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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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Greg Gutfeld Levels Ilhan Omar With Epic Response To Her Claim That “White Privilege” Is Reason Charges Were Dropped Against General Flynn

The following article, Greg Gutfeld Levels Ilhan Omar With Epic Response To Her Claim That “White Privilege” Is Reason Charges Were Dropped Against General Flynn, was first published on 100PercentFedUp.com.

Yesterday, after 3 1/2 years of having his character and integrity called into question, President Trump's first NSA, General Michael Flynn was finally...

Continue reading: Greg Gutfeld Levels Ilhan Omar With Epic Response To Her Claim That “White Privilege” Is Reason Charges Were Dropped Against General Flynn ...




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Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut

The following article, Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut, was first published on 100PercentFedUp.com.

When Dallas, Texas salon owner Shelley Luther opened her salon in defiance of the lockdown order in Texas, she was visited numerous times by the local police and then sentenced to 7 days in jail with a fine of $7,000. After public outrage at her punishment, the Texas Supreme Court stepped in to demand her […]

Continue reading: Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut ...




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Obama Private Call Released: Implores Political Operatives to Help Protect Him…”We gotta make this happen”

The following article, Obama Private Call Released: Implores Political Operatives to Help Protect Him…”We gotta make this happen”, was first published on 100PercentFedUp.com.

Michael Isikoff at Yahoo News on Friday night released audio of a call from former President Barack Obama to political operatives and the media to help protect “the rule of law” by protecting him. Obama desperately wants the Deep State and media to protect him by helping elect Joe Biden: “The fact that there is […]

Continue reading: Obama Private Call Released: Implores Political Operatives to Help Protect Him…”We gotta make this happen” ...




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Windsor Assembly Plant on track for May 19 restart

The Fiat-Chrysler Windsor Assembly Plant looks to be on track for a May 19 reopening according to union leadership.




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OPP release composite drawing of man who allegedly impersonated an officer

Essex County OPP have released a composite drawing of a suspect reported to be impersonating a police officer in Lakeshore.




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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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VIDEO: Man seen kicking gas pump to avoid prepayment

Brandon police officers are searching for a man who was caught on camera attempting to pump gas in his car – without prepaying.




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Overnight snow expected in areas of Southern Manitoba

Environment Canada has issued a special weather statement for the southwestern area of Manitoba.




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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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Heterotrimeric Gq proteins as therapeutic targets? [Molecular Bases of Disease]

Heterotrimeric G proteins are the core upstream elements that transduce and amplify the cellular signals from G protein–coupled receptors (GPCRs) to intracellular effectors. GPCRs are the largest family of membrane proteins encoded in the human genome and are the targets of about one-third of prescription medicines. However, to date, no single therapeutic agent exerts its effects via perturbing heterotrimeric G protein function, despite a plethora of evidence linking G protein malfunction to human disease. Several recent studies have brought to light that the Gq family–specific inhibitor FR900359 (FR) is unexpectedly efficacious in silencing the signaling of Gq oncoproteins, mutant Gq variants that mostly exist in the active state. These data not only raise the hope that researchers working in drug discovery may be able to potentially strike Gq oncoproteins from the list of undruggable targets, but also raise questions as to how FR achieves its therapeutic effect. Here, we place emphasis on these recent studies and explain why they expand our pharmacological armamentarium for targeting Gq protein oncogenes as well as broaden our mechanistic understanding of Gq protein oncogene function. We also highlight how this novel insight impacts the significance and utility of using G(q) proteins as targets in drug discovery efforts.




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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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Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2 [Signal Transduction]

The protein-tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstream of growth factor receptors. Mutations in the SHP2 gene have been linked to many different types of human diseases, including developmental disorders, leukemia, and solid tumors. Unlike most SHP2-activating mutations, the T507K substitution in SHP2 is unique in that it exhibits oncogenic Ras-like transforming activity. However, the biochemical basis of how the SHP2/T507K variant elicits transformation remains unclear. By combining kinetic and biophysical methods, X-ray crystallography, and molecular modeling, as well as using cell biology approaches, here we uncovered that the T507K substitution alters both SHP2 substrate specificity and its allosteric regulatory mechanism. We found that although SHP2/T507K exists in the closed, autoinhibited conformation similar to the WT enzyme, the interactions between its N-SH2 and protein-tyrosine phosphatase domains are weakened such that SHP2/T507K possesses a higher affinity for the scaffolding protein Grb2-associated binding protein 1 (Gab1). We also discovered that the T507K substitution alters the structure of the SHP2 active site, resulting in a change in SHP2 substrate preference for Sprouty1, a known negative regulator of Ras signaling and a potential tumor suppressor. Our results suggest that SHP2/T507K's shift in substrate specificity coupled with its preferential association of SHP2/T507K with Gab1 enable the mutant SHP2 to more efficiently dephosphorylate Sprouty1 at pTyr-53. This dephosphorylation hyperactivates Ras signaling, which is likely responsible for SHP2/T507K's Ras-like transforming activity.




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Modification of a PE/PPE substrate pair reroutes an Esx substrate pair from the mycobacterial ESX-1 type VII secretion system to the ESX-5 system [Molecular Bases of Disease]

Bacterial type VII secretion systems secrete a wide range of extracellular proteins that play important roles in bacterial viability and in interactions of pathogenic mycobacteria with their hosts. Mycobacterial type VII secretion systems consist of five subtypes, ESX-1–5, and have four substrate classes, namely, Esx, PE, PPE, and Esp proteins. At least some of these substrates are secreted as heterodimers. Each ESX system mediates the secretion of a specific set of Esx, PE, and PPE proteins, raising the question of how these substrates are recognized in a system-specific fashion. For the PE/PPE heterodimers, it has been shown that they interact with their cognate EspG chaperone and that this chaperone determines the designated secretion pathway. However, both structural and pulldown analyses have suggested that EspG cannot interact with the Esx proteins. Therefore, the determining factor for system specificity of the Esx proteins remains unknown. Here, we investigated the secretion specificity of the ESX-1 substrate pair EsxB_1/EsxA_1 in Mycobacterium marinum. Although this substrate pair was hardly secreted when homologously expressed, it was secreted when co-expressed together with the PE35/PPE68_1 pair, indicating that this pair could stimulate secretion of the EsxB_1/EsxA_1 pair. Surprisingly, co-expression of EsxB_1/EsxA_1 with a modified PE35/PPE68_1 version that carried the EspG5 chaperone-binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in redirection and co-secretion of the Esx pair via ESX-5. Our results suggest a secretion model in which PE35/PPE68_1 determines the system-specific secretion of EsxB_1/EsxA_1.




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Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence [Molecular Biophysics]

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.




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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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{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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Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy [Molecular Bases of Disease]

Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.




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As Parliamentary Elections Loom, the Legitimacy of Iran’s Regime Has Been Shaken

5 December 2019

Dr Sanam Vakil

Deputy Director and Senior Research Fellow, Middle East and North Africa Programme
The latest wave of protests highlights a fracturing social contract in the Islamic Republic.

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Iranian protesters block a road during a demonstration against an increase in gasoline prices in Isfahan on 16 November. Photo: Getty Images.

For four decades, the rule of Iran’s Islamic Republic has rested on the pillars of redistributive social justice, foreign policy independence, Islam and a managed form of electoral legitimacy.  These pillars, each of equal importance, have served as guiding principles bolstering Iran’s domestic and foreign policy decisions.  Amid the latest round of protests to have gripped Iran, it is clear that these pillars are fracturing. 

On 15 November at midnight, the Iranian government, in a move supported by Supreme Leader Ali Khamenei, President Hassan Rouhani, Speaker of the Parliament Ali Larijani and Head of the Judiciary Ebrahim Raisi, announced a 200 per cent increase in fuel prices – a redistributive measure designed to provide cash transfers to the population.

In immediate reaction, Iranian citizens took to the streets to express their discontent with this policy move alongside mounting economic and political grievances.

