con Lipid Conformational Order and the Etiology of Cataract and Dry Eye [Thematic Reviews] By www.jlr.org Published On :: 2020-06-18T14:30:29-07:00 Lens and tear film lipids are as unique as the systems they reside in. The major lipid of the human lens is dihydrosphingomylein, found in quantity only in the lens. The lens contains a cholesterol to phospholipid molar ratio as high as 10:1, more than anywhere in the body. Lens lipids contribute to maintaining lens clarity, and alterations in lens lipid composition due to age are likely to contribute to cataract. Lens lipid composition reflects adaptations to the unique characteristics of the lens: no turnover of lens lipids or proteins; the lowest amount of oxygen than any other tissue and contains almost no intracellular organelles. The tear film lipid layer (TFLL) is also unique. The TFLL is a thin, 100 nm layer of lipid on the surface of tears covering the cornea that contributes to tear film stability. The major lipids of the TFLL are wax esters and cholesterol esters that are not found in the lens. The hydrocarbon chains associated with the esters are longer than those found anywhere in the body, as long as 32 carbons, and many are branched. Changes in the composition and structure of the 30,000 different moieties of TFLL contribute to the instability of tears. The focus of the current review is how spectroscopy has been used to elucidate the relationships between lipid composition, conformational order and function and the etiology of cataract and dry eye. Full Article
con Generation and validation of a conditional knockout mouse model for the study of the Smith-Lemli-Opitz Syndrome [Research Articles] By www.jlr.org Published On :: 2020-11-17T11:30:28-08:00 Smith-Lemli-Opitz Syndrome (SLOS) is a developmental disorder (OMIM #270400) caused by autosomal recessive mutations in the Dhcr7 gene, which encodes the enzyme 3β-hydroxysterol-7 reductase. SLOS patients present clinically with dysmorphology and neurological, behavioral and cognitive defects, with characteristically elevated levels of 7-dehydrocholesterol (7-DHC) in all bodily tissues and fluids. Previous mouse models of SLOS have been hampered by postnatal lethality when Dhcr7 is knocked out globally, while a hypomorphic mouse model showed improvement in the biochemical phenotype with ageing, and did not manifest most other characteristic features of SLOS. We report the generation of a conditional knockout of Dhcr7 (Dhcr7flx/flx), validated by generating a mouse with a liver-specific deletion (Dhcr7L-KO). Phenotypic characterization of liver-specific knockout mice revealed no significant changes in viability, fertility, growth curves, liver architecture, hepatic triglyceride secretion, or parameters of systemic glucose homeostasis. Furthermore, qPCR and RNA-Seq analyses of livers revealed no perturbations in pathways responsible for cholesterol synthesis, either in male or female Dhcr7L-KO mice, suggesting hepatic disruption of post-squalene cholesterol synthesis leads to minimal impact on sterol metabolism in the liver. This validated conditional Dhcr7 knockout model may now allow us to systematically explore the pathophysiology of SLOS, by allowing for temporal, cell and tissue-specific loss of DHCR7. Full Article
con Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control [Research Articles] By www.jlr.org Published On :: 2020-12-17T12:30:20-08:00 Perilipin (PLIN) 5 is a lipid droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. We detected phosphorylation on S155, S161 and S163 of recombinant PLIN5 by PKA in vitro and identified S155 as a functionally important site for lipid metabolism. Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation compared with cells expressing wildtype PLIN5. These differences in lipid metabolism were not associated with differences in the cellular distribution of PLIN5. Rather, FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase (ATGL) at the lipid droplet, but not with the co-activator of ATGL, α-β hydrolase domain-containing 5 (ABHD5). Re-expression of PLIN5 S155A in the liver of Plin5 liver-specific null mice reduced lipolysis when compared to mice with wildtype PLIN5 re-expression, but was not associated with other changes in hepatic lipid metabolism, such as fatty acid oxidation, de novo lipogenesis and triglyceride secretion. Furthermore, glycemic control was impaired in mice with expression of PLIN5 S155A compared with mice expressing PLIN5. Together, these studies demonstrate that PLIN5 S155 is required for PKA-mediated lipolysis and builds on the body of evidence demonstrating a critical role for PLIN5 in coordinating lipid and glucose metabolism Full Article
con Risks of duloxetine for stress incontinence outweigh benefits, say researchers By www.bmj.com Published On :: Tuesday, November 15, 2016 - 06:30 Full Article
con Trial of novel leukaemia drug is stopped for second time after two more deaths By www.bmj.com Published On :: Friday, November 25, 2016 - 10:46 Full Article
con First case of Zika virus spread through sexual contact is detected in UK By www.bmj.com Published On :: Thursday, December 1, 2016 - 15:45 Full Article
con Interleukin 6 reduces allopregnanolone synthesis in the brain and contributes to age-related cognitive decline in mice [Research Articles] By www.jlr.org Published On :: 2020-10-01T00:05:17-07:00 Cognitive decline with age is a harmful process that can reduce quality of life. Multiple factors have been established to contribute to cognitive decline, but the overall etiology remains unknown. Here, we hypothesized that cognitive dysfunction is mediated, in part, by increased levels of inflammatory cytokines that alter allopregnanolone (AlloP) levels, an important neurosteroid in the brain. We assessed the levels and regulation of AlloP and the effects of AlloP supplementation on cognitive function in 4-month-old and 24-month-old male C57BL/6 mice. With age, the expression of enzymes involved in the AlloP synthetic pathway was decreased and corticosterone (CORT) synthesis increased. Supplementation of AlloP improved cognitive function. Interestingly, interleukin 6 (IL-6) infusion in young animals significantly reduced the production of AlloP compared with controls. It is notable that inhibition of IL-6 with its natural inhibitor, soluble membrane glycoprotein 130, significantly improved spatial memory in aged mice. These findings were supported by in vitro experiments in primary murine astrocyte cultures, indicating that IL-6 decreases production of AlloP and increases CORT levels. Our results indicate that age-related increases in IL-6 levels reduce progesterone substrate availability, resulting in a decline in AlloP levels and an increase in CORT. Furthermore, our results indicate that AlloP is a critical link between inflammatory cytokines and the age-related decline in cognitive function. Full Article
con {beta}-Carotene conversion to vitamin A delays atherosclerosis progression by decreasing hepatic lipid secretion in mice [Research Articles] By www.jlr.org Published On :: 2020-11-01T00:05:43-07:00 Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of CVDs, and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affects atherosclerosis progression in the atheroprone LDLR-deficient mice. Compared with control-fed Ldlr–/– mice, β-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and reduced plasma cholesterol levels. These changes were absent in Ldlr–/–/Bco1–/– mice despite accumulating β-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments. Lipid production assays found that retinoic acid, the active form of vitamin A, reduced the secretion of newly synthetized triglyceride and cholesteryl ester in cell culture and mice. Overall, our findings provide insights into the role of BCO1 activity and vitamin A in atherosclerosis progression through the regulation of hepatic lipid metabolism. Full Article
con Novel contact sites between lipid droplets, early endosomes, and the endoplasmic reticulum [Images in Lipid Research] By www.jlr.org Published On :: 2020-11-01T00:05:43-07:00 Full Article
con Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood [Research Articles] By www.jlr.org Published On :: 2020-12-01T00:05:39-08:00 Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1+/+ and Abca1–/– mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain. Full Article
