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Legal Immigrant in Michigan Sends a Message to MI Gov Whitmer and Media Criticizing Freedom-Loving Protesters

The following article, Legal Immigrant in Michigan Sends a Message to MI Gov Whitmer and Media Criticizing Freedom-Loving Protesters, was first published on 100PercentFedUp.com.

The media and even some governors are trying to paint the Americans who are protesting to open businesses up as racists and even Nazis. The Governor of Michigan recently made a derogatory statement about the protesters implying they are racists. Painting a negative picture of the people who want their freedom and businesses demonizes our […]

Continue reading: Legal Immigrant in Michigan Sends a Message to MI Gov Whitmer and Media Criticizing Freedom-Loving Protesters ...




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Dem Congresswoman: Biden Allegation ‘Put To Rest’ Because He ‘Went on TV’ And Denied It

The following article, Dem Congresswoman: Biden Allegation ‘Put To Rest’ Because He ‘Went on TV’ And Denied It, was first published on 100PercentFedUp.com.

Democrat Rep. Dina Titus says that the allegations against 2020 Democrat presidential candidate Joe Biden are “put to rest” because he “went on TV” and denied them. Rep. Titus spoke with MSNBC’s Ayman Mohyeldin today about how she believes Biden because he flatly said he didn’t do it and didn’t say he doesn’t remember. It’s […]

Continue reading: Dem Congresswoman: Biden Allegation ‘Put To Rest’ Because He ‘Went on TV’ And Denied It ...




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BREAKING: Michigan’s Radical Governor Extends Lockdown AGAIN…Only One Day After Church Leaders and MI Lawmakers File Suit Against Her

The following article, BREAKING: Michigan’s Radical Governor Extends Lockdown AGAIN…Only One Day After Church Leaders and MI Lawmakers File Suit Against Her, was first published on 100PercentFedUp.com.

Michigan was the first state to see protests against draconian lockdown measures by an overreaching governor. On April 15, the Michigan Conservative Coalition organized an in-vehicle protest in Lansing, MI that drew an estimated 15,000 vehicles. Since that time, several protests by Michigan workers who are being devastated by the one-size-fits-all shut down of the […]

Continue reading: BREAKING: Michigan’s Radical Governor Extends Lockdown AGAIN…Only One Day After Church Leaders and MI Lawmakers File Suit Against Her ...




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Mother of the Year, Michelle Obama Explains How Having Kids Was A “Concession”… Had To Give Up Her “Aspirations and Dreams” [VIDEO]

The following article, Mother of the Year, Michelle Obama Explains How Having Kids Was A “Concession”… Had To Give Up Her “Aspirations and Dreams” [VIDEO], was first published on 100PercentFedUp.com.

While campaigning for her community organizer turned presidential candidate husband, Barack, Michelle Obama told a crowd of his supporters in Milwaukee, Wisconsin that for the first time in her life, she was proud to be an American. Four years later, Michelle Obama was a keynote speaker at the DNC convention, where she told Democrats how […]

Continue reading: Mother of the Year, Michelle Obama Explains How Having Kids Was A “Concession”… Had To Give Up Her “Aspirations and Dreams” [VIDEO] ...




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BREAKING: Ex-Cop Father and Son Arrested and Charged With Murder of Black Man Jogging In Neighborhood…President Trump Responds [VIDEO]

The following article, BREAKING: Ex-Cop Father and Son Arrested and Charged With Murder of Black Man Jogging In Neighborhood…President Trump Responds [VIDEO], was first published on 100PercentFedUp.com.

The Georgia Bureau of Investigations has arrested a father and son duo, 64-year-old ex-cop, Gregory McMichael, and his son, 34-year-old Travis McMichael for the February murder of  24-year-old Ahmaud Arbery, a black man who was jogging through their neighborhood when they jumped in their truck and pursued him. Yashar Ali shared the news of the […]

Continue reading: BREAKING: Ex-Cop Father and Son Arrested and Charged With Murder of Black Man Jogging In Neighborhood…President Trump Responds [VIDEO] ...




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BREAKING: President Trump’s Fiery Interview On Fox & Friends…”These are dirty politicians and dirty cops…They put our nation in danger with other nations, including Russia” [VIDEO]

The following article, BREAKING: President Trump’s Fiery Interview On Fox & Friends…”These are dirty politicians and dirty cops…They put our nation in danger with other nations, including Russia” [VIDEO], was first published on 100PercentFedUp.com.

This morning during a nearly one hour interview with Fox & Friends, President Trump addressed the decision by the DOJ to drop the case against the innocent General Michael Flynn. Trump ripped into the “dirty politicians and dirty cops” who went after General Michael Flynn. President Trump called the players involved in the horrible plot […]

Continue reading: BREAKING: President Trump’s Fiery Interview On Fox & Friends…”These are dirty politicians and dirty cops…They put our nation in danger with other nations, including Russia” [VIDEO] ...




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Fed Judge Releases 21-Yr-Old Man To “Clean and Sober House” After Appearing In Court For Sexually Assaulting 12-Yr-Old Girl For One Month While Hiding In Her Bedroom

The following article, Fed Judge Releases 21-Yr-Old Man To “Clean and Sober House” After Appearing In Court For Sexually Assaulting 12-Yr-Old Girl For One Month While Hiding In Her Bedroom, was first published on 100PercentFedUp.com.

The normalizing of pedophilia is not a far-right conspiracy theory...

Continue reading: Fed Judge Releases 21-Yr-Old Man To “Clean and Sober House” After Appearing In Court For Sexually Assaulting 12-Yr-Old Girl For One Month While Hiding In Her Bedroom ...




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Traffic stop in Windsor leads to multiple charges and discovery of homemade conducted energy weapon

After being pulled over for what started as a traffic violation, two Windsor men were arrested and face multiple drug, property, and weapon related charges.




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One new death and nine new COVID-19 cases in Windsor-Essex

One more person has died from the coronavirus in the Windsor-Essex region on Saturday and nine new cases have been reported by the health unit.




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To Advance Trade and Climate Goals, ‘Global Britain’ Must Link Them

19 March 2020

Carolyn Deere Birkbeck

Associate Fellow, Global Economy and Finance Programme, and Hoffmann Centre for Sustainable Resource Economy

Dr Emily Jones

Associate Professor, Blavatnik School of Government

Dr Thomas Hale

Associate Professor, Blavatnik School of Government
COVID-19 is a sharp reminder of why trade policy matters. As the UK works to forge new trade deals, it must align its trade policy agenda with its climate ambition.

2020-03-19-Boris-Johnson-COP26.jpg

Boris Johnson at the launch of the UK-hosted COP26 UN Climate Summit at the Science Museum, London on February 4, 2020. Photo by Jeremy Selwyn - WPA Pool/Getty Images.

COVID-19 is a sharp reminder of why trade and climate policy matters. How can governments maintain access to critical goods and services, and ensure global supply chains function in times of crisis?

The timing of many trade negotiations is now increasingly uncertain, as are the UK’s plans to host COP26 in November. Policy work continues, however, and the EU has released its draft negotiating text for the new UK-EU trade deal, which includes a sub-chapter specifically devoted to climate. 

This is a timely reminder both of the pressing need for the UK to integrate its trade and climate policymaking and to use the current crisis-induced breathing space in international negotiations - however limited - to catch up on both strategy and priorities on this critical policy intersection.

The UK government has moved fast to reset its external trade relations post-Brexit. In the past month it formally launched bilateral negotiations with the EU and took up a seat at the World Trade Organization (WTO) as an independent member. Until the COVID-19 crisis hit, negotiations were also poised to start with the US.

The UK is also in the climate spotlight as host of COP26, the most important international climate negotiation since Paris in 2015, which presents a vital opportunity for the government to show leadership by aligning its trade agenda with its climate and sustainability commitments in bold new ways.

Not just an empty aspiration

This would send a signal that ‘Global Britain’ is not just an empty aspiration, but a concrete commitment to lead.

Not only is concerted action on the climate crisis a central priority for UK citizens, a growing and increasingly vocal group of UK businesses committed to decarbonization are calling on the government to secure a more transparent and predictable international market place that supports climate action by business.

With COP26, the UK has a unique responsibility to push governments to ratchet up ambition in the national contributions to climate action – and to promote coherence between climate ambition and wider economic policymaking, including on trade. If Britain really wants to lead, here are some concrete actions it should take.

At the national level, the UK can pioneer new ways to put environmental sustainability – and climate action in particular - at the heart of its trade agenda. Achieving the government’s ambitious Clean Growth Strategy - which seeks to make the UK the global leader in a range of industries including electric cars and offshore wind – should be a central objective of UK trade policy.

The UK should re-orient trade policy frameworks to incentivize the shift toward a more circular and net zero global economy. And all elements of UK trade policy could be assessed against environmental objectives - for example, their contribution to phasing out fossil fuels, helping to reverse overexploitation of natural resources, and support for sustainable agriculture and biodiversity.

In its bilateral and regional trade negotiations, the UK can and should advance its environment, climate and trade goals in tandem, and implementation of the Paris Agreement must be a core objective of the UK trade strategy.

A core issue for the UK is how to ensure that efforts to decarbonise the economy are not undercut by imports from high-carbon producers. Here, a ‘border carbon adjustment (BCA)’ - effectively a tax on the climate pollution of imports - would support UK climate goals. The EU draft negotiating text released yesterday put the issue of BCAs front and centre, making crystal clear that the intersection of climate, environment and trade policy goals will be a central issue for UK-EU trade negotiations.