What ensued over the subsequent days was an outbreak of protests through 100 Iranian cities, including at universities and bazaars, that was followed by a weeklong internet blackout and a brutal crackdown that has left at least 200 people dead and 7,000 arrested. Initially, public anger focused on the price increases but quickly targeted the political leadership, lack of government accountability, effective governance and corruption.

This wave of protests is the fourth in a two-decade period – 1999, 2009, 2017 and 2019 – for the Islamic Republic and comes at time when the Iranian government is under severe economic strain from Washington’s maximum pressure campaign. It is equally burdened by endemic factional politicking.

These protests are one of many reminders of the shattered social contract between state and society in Iran, which without repair will continue to resurface.

With internet connectivity resumed and news of the regime’s brutality spreading, conservatives and reformists are both trying to distance themselves from this internal crisis and reposition themselves in advance of the 2020 parliamentary elections.

Parliamentary elections for Iran’s 290-person legislature are expected to be held on 21 February. Amid concerns over public apathy and lower political participation, both reformists and conservatives are trying to develop strategies to maximize gains at their ballot box.

Even before these protests, voter turnout was anticipated to be lower than normal. Participation in the July 2019 Tehran municipality election was at a nadir of 9 per cent.  To prepare for this challenge, Iran’s parliament has lowered the vote threshold for a valid result from 25 to 20 per cent.

Elections in Iran, while by no means completely free and fair due to the vetting of candidates by the Guardian Council, have repeatedly been an important barometer of public support and participation. Electoral participation, which is traditionally higher than in most Western democracies, and compared to the lack of electoral opportunities in the Middle East, is heralded as a sign of public legitimacy. 

Voter participation is generally higher in presidential elections than in legislative ones.

For example, 73% voted in the 2017 presidential elections, 72% in 2013, 80% in the contested 2009 elections, and 59% in 2005 elections that brought Mahmood Ahmadinejad to office. Comparatively, in the 2016 parliamentary elections 62% voted, in 2012, 66%, in 2008, 47%, and in 2004, 51% participated.

Voter turnout in the 2008 parliamentary elections, reflective of public apathy, mounting international tensions over the nuclear programme, and Guardian Council vetting of reformist candidates, could be emblematic of what to expect next year. 

In the run up to the election, conservative groups are trying to capitalize on popular economic frustrations, disappointment with reformists, wider regional security concerns and tensions with the United States to rally voters. 

Reformists associated with the Rouhani government, who also supported the Iran nuclear agreement, have been severely weakened by the US maximum pressure campaign and the return of US sanctions.  They are also blamed for the current economic downturn and remain frustrated by their ability to affect change in a political system that affords more power to unelected figures.

Amidst this stalemate, Rouhani has continued to call for a national referendum to no avail, while reformist groups are debating how to position themselves – some even calling for greater accountability – so as not be tainted by the government crackdown. Leading reformist politicians such as Mohammad Khatami have called on reformists to stay united and avoid boycotting the elections. It remains to be seen how their strategy will develop after the protests.

Should the Guardian Council bar too many reformists from running, calls for a boycott could snowball and even incite new protests. Together with low turnout at the ballot box, the outcome of this election could further damage the regime’s already fragile electoral pillar and weaken its claims to legitimacy.




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How the Soleimani Assassination Will Reverberate Throughout the Middle East

6 January 2020

Dr Sanam Vakil

Deputy Director and Senior Research Fellow, Middle East and North Africa Programme

Dr Renad Mansour

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

Dr Lina Khatib

Director, Middle East and North Africa Programme
Regional experts examine how Iran benefits from the fallout of the killing, the implications for politics in Iraq and how Tehran might respond with its proxies in the region.

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Protesters hold up an image of Qassem Soleimani during a demonstration in Tehran on 3 January. Photo: Getty Images.

An unexpected bounty for Iran

Sanam Vakil

The assassination of Qassem Soleimani has been an unexpected bounty for the Islamic Republic at a time when Iran was balancing multiple economic, domestic and regional pressures stemming from the Trump administration’s maximum pressure campaign.

Coming on the heels of anti-Iranian demonstrations in Iraq and Lebanon, and following Iran’s own November 2019 protests that resulted in a brutal government crackdown against its own people, the Soleimani killing has helped the Iranian government shift the narrative away from its perceived regional and domestic weaknesses to one of strength.  

The massive funeral scenes in multiple Iranian cities displaying unending waves of mourners chanting against the United States has provided the Islamic Republic with a unique opportunity to showcase its mobilizing potential. This potential is not limited to Iran but also extends to Iraq and Lebanon, where Tehran’s transnational summoning power has also been visible. The Iraqi parliamentary vote to end the American military presence is one early negative consequence. While the region awaits Iran’s response, further anti-American rallying cries will continue to reverberate.  

Domestically, Soleimani’s death and President Donald Trump’s continued provocations on Twitter, including threats to attack 52 Iranian cultural sites, are being used as a nationalist rallying cry. This sentiment should not be seen solely as Islamic or ideological, but rather an opportunity for the state to pivot to an Iranian-based nationalism that is more inclusive and empowering for much of the country’s disgruntled youth.

Iran’s notoriously divided political factions have also unified in the face of this crisis. With parliamentary elections looming in February and turnout previously expected to be low, the political establishment is likely to use this crisis to mobilize voters in favour of conservative candidates.  

How Tehran chooses to respond to Qassem Soleimani’s death will very much determine its ability to continue to control the narrative and manage its swell of domestic and regional support. For these benefits to continue to manifest, it is important for Tehran to balance the mix of public sympathy and international anxiety and not overplay its hand in its quest for revenge.

A reset for Iraqi politics

Renad Mansour

The US strike which killed Qassem Soleimani and Abu Mehdi al-Muhandis has grave implications for Iraq. The act jeopardizes Iraq’s recently stabilized security situation, and threatens to reshape the country’s political environment, moving backwards to the days of anti-Americanism and sect-based mobilization. If Baghdad loses relations with the US and other diplomatic representations, it risks turning into a pariah state. 

Over the past few years, and notably since October 2019, young Iraqis have taken to the streets demanding reform and the downfall of the political establishment, and its main external backer Iran. The political establishment, including political parties and militias close to Tehran, failed to appease or suppress these protests. Now, these political elites are using the deaths of Muhandis and Soleimani to (re)gain popularity from their own population, by drawing on the old tool of anti-Americanism. 

Following the attacks, Shia populist cleric Muqtada al-Sadr – who until recently had called for an end to Iranian and pro-Iranian militia influence in Iraq – has called to revamp the Mehdi Army that he led until 2008 and is calling for ‘Islamic resistance’ to the US. In seeking to regain control of his former movement, he is coming closer to former Shia foes.

For years, pro-Iranian groups attempted to push the US out of Iraq. Their calls often fell on deaf ears, as public opinion in Iraq did not consider the US as a threat and some even supported the US and international effort against ISIS. Following the attacks, however, anti-American voices have gained more ammunition.

A complete American withdrawal would not only have direct security implications but force other countries and organizations, from European states to NATO, to reconsider their positions and role.

Limited options for ‘revenge’ in the Levant

Lina Khatib

Iran’s use of Lebanon and Syria as spaces for revenge against the US is unlikely.

On Sunday, Hezbollah leader Hassan Nasrallah vowed revenge for Soleimani’s death by singling out American soldiers as a target. However, Hezbollah’s options are limited. Lebanon is in the middle of wide-ranging protests against the country’s ruling political class, of which Nasrallah is a key figure.

Unlike in 2006, when Hezbollah’s military actions against Israel rallied the public around it, today there is no public appetite for dragging Lebanon into a war. Were Hezbollah to instigate one, it would incur public anger, if only for the economic repercussions that would exacerbate an already severe financial crisis in Lebanon. Lebanon also does not have any US military bases that could be a target for Hezbollah.