con Site-specific deacylation by ABHD17a controls BK channel splice variant activity [Signal Transduction] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 S-Acylation, the reversible post-translational lipid modification of proteins, is an important mechanism to control the properties and function of ion channels and other polytopic transmembrane proteins. However, although increasing evidence reveals the role of diverse acyl protein transferases (zDHHC) in controlling ion channel S-acylation, the acyl protein thioesterases that control ion channel deacylation are very poorly defined. Here we show that ABHD17a (α/β-hydrolase domain-containing protein 17a) deacylates the stress-regulated exon domain of large conductance voltage- and calcium-activated potassium (BK) channels inhibiting channel activity independently of effects on channel surface expression. Importantly, ABHD17a deacylates BK channels in a site-specific manner because it has no effect on the S-acylated S0–S1 domain conserved in all BK channels that controls membrane trafficking and is deacylated by the acyl protein thioesterase Lypla1. Thus, distinct S-acylated domains in the same polytopic transmembrane protein can be regulated by different acyl protein thioesterases revealing mechanisms for generating both specificity and diversity for these important enzymes to control the properties and functions of ion channels. Full Article
con Functional impact of a congenital stationary night blindness type 2 mutation depends on subunit composition of Cav1.4 Ca2+ channels [Neurobiology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Voltage-gated Cav1 and Cav2 Ca2+ channels are comprised of a pore-forming α1 subunit (Cav1.1-1.4, Cav2.1-2.3) and auxiliary β (β1-4) and α2δ (α2δ−1−4) subunits. The properties of these channels vary with distinct combinations of Cav subunits and alternative splicing of the encoding transcripts. Therefore, the impact of disease-causing mutations affecting these channels may depend on the identities of Cav subunits and splice variants. Here, we analyzed the effects of a congenital stationary night blindness type 2 (CSNB2)-causing mutation, I745T (IT), in Cav1.4 channels typical of those in human retina: Cav1.4 splice variants with or without exon 47 (Cav1.4+ex47 and Cav1.4Δex47, respectively), and the auxiliary subunits, β2X13 and α2δ-4. We find that IT caused both Cav1.4 splice variants to activate at significantly more negative voltages and with slower deactivation kinetics than the corresponding WT channels. These effects of the IT mutation, along with unexpected alterations in ion selectivity, were generally larger in channels lacking exon 47. The weaker ion selectivity caused by IT led to hyperpolarizing shifts in the reversal potential and large outward currents that were evident in channels containing the auxiliary subunits β2X13 and α2δ-4 but not in those with β2A and α2δ-1. We conclude that the IT mutation stabilizes channel opening and alters ion selectivity of Cav1.4 in a manner that is strengthened by exclusion of exon 47 and inclusion of β2X13 and α2δ-4. Our results reveal complex actions of IT in modifying the properties of Cav1.4 channels, which may influence the pathological consequences of this mutation in retinal photoreceptors. Full Article
con Neuroligin-2 dependent conformational activation of collybistin reconstituted in supported hybrid membranes [Membrane Biology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 The assembly of the postsynaptic transmitter sensing machinery at inhibitory nerve cell synapses requires the intimate interplay between cell adhesion proteins, scaffold and adaptor proteins, and γ-aminobutyric acid (GABA) or glycine receptors. We developed an in vitro membrane system to reconstitute this process, to identify the essential protein components, and to define their mechanism of action, with a specific focus on the mechanism by which the cytosolic C terminus of the synaptic cell adhesion protein Neuroligin-2 alters the conformation of the adaptor protein Collybistin-2 and thereby controls Collybistin-2-interactions with phosphoinositides (PtdInsPs) in the plasma membrane. Supported hybrid membranes doped with different PtdInsPs and 1,2-dioleoyl-sn-glycero-3-{[N-(5-amino-1-carboxypentyl)iminodiacetic acid]succinyl} nickel salt (DGS-NTA(Ni)) to allow for the specific adsorption of the His6-tagged intracellular domain of Neuroligin-2 (His-cytNL2) were prepared on hydrophobically functionalized silicon dioxide substrates via vesicle spreading. Two different collybistin variants, the WT protein (CB2SH3) and a mutant that adopts an intrinsically 'open' and activated conformation (CB2SH3/W24A-E262A), were bound to supported membranes in the absence or presence of His-cytNL2. The corresponding binding data, obtained by reflectometric interference spectroscopy, show that the interaction of the C terminus of Neuroligin-2 with Collybistin-2 induces a conformational change in Collybistin-2 that promotes its interaction with distinct membrane PtdInsPs. Full Article
con Conserved biophysical features of the CaV2 presynaptic Ca2+ channel homologue from the early-diverging animal Trichoplax adhaerens [Membrane Biology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 The dominant role of CaV2 voltage-gated calcium channels for driving neurotransmitter release is broadly conserved. Given the overlapping functional properties of CaV2 and CaV1 channels, and less so CaV3 channels, it is unclear why there have not been major shifts toward dependence on other CaV channels for synaptic transmission. Here, we provide a structural and functional profile of the CaV2 channel cloned from the early-diverging animal Trichoplax adhaerens, which lacks a nervous system but possesses single gene homologues for CaV1–CaV3 channels. Remarkably, the highly divergent channel possesses similar features as human CaV2.1 and other CaV2 channels, including high voltage–activated currents that are larger in external Ba2+ than in Ca2+; voltage-dependent kinetics of activation, inactivation, and deactivation; and bimodal recovery from inactivation. Altogether, the functional profile of Trichoplax CaV2 suggests that the core features of presynaptic CaV2 channels were established early during animal evolution, after CaV1 and CaV2 channels emerged via proposed gene duplication from an ancestral CaV1/2 type channel. The Trichoplax channel was relatively insensitive to mammalian CaV2 channel blockers ω-agatoxin-IVA and ω-conotoxin-GVIA and to metal cation blockers Cd2+ and Ni2+. Also absent was the capacity for voltage-dependent G-protein inhibition by co-expressed Trichoplax Gβγ subunits, which nevertheless inhibited the human CaV2.1 channel, suggesting that this modulatory capacity evolved via changes in channel sequence/structure, and not G proteins. Last, the Trichoplax channel was immunolocalized in cells that express an endomorphin-like peptide implicated in cell signaling and locomotive behavior and other likely secretory cells, suggesting contributions to regulated exocytosis. Full Article
con Correction: Concentration Determination of >200 Proteins in Dried Blood Spots for Biomarker Discovery and Validation [Addition and Correction] By www.mcponline.org Published On :: 2020-10-01T00:05:25-07:00 Full Article
con Novel Proteome Extraction Method Illustrates a Conserved Immunological Signature of MSI-H Colorectal Tumors [Research] By www.mcponline.org Published On :: 2020-10-01T00:05:25-07:00 Using a simple, environment friendly proteome extraction (TOP), we were able to optimize the analysis of clinical samples. Using our TOP method we analyzed a clinical cohort of microsatellite stable (MSS) and unstable (MSI-H) colorectal carcinoma (CRC). We identified a tumor cell specific, STAT1-centered, immune signature expressed by the MSI-H tumor cells. We then showed that long, but not short, exposure to Interferon- induces a similar signature in vitro. We identified 10 different temporal protein expression patterns, classifying the Interferon- protein temporal regulation in CRC. Our data sheds light on the changes that tumor cells undergo under long-term immunological pressure in vivo, the importance of STAT proteins in specific biological scenarios. The data generated could help find novel clinical biomarkers and therapeutic approaches. Full Article