Even with the United States, a trade deal can and should still be seized as a way to incentivize the shift toward a net zero and more circular economy. At the multilateral level, as a new independent WTO member, the UK has an opportunity to help build a forward-looking climate and trade agenda.

The UK could help foster dialogue, research and action on a cluster of ‘climate and trade’ issues that warrant more focused attention at the WTO. These include the design of carbon pricing policies at the border that are transparent, fair and support a just transition; proposals for a climate waiver for WTO rules; and identification of ways multilateral trade cooperation could promote a zero carbon and more circular global economy.  

To help nudge multilateral discussion along, the UK could also ask to join a critical ‘path finder’ effort by six governments, led by New Zealand, to pursue an agreement on climate change, trade and sustainability (ACCTS). This group aims to find ways forward on three central trade and climate issues: removing fossil fuel subsidies, climate-related labelling, and promoting trade in climate-friendly goods and services.

At present, the complex challenges at the intersection of climate, trade and development policy are too often used to defer or side-step issues deemed ‘too hard’ or ‘too sensitive’ to tackle. The UK could help here by working to ensure multilateral climate and trade initiatives share adjustment burdens, recognise the historical responsibility of developed countries, and do not unfairly disadvantage developing countries - especially the least developed.

Many developing countries are keen to promote climate-friendly exports as part of wider export diversification strategies  and want to reap greater returns from greener global value chains. Further, small island states and least-developed countries – many of which are Commonwealth members – that are especially vulnerable to the impacts of climate change and natural disasters, need support to adapt in the face of trade shocks and to build climate-resilient, trade-related infrastructure and export sectors.

As an immediate next step, the UK should actively support the growing number of WTO members in favour of a WTO Ministerial Statement on environmental sustainability and trade. It should work with its key trading partners in the Commonwealth and beyond to ensure the agenda is inclusive, supports achievement of the UN Sustainable Development Goals (SDGs) and helps developing countries benefit from a more environmentally sustainable global economy.

As the UK prepares to host COP26, negotiates deals with the EU and US, and prepares for its first WTO Ministerial meeting as an independent member, it must show it can lead the way nationally, bilaterally, and multilaterally. And to ensure the government acts, greater engagement from the UK’s business, civil society and research sectors is critical – we need all hands on deck to forge and promote concrete proposals for aligning UK trade policy with the climate ambition our world needs.




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A comprehensive evaluation of a typical plant telomeric G-quadruplex (G4) DNA reveals the dynamics of G4 formation, rearrangement, and unfolding [Plant Biology]

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.




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Spectral and photochemical diversity of tandem cysteine cyanobacterial phytochromes [Plant Biology]

The atypical trichromatic cyanobacterial phytochrome NpTP1 from Nostoc punctiforme ATCC 29133 is a linear tetrapyrrole (bilin)-binding photoreceptor protein that possesses tandem-cysteine residues responsible for shifting its light-sensing maximum to the violet spectral region. Using bioinformatics and phylogenetic analyses, here we established that tandem-cysteine cyanobacterial phytochromes (TCCPs) compose a well-supported monophyletic phytochrome lineage distinct from prototypical red/far-red cyanobacterial phytochromes. To investigate the light-sensing diversity of this family, we compared the spectroscopic properties of NpTP1 (here renamed NpTCCP) with those of three phylogenetically diverged TCCPs identified in the draft genomes of Tolypothrix sp. PCC7910, Scytonema sp. PCC10023, and Gloeocapsa sp. PCC7513. Recombinant photosensory core modules of ToTCCP, ScTCCP, and GlTCCP exhibited violet-blue–absorbing dark-states consistent with dual thioether-linked phycocyanobilin (PCB) chromophores. Photoexcitation generated singly-linked photoproduct mixtures with variable ratios of yellow-orange and red-absorbing species. The photoproduct ratio was strongly influenced by pH and by mutagenesis of TCCP- and phytochrome-specific signature residues. Our experiments support the conclusion that both photoproduct species possess protonated 15E bilin chromophores, but differ in the ionization state of the noncanonical “second” cysteine sulfhydryl group. We found that the ionization state of this and other residues influences subsequent conformational change and downstream signal transmission. We also show that tandem-cysteine phytochromes present in eukaryotes possess similar amino acid substitutions within their chromophore-binding pocket, which tune their spectral properties in an analogous fashion. Taken together, our findings provide a roadmap for tailoring the wavelength specificity of plant phytochromes to optimize plant performance in diverse natural and artificial light environments.




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Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease]

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.




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The FKH domain in FOXP3 mRNA frequently contains mutations in hepatocellular carcinoma that influence the subcellular localization and functions of FOXP3 [Molecular Bases of Disease]

The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC.




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Inhibition of the erythropoietin-producing receptor EPHB4 antagonizes androgen receptor overexpression and reduces enzalutamide resistance [Molecular Bases of Disease]

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.




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N{alpha}-Acetylation of the virulence factor EsxA is required for mycobacterial cytosolic translocation and virulence [Molecular Bases of Disease]

The Mycobacterium tuberculosis virulence factor EsxA and its chaperone EsxB are secreted as a heterodimer (EsxA:B) and are crucial for mycobacterial escape from phagosomes and cytosolic translocation. Current findings support the idea that for EsxA to interact with host membranes, EsxA must dissociate from EsxB at low pH. However, the molecular mechanism by which the EsxA:B heterodimer separates is not clear. In the present study, using liposome-leakage and cytotoxicity assays, LC-MS/MS–based proteomics, and CCF-4 FRET analysis, we obtained evidence that the Nα-acetylation of the Thr-2 residue on EsxA, a post-translational modification that is present in mycobacteria but absent in Escherichia coli, is required for the EsxA:B separation. Substitutions at Thr-2 that precluded Nα-acetylation inhibited the heterodimer separation and hence prevented EsxA from interacting with the host membrane, resulting in attenuated mycobacterial cytosolic translocation and virulence. Molecular dynamics simulations revealed that at low pH, the Nα-acetylated Thr-2 makes direct and frequent “bind-and-release” contacts with EsxB, which generates a force that pulls EsxB away from EsxA. In summary, our findings provide evidence that the Nα-acetylation at Thr-2 of EsxA facilitates dissociation of the EsxA:B heterodimer required for EsxA membrane permeabilization and mycobacterial cytosolic translocation and virulence.




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ER stress increases store-operated Ca2+ entry (SOCE) and augments basal insulin secretion in pancreatic beta cells [Molecular Bases of Disease]

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.




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Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3 [Cell Biology]

Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin–Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of WT PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor–like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights into ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies.




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Zinc promotes liquid-liquid phase separation of tau protein [Protein Structure and Folding]

Tau is a microtubule-associated protein that plays a major role in Alzheimer's disease (AD) and other tauopathies. Recent reports indicate that, in the presence of crowding agents, tau can undergo liquid–liquid phase separation (LLPS), forming highly dynamic liquid droplets. Here, using recombinantly expressed proteins, turbidimetry, fluorescence microscopy imaging, and fluorescence recovery after photobleaching (FRAP) assays, we show that the divalent transition metal zinc strongly promotes this process, shifting the equilibrium phase boundary to lower protein or crowding agent concentrations. We observed no tau LLPS-promoting effect for any other divalent transition metal ions tested, including Mn2+, Fe2+, Co2+, Ni2+, and Cu2+. We also demonstrate that multiple zinc-binding sites on tau are involved in the LLPS-promoting effect and provide insights into the mechanism of this process. Zinc concentration is highly elevated in AD brains, and this metal ion is believed to be an important player in the pathogenesis of this disease. Thus, the present findings bring a new dimension to understanding the relationship between zinc homeostasis and the pathogenic process in AD and related neurodegenerative disorders.




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Effects of deficiency in the RLBP1-encoded visual cycle protein CRALBP on visual dysfunction in humans and mice [Cell Biology]

Mutations in retinaldehyde-binding protein 1 (RLBP1), encoding the visual cycle protein cellular retinaldehyde-binding protein (CRALBP), cause an autosomal recessive form of retinal degeneration. By binding to 11-cis-retinoid, CRALBP augments the isomerase activity of retinoid isomerohydrolase RPE65 (RPE65) and facilitates 11-cis-retinol oxidation to 11-cis-retinal. CRALBP also maintains the 11-cis configuration and protects against unwanted retinaldehyde activity. Studying a sibling pair that is compound heterozygous for mutations in RLBP1/CRALBP, here we expand the phenotype of affected individuals, elucidate a previously unreported phenotype in RLBP1/CRALBP carriers, and demonstrate consistencies between the affected individuals and Rlbp1/Cralbp−/− mice. In the RLBP1/CRALBP-affected individuals, nonrecordable rod-specific electroretinogram traces were recovered after prolonged dark adaptation. In ultrawide-field fundus images, we observed radially arranged puncta typical of RLBP1/CRALBP-associated disease. Spectral domain-optical coherence tomography (SD-OCT) revealed hyperreflective aberrations within photoreceptor-associated bands. In short-wavelength fundus autofluorescence (SW-AF) images, speckled hyperautofluorescence and mottling indicated macular involvement. In both the affected individuals and their asymptomatic carrier parents, reduced SW-AF intensities, measured as quantitative fundus autofluorescence (qAF), indicated chronic impairment in 11-cis-retinal availability and provided information on mutation severity. Hypertransmission of the SD-OCT signal into the choroid together with decreased near-infrared autofluorescence (NIR-AF) provided evidence for retinal pigment epithelial cell (RPE) involvement. In Rlbp1/Cralbp−/− mice, reduced 11-cis-retinal levels, qAF and NIR-AF intensities, and photoreceptor loss were consistent with the clinical presentation of the affected siblings. These findings indicate that RLBP1 mutations are associated with progressive disease involving RPE atrophy and photoreceptor cell degeneration. In asymptomatic carriers, qAF disclosed previously undetected visual cycle deficiency.