In theory, Hezbollah or other Iranian-backed groups could attack American bases in Syria. But these bases are staffed by multinational forces from the international anti-ISIS coalition. Attacking them would therefore put Iran in confrontation with other countries besides the US, which is not in Iran’s interest.

Attacking US soldiers in northeast Syria would also go against Kurdish interests because it would weaken the anti-ISIS coalition front of which Kurdish forces are part. It would, furthermore, anger Arab tribes in the area, opening up possibilities for ISIS to take advantage of public dissent to stage a comeback. Iran would then find itself fighting on several fronts at once, which it does not have the capacity to handle. 

More likely, Iran’s allies and proxies in the Levant are going to engage in strong rhetoric without taking hasty actions. When a key Hezbollah leader, Imad Mughniyeh, was assassinated in Damascus on 2008, there were strong words and public vows to seek revenge for his killing, but ultimately there was no response.    




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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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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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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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Webinar: Will COVID-19 Mark the Endgame for Iraq's Muhasasa Ta'ifia?

Research Event

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

Event participants

Ahmed Tabaqchali, Chief Investment Officer, Asia Frontier Capital Iraq Fund; Adjunct Assistant Professor, American University of Iraq Sulaimani
Moderator: Renad Mansour, Senior Research Fellow, Middle East and North Africa Programme, Chatham House

Control of oil rents underpins Iraq’s post-2003 political order. This political order, known as Muhasasa Ta’ifia (ethno-sectarian apportionment), features an elite bargain inclusive of all major ethnic and sect-based political groups. It has enabled the state's continuity and apparent stability through multiple crises, including the 2008 financial crisis, the 2014 oil crisis, and the war with ISIS.

In a recent article, Ahmed Tabaqchali examines how the crash in oil rents, brought about by COVID-19’s disruption of the world economy, exposes the structural inconsistencies and inherent contradictions of the Muhasasa Tai’fia system. The article argues that the current Iraqi political elite is ill-equipped to resolve the multi-faceted challenge facing the country because of its increasing fragmentation and the erosion of its legitimacy, advanced institutional decay and fundamentally different oil dynamics.

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 deficiencies of the Muhasasa Ta’ifia system and will offer his insight into the future of this governance model in the context of a worsening economic crisis resulting from the COVID-19 pandemic and existing demographic pressures.
 
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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Basem Mahmoud

Project Manager, Middle East and North Africa Programme

Biography

Basem Mahmoud is a project manager with the Middle East and North Africa Programme at Chatham House.

Basem joined Chatham House in 2019 and has contributed to the projects Future of Statehood in the MENA Region, Transformative Policies towards Syria, and Post-Conflict State Dynamics in Syria.

Prior to joining Chatham House, Basem worked in managing wide range of projects and programmes with the Anna Lindh Euro-Mediterranean Foundation, Freedom House, and Friedrich Naumann Foundation.

Basem has an MA in conflict, security, and development from the University of Bradford.

+44 (0) 20 7314 3658




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COVID-19 Crisis – Business as Usual for Gaza?

6 May 2020

Mohammed Abdalfatah

Asfari Foundation Academy Fellow
The COVID-19 pandemic has brought unprecedented challenges, economic collapse and strict lockdowns in many parts of the world. For the people of Gaza, this reality is nothing new.

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Palestinians light fireworks above the rubble during the Muslim holy month of Ramadan amid concerns about the spread of the coronavirus disease (COVID-19), in Gaza City , 30 April 2020. Photo by Majdi Fathi/NurPhoto via Getty Images.

In August 2012, when the UN released its report Gaza in 2020: A liveable place?, they could not have imagined what the world would look like in 2020: cities under lockdown, restrictions on movement, border closures, widespread unemployment, economic collapse, fear and anxiety and, above all, uncertainty about what the future holds.

For Gaza’s population of 2 million people this reality is nothing new. The conditions that the rest of the world are currently experiencing as a result of the COVID-19 pandemic is similar to the tight blockade Gaza has been living under ever since Hamas took over in 2007. Israel has imposed severe restrictions on the movement of people and goods, youth unemployment has reached 60 per cent, and over 80 per cent of Gaza’s population are now dependent on international aid.

The people of Gaza are having to face the COVID-19 crisis already at a disadvantage, with poor infrastructure, limited resources and a shortage of the most basic services, such as water and power supply. It also has a fragile health system, with hospitals lacking essential medical supplies and equipment, as well as the capacity to deal with the outbreak as there are only 84 ICU beds and ventilators available.

 

Meanwhile, intra-Palestinian divisions have persisted and were evident in the initial reaction to the pandemic. When President Mahmoud Abbas announced a state of emergency, it took two days for the Hamas-led government in Gaza to follow suit and shut down schools and universities. They later made a separate emergency appeal to address the crisis and prepare for a COVID-19 response in Gaza. This lack of coordination is typical of the way the Palestinian Authority and Hamas approach crisis situations.

After the initial uncoordinated response, Hamas, as the de-facto ruler of Gaza, has asserted its ability to control Gaza’s borders by putting in place quarantine measures for everyone who enters the strip, whether through the Erez checkpoint with Israel or the Rafah border with Egypt. They have also assigned 21 hospitals, hotels, and schools as compulsory quarantine centres for all arrivals from abroad, who have to stay in quarantine for 21 days. In comparison, there are 20 quarantine centres in the West Bank.  These strict measures have prevented the spread of the virus in the community and confined it to the quarantine centres, with only 20 confirmed cases of COVID-19 as of 6 May. Gaza’s de-facto authorities have also been able to monitor markets and prices to ensure the availability of essential goods.

Faced with a major crisis, Al-Qassam Brigades – the armed wing of Hamas – have tried to play the role of a national army by participating in efforts to fight the pandemic. They have relatively good logistical capacity and have contributed to the construction of two quarantine facilities with a total capacity of 1,000 units to prepare for more arrivals into Gaza. At the local level, municipalities have been disinfecting public spaces and facilities in addition to disseminating information about the virus and related preventative and protective measures. Other precautionary measures put in place include closing the weekly open markets, and restricting social gatherings like weddings and funerals.

Despite COVID-19, it’s business as usual when it comes to international dealings with Gaza. The key parties in the conflict – Israel, Hamas and the Palestinian Authority – along with the main external actors – Egypt, the United Nations and Qatar – have continued to stick to their policies aimed at keeping the security situation under control and preventing further escalation. Although Israel has allowed entry of pharmaceutical supplies and medical equipment into Gaza during the pandemic, it has kept its restrictions on the movement of goods and people in place, while keeping a close eye on the development of the COVID-19 outbreak in Gaza – a major outbreak here would be a nightmare scenario for Israel.

Meanwhile, Qatar has continued to address the humanitarian and economic needs of Gaza in an attempt to ease the pressure and prevent further escalation. It has pledged $150 million over the next six months to help families in Gaza from poorer backgrounds. Gaza has also been discussed by the Middle East Quartet, as Nickolay Mladenov, the UN special coordinator for the Middle East Peace Process, expressed his concern about the risk of a disease outbreak in Gaza during a call with the members of the Quartet.

Amid the pandemic, threats are still being exchanged between Israel and Hamas. The Israeli defence minister, Naftali Bennett, requested that in return for providing humanitarian aid to Gaza, Hamas agrees to return the remains of two Israeli soldiers killed in the 2014 war. While openly rejecting Bennett's statement, the leader of Hamas in Gaza, Yahya Sinwar, has offered to move forward with a prisoner swap deal if Israel agrees to release elderly prisoners and detainees in addition to detained women and children. Though dealing with its own COVID-19 outbreak, Egypt has started to mediate between the two parties in an attempt to stabilize the situation and reach a prisoner swap deal.