con Examining and Fine-tuning the Selection of Glycan Compositions with GlyConnect Compozitor [Research] By www.mcponline.org Published On :: 2020-10-01T00:05:25-07:00 A key point in achieving accurate intact glycopeptide identification is the definition of the glycan composition file that is used to match experimental with theoretical masses by a glycoproteomics search engine. At present, these files are mainly built from searching the literature and/or querying data sources focused on posttranslational modifications. Most glycoproteomics search engines include a default composition file that is readily used when processing MS data. We introduce here a glycan composition visualizing and comparative tool associated with the GlyConnect database and called GlyConnect Compozitor. It offers a web interface through which the database can be queried to bring out contextual information relative to a set of glycan compositions. The tool takes advantage of compositions being related to one another through shared monosaccharide counts and outputs interactive graphs summarizing information searched in the database. These results provide a guide for selecting or deselecting compositions in a file in order to reflect the context of a study as closely as possible. They also confirm the consistency of a set of compositions based on the content of the GlyConnect database. As part of the tool collection of the Glycomics@ExPASy initiative, Compozitor is hosted at https://glyconnect.expasy.org/compozitor/ where it can be run as a web application. It is also directly accessible from the GlyConnect database. Full Article
con Sialylation of Asparagine 612 Inhibits Aconitase Activity during Mouse Sperm Capacitation; a Possible Mechanism for the Switch from Oxidative Phosphorylation to Glycolysis [Research] By www.mcponline.org Published On :: 2020-11-01T00:05:37-07:00 After ejaculation, mammalian spermatozoa must undergo a process known as capacitation in order to successfully fertilize the oocyte. Several post-translational modifications occur during capacitation, including sialylation, which despite being limited to a few proteins, seems to be essential for proper sperm-oocyte interaction. Regardless of its importance, to date, no single study has ever identified nor quantified which glycoproteins bearing terminal sialic acid (Sia) are altered during capacitation. Here we characterize sialylation during mouse sperm capacitation. Using tandem MS coupled with liquid chromatography (LC–MS/MS), we found 142 nonreductant peptides, with 9 of them showing potential modifications on their sialylated oligosaccharides during capacitation. As such, N-linked sialoglycopeptides from C4b-binding protein, endothelial lipase (EL), serine proteases 39 and 52, testis-expressed protein 101 and zonadhesin were reduced following capacitation. In contrast, mitochondrial aconitate hydratase (aconitase; ACO2), a TCA cycle enzyme, was the only protein to show an increase in Sia content during capacitation. Interestingly, although the loss of Sia within EL (N62) was accompanied by a reduction in its phospholipase A1 activity, a decrease in the activity of ACO2 (i.e. stereospecific isomerization of citrate to isocitrate) occurred when sialylation increased (N612). The latter was confirmed by N612D recombinant protein tagged with both His and GFP. The replacement of Sia for the negatively charged Aspartic acid in the N612D mutant caused complete loss of aconitase activity compared with the WT. Computer modeling show that N612 sits atop the catalytic site of ACO2. The introduction of Sia causes a large conformational change in the alpha helix, essentially, distorting the active site, leading to complete loss of function. These findings suggest that the switch from oxidative phosphorylation, over to glycolysis that occurs during capacitation may come about through sialylation of ACO2. Full Article
con Quels sont les effets secondaires de seroplex ? By www.orthodfr.org Published On :: Fri, 02 Aug 2024 09:39:45 +0000 Les médicaments utilisés pour le traitement des troubles mentaux peuvent avoir des effets secondaires plus ou moins graves sur la santé des patients. C’est le cas de seroplex, un médicament largement utilisé comme traitement dans le domaine de la santé mentale. Mais en réalité, quelle est la composition de ce médicament et quels sont ses […] L’article Quels sont les effets secondaires de seroplex ? est apparu en premier sur Ortho Doc France. Full Article Santé
con Quelle est la meilleure recette minceur à base de biscuits aux flocons d’avoine ? By www.orthodfr.org Published On :: Thu, 26 Sep 2024 13:34:24 +0000 Pour beaucoup de personnes, la perte de poids rime obligatoirement avec une période de privation. Mais contrairement à ces idées reçues, il est bien possible d’observer un régime pour perdre du poids tout en vous faisant plaisir. Découvrez notre recette minceur de biscuits croquants sans beurre aux flocons d’avoine qui raviront vos papilles sans pour autant vous apporter […] L’article Quelle est la meilleure recette minceur à base de biscuits aux flocons d’avoine ? est apparu en premier sur Ortho Doc France. Full Article Minceur
con The ProteoRed MIAPE web toolkit: A user-friendly framework to connect and share proteomics standards [Technology] By www.mcponline.org Published On :: 2011-06-19T13:05:33-07:00 The development of the HUPO-PSI's (Proteomics Standards Initiative) standard data formats and MIAPE (Minimum Information About a Proteomics Experiment) guidelines should improve proteomics data sharing within the scientific community. Proteomics journals have encouraged the use of these standards and guidelines to improve the quality of experimental reporting and ease the evaluation and publication of manuscripts. However, there is an evident lack of bioinformatics tools specifically designed to create and edit standard file formats and reports, or embed them within proteomics workflows. In this article, we describe a new web-based software suite (The ProteoRed MIAPE web toolkit) that performs several complementary roles related to proteomic data standards. Firstly, it can verify the reports fulfill the minimum information requirements of the corresponding MIAPE modules, highlighting inconsistencies or missing information. Secondly, the toolkit can convert several XML-based data standards directly into human readable MIAPE reports stored within the ProteoRed MIAPE repository. Finally, it can also perform the reverse operation, allowing users to export from MIAPE reports into XML files for computational processing, data sharing or public database submission. The toolkit is thus the first application capable of automatically linking the PSI's MIAPE modules with the corresponding XML data exchange standards, enabling bidirectional conversions. This toolkit is freely available at http://www.proteored.org/MIAPE/. Full Article
con Plasma proteomic data can contain personally identifiable, sensitive information and incidental findings [Research] By www.mcponline.org Published On :: 2020-12-17T07:31:07-08:00 The goal of clinical proteomics is to identify, quantify, and characterize proteins in body fluids or tissue to assist diagnosis, prognosis, and treatment of patients. In this way, it is similar to more mature omics technologies, such as genomics, that are increasingly applied in biomedicine. We argue that, similar to those fields, proteomics also faces ethical issues related to the kinds of information that is inherently obtained through sample measurement, although their acquisition was not the primary purpose. Specifically, we demonstrate the potential to identify individuals both by their characteristic, individual-specific protein levels and by variant peptides reporting on coding single nucleotide polymorphisms. Furthermore, it is in the nature of blood plasma proteomics profiling that it broadly reports on the health status of an individual – beyond the disease under investigation. Finally, we show that private and potentially sensitive information, such as ethnicity and pregnancy status, can increasingly be derived from proteomics data. Although this is potentially valuable not only to the individual, but also for biomedical research, it raises ethical questions similar to the incidental findings obtained through other omics technologies. We here introduce the necessity of - and argue for the desirability for - ethical and human rights-related issues to be discussed within the proteomics community. Those thoughts are more fully developed in our accompanying manuscript. Appreciation and discussion of ethical aspects of proteomic research will allow for deeper, better-informed, more diverse, and, most importantly, wiser guidelines for clinical proteomics. Full Article
con Global lysine acetylation and 2-hydroxyisobutyrylation reveal the metabolism conversion mechanism in Giardia lamblia [Research] By www.mcponline.org Published On :: 2020-12-29T13:35:14-08:00 Giardia lamblia (G. lamblia) disease is a zoonosis with a-infection rate affecting the general population of the world. Despite the constant possibility of damage due to their own metabolism, G. lamblia have survived and evolved to adapt to various environments. However, research on energy-metabolism conversion in G. lamblia is limited. This study aimed to reveal the dynamic metabolism-conversion mechanism in G. lamblia under sugar starvation by detecting global lysine acetylation and 2-hydroxyisobutyrylation sites combined with quantitative proteome analyses. A total of 2999 acetylation sites on 956 proteins and 8877 2-hydroxyisobutyryl sites on 1546 proteins were quantified under sugar starvation. Integrated Kac and Khib data revealed that modified proteins were associated with arginine biosynthesis, glycolysis/gluconeogenesis, and alanine, aspartate, and glutamate metabolism. These findings suggested that lysine acetylation and 2-hydroxyisobutyrylation were ubiquitous and provided deep insight into the metabolism-conversion mechanism in G. lamblia under sugar starvation. Overall, these results can help understand the biology of G. lamblia infections and reveal the evolution rule from prokaryote to eukaryote. Full Article