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{alpha}-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are maȷor seed-competent species [Molecular Bases of Disease]

Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies.




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Non-photopic and photopic visual cycles differentially regulate immediate, early, and late phases of cone photoreceptor-mediated vision [Molecular Bases of Disease]

Cone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Müller glia. In the RPE, isomerization of all-trans-retinyl esters to 11-cis-retinol is mediated by the retinoid isomerohydrolase Rpe65. A putative alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Müller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early, and late phases of cone photopic vision. In zebrafish larvae raised under cyclic light conditions, fenretinide impaired late cone photopic vision, while the emixustat-treated zebrafish unexpectedly had normal vision. In contrast, emixustat-treated larvae raised under extensive dark-adaptation displayed significantly attenuated immediate photopic vision concomitant with significantly reduced 11-cis-retinaldehyde (11cRAL). Following 30 min of light, early photopic vision was recovered, despite 11cRAL levels remaining significantly reduced. Defects in immediate cone photopic vision were rescued in emixustat- or fenretinide-treated larvae following exogenous 9-cis-retinaldehyde supplementation. Genetic knockout of Des1 (degs1) or retinaldehyde-binding protein 1b (rlbp1b) did not eliminate photopic vision in zebrafish. Our findings define molecular and temporal requirements of the nonphotopic or photopic visual cycles for mediating vision in bright light.




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Pro-515 of the dynamin-like GTPase MxB contributes to HIV-1 inhibition by regulating MxB oligomerization and binding to HIV-1 capsid [Microbiology]

Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505–527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515–519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function.




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A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning [Molecular Biophysics]

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.




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Reactive dicarbonyl compounds cause Calcitonin Gene-Related Peptide release and synergize with inflammatory conditions in mouse skin and peritoneum [Molecular Bases of Disease]

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.




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Brain manganese and the balance between essential roles and neurotoxicity [Molecular Bases of Disease]

Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity.




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The Struggle for Reform in Iraq and Lebanon

Research Event

3 December 2019 - 9:30am to 10:45am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Renad Mansour, Research Fellow, Middle East and North Africa Programme, Chatham House
Alia Moubayed, Managing Director, Jefferies
Chair: Lina Khatib, Head, Middle East and North Africa Programme, Chatham House

Over recent weeks, widespread popular protests have engulfed Iraq and Lebanon. What began as calls for reform in the context of high unemployment and endemic corruption have evolved into direct challenges to the existing political order in both countries.

In response, ruling elites have moved to protect the systems from which they draw power. In Iraq, the state has responded to protests with violence, killing more than 300 people and injuring over 15,000. In Lebanon, protesters are facing attempts at co-optation and intransigence by their leaders. These developments have served to underline the widening gap between elites and ordinary citizens and to highlight geopolitical tensions in the region that have contributed to both countries' woes.

This event will delve into what is at stake for those mobilizing in Iraq and Lebanon. Speakers will discuss the obstacles to meaningful reform and possible routes out of the current crises.

To attend this event, please e-mail Reni Zhelyazkova.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Webinar – Analysis: Protests in Iraq and Lebanon

Invitation Only Research Event

3 December 2019 - 2:30pm to 3:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Lina Khatib, Head, Middle East and North Africa Programme, Chatham House
Dr Renad Mansour, Research Fellow, Middle East and North Africa Programme, Chatham House

Over recent weeks, widespread popular protests have engulfed Iraq and Lebanon. What began as calls for reform in the context of high unemployment and endemic corruption have evolved into direct challenges to the existing political order in both countries. How have the ruling elites responded to the popular uprisings? What do these developments mean for the future of the two countries and the region more broadly?

Dr Lina Khatib and Dr Renad Mansour will discuss what is at stake for protesters and what are the obstacles to meaningful and sustainable reform in Iraq and Lebanon.

Please note this webinar is for Middle East and North Africa Programme supporters only and will be taking place online.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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The Middle East and North Africa Region in 2020

Invitation Only Research Event

15 January 2020 - 8:15am to 9:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Chair: Dr Lina Khatib, Director, Middle East and North Africa Programme, Chatham House

2019 was a turbulent year for the Middle East and North Africa. The region was swept by a wave of anti-government protests with popular unrest erupting across Algeria, Egypt, Lebanon, Iraq and Iran. Tensions in the Gulf escalated following clashes between Iran, Saudi Arabia and the United States. Nearly a decade after the Arab Spring, civil wars in Libya, Syria and Yemen continue to rage with little hope for political solutions to the crises.

At this breakfast briefing, Chatham House's Middle East and North Africa Programme researchers will discuss possible scenarios for the region in the year ahead. The experts will explore key trends relevant to the business community and will share insights from recent research trips and discussions with key stakeholders in the MENA region. 

Please note that participation in this event is only open to supporters of the Chatham House Middle East and North Africa Programme and selected guests.

Event attributes

Chatham House Rule

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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How Donald Trump’s Peace Plan Looks to the Gulf and Europe

19 February 2020

Dr Neil Quilliam

Associate Fellow, Middle East and North Africa Programme

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
Neil Quilliam and Reni Zhelyazkova examine how the GCC states and the EU have reacted to the US president’s proposed plan for Israeli-Palestinian peace.

2020-02-19-Gaza.jpg

Palestinians watch the televised press conference of Donald Trump and Benjamin Netanyahu on 28 January 2020 at a barber shop in Gaza City. Photo: Getty Images.

The view from the Gulf

Neil Quilliam

There has been no coordinated response among states of the GCC, but the messages have been universal, and surprisingly each one has welcomed US efforts to restart peace talks and praised this particular US administration for doing so. But in each case, the same set of issues and concerns has been highlighted, namely the status of Jerusalem, the situation of refugees and ultimately a simple absence of a revival contiguous Palestinian state.

While much has been made of younger Gulf generation’s apparent disconnect from the emotive issues around Palestinian statehood, the state of Jerusalem and the larger refugee issue, older leaders in the Gulf continue to pay them heed. And despite a desire to coordinate with Israel on matters of security, intelligence sharing and tech, they will not advance the relationship under the terms of the so-called ‘deal of the century’.

Put simply, the deal forces Palestinians to concede ground on all matters of importance. And should the Arab Gulf states sign up to it, they will be judged harshly by history for not only selling out Palestine for $50 billion, but also footing the bill. As such, they all feel compelled to hedge and pay salutary lip-service to US efforts but know quietly they will die on the vine and that the Arab Peace Initiative is the only viable framework for advancing talks.

Even younger leaders know that the greater risk will come from signing up to the deal rather than twitter wrath of the US president.

Kuwaiti Parliament Speaker Marzouq Al-Ghanim threw a copy in the bin, emphasizing that it ‘was born dead’ and ‘should be thrown in the dustbin of history’.

While the Saudi official position towards the deal was one of qualified support, the Saudi press reported that King Salman had spoken with Palestinian Authority President Mahmoud Abbas, who has rejected the plan, to ‘stress to him the Kingdom's steadfast position vis-à-vis the Palestinian cause and the rights of the Palestinian people’. The king reportedly added: ‘The Kingdom stands alongside the Palestinian people and supports its choices and what[ever] will actualize its hopes and aspirations.’

Turki Al-Faisal, the former Saudi intelligence chief, described the deal’s idea of a Palestinian state as ‘a brutal conception’ and the deal itself as a ‘modern-day Frankenstein’. ‘For Palestine, it is definitely a step back,’ Al-Faisal said. ‘[The Trump administration has] given up the legitimate history and weight of the United Nations Security Council resolutions and adopted a unilateral path.’

The view from Europe

Reni Zhelyazkova

The initial EU response to President Trump’s ‘Peace to Prosperity’ plan was one of caution. An official statement soon after the announcement declared that the proposal needs to be studied and assessed but only a few days later the EU’s High Representative for Foreign Affairs, Josep Borrell, condemned the plan for being out of line with internationally agreed parameters.

Some member states like Luxembourg have expressed support for the foreign policy chief’s position. Ireland, historically a strong supporter of the Palestinian cause, and Sweden, the only country to recognize the Palestinian state after becoming an EU member, have responded negatively to the US proposal, expressing concern over mentions of Israeli annexation of Palestinian land and stating that it falls short from previous international agreements.

Other EU countries, however, have been much more guarded in their reactions. Responses from Germany and France have so far been lukewarm – on the one hand, welcoming US attempts at re-igniting peace talks between Israelis and Palestinians, and, on the other, warning that any future negotiations and agreements must be carried out in accordance with internationally established parameters and legal frameworks.

A strong voice of support for Trump’s proposal was that of Hungary, whose minister of foreign affairs and trade, Péter Szijjártó, commended White House adviser Jared Kushner on the plan during a meeting in Washington last week. Other EU countries are yet to respond publicly to the proposal but unity among all EU countries is far from certain.

The EU’s official position is that a two-state solution based on pre-1967 borders and in line with previous agreements and UN resolutions is the only viable option for lasting peace between Israelis and Palestinians.

However, Israeli foreign policy under Netanyahu has focused on strengthening bilateral relations with countries in eastern and central Europe. Cooperation with Romania, Bulgaria, Greece, Croatia, Cyprus, Czech Republic, Estonia, Latvia, Lithuania and most recently Slovakia and Hungary has improved in all areas – from security and trade to tourism and cultural exchanges.