In the wake of this pandemic, lessons should be learned and policies should be examined, by all parties. Firstly, Israel should re-evaluate its security measures towards Gaza by easing restrictions on movement and trade which would have a positive impact on living conditions for Gaza’s population. The current measures have proven to be unsustainable and have contributed to the endless cycle of violence. Secondly, the intra-Palestinian division should end, to save Palestinians from contradictory policies and insufficient capacity on both sides. In fact, all previous attempts have failed to end this self-destructive division and this is due to the absence of political will on both sides. Elections seem to be the only viable path towards unity. Finally, efforts by the international community should go beyond stabilizing the security situation and ongoing crisis inside Gaza, where disruption of normal life is the norm.

While the world has reacted to this pandemic with a whole host of new policies and emergency measures, it has remained business as usual when dealing with Gaza. Should COVID-19 spread in Gaza, its people – who have already paid the price of a continuous blockade and intra-Palestinian division for 13 years – will pay a heavy price yet again. However, this time it is not a crisis that they alone will have to face.




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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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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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Modification of a PE/PPE substrate pair reroutes an Esx substrate pair from the mycobacterial ESX-1 type VII secretion system to the ESX-5 system [Molecular Bases of Disease]

Bacterial type VII secretion systems secrete a wide range of extracellular proteins that play important roles in bacterial viability and in interactions of pathogenic mycobacteria with their hosts. Mycobacterial type VII secretion systems consist of five subtypes, ESX-1–5, and have four substrate classes, namely, Esx, PE, PPE, and Esp proteins. At least some of these substrates are secreted as heterodimers. Each ESX system mediates the secretion of a specific set of Esx, PE, and PPE proteins, raising the question of how these substrates are recognized in a system-specific fashion. For the PE/PPE heterodimers, it has been shown that they interact with their cognate EspG chaperone and that this chaperone determines the designated secretion pathway. However, both structural and pulldown analyses have suggested that EspG cannot interact with the Esx proteins. Therefore, the determining factor for system specificity of the Esx proteins remains unknown. Here, we investigated the secretion specificity of the ESX-1 substrate pair EsxB_1/EsxA_1 in Mycobacterium marinum. Although this substrate pair was hardly secreted when homologously expressed, it was secreted when co-expressed together with the PE35/PPE68_1 pair, indicating that this pair could stimulate secretion of the EsxB_1/EsxA_1 pair. Surprisingly, co-expression of EsxB_1/EsxA_1 with a modified PE35/PPE68_1 version that carried the EspG5 chaperone-binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in redirection and co-secretion of the Esx pair via ESX-5. Our results suggest a secretion model in which PE35/PPE68_1 determines the system-specific secretion of EsxB_1/EsxA_1.




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The streptococcal multidomain fibrillar adhesin CshA has an elongated polymeric architecture [Microbiology]

The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. Streptococcus gordonii is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans. The fibrillar adhesin CshA is an important determinant of S. gordonii adherence, forming peritrichous fibrils on its surface that bind host cells and other microorganisms. CshA possesses a distinctive multidomain architecture comprising an N-terminal target-binding region fused to 17 repeat domains (RDs) that are each ∼100 amino acids long. Here, using structural and biophysical methods, we demonstrate that the intact CshA repeat region (CshA_RD1–17, domains 1–17) forms an extended polymeric monomer in solution. We recombinantly produced a subset of CshA RDs and found that they differ in stability and unfolding behavior. The NMR structure of CshA_RD13 revealed a hitherto unreported all β-fold, flanked by disordered interdomain linkers. These findings, in tandem with complementary hydrodynamic studies of CshA_RD1–17, indicate that this polypeptide possesses a highly unusual dynamic transitory structure characterized by alternating regions of order and disorder. This architecture provides flexibility for the adhesive tip of the CshA fibril to maintain bacterial attachment that withstands shear forces within the human host. It may also help mitigate deleterious folding events between neighboring RDs that share significant structural identity without compromising mechanical stability.




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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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Progress in tackling illegal logging slows as new trends offset effective reforms

15 July 2015

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Efforts to address illegal logging and reduce the trade in illegal timber have borne fruit and prompted some positive reforms in producer countries, a new report from Chatham House has found. However, changes in the sector mean overall trade in illegal timber has not fallen in the last decade. 
  
EU and US policies designed to reduce demand for illegal timber have helped cut illegal imports to those markets. These reforms and the EU’s partnership agreements with producer countries have prompted improvements in forest governance and a fall in large-scale illegal timber production.

But growth of demand in emerging markets means that the progressive policies of so-called ‘sensitive markets’ are now less influential. China is now the world’s largest importer and consumer of wood-based products, as well as a key processing hub. India, South Korea, and Vietnam are also growing markets. The increasing role of small-scale producers, whose activities often fall outside legal frameworks, and a rapid increase in illegal forest conversion, also present new challenges. 
  
Alison Hoare: 'The EU and US have spearheaded some progressive and effective reforms. However, the changing scale and nature of the problem demands more coordinated international action. To stop further deforestation and associated carbon emissions, and to help achieve global objectives for sustainable development, the EU and US need to maintain their leadership while other countries - especially China, Japan, India and South Korea - need to step up their efforts to tackle illegal logging.'

The Chatham House report, which is based on the studies of 19 countries, which include key producers, consumers, or processors of timber, and is an update of a 2010 study found: 

Timber production

  • More than 80 million m3 of timber was illegally produced in 2013 in the nine producer countries assessed, accounting for about one-third of their combined total production.
  • An estimated 60% of this illegal timber is destined for these countries’ domestic markets.
  • Small-scale producers are increasingly important – for example, in Cameroon, the DRC and Ghana, they account for an estimated 50, 90 and 70% respectively of annual timber production. The majority of this is illegal.
  • For the nine producer countries, the area of forest under voluntary legality verification or sustainability certification schemes increased by nearly 80% between 2000 and 2013. 

Imports of illegal wood-based products 

  • In most of the consumer and producer countries assessed, the volume of illegal imports of wood-based products fell during the period 2000–13. 
  • The exceptions were China, and India and Vietnam where the volume of illegal imports more than doubled. 
  • As a proportion of the whole, illegal imports declined for nearly all countries. 
  • However, at the global level, the proportion of illegal timber imports remained steady at 10% - a result of the growth of the Chinese market. 

The EU and US 

  • The volumes of illegal imports into the UK, France and the Netherlands nearly halved over the period 2000-13, from just under 4 million m3 to 2 million m3. 
  • The volume of illegal imports into the US increased between 2000 and 2006, from around 5 to 9 million m3, and then declined to just under 6 million m3 in 2013. 
  • In 2013, more than 60% of illegal imports of wood-based products to the UK and US came from China.

China

  • The volume of illegal imports into China doubled between 2000 and 2013 from 17 to 33 million m3; but as a proportion of the whole illegal imports fell, from 26 to 17%.
  •  The volume of exports of wood-based products (legal and illegal) from the nine producer countries to China nearly tripled, from 12 million m3 in 2000 to 34 million m3 in 2013.

The Chatham House report makes the following recommendations:

  • The EU and US need to maintain and reinforce current efforts 
  • Other countries need to take stronger action – China in particular, but also India, Japan and South Korea
  • Strong international cooperation is needed to maintain & reinforce current efforts – the G20 could provide a forum to galvanise international action
  • Producer countries need to focus on strengthening efforts to tackle corruption, improving legality within the small-scale sector, and reforming land-use governance 

     
Alison Hoare: 'Developing countries are losing significant amounts of potential revenue from illegal logging, which is also causing the loss and degradation of forests, depleting livelihoods, and contributing to social conflict and corruption. Tackling illegal logging and strengthening forest governance are essential for achieving critical climate and development goals. Having seen the progress that can be made, it’s imperative that governments agree to work together to rise to new challenges and promote a more sustainable forest sector for the benefit of all.'   

Read the report >>

Editor's notes

For more information or to arrange interviews please contact:
 
Alison Hoare, report author, Chatham House, +44 (0) 2073143651

Amy Barry, Di:ga Communications, +44 (0) 7980 664397

The report and associated infographics will be available to download from the project website and the Chatham House website from 15 July 2015. 