con Ethical principles, opportunities and constraints in clinical proteomics [Research] By www.mcponline.org Published On :: 2021-01-04T06:35:18-08:00 Recent advances in MS-based proteomics have vastly increased the quality and scope of biological information that can be derived from human samples. These advances have rendered current workflows increasingly applicable in biomedical and clinical contexts. As proteomics is poised to take an important role in the clinic, associated ethical responsibilities increase in tandem with the impact on the health, privacy, and well-being of individuals. Here we conducted and report a systematic literature review of ethical issues in clinical proteomics. We add our perspectives from a background of bioethics, the results of our accompanying paper extracting individual-sensitive results from patient samples, and the literature addressing similar issues in genomics. The spectrum of potential issues ranges from patient re-identification to incidental findings of clinical significance. The latter can be divided into actionable and unactionable findings. Some of these have the potential to be employed in discriminatory or privacy-infringing ways. However, incidental findings may also have great positive potential. A plasma proteome profile, for instance, could inform on the general health or disease status of an individual regardless of the narrow diagnostic question that prompted it. We suggest that early discussion of ethical issues in clinical proteomics is important to ensure that eventual regulations reflect the considered judgment of the community as well as to anticipate opportunities and problems that may arise as the technology matures further. Full Article
con Libya’s War Economy: Predation, Profiteering and State Weakness By www.chathamhouse.org Published On :: Mon, 09 Apr 2018 11:02:14 +0000 Libya’s War Economy: Predation, Profiteering and State Weakness Research paper sysadmin 9 April 2018 As Libya’s war economy persists, prospects for the restoration of functioning central governance become more distant. Summary Libya suffers from interlinked political, security and economic crises that are weakening state institutions, damaging its economy and facilitating the continued existence of non-state armed groups. As rival authorities continue to compete for power, the resulting fragmentation and dysfunction have provided a fertile environment for the development of a pervasive war economy dependent on violence. This war economy is dynamic and constantly in flux. Relative to earlier problems, there were signs of progress on several fronts in 2017: a reduction in human smuggling, a tripling in oil revenues, and increased local action against fuel smuggling. Yet the dynamics that have supported the war economy’s rise remain. Libya’s war economy is highly damaging for the future of the state for three reasons: First, it provides an enabling environment for networks of armed groups, criminal networks, corrupt businessmen and political elites to sustain their activities through illicit sales and predatory practices. Their operations are closely linked to the dispensation of violence, and are thus a spur for further conflict. Second, the war economy perpetuates negative incentives for those who profit from the state’s dysfunction. Only effective governance, supported by a durable political settlement, can tackle the foundations of Libya’s war economy. But neither a return to functioning central governance nor the development of a security sector that is fit for purpose is in the interests of war economy profiteers, who are therefore motivated to act as powerful spoilers of reform. Third, the political contestation and resource predation practised by those engaged in the war economy are having a disastrous impact on Libya’s formal economy, undermining what remains of its institutions. As the war economy persists, therefore, the prospects for the restoration of functioning central governance become more distant. This threatens to create a vicious cycle that accelerates further state collapse. Due to the limited capacity for coercion available to any actor or entity connected with the state, a strategy of co-opting networks of war economy profiteers has almost exclusively prevailed. This has failed. Drawing on the lessons from these attempts, a more successful policy must pursue targeted measures to combat the enabling structures of Libya’s war economy where possible, and to co-opt war economy profiteers only where necessary. In this, state authorities can do more to utilize what power they have to name and shame war economy profiteers in order to weaken the local legitimacy critical to profiteers’ survival. The state must present credible alternative livelihood opportunities to those engaged in, or benefiting from, the war economy. Progress will depend in part on the creation of positive incentives to abandon such activity. Where profiteers cannot be incentivized to move towards more legitimate economic activities, greater and more effective efforts must be made to reduce the profit margins of illicit schemes. The international community can do more to support Libyan efforts in countering the war economy. Cooperation over the targeting of criminal groups’ overseas assets, support for increased transparency over the dispensation of state funds, and measures to reduce the viability of illicit activities can all help to strengthen the position of state authorities. Further reading Discover the six things you need to know about Libya’s war economy 2018-04-12-libyas-war-economy-eaton-final (PDF) Full Article
con Tackling Illegal Wildlife Trade in Africa: Economic Incentives and Approaches By www.chathamhouse.org Published On :: Fri, 05 Oct 2018 15:21:13 +0000 Tackling Illegal Wildlife Trade in Africa: Economic Incentives and Approaches Research paper sysadmin 5 October 2018 Combating illegal wildlife trade and further pursuing conservation-development models could help generate considerable economic benefits for African countries, while ensuring the long-term preservation of Africa’s wealth of natural capital. — Field scout recording desert black rhino data, Save the Rhino Trust, Palmwag, Torra Conservancy, Damaraland, Namibia. Photo: Mint Images/Frans Lanting/Getty Images. Summary The illegal wildlife trade (IWT) significantly impacts African economies by destroying and corroding natural, human and social capital stocks. This hinders the achievement of the Sustainable Development Goals (SDGs) and has an impact on national budgets. Illicit financial flows from IWT deny revenue to governments where legal wildlife product trade exists and perpetuate cash externalization. IWT diverts national budgets away from social or development programmes, increases insecurity and threatens vulnerable populations. In expanding wildlife economies and pursuing conservation-driven development models, governments can protect their citizens, derive revenue from wildlife products, and establish world class tourism offerings. The illegal exploitation of wildlife is often due to a failure to enforce rights over those resources, where rights are unclearly defined or not fully exercised. Southern African countries have defined these rights in various ways, contributing to regional differences in conservation practices and the socio-economic benefits derived from wildlife resources. Combating IWT is an important step towards allowing legitimate business and communities to develop livelihoods that incentivize stewardship and connect people to conservation. The Southern African Development Community (SADC) has several framework policies for the establishment of transfrontier conservation areas (TFCAs). These promote local stewardship across multiple land-use areas to conserve biodiversity and increase the welfare and socioeconomic development of rural communities. Private-sector partnerships also increase skills transfer, improve access to investment finance, and expand economic opportunities, including through the promotion of local procurement. The economic benefits of TFCAs extend beyond tourism. The economic value of African ecosystems is often under-recognized because they remain unquantified, partly due to the lack of available data on the broader economic costs of IWT. Improved monitoring and evaluation with key performance indicators would help governments and citizens to appreciate the economic value of combating IWT. 2018-10-11-tackling-illegal-wildlife-trade-africa-vandome-vines-final2 (PDF) Full Article