Five of these countries, namely, the Czech Republic, Slovakia, Hungary, Romania and Bulgaria recognized the State of Palestine prior to joining the EU, but the rise of populist nationalism, concerns over migration and terrorism, and improving relations with the Trump administration in the US have contributed to an alignment in views between Israel and the right-leaning governments in southern and eastern Europe, as well as those in Italy and Austria.

Improved bilateral relations have translated into political acts of good will towards Israel with a number of EU countries expressing support for Israel in the United Nations and other international forums. Austria, Romania, Hungary and the Czech Republic defied official EU position and attended the US embassy opening in Jerusalem in May 2018.

In this sense, Israel’s strategy in eastern and central Europe can be seen as a deliberate effort to break up consensus within the EU, and, ideally, reverse the bloc’s position towards the Middle East conflict, but also towards Iran. 

At a time when the EU is managing Brexit, a complex internal agenda, including arguments over the EU budget, and with its relationship with the US strained over Iran, trade and other issues, it is unlikely that the bloc will contribute significant efforts to the Middle East Peace Process. It is even more difficult to see the EU coming up with its own proposal and even less likely that all member states will be able to agree on such an initiative given internal divisions. 

Under the EU Neighbourhood Policy, the European Joint Strategy in Support of Palestine for the period 2017-20 has focused on supporting the Palestinian Authority (PA) with institutional reform, economic development and service delivery. Progress, however, has been limited as the success of programming is dependent on Israeli policy towards the West Bank and Gaza. This has hardened under Netanyahu, who enjoys the full support of the current US administration and sees the EU as biased towards the Palestinians. 

Any plan that replaces the 2017-20 joint strategy will most likely be a continuation of the current approach which focuses on conflict management and supporting the already crumbling two-state solution by keeping the PA alive. 

Some room for cautious hope remains, as much depends on the outcome of the Israeli election on 2 March and the US presidential election in November. Changes in leadership could open up space for EU to actively support the reinvigoration of peace talks and regain its relevance as a mediator in the Middle East Peace Process.




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Iran Workshop Series: Domestic, Regional and International Outlook

Invitation Only Research Event

17 December 2019 - 10:00am to 3:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

After a summer of regional tensions and continued uncertainty regarding the future of the JCPOA, the Chatham House MENA Programme held a closed workshop to examine the impact of the Trump administration’s maximum pressure campaign.

Discussions focused on the domestic developments and challenges inside Iran, prospects for new negotiations with Iran, and the regional issues facing the country. Participants also considered the differences between American and European approaches towards Iran.

 

Event attributes

Chatham House Rule

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Conflict and the Water Crisis in Iraq

Invitation Only Research Event

9 March 2020 - 9:00am to 10:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Azzam Alwash, Founder & CEO, Nature Iraq
Peter Schwartzstein, Independent Journalist; Non-Resident Fellow, Centre for Climate Security
Discussant: Dr Jehan Baban, Founder & President, The Iraqi Environment and Health Society-UK
Chair: Dr Glada Lahn, Senior Research Fellow, Energy, Environment and Resources Department, Chatham House

Water is a critical issue for Iraq’s future stability and prosperity. Only a few decades ago, the country was one of the most fertile in the region, with two major rivers flowing through it. Today, national and transboundary pollution, mismanagement, and debilitating cycles of conflict have contributed to a situation where only half of current water needs are being met, and where an 80% reduction in the flow of water down the Tigris and Euphrates rivers has led to the loss of millions of acres of formerly productive land and the displacement of rural communities.

Water scarcity can be a driver of violence and conflict. Tribal conflicts over water sources have erupted sporadically in the south and the contamination of municipal water which led to the hospitalization of some 118,000 citizens was a trigger for the large-scale protests in Basra in late 2018. Without concerted action by national and local governments, companies and international agencies, the situation will only worsen as higher temperatures and reduced rainfall drive rural-to-urban migration and increase the risk of drought, food insecurity and water-related diseases.

At this roundtable, part of the Chatham House Iraq Initiative, experts will discuss the domestic, regional and international factors that continue to exacerbate the water crisis in Iraq, and propose solutions, including technical innovation, public sector capacity-building and greater international cooperation, that might contribute to effective state-building, build resilience to the effects of climate change and reduce the risk of further conflict.

Event attributes

Chatham House Rule

Georgia Cooke

Project Manager, Middle East and North Africa Programme
+44 (0)20 7957 5740




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Expanding Sino–Maghreb Relations: Morocco and Tunisia

26 February 2020

Over the past two decades, China has increased its presence in North Africa in terms of trade and investment. This paper looks at China’s policy within the context of its Africa and Middle East policies to better understand its approach to Morocco and Tunisia.

Yahia H. Zoubir

Senior Professor of International Studies, KEDGE Business School, France and Visiting Fellow, Brookings Doha Center

2020-02-26-Xi-Jinping-King-Mohammed.jpg

Chinese President Xi Jinping and King Mohammed VI of Morocco wave during a welcoming ceremony outside the Great Hall of the People in Beijing on 11 May 2016. Photo: Getty Images.

Summary

  • China’s presence in the Maghreb has increased in recent years, raising concerns among Western powers. China has focused on bilateral relations with these countries while also working within the Forum on China–Africa Cooperation (FOCAC) and the China–Arab States Cooperation Forum (CASCF). However, this engagement has limited strategic value compared to relations China has with Saudi Arabia or the United Arab Emirates.
  • Since the launch of the Belt and Road Initiative (BRI) in 2013, China has shown greater interest in the Maghreb as an entry point to European and African markets. China has pursued commercial relations over political influence in the region. Morocco and Tunisia are still dependent on France, their former colonial power, and the European Union, which exert great political, economic, security and cultural influence over the two countries.
  • The Maghreb countries’ economic relations with China have grown exponentially, with Algeria forming the closest relationship. However, Morocco and Tunisia are keen to attract China’s investment and involvement in major construction and infrastructure projects to boost industrial and economic development. While China’s investments in Morocco and Tunisia remain at a low level, trade relations with both countries have grown steadily. Politically, China’s policy of noninterference in domestic affairs appeals to Maghreb states, which resent Western interference.
  • China’s influence in the Maghreb remains minimal. Its soft power push has struggled to promote advantages of strong relations with China beyond economics. Furthermore, Morocco and Tunisia’s populations have generally scant knowledge about China’s politics and culture. China has tried to address this lack of familiarity through the establishment of Confucius Institutes and other cultural activities. However, language and cultural barriers still impede the development of close relations, compared to those China has with other countries in Africa.




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POSTPONED: The Development of Libyan Armed Groups since 2014: Community Dynamics and Economic Interests

Invitation Only Research Event

18 March 2020 - 9:00am to 10:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Abdul Rahman Alageli, Associate Fellow, MENA Programme, Chatham House
Emaddedin Badi, Non-Resident Scholar, Middle East Institute
Tim Eaton, Senior Research Fellow, MENA Programme Chatham House
Valerie Stocker, Independent Researcher

Since the overthrow of the regime of Muammar Gaddafi in 2011, Libya’s multitude of armed groups have followed a range of paths. While many of these have gradually demobilized, others have remained active, and others have expanded their influence. In the west and south of the country,  armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks.

In the east, the Libyan Arab Armed Forces projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will need to address the fears, grievances and desires of the surrounding communities, even while the development of armed groups’ capacities dilutes their accountability to those communities.

This roundtable will discuss the findings of a forthcoming Chatham House research paper, ‘The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests’, which presents insights from over 200 interviews of armed actors and members of local communities and posits how international policymakers might seek to curtail the continued expansion of the conflict economy.

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Event attributes

Chatham House Rule

Georgia Cooke

Project Manager, Middle East and North Africa Programme
+44 (0)20 7957 5740




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The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests

17 March 2020

This paper explores armed group–community relations in Libya and the sources of revenue that have allowed armed groups to grow in power and influence. It draws out the implications for policy and identifies options for mitigating conflict dynamics.

Tim Eaton

Senior Research Fellow, Middle East and North Africa Programme

Abdul Rahman Alageli

Associate Fellow, Middle East and North Africa Programme

Emadeddin Badi

Policy Leader Fellow, School of Transnational Governance, European University Institute

Mohamed Eljarh

Co-founder and CEO, Libya Outlook

Valerie Stocker

Researcher

Amru_24-2_13.jpg

Fighters of the UN-backed Government of National Accord patrol in Ain Zara suburb in Tripoli, February 2020. Photo: Amru Salahuddien