These findings are part of Chatham House’s Indicators of Illegal Logging and Related Trade project, which looks at consumer, producer and processing countries. 

Follow us on Twitter: @CH_logging    


External expert spokespeople available for comment: 
 
Téodyl Nkuintchua, Programmes Coordinator, Centre pour l’Environnement et le Développement, Cameroon, (+237) 674 37 96 43, Skype: teodyl
 
Rod Taylor, Director, Forests, WWF International via Huma Khan, +1 202-203-8432  
Approved quote: 'The report shows the progress made in keeping illegally-sourced wood out of Western markets, but also highlights the urgent need to focus more on emerging countries and informal markets. It also highlights the global problem of illegal forest clearing, and the need for new policy measures to help sound forest stewardship compete with the conversion of forests to other land-uses.'
 
Ben Cashore, Professor of Environmental Governance and Political Science, Yale University, +1 203 432-3009
 
Mauricio Volvodic, Executive Director, Imaflora, Brazil, +55 19 3429 0810, +55 19 98157 2129
 
Chris Davies MP, Chair of the All Party Parliamentary Group on Forestry and Conservative MP for Brecon and Radnorshire, via Simon Francis, 020 7061 6252 
Approved quote: 'While it is encouraging that illegal timber imports to the UK have halved, it is vital that we remove the market for illegally logged timber in the UK altogether. One way is to ensure we have a sustainable forestry and wood processing sector that can supply more of our timber needs. Government can aid this by enabling the sector to plant more trees now and in the future.'




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Eliza Manningham-Buller Appointed as Co-President of Chatham House

22 July 2015

Eliza Manningham-Buller is confirmed as a president of Chatham House replacing Paddy Ashdown who steps down after 10 years.

The appointment of Baroness Manningham-Buller as a president of Chatham House was confirmed at the institute’s annual general meeting on Tuesday 21 July. Baroness Manningham-Buller joins Sir John Major and Baroness Scotland of Asthal as a co-president and succeeds Lord Ashdown of Norton-sub-Hamdon who has stepped down from the role after two terms.

Eliza Manningham-Buller was director-general of the UK Security Service (MI5) between 2002 and 2007 and became an independent life peer in 2008. She served as Chairman of Imperial College London from 2011 to 2015. She brings to Chatham House an extensive knowledge of and experience in international security as well as a deep interest in medical research and global health, having served as a member of the Board of Governors of the Wellcome Trust since 2008. In October 2015, Baroness Mannigham-Buller will become Chairman of the Trust’s Board of Governors.

Paddy Ashdown steps down after serving as a president for 10 years alongside Sir John Major, Patricia Scotland and their predecessors Lord Hurd of Westwell and Lord Robertson of Port Ellen, respectively. Over that period, the institute benefitted enormously from his extensive experience in international politics and conflict resolution, including as High Representative for Bosnia and Herzegovina from 2002 to 2006.

Dr Robin Niblett, director of Chatham House, said:

'I am delighted to welcome Elizabeth Manningham-Buller as a president of Chatham House. Throughout her career, she has brought deep knowledge, careful analysis and sound judgement to bear upon some of the most difficult dimensions of public policy. The institute will benefit greatly from these qualities as it draws on her engagement with Chatham House over the coming years.

I would like to pay tribute to Paddy Ashdown for his long-standing support of Chatham House. His contributions to our substantive debates, both internally and externally, have been invaluable on numerous occasions, and we look forward to his continued involvement with the institute as a member of our Panel of Senior Advisers.'

Baroness Manningham-Buller said:

“I am delighted to be elected as a Chatham House president at this important time in the institute’s history, as it grapples with a complex and inter-connected agenda of policy challenges. I look forward to working with John Major and Patricia Scotland in supporting Chatham House and its valuable and necessary work.

Editor's notes

A president’s term at Chatham House is for five years, renewable once. There are no governance responsibilities, which reside solely with the institute’s Council.

Chatham House’s three presidents underpin the institute’s independent, non-partisan voice on international affairs. The presidents confirm, through their experiences at the highest levels of government and diplomacy, the connection between Chatham House and policy-makers.




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Asia-Pacific security is about more than just China and the US

21 September 2015

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Photo: Jacob Parakilas/Chatham House.

Seeing geo-strategic rivalry between the US and China as the sole variable in Asia-Pacific security risks becoming a self-fulfilling prophecy, according to a forthcoming Chatham House paper.            

As Xi Jinping’s visit to the US approaches, The Asia-Pacific Power Balance: Beyond the US–China Narrative, warns against deploying Cold War-type narratives that pit the two countries against each other. Such narratives not only misunderstand the complexity of the region and the growing influence of India, Japan and Indonesia, but also risk increasing the likelihood of conflict and of missing vital opportunities for future cooperation.                

The paper, by John Nilsson-Wright, Tim Summers and Xenia Wickett argues that by focusing too heavily on the US and China, policymakers risk narrowing the aperture through which they evaluate policy choices regarding major regional challenges. Some of the key findings include the following:

Military

  • Despite rapidly rising defence spending across Asia, the relative importance of traditional military means is declining relative to instruments such as development assistance and cyber offence.
  • The militaries of Japan and India are becoming – in very different ways – more versatile and potentially expanding their remits. In the future, there will be a larger number of more capable military powers in the region, including South Korea and Vietnam.
  • Current perceptions that the main dynamic is China’s rising military capabilities outstripping others in the region, therefore, need to be tempered. India’s defence spending, for example, as a percentage of GDP has surpassed China’s for the past several decades.

Economics

  • Although China has the world’s second-largest economy and – despite recent problems – is growing faster than most major economies, its growth rate is in secular decline. China has gone from near-constant double-digit growth over the past four decades to 7.4 per cent in 2014 and could dip below 7 per cent this year.
  • Whilst India’s economy remains notably smaller than those of China, the US and Japan, it will surpass China’s growth rate this year and has a lot of potential.
  • If the Trans-Pacific Partnership (TPP) is successfully negotiated, the potential for integration and growth between the United States, Japan and the other 10 TPP members may reduce their current trade dependence on China.

Demography

  • The demography of Asia is another reason to look beyond the US-China nexus, as China faces the challenge of an aging society, while countries such as India have the advantage of a younger population and decades of demographic dividend ahead of them.
  • Likewise populations across much of Southeast Asia, such as the Philippines and Indonesia are growing rapidly and expanding their middle classes. 

Editor's notes

Read the report The Asia-Pacific Power Balance: Beyond the US–China Narrative from Chatham House.

For all enquiries, including requests to speak with the authors of this paper, please contact the press office.

Contacts

Press Office

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The resource curse has not been lifted

5 August 2015

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Hoping to make a little money from Sudan's ocean of black gold, a woman sells tea to roughnecks at an oil rig near Bentiu, Sudan. Photo by Getty Images.

During a decade-long commodities boom, new or emerging producers of oil, gas or mineral resources registered some of the fastest rates of economic growth in the world. Development banks, governments giving foreign aid, extractives companies and major consultancies broadly agreed that ‘extractives-led growth’ is a viable path to socio-economic development for poor countries. 
               
Following over a year of decline in global commodities prices and as efforts to tackle climate change mount, a new paper re-examines the 'curse of natural resources'. It finds that a policy of extractives-led growth entails serious risks. As governments of countries as diverse as Afghanistan, Mauritania, Somalia, Liberia and Cuba prepare to follow an extractives-led growth path, both the advice being handed to them and the growth model itself require a fundamental rethink.

The Resource Curse Revisited argues that:

  • The steep decline in the oil price in the second half of 2014 demolished the main assumption of the extractives-led growth agenda. The assumption that prices of raw materials would continue to increase as global demand grew and well-established sources were exhausted has actually led several low- to middle-income producers such as Ghana into unmanageable debt. At the very least, the current price context  puts new producers at a serious disadvantage, as the focus on cost-cutting has made investors reluctant to accept the risks of developing projects in countries with little infrastructure or capacity to support them.