con Proportionality in the Conduct of Hostilities: The Incidental Harm Side of the Assessment By www.chathamhouse.org Published On :: Thu, 06 Dec 2018 14:56:29 +0000 Proportionality in the Conduct of Hostilities: The Incidental Harm Side of the Assessment Research paper sysadmin 6 December 2018 Clarification of international humanitarian law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups is also crucial. — Members of civil right defence conduct a search and rescue operation on destroyed buildings after an airstrike was carried out over the city of Jisr al-Shughur in Idlib province in Syria, on 6 May 2018. Photo: Hadi Harrat/Anadolu Agency/Getty Images. Summary Military operations are taking place with increasing frequency in densely populated areas. Such operations result in loss of life and harm to civilians, as well as damage to civilian objects, (including infrastructure providing essential services). In order to protect civilians, it is imperative that armed forces and groups comply with the rules of international humanitarian law on the conduct of hostilities, including the rule of proportionality. The rule of proportionality prohibits attacks which may be expected to cause incidental loss of civilian life, injury to civilians, damage to civilian objects or a combination thereof, which would be excessive in relation to the concrete and direct military advantage anticipated. This research paper analyses the key steps that belligerents must take to give effect to the rule, with a particular focus on one side of proportionality assessments – the expected incidental harm. Those undertaking proportionality assessments before or during an attack must consider whether the expected harm will be caused by the attack, and whether that harm could be expected (that is, was it reasonably foreseeable). For the purpose of proportionality assessments, injury to civilians includes disease, and there is no reason in principle to exclude mental harm, even though it is currently challenging to identify and quantify it. Damage to civilian objects includes damage to elements of the natural environment. Once the incidental harm to be considered has been identified, a value or weight must be assigned to it. This is then balanced against the value or weight of the military advantage anticipated from the attack to determine whether the harm would be excessive. In the determination of whether the expected incidental harm would be excessive compared to the anticipated military advantage, ‘excessive’ is a wide but not indeterminate standard. Belligerents should develop methodologies so that those planning and deciding attacks are provided with all necessary information on expected incidental harm, and to assist them in assigning weight to the incidental harm to be considered. If it becomes apparent that the rule of proportionality will be contravened, the attack in question must be cancelled or suspended. Clarification of the law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups, inculcated by their leaders, is also crucial. 2018-12-10-proportionality-conduct-hostilities-incidental-harm-gillard-final (PDF) Full Article
con Moscow Rules: What Drives Russia to Confront the West By www.chathamhouse.org Published On :: Thu, 17 Jan 2019 14:54:55 +0000 Moscow Rules: What Drives Russia to Confront the West Book sysadmin 17 January 2019 Keir Giles surveys Russia’s history and the present day to explain why its current leadership feels it has no choice but to challenge and attack the West. Recognising and accepting that this will not change in the near future will help the West find a way of dealing with Russia without risking a deeper conflict. This book is for anyone that cannot understand why Russia and its leaders behave as they do. The relationship between Russia and the West is once again deep in crisis. A major reason is that Western leaders have too often believed or hoped that Russia sees the world as they do — but things look very different from Moscow. This book shows that efforts at engagement with Russia that do not take this into account are a key reason for repeated disappointment and crisis. In confronting the West, Russia is implementing strategic and doctrinal approaches that have been consistent for centuries. The roots of current Russian behaviour and demands can be traced not just to the Soviet era, but back into Tsarist foreign and domestic policy, and further to the structure and rules of Russian society. But this also gives the US and the West pointers for how to behave — and how not to — in order to manage the challenge of Russia effectively, based on past experience of both successful and unsuccessful engagement with Moscow. The book recognizes the reality of confrontation and provides an essential introduction to grasping why Russia sees it as inevitable. Consequently, it offers a basis for building a less crisis-prone relationship with Russia. This book is part of the Insights series. Praise for Moscow Rules My only regret is that I did not have this book 35 years ago Toomas Ilves, former President of Estonia Should be required reading for all who deal with Western policy towards Russia Roderic Lyne, former British Ambassador to Moscow About the author Keir Giles is a senior consulting fellow at Chatham House, the Royal Institute of International Affairs. He also works with the Conflict Studies Research Centre (CSRC), a group of subject matter experts in Eurasian security with a particular focus on the wide range of security challenges coming from Russia. Purchase UK (via Amazon) Rest of world (via Brookings Institution Press) Students (via Browns Books) Full Article
con Adopting a Market-based Approach to Boost Energy Access in Displaced Contexts By www.chathamhouse.org Published On :: Mon, 25 Mar 2019 10:18:12 +0000 Adopting a Market-based Approach to Boost Energy Access in Displaced Contexts Research paper sysadmin 25 March 2019 This paper evaluates the market-based approaches adopted in the MEI projects in Kenya and Burkina Faso. It articulates how such commercial strategies can be applied to the delivery of energy in displacement settings and compares this to real world examples. — A shop selling fabric and electronics inside the Dagahaley Camp, one of five camps that make up Dadaab, the world’s largest and oldest camp for refugees. Photo: Michelle Shephard/Toronto Star via Getty Images. Development of long-term energy solutions in displacement settings tends to be perceived as investment that falls outside the remit of emergency responses. In addition, when emergency energy supply measures are implemented they often result in expensive, unreliable and unhealthy energy provision for those in protracted or recurrent crises. There is widespread agreement among humanitarian and development experts that an effective refugee response should include long-term development solutions as well as emergency relief. The energy access imperative is more pronounced when considering the need for effective energy distribution in practically all camp activities and basic necessities: pumping and treatment of clean water; heating and cooling for food storage and cooking; energy for livelihood activities; and provision of light for schooling, hospitals and the prevention of violence against women and children. Minor shifts in household energy use to basic solar lighting options and non-wood fuels would save $303 million annually on refugee fuel costs. Within refugee contexts in Kenya and Burkina Faso, the MEI sought to examine opportunities to use market interventions, rather than in-kind distributions, to improve clean energy access over the long-term and test the delivery of market-based approaches. 2019-03-25-MEIWhitehouse (PDF) Full Article
