00:00 +0000

As a practicing sex therapist, I often see two partners legitimately trying to bridge a satisfaction gap between each other, but they can’t seem to get the moves just right. If left unchecked, this can lead to resentment and conflict; however, couples who figure out how to speak to each other sexually (both verbally and nonverbally) have the highest success in terms of finding something that works for both of them. Making an environment conducive to this sort of positive growth requires a little bit of effort and the ability to listen. Drawing on my clinical experience, here are my top tips for increasing sexual satisfaction:


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Texas Directed to Take Additional Actions to Remedy Special Education Violations

By feedproxy.google.com
Published On :: Sat, 20 Oct 2018 00:00:00 +0000

Thousands of Texas children are believed to have been kept from special education services because of a now-prohibited special education enrollment target of 8.5 percent, which is well below the national average.


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Washington voters reject affirmative action referendum

By feedproxy.google.com
Published On :: Wed, 13 Nov 2019 00:00:00 +0000


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Inactive Actions: The consequences if actions are placed in the inactive cases list and are not removed, establishment of “Special Reasons”, and the moratorium of steps procedure.

By www.catalog.slsa.sa.gov.au
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Australia's Second Open Government National Action Plan 2018-20 / Department of the Prime Minister and Cabinet.

By www.catalog.slsa.sa.gov.au
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End of Term Self-Assessment Report for Australia's First Open Government National Action Plan 2016-18.

By www.catalog.slsa.sa.gov.au
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