  • Good governance initiatives are not the antidote to the resource curse. There has often been a mismatch in terms of policy advice given (for example on transparency and revenue management) and the capacity of a country to implement it. Furthermore, basing economic growth on the extraction of below-ground resources will create strong pressures towards poor governance. In the absence of strong institutions, this path leads to the enrichment of minority elite groups, whose interest in capturing rents is likely to become a barrier to improving governance.

  • Both governments with extractives potential and those advising them give too little consideration to the size and nature of the resource base. If extractives-led growth is to be sustained, resource extraction must persist long enough for new economic sectors to emerge and generate revenues that can support government spending and import needs as income from extractives declines.
  • The extractives-led growth model, in its current form, is at odds with green growth strategies. The advice from international agencies and initiatives to countries with extractive resources offers no suggestions on how governments should manage the risk of stranded assets or how they can reconcile extractives-led growth with national sustainable-development goals.

The report concludes that the extractives-led growth agenda has tended to reinforce domestic, government and investor pressures to ‘develop fast’. However, this can threaten long-term opportunities for robust economic diversification. In many cases, there is a strong case for slowing development of extractives projects to allow time to develop the capacity of the government and the private sector to maximize the linkages with the rest of the economy.

Avoiding the resource curse needs not only good governance but also an economic policy that provides for the transition of an economy over time in accordance with its competitive advantages. This report recommends that countries considering extractives development, and their would-be advisors, take into account a wider set of issues at the outset including the likely value of the asset to the economy over time, the options for slow or indeed no development of extractives, and how the rest of the economy would lessen reliance on support from the extractives sector over time.

Editor's notes

Read the report The Resource Curse Revisited from the Energy, Environment and Resources Department, Chatham House.

For all enquiries, please contact the press office

Contacts

Press Office

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Britain should treat Europe as its ‘inner circle’ or risk losing international influence

13 October 2015

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British Prime Minister David Cameron sits with other world leaders at the G20 summit in Brisbane, Australia on 15 November 2014. Photo by Getty Images.

Given the international context, it is in Britain’s best interests to treat Europe as the ‘inner circle’ of its foreign, security and international economic policy, argues Dr Robin Niblett, director of Chatham House, in a new paper.

The British government’s approach since 2010 of seeking to enhance the UK's relations with the world’s emerging powers while balancing these with relationships with the United States and Europe has had only limited success. With constrained resources, and in the face of intense global economic competition, mounting security challenges and decaying international institutions, trying to commit the UK equally on all three fronts will not succeed in the future.

Britain, Europe and the World: Rethinking the UK’s Circles of Influence calls for a different mindset and strategy towards the UK’s place in the world – one in which Britain is surrounded by three concentric circles of influence:

  • The first or ‘inner circle’ is the EU, the region with which the UK’s relationships need to be strongest and most active.
  • The ‘second circle’ consists of the protective and enabling set of economic and security relationships with the US.
  • Finally, an ‘outer circle’ comprises the UK’s other key bilateral and institutional relationships.

Should the UK vote to remain in the EU, policy-makers should commit to placing the EU at the centre of Britain's foreign policy, using the country’s economic weight, diplomatic skills and networks to play a leading role in leveraging more effective EU-wide policies.
 
Should the country vote to leave, the UK and the EU would enter an extended period of dislocation before arriving at a new, mutually diminished settlement. British policy-makers would be forced to deal and negotiate with the EU on critical policy issues from the outside. It is hard to see, argues Dr Niblett, how that could lead to EU policies or an international context more in line with British interests.                          

Despite its structural flaws and competing national interests, the EU offers the best prospects for managing the rapidly changing global context, for three main reasons:

First, it allows the UK to leverage the EU’s global economic weight to enhance the UK’s economic interests internationally, including securing beneficial trade agreements and contributing to EU and global standard-setting and rule-writing. Conversely, leaving would require the UK to renegotiate over 100 trade agreements, and would disadvantage UK interests in EU markets, including making EU governments less likely to liberalize services.                          

Second, it gives the UK a say in designing new EU initiatives to strengthen both British and European security in the face of diverse threats, whether managing the flow of refugees and other emigrants; combatting terrorism; or managing a more assertive Russia and the fallout from a disintegrating Middle East.                          

Third, cooperating with other EU members offers a way of maximizing opportunities to find joint solutions to shared problems, whether in terms of responding to climate change; managing growing cyber insecurity; reversing the decay of governance in failing states; or combating the rise of dangerous non-state actors.

Dr Robin Niblett said:

‘Britain is likely to be richer, safer and more influential in the coming decades if it treats Europe as the ‘inner circle’ of its foreign policy. For a mid-sized country like the UK, being a major player in a strong regional institution can offer a critical lever for international influence. In the UK’s case, this means choosing to be a leading player in the world’s principal civilian power, the European Union.’

                          

Editor's notes

Read Britain, Europe and the World: Rethinking the UK's Circles of Influence

Chatham House will host a press briefing with Dr Robin Niblett on Monday 19 October at 11:00-11:45 BST. To register, or for interview requests, please contact the press office.

The views expressed in this paper are those of the author. Chatham House experts will publish a series of papers and commentaries in the run up to the UK’s referendum on its membership of the EU. The institute will also offer a platform for debate on the referendum and Britain’s role in Europe via a series of events and meetings.

Read more about the EU referendum.

Contacts

Press Office

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First ever global analysis of refugees’ energy use: High costs and poor supply undermine humanitarian assistance

11 November 2015

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A migrant girl looks at a light illuminating a camp site of refugees and migrants on the Greek island of Lesbos, 4 October 2015. Photo: Getty Images.

About 90 per cent of refugees living in camps have no access to electricity and many lack any form of lighting at night, says a Chatham House report for the Moving Energy Initiative. Energy poverty in refugee settlements is not on the radar of international initiatives and humanitarian agencies are ill-equipped to deal with the scale of need. 

Heat Light and Power for Refugees: Saving Lives, Reducing Costs zooms in on the energy needs of refugees and displaced people worldwide, and presents the first ever estimates of the volume and costs of what they use.

'The problem goes beyond electricity. 80 per cent of those in camps rely on firewood for cooking and, as a result, we estimate that some 20,000 people die prematurely each year due to the pollution from indoor fires. Exposure to extremes of cold and heat are also killers for people living in flimsy, temporary shelter,' says Glada Lahn, senior research fellow at Chatham House. 'The current lack of provision for energy undermines the fundamental aims of humanitarian assistance,' she adds.

There are nearly 60 million forcibly displaced people in the world, and they pay staggering costs for energy. The 83,277 households living in Dadaab in Kenya, the world’s largest refugee settlement, spent an estimated $6.2 million on firewood last year, which accounts for approximately 24 per cent of their overall household income. (The average UK household spent 4 per cent of its income on energy in 2011.) In Uganda, almost half of refugee households surveyed by the UNHCR skip meals because they do not have enough fuel to cook with.

'The imperative is to find humane, creative and cost-effective ways to respond to the needs of so many individuals, most of whom are women and children.  Improving access to clean, safe and sustainable energy offers a promising way forward,' says Kofi Annan in the report’s foreword.

The report calls for an overhaul in the way that heat, light and power are delivered in humanitarian crises. It makes the case for new partnerships between humanitarian agencies and private providers to increase clean energy access in refugee settlements. Investment in energy infrastructure will also benefit host communities in some of the world’s poorest countries.

'As refugee households spend approximately $2.1 billion on energy each year, developing local markets for energy services could be part of a mix of solutions,' adds Lahn. 'Using green, culturally appropriate technologies could save lives, reduce CO2 emissions by 11 million tonnes per year and radically improve living standards. Introducing even the most basic solutions, such as improved cookstoves and basic solar lanterns, could save $323 million a year in fuel costs.' 