con Infrastructure Management Contracts: Improving Energy Asset Management in Displacement Settings By www.chathamhouse.org Published On :: Wed, 17 Apr 2019 15:09:12 +0000 Infrastructure Management Contracts: Improving Energy Asset Management in Displacement Settings Research paper sysadmin 17 April 2019 This paper highlights a number of options for managing electricity infrastructure in refugee camps and outlines the challenges, opportunities and operational implications associated with them. It takes the Kalobeyei settlement in Kenya as a case study. — A solar array installed for International Rescue Committee health clinics in Kakuma refugee camp, Kenya. Photo: Kube Energy Building and maintaining electricity infrastructure to power offices, businesses, households and other operations in displacement settings is difficult. It is especially challenging for the Office of the United Nations High Commissioner for Refugees (UNHCR) and its partner agencies, because supplying electricity is not their core business. Private-sector companies exist that are willing and able to develop infrastructure management contracts to provide energy as a service in displacement settings. However, institutional barriers within humanitarian agencies persist, with short budgeting cycles in particular preventing humanitarian agencies from entering into the sorts of long-term service agreements required by the private sector. A number of options exist to leverage the expertise of the private sector through ‘public–private partnership’ (P3) structures. Such mechanisms can promote more efficient management of infrastructure by drawing on private-sector experience and expertise, incentivizing appropriate risk-sharing and providing options to leverage private capital in project development. Field work from the Kalobeyei settlement in Kenya suggests that a solar/diesel hybrid mini-grid solution was the most economical option to power camp services and infrastructure there. Compared to distributed diesel generation, the annual savings in operating costs were estimated at $49,880, with the additional investment paid back within 3.6 years. Humanitarian agencies need to be willing to change their policies to enable long-term service agreements. Alternatively (or, more likely, in conjunction with this option), financial mechanisms such as partial risk guarantees need to be developed to offset some of the risks. This change will need high-level support from donors and humanitarian agencies. Once the first infrastructure management contracts can be signed and tested in displacement locations (through the use of donor funding or otherwise) and associated data collected, it will ease the way for future investments in these types of projects. 2019-04-17-MEI-Infrastructure Management Contracts (PDF) Full Article
con Optimized incorporation of an unnatural fluorescent amino acid affords measurement of conformational dynamics governing high-fidelity DNA replication [DNA and Chromosomes] By www.jbc.org Published On :: 2020-12-11T00:06:21-08:00 DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication. Full Article
con Phosphorylation of SMURF2 by ATM exerts a negative feedback control of DNA damage response [DNA and Chromosomes] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Timely repair of DNA double-strand breaks (DSBs) is essential to maintaining genomic integrity and preventing illnesses induced by genetic abnormalities. We previously demonstrated that the E3 ubiquitin ligase SMURF2 plays a critical tumor suppressing role via its interaction with RNF20 (ring finger protein 20) in shaping chromatin landscape and preserving genomic stability. However, the mechanism that mobilizes SMURF2 in response to DNA damage remains unclear. Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20. We demonstrate that a SMURF2 mutant with an S384A substitution has reduced capacity to ubiquitinate RNF20 while promoting Smad3 ubiquitination unabatedly. More importantly, mouse embryonic fibroblasts expressing the SMURF2 S384A mutant show a weakened ability to sustain the DSB response compared with those expressing WT SMURF2 following etoposide treatment. These data indicate that SMURF2-mediated RNF20 ubiquitination and degradation controlled by ataxia telangiectasia mutated–induced phosphorylation at Ser384 constitutes a negative feedback loop that regulates DSB repair. Full Article
con Who will hit second and third for Phillies? By mlb.mlb.com Published On :: Sat, 16 Feb 2019 16:54:46 EDT Phillies manager Gabe Kapler believes the two most important spots in a lineup are the Nos. 2 and 4 holes. Rhys Hoskins and Carlos Santana hit there most of last season. But with J.T. Realmuto, Andrew McCutchen and Jean Segura joining the Phillies in the offseason, Kapler has more options. Full Article
con Segura moving forward with contending Phillies By mlb.mlb.com Published On :: Sat, 16 Feb 2019 18:17:05 EDT Jean Segura became one of the Phillies' most notable offseason acquisitions, a two-time All-Star expected to give the organization its best overall production at shortstop since Jimmy Rollins left town, in part because of a little brawl he had late last season with Mariners teammate Dee Gordon. Full Article
con Trout on contract talks: 'I don't want to comment' By mlb.mlb.com Published On :: Mon, 18 Feb 2019 14:54:02 EDT Mike Trout and owner Arte Moreno met separately with the media on Monday, but neither would confirm that extension talks have begun between the Angels and Trout's agent, Craig Landis. Full Article
con Francona: Allen 'one of the best competitors' By mlb.mlb.com Published On :: Tue, 19 Feb 2019 19:44:24 EDT The Angels have a new closer in Cody Allen and there isn't any manager in baseball who knows him better than Indians skipper Terry Francona. Full Article
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con South Africa Needs a Strategic Vision for Its Continent By www.chathamhouse.org Published On :: Fri, 24 Nov 2017 13:45:43 +0000 South Africa Needs a Strategic Vision for Its Continent Expert comment sysadmin 24 November 2017 South Africa has the potential to catalyse growth across its sub-region and the continent, but the government must develop a comprehensive strategy that aligns political, ideological and commercial interests. — Departure lounge at OR Tambo International Airport near Johannesburg. Photo: Getty Images. South Africa’s status as the ‘gateway to Africa’ is under serious threat. Its companies continue to flourish, but complex relationships at home and abroad constrain government capacity to match its economic dominance with political reach and influence. South Africa’s policies towards the rest of the continent are often accused of being inconsistent and incoherent. It has been a development partner to the region and to international donors; a moral leader, championing human rights and exporting its own model of transition; and an advocate and representative for the continent in international forums. However, it has simultaneously been accused of exploiting its economic dominance at the expense of its neighbours; handicapped by the political debts owed by the ANC to other liberation movements for their assistance in the struggle; and criticized for its arrogance in seeking to position itself as the ‘legitimate’ voice of Africa. At the same time, reputational risks, a weakened policy environment and poor growth have taken the shine off South Africa’s ‘Gateway to Africa’ rhetoric. South Africa faces considerable domestic economic issues. Growth forecasts have fallen from 1.3 to 0.7 per cent, State owned enterprises are a huge burden on the treasury, and the forecast budget deficit is R50.8 billion (£2.7 billion), at a time when the cost of borrowing is increasing following downgrades of the country’s credit ratings. Political risk is high, lowering investor confidence. Corruption, poor service delivery and the government’s under-delivery on citizen’s expectations are exacerbating social tensions in a country with expanded unemployment at 36.4 per cent, and one of the highest rates of inequality in the world. McKinsey, KPMG and HSBC have all become entangled in scandal relating to their dealings with government entities that have become ‘captured’ by private interests. Despite these concerns, South Africa nonetheless remains the backbone of the regional economy, and its firms are key players across the continent. Johannesburg hosts the deepest and most sophisticated capital market on the continent, and Pretoria has one of the highest numbers of diplomatic missions in the world. ESKOM provides around 75 per cent of the electricity contribution to the Southern Africa SADC Power pool – comprising 12 countries, including those as far north as DRC and Tanzania – and South African ports facilitate over half of sub-Saharan Africa’s non-commodity trade with the rest of the world. Post-apartheid expansion across the continent by South African companies was initially met with resistance, but these relationships have improved significantly – and South African firms retain significant advantages. South African retailers have the scale to incorporate regional producers into continental supply chains, purchasing fresh produce at a competitive price from regional agri-businesses, then re-selling further afield. For example, Zambeef supplies meat from Zambia to Shoprite stores in west