Summary

  • Libya’s multitude of armed groups have followed a range of paths since the emergence of a national governance split in 2014. Many have gradually demobilized, others have remained active, and others have expanded their influence. However, the evolution of the Libyan security sector in this period remains relatively understudied. Prior to 2011, Libya’s internal sovereignty – including the monopoly on force and sole agency in international relations – had been personally vested in the figure of Muammar Gaddafi. After his death, these elements of sovereignty reverted to local communities, which created armed organizations to fill that central gap. National military and intelligence institutions that were intended to protect the Libyan state have remained weak, with their coherence undermined further by the post-2014 governance crisis and ongoing conflict. As a result, the most effective armed groups have remained localized in nature; the exception is the Libyan Arab Armed Forces (LAAF), which has combined and amalgamated locally legitimate forces under a central command.
  • In the west and south of the country, the result of these trends resembles a kind of inversion of security sector reform (SSR) and disarmament, demobilization and reintegration (DDR): the armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks; and have continued to arm, mobilize and integrate themselves into the state’s security apparatus without becoming subservient to it. In the eastern region, the LAAF projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. The LAAF has co-opted social organizations to dominate political and economic decision-making.
  • The LAAF has established a monopoly over the control of heavy weapons and the flow of arms in eastern Libya, and has built alliances with armed groups in the east. Armed groups in the south have been persuaded to join the LAAF’s newly established command structure. The LAAF’s offensive on the capital, which started in April 2019, represents a serious challenge to armed groups aligned with the Tripoli-based Government of National Accord (GNA). The fallout from the war will be a challenge to the GNA or any future government, as groups taking part in the war will expect to be rewarded. SSR is thus crucial in the short term: if the GNA offers financial and technical expertise and resources, plus legal cover, to armed groups under its leadership, it will increase the incentive for armed groups to be receptive to its plans for reform.
  • Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will necessarily rely on addressing the fears, grievances and desires of the surrounding communities. Yet the development of armed groups’ capacities, along with their increasing access to autonomous means of generating revenue, has steadily diluted their accountability to local communities. This process is likely to be accelerated by the ongoing violence around Tripoli.
  • Communities’ relationship to armed groups varies across different areas of the country, reflecting the social, political, economic and security environment:
  • Despite their clear preference for a more formal, state-controlled security sector, Tripoli’s residents broadly accept the need for    the presence of armed groups to provide security. The known engagement of the capital’s four main armed groups in criminal activity is a trade-off that many residents seem able to tolerate, providing that overt violence remains low. Nonetheless, there is a widespread view that the greed of Tripoli’s armed groups has played a role in stoking the current conflict.
  • In the east, many residents appear to accept (or even welcome) the LAAF’s expansion beyond the security realm, provided that it undertakes these roles effectively. That said, such is the extent of LAAF control that opposition to the alliance comes at a high price.
  • In the south, armed groups draw heavily on social legitimacy, acting as guardians of tribal zones of influence and defenders of their respective communities against outside threats, while also at times stoking local conflicts. Social protections continue to hold sway, meaning that accountability within communities is also limited.
  • To varying extents since 2014, Libya’s armed groups have developed networks that enmesh political and business stakeholders in revenue-generation models:
  • Armed groups in Tripoli have compensated for reduced financial receipts from state budgets by cultivating unofficial and illicit sources of income. They have also focused on infiltrating state institutions to ensure access to state budgets and contracts dispersed in the capital.
  • In the east of the country, the LAAF has developed a long-term strategy to dominate the security, political and economic spheres through the establishment of a quasi-legal basis for receiving funds from Libya’s rival state authorities. It has supplemented this with extensive intervention in the private sector. External patronage supports military operations, but also helps to keep this financial system, based on unsecured debt, afloat.
  • In the south, limited access to funds from the central state has spurred armed groups to become actively involved in the economy. This has translated into the taxation of movement and the imposition of protection fees, particularly on informal (and often illicit) activity.
  • Without real commitment from international policymakers to enforcing the arms embargo and protecting the economy from being weaponized, Libya will be consigned to sustained conflict, further fragmentation and potential economic collapse. Given the likely absence of a political settlement in the short term, international policymakers should seek to curtail the continued expansion of the conflict economy by reducing armed groups’ engagement in economic life.
  • In order to reduce illicit activities, international policymakers should develop their capacity to identify and target chokepoints along illicit supply chains, with a focus on restraining activities and actors in closest proximity to violence. Targeted sanctions against rent maximizers (both armed and unarmed) is likely to be the most effective strategy. More effective investigation and restraint of conflict economy actors will require systemic efforts to improve transparency and enhance the institutional capacity of anti-corruption authorities. International policymakers should also support the development of tailored alternative livelihoods that render conflict economy activities less attractive.




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Webinar: Can the Justice and Development Party Still Absorb Popular Anger in Morocco?

Webinar Research Event

8 April 2020 - 1:00pm to 2:00pm

Event participants

Mohammed Masbah, Director, Moroccan Institute for Policy Analysis; Associate Fellow, MENA Programme, Chatham House
Moderator: Lina Khatib, Director, MENA Programme, Chatham House

Ever since independence, the Moroccan monarchy has used political parties to legitimize the country’s authoritarian political process and structure, and to absorb social and political anger. The palace puts successive governments and other elected institutions, such as local and regional councils, at the frontline of public blame, and replaces them once they fail this function.

In a recent article, MENA Programme Associate Fellow, Mohammed Masbah, examines how the Moroccan monarchy has used this strategy with the ruling Justice and Development Party (PJD) so that the palace remains the centre of political power, while the PJD – and other political parties before it– takes responsibility for coping with the mounting socio-economic crisis.

In this webinar, part of the Chatham House project on The Future of the State in the Middle East and North Africa, the article’s author will discuss the risks this approach presents for the long-term stability of Morocco and what reforms are needed to increase citizens’ dwindling confidence in the political process.

You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful.




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Webinar: The Environmental Crisis in the MENA Region – Impacts and Mitigation

Research Event

16 April 2020 - 11:30am to 12:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Glada Lahn, Senior Research Fellow, Energy, Environment and Resources Programme, Chatham House
Greg Shapland, Associate Fellow, Middle East and North Africa Programme, Chatham House 
Moderator: Sanam Vakil, Deputy Director and Senior Research Fellow, Middle East and North Africa Programme, Chatham House

The event will be livestreamed on the MENA Programme Facebook page.

Climate and environmental issues have largely been marginalized in discussions about the Middle East and North Africa region and yet are critical to peace and security. In this webinar, experts will explore mounting pressures including those related to water (reduced, less reliable and more polluted sources), extreme temperatures, air pollution, land degradation and sea-level rise. Panelists will discuss the potential impact of worsening environmental conditions and what the region's governments can do to protect the health and livelihoods of their peoples.

This webinar is part of the Chatham House MENA Programme's Online Event Series and will be held on the record.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Can Morocco Effectively Handle the COVID-19 Crisis?

6 April 2020

Dr Mohammed Masbah

Associate Fellow, Middle East and North Africa Programme

Anna Jacobs

Senior Research Assistant, Brookings Doha Center
The Moroccan government is capitalizing on a burst of unity, social solidarity and public support in the face of a crisis. However, if it fails to effectively mitigate the public health and economic impacts of the COVID-19 pandemic, this spirit of solidarity and cooperation will not last long.

GettyImages-1208907580.jpg

A general view of empty stores during curfew as a precaution against the new type of coronavirus (COVID-19) in Rabat, Morocco on 1 April 2020. Photo by Jalal Morchidi/Anadolu Agency via Getty Images.

In Morocco, the COVID-19 pandemic has increased public trust in government, but people still have doubts about the effectiveness of the healthcare system. According to a recent study conducted by the Moroccan Institute for Policy Analysis (MIPA), the majority of Moroccans surveyed are generally satisfied with the measures taken by the government to battle the coronavirus. However, the same survey also shows that Moroccans do not have confidence in the healthcare sector’s ability to respond to this pandemic.

The positive perceptions of the government’s response can be explained by the swift and strict measures enacted. King Mohammed VI held a high-level meeting with the prime minister, the minister of health, and top security officials on 17 March and a few days later, on 20 March, the Moroccan government declared a state of health emergency and began to implement aggressive measures to contain the virus.

This has included closing airports, schools, mosques, cafés and shops – with the exception of food markets – preventing large gatherings, as well as strict guidelines to ensure social distancing. As of 2 April, nearly 5000 people have been arrested for violating the state of health emergency.

In order to address urgent medical needs and to mitigate the economic impact of the pandemic, the King ordered the creation of an emergency fund, raising more than 32.7 billion Moroccan Dirhams ($3.2 billion). The Ministry of Finance will begin to make cash transfers to vulnerable citizens, and especially those who have lost their jobs. However, the stipulations surrounding these cash transfers will be decided in the coming weeks.

Updates about the virus are communicated daily by the Ministry of Health, despite growing criticism of its communication strategy. As of 4 April, Moroccan authorities have confirmed 883 cases and 58 deaths.

Call for national unity

In times like these, there is a call for unity in the face of a national and global crisis, and opposition groups such as Adl wal Ihssan and Rif activists have expressed their support for government measures and have encouraged people to follow the new guidelines and restrictions. However, despite calls to release political prisoners, Moroccan authorities have not indicated that they will do so. This is a missed opportunity vis-à-vis the opposition because it could have served as a way to further strengthen national unity during the crisis.

These are all promising signs and point to what is likely to be a short-term burst in unity and institutional trust. However, the institutional weaknesses in governance and the healthcare system have not disappeared, which is why this increase in institutional trust should be taken with a grain of salt.

Public trust issues

This pandemic poses tremendous challenges for governments across the globe, and this holds especially true for states in the Middle East and North Africa region, where citizens do not approve of government performance and do not trust key state institutions. The 2019 Arab Barometer survey found that Moroccans do not trust most of the country’s political institutions (notably the parliament and the Council of Ministers) and the level of satisfaction with the government’s performance remains extremely low.

On the public health front, as shown in two of MIPA’s recent surveys, trust in the healthcare system is also very low. Around three-quarters of those surveyed do not trust Moroccan hospitals, highlighting the acute structural problems in the healthcare system. In fact, there is a stark divide between private and public healthcare, as well as a huge gap in access to healthcare facilities between urban and rural areas. Most of the country’s hospitals and doctors are located in major urban areas and the only three laboratories with capabilities for COVID-19 testing are located in Rabat and Casablanca, but even there, testing capacity is very limited.

Similar to other countries, there could be a major shortage of doctors and medical equipment throughout Morocco. So far, the Ministry of Finance has said that 2 billion dirhams of the emergency fund will go towards purchasing medical equipment such as beds, ventilators, tests, prevention kits and radiology equipment, but the timeline remains unclear.