Other findings include:

  • Rape and violence against women is common in many unlit camps. Only 4 per cent of women and girls in households in the Goudoubo camp in Burkina Faso would go out after dark due to the lack of streetlights.
  • Wood equalling around 49,000 football pitches worth of forest (64,700 acres) is burned by displaced families living in camps each year, mainly in countries suffering severe deforestation, because they have no alternative sources of energy.
  • Firewood consumption emits nearly twice as much CO2 as liquid petroleum gas and produces little energy in comparison to its carbon intensity.

International Development Minister Grant Shapps said:

‘Across sub-Saharan Africa, hundreds of millions of people still do not have access to electricity. Women and girls are at risk of violence after dark, families are forced to inhale toxic kerosene fumes, and energy remains unaffordable for many.

‘With the technology in place and investors coming on board, the time to act is now. The UK's Energy Africa campaign is already kick-starting a solar revolution across the continent.

‘Supporting the Moving Energy Initiative is another way Britain can help boost access to clean, reliable and affordable energy. This will transform people’s lives and help achieve the UN’s goal of universal energy access by 2030.’

Editor's notes

  • Read Heat Light and Power for Refugees: Saving Lives, Reducing Costs by Glada Lahn and Owen Grafham.
  • To link back to the report in an article, please use this landing page for the final report.
  • The Moving Energy Initiative (MEI) is a collaboration between GVEP International, Chatham House, Practical Action Consulting, the Norwegian Refugee Council (NRC) and the United Nations High Commissioner for Refugees (UNHCR). The report is supported by the UK Department for International Development through the Humanitarian Innovation and Evidence Programme.
  • The number of refugee households in Dadaab, Kenya is as of May 2015.
  • Chatham House will host a press briefing with MEI programme board member Michael Keating and authors Glada Lahn and Owen Grafham on Thursday 12 November at 10:30-11:30 GMT. To register, or for interview requests, please contact the press office.
  • All figures are original and based on estimations and calculations prepared for the Moving Energy Initiative. Chatham House designed a model offering the first estimates of the scale and cost of energy use and CO2 emissions among forcibly displaced households worldwide, not including people affected by natural disasters. For more details on the populations considered in the report and used in the model, contact the authors.
  • The authors are available to answer questions from the media. Please contact the press office.

Contacts

Press Office

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By enabling formal trade, Nigeria can unleash its vast potential

3 December 2015

Nigeria’s booming informal trade is costly for society, business and government, yet a critical opportunity exists to formalize such trade and drive more sustainable and less volatile growth, argues a new report from Chatham House.

According to one estimate, informal activity accounts for up to 64 per cent of Nigeria’s GDP. Nigeria's Booming Borders: The Drivers and Consequences of Unrecorded Trade finds that this is a result of obstacles that impede trading through formal channels. These drivers include bureaucratic burdens and other factors, such as:

  • The need for Nigerian businesses to produce at least nine documents in order to send an export shipment and at least 13 in order to bring in an import consignment.
  • Rigid and dysfunctional foreign-exchange regulations that push most smaller traders into the incompletely regulated parallel exchange market.
  • Corruption and unofficial ‘taxation’, especially on major border highways, which delegitimize formal channels and encourage the use of smuggling routes.

As a result, the state loses direct tax revenues that would be generated by formal cross-border trade. This is not just siphoned into the informal economy; some is lost entirely. For example, many shippers opt to dock in neighbouring countries rather than deal with the expense and difficulty of using Nigeria’s ports.

Informal trade also undermines the social contract between the private sector and government. The state lacks tax revenues to pay its officials, improve infrastructure or implement reforms, while traders feel the government provides no services in return for any taxes they might pay.

‘Every day tens of thousands of unofficial payments are made, none destined for the government. Policy-makers need to create an environment that encourages trade to flow through formal channels and capture lost revenue’, says co-author Leena Koni Hoffmann.

‘Formalization would assist Nigeria to pursue more high-quality, high-tech economic activity at a time when rising labour costs in Asia are creating scope for Nigerian manufacturers to compete’, she adds.

The report makes a number of recommendations for how Nigeria could encourage more formal trade, including:

  • Strengthening the resources and capacity of the Federal Ministry of Industry, Trade and Investment to coordinate action across key government ministries, departments and agencies, as well as public and private stakeholders.
  • Prioritizing engagement in the development of Economic Community of West African States (ECOWAS) trade policies and fully implementing the ECOWAS Protocol on Free Movement of Persons to reduce harassment at borders.
  • Allowing banks to operate simple services for small and medium-sized businesses to make trade payments directly from Nigerian naira to CFA francs and vice versa.
  • Improving basic facilities that support traders, including improving the efficiency of border posts, installing truck parks and all-weather surfacing on market access roads, and introducing online booking for trucks to enter ports.
  • Separating responsibilities for assessing duty and tariff liabilities from revenue collection in order to reduce opportunities for corruption, an approach already tested with success by the Lagos State Internal Revenue Service.
  • Increasing funding and technical support for the National Bureau of Statistics, which has a significant role to play in measuring and capturing more of Nigeria’s external trade.

Interviews conducted for the report reveal that business people would welcome the opportunity to pay taxes, but only if they received assurance that these payments would represent a contract with government guaranteeing that conditions for business would be improved.

‘As Africa’s largest economy, formalizing external trade would allow Nigeria to fulfil its potential as the trading engine of the West and Central African economy and shape the business landscape across the region,’ says co-author Paul Melly.

Editor's notes

  • Read Nigeria's Booming Borders: the Drivers and Consequences of Unrecorded Trade (embargoed until 17:00 GMT on Monday 7 December).
  • To request an interview with the authors, contact the press office.
  • Nigeria’s recorded external trade for 2014 was $135.8 billion.
  • Estimate of informal activity as a percentage of GDP from Jonathan Emenike Ogbuabor and Victor A. Malaolu, ‘Size and Causes of the Informal Sector of the Nigerian Economy: Evidence from Error Correction Mimic Model’, Journal of Economics and Sustainable Development, Vol. 4, No. 1, 2013.

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Dr Lina Khatib to head Middle East and North Africa Programme

3 May 2016

Chatham House is pleased to announce that Dr Lina Khatib has joined the institute as head of the Middle East and North Africa Programme.

Dr Lina Khatib takes up her role at Chatham House as of 3 May 2016. She joins Chatham House from her position as a senior research associate with the Arab Reform Initiative. Previously, she was director of the Carnegie Middle East Center in Beirut and, prior to that, the co-founding head of the Program on Arab Reform and Democracy at Stanford University’s Center on Democracy, Development, and the Rule of Law.

Dr Robin Niblett, director of Chatham House, said: ‘I take great pleasure in welcoming Dr Lina Khatib to Chatham House. Dr Khatib joins our team at a critical time of prolonged turmoil and upheaval in the Middle East and North Africa. Her significant international experience of analysing developments in the region will be a great asset to Chatham House as it assesses the core political, economic, societal and security issues affecting peace and prosperity across this region. I would also like to thank Dr Neil Quilliam for his strong leadership of the Middle East and North Africa Programme since 2014.’

Dr Lina Khatib, said: ‘At a time when countries in the Middle East and North Africa face critical challenges, from continuing conflicts in Syria, Libya, and elsewhere, to increasing socio-economic pressures, it is essential for policy decisions to be informed by rigorous and forward-thinking research and debate. I look forward to working with the team at Chatham House to assist decision-makers and the public in understanding the complexities of an important region at this turbulent moment and seeking creative ways of alleviating its challenges.’ 

Dr Neil Quilliam, who has been acting head of the programme since December 2015, will continue with his role as senior research fellow and Syria project director. 

Editor's notes

Dr Khatib holds a BA from the American University of Beirut and an MA and PhD from the University of Leicester. Her research spans the international relations of the Middle East, Islamist groups, political transitions and foreign policy, with a focus on the regional and international political and security dimensions of the Syrian conflict.