Africa. African companies in turn rely on South Africa as a significant consumer of goods, services and primary commodities. A South African government agreement with the DRC to import about half of the electricity that will be produced by a new grand-scale hydro-power project guaranteed its bankability. Mozambique is looking to maximize the potential of its world-class natural gas reserves by building a pipeline into South Africa, thus benefitting from the purchasing power of South African parastatal electricity utility firm ESKOM. But South Africa’s status as an economic hegemon is not mirrored in its political relationships. South Africa’s GDP is five times higher than the six countries with which it shares a border, combined. But successive ANC governments have been unable to fully flex this economic muscle. Partly this is a legacy of history. It is not forgotten that the regional economic body, the Southern African Development Community, originated as the organization of Front Line States coordinating efforts to end apartheid, and ZANU-PF officials in Zimbabwe lecture their ANC counterparts on liberation. The pan-African vision of former president Thabo Mbeki, and promotion of South Africa’s transition as a model for the continent, reflected the values that have driven ANC policy since the end of apartheid. But the coherence of South Africa’s foreign policy has been undermined by conflict and contradiction within the government. Appetite for engagement in Africa is dwindling. The country’s ability to project military influence across the continent is in critical decline. Jacob Zuma’s use of regional political bodies as a means of removing political rivals from domestic politics has corroded goodwill. A new Africa Programme research paper argues that a fresh approach to South African engagement on the continent is both possible and necessary. South Africa can use its relative economic weight to play a stronger developmental role, leveraging the strengths of its business sector and its financial agencies. But it must match this with stronger and more cooperative political engagement, particularly through cultivating relationships with pivotal states such as Nigeria, Kenya, Ethiopia and Angola. In December, the ANC will elect a new leader to take the party into elections in 2019. Both leading candidates have international experience – Nkosazana Dlamini-Zuma was the chair of the African Union, and Cyril Ramaphosa has led regional responses to crises in South Sudan, Lesotho and Burundi. South Africa still has considerable foreign policy resources at its disposal. A new strategic vision for Africa that unites the interests of government and business, both domestically and in partner states, can deliver prosperity for both South Africa and the region – and need not contradict the values that have shaped South Africa’s aspirations for the continent in the post-apartheid era. Full Article
con Rebuilding Zimbabwe's Economy: Emmerson Mnangagwa’s Immediate Priorities By www.chathamhouse.org Published On :: Wed, 13 Dec 2017 14:41:18 +0000 Rebuilding Zimbabwe's Economy: Emmerson Mnangagwa’s Immediate Priorities Expert comment sysadmin 13 December 2017 Zimbabwe cannot expect to rebuild in the same economic model that brought previous prosperity. — Emmerson Mnangagwa is sworn in as president on 24 November. Photo: Getty Images. Returning to Harare as Zimbabwe’s president-designate Emmerson Mnangagwa declared, ‘We want to grow our economy, we want peace, we want jobs, jobs, jobs.’ Robert Mugabe leaves a legacy of an independent Zimbabwe in a deep economic crisis. Much remains uncertain as to what a new government in Zimbabwe will look like, and there is sure to be continuity as well as considerable change. What is clear is that a new administration under Mnangagwa will need to turn the economy around to garner support and legitimacy from the Zimbabwean people. Zimbabwe’s economic output halved over the period 1997–2008, and it has not recovered. With more than 80 per cent of Zimbabweans in the informal economy, and with social and economic resilience undermined by previous crises and decades of mismanagement, the stakes for the new leader are very high. Reform will be difficult particularly because politically connected elites have acquired businesses through uncompetitive means. They will be reluctant to see significantly more competition. But they will also want an improved economic environment. And there is scope for the people of Zimbabwe to benefit from this. An important change will be in the prioritization of economic stability. Mugabe demonstrated that he was willing to make political decisions irrespective of the economic consequences. Mnangagwa is thought to be less ideological and more of a pragmatist. For him, delivering economic recovery will be crucial to building political support. The most pressing fiscal priority is the public wage bill. Employment costs account for over 80 per cent of government expenditure, crowding out spending on social programmes, health and education. But the fragility of the economy means that reform cannot be fast-tracked. The public wage bill accounts for over 20 per cent of GDP and is an essential driver of demand. Public sector workers are also politically influential. Another further priority is the reform of state-owned enterprises that are pressuring the fiscus. A new administration will need to rebuild confidence. Policymakers have been operating in a low-confidence environment for a long time, but for any meaningful change to take root there has to be trust between the government, businesses and the people of Zimbabwe. Businesses and citizens will want to see a plan of action for remonetizing the economy. Zimbabwe faces an acute liquidity crisis. A shortage of US dollars and a lack of confidence in government-issued bond notes are testing resilience. The financial system has recovered from a crisis of nonperforming loans – triggered by high debt amassed during the post-dollarization boom, and weak corporate governance. But the system remains highly fragile and swamped with government debt. Hard cash US dollar deposits fell from 49 per cent ($582 million) in 2009 to just six per cent ($269 million) in 2016. In 2015, industrial utilization stood at just 34.3 per cent of installed capacity, and it was estimated that just five per cent of the country’s businesses were viable. The crux of the Zimbabwean economy is the linkage between agriculture and manufacturing. Commercial agriculture contributes approximately 12 per cent of the country’s GDP, and more than 60 per cent of inputs into the manufacturing sector. Tobacco in particular is a vital earner of much needed foreign exchange. Policies to support mid-scale farmers will have multiplier effects. They drive agricultural growth and generate jobs throughout the supply chain. Zimbabwe also has world-class natural resource endowments including ferrochrome, gold, copper, iron ore, lithium, diamonds and platinum group metals. But longer investment-gestation periods and industry risk adversity will mean that payoffs from fresh investments in this sector will take longer to materialize. Domestic finance will need to be mobilized to generate recovery, and this will need to be supported by international investment. But international investors entering the country must be cognizant of Zimbabwean’s expectations and also historical perceptions – especially around the scepticism of neoliberal economics as a result of failed structural adjustment programmes in the 1990s. Zimbabweans have high social expectations for international investors. Educated, tech-savvy, internationally connected youth are at the core of the consumer class that investors will be targeting, to both sell products to but also to staff offices in country. But this cohort also has a greater expectation of international companies to adhere to the norms and standards that they abide by at home and not take advantage of weak governance or poor regulation to exploit citizens. Investors in Zimbabwe must also recognize that behind the controversial Mugabe policies of land reform and indigenization – the empowerment of local citizens through shared ownership – was a popular desire for postcolonial economic transformation. This sentiment remains. Working in partnership with local entities and communicating the economic contribution made to society will be necessary to build a long-term presence in Zimbabwe, and reap the dividend of what many hope to be a new start for the country. Fresh thinking is required from domestic policymakers and international partners. A skilled population and estimated 3-5 million-strong diaspora will bring international experience and make a considerable contribution to this process. Some of this thinking has been done. The Lima process of re-engagement with international financial institutions that was agreed at the end of 2015 has laid some of the groundwork, especially around international expectations regarding both economic and governance reform – the substance of which was analysed in a 2016 Chatham House paper. The implementation of recommendations of the well-regarded auditor-general’s report on SOE reform will also be a key prerequisite for long-term reform. Zimbabweans are not alone in processing what has happened and how to react. Investors have long been poised to capitalize on what is perceived to be one of the continent’s best long-term prospects. A lot will remain unchanged following the transition. But significantly, for the first time in decades, there is a real opportunity to effect positive change and improve the livelihoods of millions of Zimbabweans. This article was originally published at the Huffington Post. Full Article