A vulnerable economy

There is significant concern about the medium- and long-term economic impact of the virus. Two of the country’s key economic sectors have already been hit hard: agriculture and tourism. The agricultural sector was already struggling due to the impact of drought, while the coronavirus pandemic is likely to impact Morocco’s tourism industry not just this year, but well into 2021. In terms of government response, the emergency fund is a strong start, but questions surrounding the management of these funds have already been raised.

The most vulnerable parts of the population have been affected by the economic crisis because of the country’s bulging informal sector – in which most people work - and a very weak private sector. In fact, two-thirds of the workforce are not covered by a pension plan, almost half of the working population does not currently benefit from medical coverage and there is no social care system for vulnerable parts of the population. As of 1 April, more than 700,000 workers have lost their jobs.

Moving forward?

Even if public perceptions of the government’s response are positive at the moment, this is most likely a short-term surge that should not be taken for granted. Despite the efforts made by the government, Morocco’s health system is not equipped to handle this crisis. Even with the new measures that have been implemented, if the spread of the virus gets out of control, more funds, more doctors, and more equipment will be needed. Given the structural weaknesses of the healthcare system, this will be an uphill battle.

Moreover, even if the government manages to mitigate the public health impact, the economic consequences will be dire—especially in the tourism industry—and will severely hurt those workers in the informal sector who are living without a safety net. In Morocco, this category represents most of the working population.

This crisis highlights that the Moroccan government must urgently tackle its large portfolio of unfinished reforms, notably in healthcare, the economy, and labour rights. So far, the government is capitalizing on the spirit of unity, social solidarity and public support. The future trajectory of the pandemic and the effectiveness of governance will determine if this spirit of solidarity will last. If the government fails to effectively mitigate the public health and economic impacts of this pandemic, this solidarity and cooperation will not last long.




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COVID 19: Assessing Vulnerabilities and Impacts on Iraq

7 April 2020

Dr Renad Mansour

Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative

Dr Mac Skelton

Director, Institute of Regional and International Studies (IRIS), American University of Iraq, Sulaimani; Visiting Fellow, Middle East Centre, London School of Economics

Dr Abdulameer Mohsin Hussein

President of the Iraq Medical Association
Following 17 years of conflict and fragile state-society relations, the war-torn country is particularly vulnerable to the pandemic.

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Disinfecting shops in Baghdad's Bayaa neighbourhood as a preventive measure against the spread of COVID-19. Photo by AHMAD AL-RUBAYE/AFP via Getty Images.

Iraq is a country already in turmoil, suffering fallout from the major military escalation between the US and Iran, mass protests calling for an end to the post-2003 political system, and a violent government crackdown killing more than 600 and wounding almost 30,000 - all presided over by a fragmented political elite unable to agree upon a new prime minister following Adil abd al-Mehdi’s resignation back in November.

COVID-19 introduces yet another threat to the fragile political order, as the virus exposes Iraq’s ineffective public health system dismantled through decades of conflict, corruption and poor governance.

Iraqi doctors are making every effort to prepare for the worst-case scenario, but they do so with huge structural challenges. The Ministry of Health lacks enough ICU beds, human resources, ventilators, and personal protective equipment (PPE). Bogged down in bureaucracy, the ministry is struggling to process procurements of equipment and medications, and some doctors have made purchases themselves.

But individual efforts can only go so far as many Iraqi doctors are concerned the official numbers of confirmed COVID-19 cases do not reflect the complexity of the situation on the ground.

The ministry relies predominately upon patients self-presenting at designated public hospitals and has only just begun community-based testing in areas of suspected clusters. Reliance on self-presentation requires a level of trust between citizens and state institutions, which is at a historic low. This gap in trust – 17 years in the making – puts Iraq’s COVID-19 response particularly at risk.

Iraq’s myriad vulnerabilities

Certain social and political factors leave Iraq uniquely exposed to the coronavirus. The country’s vulnerability is tied directly to its social, religious and economic interconnections with Iran, an epicenter of the pandemic.

Exchanges between Iran and Iraq are concentrated in two regions, with strong cross-border links between Iraqi and Iranian Kurds in the north-east, and Iraqi and Iranian Shia pilgrims in the south. Cross-border circulation of religious pilgrims is particularly concerning, as they can result in mass ritual gatherings.

The high number of confirmed cases in the southern and northern peripheries of the country puts a spotlight on Iraq's failure in managing healthcare. The post-2003 government has failed to either rebuild a robust centralized healthcare system, or to pave the way for a federalized model.

Caught in an ambiguous middle between a centralized and federalized model, coordination across provinces and hospitals during the coronavirus crisis has neither reflected strong management from Baghdad nor robust ownership at the governorate level.

This problem is part of a wider challenge of managing centre-periphery relations and federalism, which since 2003 has not worked effectively. Baghdad has provided all 18 provinces with instructions on testing and treatment, but only a handful have enough resources to put them into practice. Advanced testing capacity is limited to the five provinces with WHO-approved centers, with the remaining 13 sending swabs to Baghdad.

But the greatest challenge to Iraq’s COVID-19 response is the dramatic deterioration of state-society relations. Studies reveal a profound societal distrust of Iraq’s public healthcare institutions, due to corruption and militarization of medical institutions. Numerous videos have recently circulated of families refusing to turn over sick members - particularly women - to medical teams visiting households with confirmed or suspected cases.

As medical anthropologist Omar Dewachi notes, the ‘moral economy of quarantine’ in Iraq is heavily shaped by a history of war and its impact on the relationship between people and the state. Although local and international media often interpret this reluctance to undergo quarantine as a matter of social or tribal norms, distrusting the state leads many families to refuse quarantine because they believe it resembles a form of arrest.

The management of coronavirus relies upon an overt convergence between medical institutions and security forces as the federal police collaborate with the Ministry of Health to impose curfews and enforce quarantine. This means that, troublingly, the same security establishment which violently cracked down on protesters and civil society activists is now the teeth behind Iraq’s COVID-19 response.

Without trust between society and the political class, civil society organizations and protest movements have directed their organizational structure towards awareness-raising across Iraq. Key religious authorities such as Grand Ayatollah Sistani have called for compliance to the curfew and mobilized charitable institutions.

However, such efforts will not be enough to make up for the lack of governance at the level of the state. In the short-term, Iraq’s medical professionals and institutions are in dire need of technical and financial support. In the long-term, COVID-19 is a lesson that Iraq’s once robust public healthcare system needs serious investment and reform.

COVID-19 may prove to be another catalyst challenging the ‘muddle through’ logic of the Iraqi political elite. International actors have largely been complicit in this logic, directing aid and technical support towards security forces and political allies in the interest of short-term stability, and neglecting institutions which Iraqis rely on for health, education, and well-being.

The response to the crisis requires cooperation and buy-in of a population neglected by 17 years of failed governance. This is a seminal event that may push the country to the brink, exposing and stirring underlying tensions in state-society relations.

This analysis was produced as part of the Iraq Initiative.




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COVID-19 and the Iranian Shadows of War

8 April 2020

Dr Sanam Vakil

Deputy Director and Senior Research Fellow, Middle East and North Africa Programme
Coronavirus has plunged Iran into the country’s biggest crisis since its war with Iraq. More than 30 years later, the lingering effects of the war are shaping Iran’s reaction to the pandemic.

2020-04-08-Iran-COVID-Tehran

Spraying disinfectant at Tajrish bazaar in Tehran, Iran, during the coronavirus pandemic in March 2020. Photo by Majid Saeedi/Getty Images.

In the face of the COVID-19 pandemic, many global leaders have invoked war analogies – from the Pearl Harbor attack to the collective spirit on display during the Second World War – to highlight past lessons learned or rally their populations.

For Iran’s leadership, more recent war analogies hold resonance and help explain the ideological and political conundrum limiting an effective COVID-19 response. While the Islamic Republic has weathered a multitude of challenges, COVID-19 is putting unprecedented strain on Iran’s already fragile, heavily-sanctioned economy and further exposing domestic political fissures amid ongoing international tensions.

Iran has been identified as the regional epicentre of the pandemic with a steadily rising number of deaths, including several of the country’s political and military elite. Yet the Iranian government has not evoked the collective memory of the war as an opportunity for national resistance and mobilization.

Sluggish and poorly managed

This is unsurprising, because thus far the Iranian government’s response to COVID-19 has been sluggish and poorly managed. After an initial slow response, Iran then attempted to downplay the impact of the virus, covering up the number of cases and deaths and blaming the United States, before implementing a poorly coordinated action plan marred by government infighting.

For the Iranian leadership, the Iran-Iraq war has been the single most influential and defining period – it has impacted its political ideology, domestic and security policies and international relations. More than half a million Iranians died, and a paranoid worldview and sense of isolation was cemented among many elite leaders such as Supreme Leader Ali Khamenei.

The war created a valiant culture of leadership from Qassem Soleimani to presidents Mahmoud Ahmadinejad and Hashemi Rafsanjani and, over time, has resulted in the development of Iran’s asymmetrical defense capabilities.

The war enabled a dark purge of political opponents and the gradual birth of Iran’s reformist faction, all while the ethos of sacrifice and martyrdom was linked to the collective notions of resistance.

These would be carried forward in other resistance campaigns both regional and economic. Most defining was Ayatollah Khomeini’s infamous 1988 decision to ‘drink the poisoned chalice’ and end the long war. Three decades later, Iran continues to contend with those outcomes.