Dr Khatib has published seven books, including Image Politics in the Middle East: The Role of the Visual in Political Struggle (I. B. Tauris, 2013), Taking to the Streets: The Transformation of Arab Activism (co-edited with Ellen Lust, Johns Hopkins University Press, 2014), and The Hizbullah Phenomenon: Politics and Communication (co-authored with Dina Matar and Atef Alshaer, Hurst/Oxford University Press, 2014). She has also published widely on public diplomacy, political communication, and political participation in the Middle East.

Since 2008, Dr Khatib has been a founding co-editor of the Middle East Journal of Culture and Communication and a research associate at the University of London’s School of Oriental and African Studies. From 2010 to 2012, she was a non-resident research fellow at the University of Southern California’s Center on Public Diplomacy. She lectured at Royal Holloway, University of London from 2003 to 2010.

Prior to joining the academic field, Dr Khatib worked in broadcast journalism in Lebanon.




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Chatham House appoints Adam Ward as deputy director

17 January 2017

Chatham House is pleased to announce that Adam Ward will join the institute in a new role as deputy director.

Adam Ward takes up the position of deputy director on 10 April 2017 and will join Chatham House from the International Institute of Strategic Studies (IISS) in London, where he has served as director of studies since 2009.

As deputy director, Adam will oversee and coordinate Chatham House's multiple areas of research, help manage the institute's relationships with key external constituencies, ensure the delivery of high-quality publications and deputize for the institute’s director, Dr Robin Niblett.

This is a new position, created after a period of sustained growth for Chatham House, especially in research and policy outputs. The appointment also coincides with the opening this spring of new working and meeting space for the institute in Ames House, the building adjacent to Chatham House on Duke of York Street in the St James's area of central London.

At IISS, publishers of the renowned annual Military Balance and other high-quality publications and organizers of influential annual security summits, including the Shangri-La Dialogue, Adam was responsible for the oversight of its worldwide research activities, which are also conducted from IISS offices in the Middle East, Asia and the US. Adam led the establishment of the office in Washington and was previously a senior fellow for East Asia.

Dr Robin Niblett, director of Chatham House, said:‘I am delighted that Adam Ward will shortly be joining Chatham House. At a time of great uncertainty and risk in international affairs, his experience in leading research at the prestigious IISS and knowledge of how research institutes can develop and communicate their ideas on public policy will be of enormous value. His wide-ranging expertise on geopolitics and the foreign policies of China and the United States will also help the institute develop integrated projects that reflect the changing balance of world power. I very much look forward to working with him.

Adam Ward said:‘I am excited to take up this opportunity to join Chatham House's executive leadership and to work with Robin Niblett and his senior management team. Chatham House has a well-deserved reputation for rigour and excellence in its research and for providing insights and solutions across a comprehensive range of international challenges. Chatham House's capacity for inter-disciplinary research is one of its distinctive strengths, and I look forward to ensuring its ideas are brought to bear on an ever more complex policy environment.’ 

Editor's notes

About Chatham House

Chatham House, the Royal Institute of International Affairs, is an independent policy institute based in London. Its mission is to help build a sustainably secure, prosperous and just world. Founded in 1920, Chatham House engages governments, the private sector, civil society and its members in open debate and confidential discussion on the most significant developments in international affairs. Each year, the institute runs more than 300 private and public events – conferences, workshops and roundtables – in London and internationally with partners. Its convening power attracts world leaders and the best analysts in their respective fields from across the globe.

About Adam Ward

As director of studies of the IISS, Adam Ward has since 2009 led the execution of the Institute’s worldwide research activities, including setting priorities, raising funds and the management of a research staff distributed across four international offices. Between 2009 and 2014 he organized the annual series of IISS Global Strategic Review conferences. He represents the institute internationally among its audiences in government, the expert community and business.

Adam was previously, from 2006, executive director of the IISS office in Washington DC, where he led the relocation of the office to larger premises, an expansion in its staff, the development of a busy events programme and research activities and acted as the institute’s principal liaison with US government agencies and the Washington-based diplomatic and academic community. Prior to this, he served from 2001 simultaneously as the IISS senior fellow for East Asian security and editor of Strategic Comments, a series of analytical briefing papers on global topics.

He began his career in 1997 as an analyst and editor at the consulting firm Oxford Analytica, focusing on the Asia-Pacific region. He holds a bachelor’s degree in German and Politics and an MA in International Relations, both from the University of Warwick, and also studied for one academic year at the University of Salzburg in Austria.




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Chatham House appoints Tim Benton as Distinguished Visiting Fellow

26 January 2017

Chatham House is pleased to announce that Tim Benton has joined the institute as a Distinguished Visiting Fellow in the Energy, Environment and Resources Department.

Professor Tim Benton has joined Chatham House’s Energy, Environment and Resources department to help develop the institute’s work on the critical challenges of climate change, resilience and sustainable development. He brings renowned expertise on food security and environmental change, and will focus on establishing new initiatives at the intersection of research and policymaking.

Previously Tim has been UK champion for global food security, acting as an ambassador and spokesperson as well as coordinating work between research councils and government departments in this increasingly important area or research. Tim is also the dean for strategic research initiatives at the University of Leeds and a global agenda steward for the World Economic Forum.

Rob Bailey, director of the Energy, Environment and Resources department, said: 'I am delighted to welcome Tim to Chatham House. He has distinguished himself as a leading thinker on climate change and food security and we are all excited at the prospect of working with him.'

Tim Benton said: 'It is an honour to join Chatham House, with its great international reputation for independent thinking. I am looking forward to making a contribution to meeting the challenges implicit in managing the world’s resources sustainably whilst the global population and economy grows.'

Editor's notes

About the Energy, Environment and Resources Department

The Energy, Environment and Resources department at Chatham House seeks to advance the international debate on energy, environment and development policy and to influence and enable decision-makers - governments, NGOs and business - to take well-informed decisions that contribute to achieving sustainable development. Independent of any actor or ideology, we do this by carrying out innovative research on major policy challenges, bringing together diverse perspectives and constituencies and injecting new ideas into the international arena.




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Chatham House is pleased to announce Koc Holding’s support for the Turkey Project

22 February 2017

Chatham House is delighted to announce Koc Holding’s support for the Turkey Project, based in the Europe Programme.

The project aims to analyze and highlight important issues emanating from Turkey’s geostrategic position and bring a Turkish perspective to important regional developments. Areas of research include Turkey’s evolving relationship with Europe and its contribution to the new ‘silk road’ known as the Belt and Road initiative, aimed at strengthening trade and infrastructure links between Asia and Europe.

Mr Ali Y Koc, vice chairman of Koc Holding, has also joined the Chatham House Panel of Senior Advisers, to which he will bring his experience and perspectives on Turkey and on wider global political, economic and social issues.

Koc Holding is the leading business group in Turkey with extensive activities in the manufacturing, energy, defence and finance sectors. Mr Ali Y Koc is a board member and executive committee member of Koc Holding and chairman of the 1907 Fenerbahce Association and the National Competitiveness Research Association. He is a board member of the Foreign Economic Relations Board (DEIK), Endeavor Turkey and vice president of the Turkish Industrialists' and Business Association (TUSIAD). He is also a member of the Bank of America Global Advisory Council.

Robin Niblett, director of Chatham House, said: 'We are grateful to Mr Ali Y Koc and Koc Holding for supporting this initiative, which builds on our established track record of work on Turkey. Turkey plays an increasingly important strategic role, and through this project, Chatham House will be able to expand its analysis and activities in this area. I am also delighted that Chatham House will benefit from the input and expertise of Mr Koc as a member of the institute’s Panel of Senior Advisers.'

Mr Ali Y Koc said: 'Koc Holding is pleased to establish a long-term partnership with Chatham House and support a distinctive research project on Turkey at a world-leading think-tank. We look forward to sharing our insights on Turkey and other significant issues in international affairs among such a distinguished globally-renowned group of individuals in foreign policy, business and civil society on the Panel of Senior Advisers.'