con Zimbabwe Ahead of the Elections: Political and Economic Challenges By www.chathamhouse.org Published On :: Thu, 03 May 2018 10:00:00 +0000 Zimbabwe Ahead of the Elections: Political and Economic Challenges 8 May 2018 — 10:00AM TO 11:00AM Anonymous (not verified) 3 May 2018 Chatham House, London The upcoming elections in Zimbabwe will be the first since 2000 in which former president Robert Mugabe and long-time opposition leader Morgan Tsvangirai are not on the ballot paper. A key electoral issue for many voters will be the economy: recent years have been marked by high unemployment rates, chronic cash shortages and mounting public debt. Although this has traditionally been a strong campaigning issue for the opposition, President Emmerson Mnangagwa has fast-tracked comprehensive economic reforms.At this event, Nelson Chamisa, MDC Alliance presidential candidate, will discuss his efforts to build a united opposition coalition with a strong message, the steps needed to ensure a free and fair election can take place, and the role that international partners can play in Zimbabwe’s democratic process. Full Article
con Improving Economic Management for Sustainable Growth in Zambia By www.chathamhouse.org Published On :: Tue, 19 Jun 2018 17:35:01 +0000 Improving Economic Management for Sustainable Growth in Zambia 13 July 2018 — 9:00AM TO 10:00AM Anonymous (not verified) 19 June 2018 Chatham House, London THIS EVENT IS POSTPONED. High levels of infrastructure investment funded by commercial loans, against a backdrop of subdued economic growth, resulted in an increase in Zambia’s public external debt from $8.7 billion in 2017 to $9.3 billion in March 2018.In June 2018 Zambia’s Ministry of Finance announced new austerity measures aimed at reducing the country’s debt burden, as part of an ongoing reform agenda that is hoped to stabilise the economy.In the meantime Zambia grapples with severe social and development challenges. Decreased spending in health, education and social protection, and poor access in rural areas, have already left Zambia ranked 139th out of 188 countries in the UNDP’s 2016 human development index. At this meeting Margaret Mwanakatwe, minister of finance, discusses the government’s financial reform agenda, its engagement with creditors and IFIs, and plans for generating sustainable growth and job creation. Full Article
con Economic Reform and Recovery in Zimbabwe By www.chathamhouse.org Published On :: Thu, 04 Oct 2018 15:20:01 +0000 Economic Reform and Recovery in Zimbabwe 8 October 2018 — 2:30PM TO 3:30PM Anonymous (not verified) 4 October 2018 Chatham House, London Zimbabwe’s economy is under strain. Liquidity shortages, renewed worries of inflation and diminishing delivery on social programmes are putting citizens under pressure and testing resilience. The post-election government has multiple policy priorities including tackling debt, reducing the government’s wage bill and reviving international investment. The agriculture and mining sectors have shown growth but to translate this into economic transformation will require balancing the need of public spending and currency reform with demands for short-term stability. At this meeting, Professor Mthuli Ncube will outline his ministry’s priorities for delivering economic reform and recovery in Zimbabwe. THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Full Article
con Zimbabwe Futures 2030: Policy Priorities for Economic Expansion By www.chathamhouse.org Published On :: Thu, 07 Feb 2019 12:36:52 +0000 Zimbabwe Futures 2030: Policy Priorities for Economic Expansion 28 February 2019 — 9:00AM TO 1:00PM Anonymous (not verified) 7 February 2019 Harare, Zimbabwe This roundtable draws on current best practice and senior level expertise to identify policy options for long term economic expansion in Zimbabwe and pathways for inclusive development.Participants discuss the necessary policies and business strategies to enable and support the effective implementation of the Transitional Stabilization Programme and longer term national development plans.The discussions highlight requisite conditions for a business-driven and inclusive process towards Zimbabwe’s long-term economic recovery.This event was held in partnership with the Zimbabwe Business Club and Konrad Adenauer Stiftung. Full Article
con Mine Action in Angola: Clearing the Legacies of Conflict to Harness the Potential of Peace By www.chathamhouse.org Published On :: Fri, 14 Jun 2019 14:40:27 +0000 Mine Action in Angola: Clearing the Legacies of Conflict to Harness the Potential of Peace Other resource sysadmin 14 June 2019 This publication draws on and updates the briefing note published following a meeting of the All- Party Parliamentary Group (APPG) on Angola on 26 April 2017. It also incorporates insights from a Chatham House Africa Programme conference session on the legacies of the Angolan Civil War, held on 23 March 2018; and draws on the Africa Programme’s research into conservation-driven development models in Southern Africa. — A mine clearance specialist in Angola preparing equipment used to look for unexploded ordnance, May 2012. Photo: Eye Ubiquitous/Contributor/Getty Images. Almost two decades after the end of its civil war, Angola remains one of the most heavily landmine-contaminated countries in the world. The Angolan government has committed to clearing its landmines by 2025, and there is constructive collaboration between the government and mine clearing agencies in this endeavour, but the target will be achievable only if a decline in funding from international donors is reversed. International funding for mine clearance in Angola fell by more than 80 per cent between 2005 and 2017, and this sharp drop in external support has compounded the impact on domestic funding for national clearance efforts as a result of the downturn in prices for Angola’s main export commodities. The national mine action agency, the Comissão Nacional Intersectorial de Desminagem e Assistência Humanitária (CNIDAH), is supported by the Mines Advisory Group (MAG), Norwegian People’s Aid (NPA) and the HALO Trust. By 2017, 15 years after the end of the civil war, these organizations had collectively helped clear 56 per cent of known landmine-contaminated land. State-led demining has focused principally on clearing areas designated for infrastructure projects. Now, it is critical that humanitarian demining in largely agricultural and conservation areas is prioritized to bring to an end the daily threat to Angola’s rural poor – as well as to the country’s livestock and wildlife – of injury or death as a result of landmine accidents. Angola has some of the world’s most important remaining wilderness, including the tributary system for the unique Okavango Delta, and the country has the potential to host one of the most diverse wildlife populations on the continent. However, the presence of landmines and other remnants of the civil war render large areas of the country unsafe both for wildlife and for the local people, whose ability to derive a sustainable livelihood from their natural environment is fundamental to its protection. Wildlife and tourism provide important economic opportunities for diversification beyond an oil-dominated economy. Critically, Angola’s economic diversification and development objectives can only be achieved if the landmines that prohibit access to land for agriculture, mining, tourism and wildlife are cleared. There are economic opportunities for released land in the most heavily mined provinces of Cuando Cubango and Moxico. Already, some new funding for mine action in Angola, if upscaled or matched by international donors, could be transformative for its people, and for the conservation of the region’s vital biodiversity. 2019-06-17-Angola (PDF) Full Article