To acknowledge that the COVID-19 crisis could have equally profound consequences would add further pressure to the Islamic Republic at a time of incomparable vulnerability. Even before this crisis, the Iranian government linked sanctions to economic warfare, making future negotiations conditional on sanctions relief.

Iranian hardliners used the opportunity to promote Iran’s subsistence-based resistance economy designed to insulate Iran’s economy from external shocks such as sanctions. While both groups recognize the economic urgency, their contending strategies help explain the muddled government response and the ongoing ideological competition between the political elites.

Rouhani has argued that a full lockdown of the Iranian economy is impossible because it is already under significant strain from sanctions - the Iranian economy experienced a 9.5% contraction in 2019 and is expected to worsen in the coming year.

That said, through Iran’s New Year holidays the government did take action to slow the spread of the virus, discouraging travel and shutting schools, pilgrimage sites and cancelling Friday prayers. Finally, on 4 April, after receiving permission from Khamenei to do so, Rouhani withdrew $1 billion from Iran’s National Development Fund and is distributing the money through loans and credits to 23 million households.

Aid from a number of Iran’s parastatal agencies was also announced. Conversely, in his annual New Year’s speech the supreme leader securitized the crisis by laying blame on the United States for spreading the virus as a form of biological terrorism. Iran’s army chief of staff Major General Bagheri was tasked with building hospitals and the Islamic Revolution Guard Corps given authority to clear the streets.

The recent expulsion of Médecins Sans Frontières from Iran highlights the mix of paranoia and resistance culture still on display. US sanctions on Iran have significantly weakened Iran’s economy and limited Tehran’s ability to purchase much needed medical supplies and equipment. Unable to access its foreign reserves due to sanctions, the Rouhani government has applied for a $5 billion loan from the IMF.

European countries alongside a number of US members of congress have appealed to the Trump administration to ease sanctions on humanitarian grounds. While Washington continues to pursue its steadfast approach, referring to Iran’s campaign as a ‘sanctions relief scam’, Germany, France, and the UK have offered $5 million in aid and launched INSTEX – a trading mechanism designed to circumvent sanctions to allow non-sanctioned humanitarian trade.

The impact of coronavirus on Iranian society remains to be seen. But the impact of sanctions has placed heavy economic and psychological burden on the people. Feeling abandoned by the Iranian state and the United States could produce a mix of contradictory nationalistic and independent impulses.

The social contract – already fragile amid protests and government repression – reveals declining trust. Without national mobilization and calls for unity reminiscent of the war period, Iranians have stepped in, highlighting the continued resilience of civil society. Support for the medical establishment has been celebrated throughout the country and on social media. Charities, the private sector - through one initiative known as Campaign Nafas (Breathe) - and diaspora groups have initiated fundraising drives and assistance measures.

Iran’s relations with the international community, and specifically the United States, remain an unresolved consequence of the war. The 2015 Iranian nuclear agreement was the closest Tehran and Washington came to resolving decades of tensions, containment and sanctions.

COVID-19 has further heightened the trajectory of tensions between Tehran and Washington suggesting that any new deal, while necessary, is not on the cards. Tit-for-tat military exchanges have been on the rise in Iraq and Yemen while American and Iranian leaders issue threats and warnings of potential escalation.

Abdullah Nasseri, an advisor to Iran’s reformists, recently stated that in order to manage the coronavirus crisis, the Iranian government needed to make a decision akin to the 1988 United Nations resolution 598 that ended war hostilities. Ayatollah Khomeini famously commented on that ceasefire, stating: ‘Happy are those who have departed through martyrdom. Unhappy am I that I still survive.… Taking this decision is more deadly than drinking from a poisoned chalice. I submitted myself to Allah's will and took this drink for His satisfaction’. 

While a similar compromise today might appear deadly to the political establishment, it is clear that a paradigm shift away from the shadows of Iran’s last war is urgently needed to manage the challenges stemming from COVID-19.




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Webinar: Are the Gulf Standoffs Resolvable?

Research Event

21 April 2020 - 1:00pm to 2:00pm

Event participants

David Roberts, Assistant Professor and School of Security Studies Lead for Regional Security and Development, King's College London
Kristian Coates Ulrichsen, Associate Fellow, Middle East and North Africa Programme, Chatham House
Chair: Sanam Vakil, Deputy Director and Senior Research Fellow, Middle East and North Africa Programme, Chatham House

This webinar, part of the MENA Programme Webinar Series, will examine the trajectory of political and security dynamics in the Gulf in view of the ongoing rift within the Gulf Cooperation Council (GCC), the death of Sultan Qaboos in Oman, the escalation of tensions between Iran and the United States, and the COVID-19 crisis.

Speakers will explore the orientation of the GCC under a new Secretary-General and the prospects for mediation between Qatar and its neighbours, the future of Omani domestic and foreign policy under Sultan Haitham bin Tariq Al Said, eventual transitions to new leadership in Bahrain and Kuwait, and whether the impact of COVID-19 may help replace the confrontation within the GCC with closer coordination among its six member states.

The webinar will be livestreamed on the MENA Programme Facebook page.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Webinar: Reimagining the Role of State and Non-State Actors in (Re)building National Health Systems in the Arab World

Research Event

22 April 2020 - 1:00pm to 2:00pm

Event participants

Fadi El-Jardali, Professor of Health Policy and Systems, American University of Beirut
Moderator: Nadim Houry, Executive Director, Arab Reform Initiative

As new cases of COVID-19 continue to surge, countries around the world struggle to mitigate the public health and economic effects of the virus. It is becoming increasingly clear that an effective pandemic response requires a whole-of-government, whole-of-society approach. In the Arab world, where health systems are already strained by armed conflicts and displaced populations, a whole-of-society response to the pandemic is particularly critical as countries have become increasingly dependent on non-state actors, notably the private sector, for healthcare provision and any response that includes the state alone may not be sufficient to address the pandemic.

In a recent article, Fadi El-Jardali, argued that while the pandemic will have grave health and economic consequences for years to come, it brings with it a valuable opportunity to re-envision the role of state and non-state actors in strengthening health systems. The article addressed the need for increased collaboration between state and non-state actors, and the rethinking of existing cooperation models to provide quality healthcare services for all.  

In this webinar, part of the Chatham House project on the future of the state in the Middle East and North Africa, Dr El-Jardali will discuss how state and non-state actors can collaborate more effectively to address the shortcomings of national health care systems amidst the pandemic and beyond. The article’s author will share insights on the different capacities available in Arab societies that governments can draw upon to ensure that Universal Health Coverage, equity considerations and social justice are at the core of health systems.

You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.

 

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Egypt and the Gulf: Allies and Rivals

20 April 2020

There is and will continue to be an edge of rivalry in Egypt’s relations with the dominant Gulf Arab powers. This paper will focus primarily on the Egypt–Gulf relationship during the Sisi era.

David Butter

Associate Fellow, Middle East and North Africa Programme

2020-04-20-Egypt-Gulf.jpg

Crown Prince of Abu Dhabi Mohammed bin Zayed is welcomed by Egypt’s President Abdel-Fattah el-Sisi in Cairo on 19 June 2017. Photo: Getty Images.

Summary

  • Egypt and the Gulf Arab region have long been important poles of political, military economic and cultural power and influence in the Middle East. Under the presidency of Gamal Abdel-Nasser, Egypt was the dominant force in the region, but the balance of power shifted towards the Gulf in the 1970s, as Egypt’s economy faltered and the Gulf Arab states reaped the benefits of resurgent oil prices in the wake of the 1973 OPEC embargo. The popular uprising against President Hosni Mubarak’s regime in 2011 elicited divergent reactions in the Gulf. The leaders of Saudi Arabia and the United Arab Emirates (UAE) were concerned about the risks of a movement for revolutionary change spreading to their own region, while Qatar saw an opportunity to strengthen its regional role through supporting the Muslim Brotherhood.
  • The forcible removal of Egypt’s elected president, Mohammed Morsi of the Muslim Brotherhood, in July 2013 by the army commander, Abdel-Fattah el-Sisi, ushered in a new era in Egypt–Gulf relations. The UAE, Saudi Arabia and Kuwait quickly mobilized financial support for the new administration. Abu Dhabi’s crown prince, Mohammed bin Zayed, known for his intense opposition to the Muslim Brotherhood, signalled his strong support for the new regime by visiting Cairo only weeks after hundreds of Morsi’s supporters were killed.
  • Between July 2013 and August 2016, the UAE, Saudi Arabia and Kuwait provided about $30 billion in aid to the Sisi regime through placing deposits with the Central Bank of Egypt and supplying petroleum products as grants. The UAE sought to link its aid to a programme of economic reforms, but the Egyptian government finally decided in mid-2016 to negotiate a loan agreement with the International Monetary Fund (IMF). Since the signing of the $12 billion loan with the IMF in November 2016, Egypt has no longer been reliant on Gulf Arab financial support, although some of the deposits placed previously have been rolled over on reaching maturity.
  • During the Sisi era, Egypt has benefited from its economic links to the Gulf over a wide spectrum of activities. The UAE and Saudi Arabia in particular are increasingly important export markets for Egyptian companies, as well as major sources of foreign direct investment. The financial aid provided by Sisi’s Gulf allies in 2013–16 has also helped to underpin the surge in Egypt’s arms procurement. Another critical element in the economic relationship is the presence of millions of expatriate Egyptian workers in the Gulf, who are responsible for a large share of the annual inflow of about $25 billion in remittances.
  • Egypt’s most important political relationships in the Gulf have been with Saudi Arabia and the UAE. Ties with Saudi Arabia were affected by the death of King Abdullah at the start of 2015 and by the subsequent emergence of Mohammed bin Salman as the most influential figure in the kingdom. During a visit by King Abdullah’s successor, King Salman, to Cairo in April 2016, Egypt announced a decision to cede sovereignty over two Red Sea islands, Tiran and Sanafir, to Saudi Arabia. Relations soured after this decision was challenged in the Egyptian courts, but the issue was resolved in favour of the deal. Egypt played no active role in the Saudi- and UAE-led intervention in Yemen, but joined its two principal Gulf allies and Bahrain in imposing sanctions on Qatar in mid-2017. 
  • Relations between Sisi and Crown Prince Mohammed bin Zayed have remained close throughout the past seven years. The UAE and Egypt have been among the most important external supporters of the Libyan National Army, commanded by Field Marshal Khalifa Haftar, although they have not created an overt alliance in this arena. Egypt has adopted a more prominent diplomatic profile in relation to Libya, while the UAE has been more deeply engaged militarily, to judge from assessments by the panel of experts tasked to monitor adherence to the UN embargo on the supply of weapons to Libya. The relationship between the Egyptian and Emirati leaders is underpinned by a strong shared ideological antipathy to the Muslim Brotherhood.
  • Following the completion of the IMF programme in 2019, the Egyptian economy is in a much stronger position than it was in the early period of Sisi’s rule, even though this has exacted a harsh toll on the 60 per cent of the population classified by the World Bank as poor or vulnerable. There is no pressing need for direct financial support from the Gulf, but Egypt still depends on economic linkages through trade, investment, tourism and remittances. In this respect, the balance of power has tilted marginally back towards Egypt. However, Egypt is still beset by deep internal political contradictions, as reflected in the regime’s heavy reliance on coercion and repression, and the economy remains vulnerable to external shocks – of which the coronavirus pandemic is a prime example.




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Webinar: Egypt and the Gulf: Allies and Rivals

Research Event

23 April 2020 - 1:00pm to 2:00pm

Event participants

Speaker: David Butter, Associate Fellow, Middle East and North Africa Programme, Chatham House
Moderator: Mohamed El Dahshan, Associate Fellow, Middle East and North Africa Programme, Chatham House

The webinar will be livestreamed on the MENA Programme Facebook page.

Egypt and the Gulf Arab region have long been important poles of political, military, economic and cultural power and influence in the Middle East. A recently published Chatham House paper examines the strategic and economic relationship between Egypt and the Gulf, focusing in particular on the period since Abdel-Fattah el-Sisi came to power in Egypt. Author David Butter offers a detailed evaluation of these economic relationships, in the broader context of a strategic alliance that, since 2013, has been informed by a common commitment between Egypt and the UAE in particular to keep in check the Muslim Brotherhood and its regional state supporters, primarily Turkey and Qatar.

In this webinar, the author will discuss the paper’s main argument, namely, that the degree of Egypt’s dependence on Gulf countries has fluctuated, and that by 2019, Egypt’s direct financial dependence on the Gulf was significantly reduced by comparison with the initial three years of the Sisi era, although other economic linkages such as investment, trade, remittances and tourism remained strong, with potential for growth. The speaker will also discuss the impact of the global crisis caused by the COVID-19 pandemic on Egypt’s and Gulf countries’ economies and will explore the implications for the relationship between Egypt and the Gulf.

This webinar is part of the Chatham House Middle East and North Africa Programme's Online Event Series. The event will be held on the record.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Webinar: Assessing the Twists and Turns in the US-Iran Stalemate

Research Event

28 April 2020 - 2:00pm to 3:30pm

Event participants

Esfandyar Batmanghelidj, Founder and Publisher, Bourse & Bazaar
Nasser Hadian, Professor of Political Sciences, Faculty of Law and Political Sciences, University of Tehran
Azadeh Zamirirad, Deputy Head, Middle East and Africa Division, SWP Berlin
Ariane Tabatabai, Middle East Fellow, Alliance for Securing Democracy, US German Marshall Fund; Adjunct Senior Research Scholar, SIPA
Moderator: Sanam Vakil, Deputy Head and Senior Research Fellow, Middle East and North Africa Programme, Chatham House
The webinar will be livestreamed on the MENA Programme Facebook page.

Since the start of 2020, Iran has been beset with multiple challenges including the spread of COVID-19, economic pressure from US sanctions, parliamentary elections in February, the killing of Qassem Soleimani and an increase in tensions in Iraq. The Trump administration interprets these domestic and regional challenges faces by Iran as evidence that its maximum pressure campaign is proving to be effective.

In this webinar, speakers will examine the economic and political impact of the Trump administration's policy towards Iran. Panelists will consider how these events are impacting internal dynamics in Iran and examine the economic impact of sanctions. They will also evaluate European diplomatic efforts to preserve the Iran nuclear agreement, and consider the future trajectory of US Iran policy and the potential for escalation in the region.
 
This webinar is part of the Chatham House Middle East and North Africa Programme's Online Event Series. The event will be held on the record.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Lebanese Women and the Politics of Disruption

Research Event

6 May 2020 - 1:00pm to 2:00pm

Event participants

Carmen Geha, Assistant Professor of Public Administration, Leadership and Organisational Development, American University of Beirut
Moderator: Lina Khatib, Director, Middle East and North Africa Programme, Chatham House
Lebanese women have been at the forefront of the protest movement that has shaken Lebanon since October 2019. The active participation by women and their visibility in Lebanon's protest movement has challenged the gender norms prevalent in Lebanese society and politics. However, the COVID-19 pandemic and the nationwide lockdown that ensued has disrupted women's ability to organize, and is threatening the fragile progress towards female inclusion in the political process.
 
In a recent article, Carmen Geha discussed the politics of representation in the context of women's participation in public life in Lebanon and argued that the country's political system is maintained through tightly-knit informal power relations among sectarian politicians, making women's participation in politics virtually impossible. The article explained how the October 2019 revolution challenged that norm by creating inclusive spaces where women activists could confront politicians and thus, transform the way women participate in politics and public life.
 
In this webinar, part of the Chatham House project on the future of the state in the Middle East and North Africa, the article's author will discuss how women's activism in Lebanon has been affected by the coronavirus-induced lockdown. The speaker will consider how, under current circumstances, women activists can speak up collectively and bring back a movement to contest gender norms in order to build an alternative political model that can better represent women's priorities.
 
You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Biosynthesis of depsipeptides with a 3-hydroxybenzoate moiety and selective anticancer activities involves a chorismatase [Metabolism]

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.




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The transcriptional regulator IscR integrates host-derived nitrosative stress and iron starvation in activation of the vvhBA operon in Vibrio vulnificus [Gene Regulation]

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.




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Substrate recognition and ATPase activity of the E. coli cysteine/cystine ABC transporter YecSC-FliY [Microbiology]

Sulfur is essential for biological processes such as amino acid biogenesis, iron–sulfur cluster formation, and redox homeostasis. To acquire sulfur-containing compounds from the environment, bacteria have evolved high-affinity uptake systems, predominant among which is the ABC transporter family. Theses membrane-embedded enzymes use the energy of ATP hydrolysis for transmembrane transport of a wide range of biomolecules against concentration gradients. Three distinct bacterial ABC import systems of sulfur-containing compounds have been identified, but the molecular details of their transport mechanism remain poorly characterized. Here we provide results from a biochemical analysis of the purified Escherichia coli YecSC-FliY cysteine/cystine import system. We found that the substrate-binding protein FliY binds l-cystine, l-cysteine, and d-cysteine with micromolar affinities. However, binding of the l- and d-enantiomers induced different conformational changes of FliY, where the l- enantiomer–substrate-binding protein complex interacted more efficiently with the YecSC transporter. YecSC had low basal ATPase activity that was moderately stimulated by apo FliY, more strongly by d-cysteine–bound FliY, and maximally by l-cysteine– or l-cystine–bound FliY. However, at high FliY concentrations, YecSC reached maximal ATPase rates independent of the presence or nature of the substrate. These results suggest that FliY exists in a conformational equilibrium between an open, unliganded form that does not bind to the YecSC transporter and closed, unliganded and closed, liganded forms that bind this transporter with variable affinities but equally stimulate its ATPase activity. These findings differ from previous observations for similar ABC transporters, highlighting the extent of mechanistic diversity in this large protein family.




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The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus [Protein Synthesis and Degradation]

The formation of translationally inactive 70S dimers (called 100S ribosomes) by hibernation-promoting factor is a widespread survival strategy among bacteria. Ribosome dimerization is thought to be reversible, with the dissociation of the 100S complexes enabling ribosome recycling for participation in new rounds of translation. The precise pathway of 100S ribosome recycling has been unclear. We previously found that the heat-shock GTPase HflX in the human pathogen Staphylococcus aureus is a minor disassembly factor. Cells lacking hflX do not accumulate 100S ribosomes unless they are subjected to heat exposure, suggesting the existence of an alternative pathway during nonstressed conditions. Here, we provide biochemical and genetic evidence that two essential translation factors, ribosome-recycling factor (RRF) and GTPase elongation factor G (EF-G), synergistically split 100S ribosomes in a GTP-dependent but tRNA translocation-independent manner. We found that although HflX and the RRF/EF-G pair are functionally interchangeable, HflX is expressed at low levels and is dispensable under normal growth conditions. The bacterial RRF/EF-G pair was previously known to target only the post-termination 70S complexes; our results reveal a new role in the reversal of ribosome hibernation that is intimately linked to bacterial pathogenesis, persister formation, stress responses, and ribosome integrity.