Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking in LDLR^W483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis-related miRNA, miR-23a-3p, by microarray analysis of mouse aortic tissue specimens and human aortic endothelial cells (HAECs). miR-23a-3p was consistently downregulated in both models, which was confirmed by qPCR. Bioinformatics analysis and further validation experiments revealed that the TNFα-induced protein 3 (TNFAIP3) gene was the key target of miR-23a-3p. The miR-23a-3p-related functional pathways were then analyzed in HAECs. Collectively, the present results suggest that miR-23a-3p regulates inflammatory and apoptotic pathways in atherogenesis by targeting TNFAIP3 through the NF-B and p38/MAPK signaling pathways.

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined by LC coupled to MS/MS and MALDI coupled to MS imaging. The omega-3 content in the lipids of plasma and erythrocytes suggests that PLs as well as TGs are good omega-3 carriers for retina. However, a significant increase in DHA content in retina was observed, especially molecular species as di-DHA-containing PC and PE, as well as an increase in very long chain PUFAs (more than 28 carbons) following PL-EPA and TG-DHA diets only. All supplemented diets triggered spatial organization changes of DHA in the photoreceptor layer around the optic nerve. Taken together, these findings suggest that dietary omega-3 supplementation can modify the content of FAs in the rat retina.

ABCB4/MDR3 is located in the canalicular membrane of hepatocytes and translocates PC-lipids from the cytoplasmic to the extracellular leaflet. ABCB4 is an ATP-dependent transporter that reduces the harsh detergent effect of the bile salts by counteracting self-digestion. To do so, ABCB4 provides PC lipids for extraction into bile. PC lipids account for 40% of the entire pool of lipids in the canalicular membrane with an unknown distribution over both leaflets. Extracted PC lipids end up in so-called mixed micelles. Mixed micelles are composed of phospholipids, bile salts, and cholesterol. Ninety to ninety-five percent of the phospholipids are members of the PC family, but only a subset of mainly 16.0-18:1 PC and 16:0-18:2 PC variants are present. To elucidate whether ABCB4 is the key discriminator in this enrichment of specific PC lipids, we used in vitro studies to identify crucial determinants in substrate selection. We demonstrate that PC-lipid moieties alone are insufficient for stimulating ABCB4 ATPase activity, and that at least two acyl chains and the backbone itself are required for a productive interaction. The nature of the fatty acids, like length or saturation has a quantitative impact on the ATPase activity. Our data demonstrate a two-step enrichment and protective function of ABCB4 to mitigate the harsh detergent effect of the bile salts, because ABCB4 can translocate more than just the PC-lipid variants found in bile.

The organic anion transporters (OATs) and organic anion–transporting polypeptides (OATPs) belong to the solute carrier (SLC) transporter superfamily and play important roles in handling various endogenous and exogenous compounds of anionic charge. The OATs and OATPs are often implicated in drug therapy by impacting the pharmacokinetics of clinically important drugs and, thereby, drug exposure in the target organs or cells. Various mechanisms (e.g. genetic, environmental, and disease-related factors, drug-drug interactions, and food-drug interactions) can lead to variations in the expression and activity of the anion drug-transporting proteins of OATs and OATPs, possibly impacting the therapeutic outcomes. Previous investigations mainly focused on the regulation at the transcriptional level and drug-drug interactions as competing substrates or inhibitors. Recently, evidence has accumulated that cellular trafficking, post-translational modification, and degradation mechanisms serve as another important layer for the mechanisms underlying the variations in the OATs and OATPs. This review will provide a brief overview of the major OATs and OATPs implicated in drug therapy and summarize recent progress in our understanding of the post-translational modifications, in particular ubiquitination and degradation pathways of the individual OATs and OATPs implicated in drug therapy.

SLC19A2 and SLC19A3, also known as thiamine transporters (THTR) 1 and 2, respectively, transport the positively charged thiamine (vitamin B1) into cells to enable its efficient utilization. SLC19A2 and SLC19A3 are also known to transport structurally unrelated cationic drugs, such as metformin, but whether this charge selectivity extends to other molecules, such as pyridoxine (vitamin B6), is unknown. We tested this possibility using Madin-Darby canine kidney II (MDCKII) cells and human embryonic kidney 293 (HEK293) cells for transfection experiments, and also using Caco-2 cells as human intestinal epithelial model cells. The stable expression of SLC19A2 and SLC19A3 in MDCKII cells (as well as their transient expression in HEK293 cells) led to a significant induction in pyridoxine uptake at pH 5.5 compared with control cells. The induced uptake was pH-dependent, favoring acidic conditions over neutral to basic conditions, and protonophore-sensitive. It was saturable as a function of pyridoxine concentration, with an apparent Km of 37.8 and 18.5 μm, for SLC19A2 and SLC19A3, respectively, and inhibited by the pyridoxine analogs pyridoxal and pyridoxamine as well as thiamine. We also found that silencing the endogenous SLC19A3, but not SLC19A2, of Caco-2 cells with gene-specific siRNAs lead to a significant reduction in carrier-mediated pyridoxine uptake. These results show that SLC19A2 and SLC19A3 are capable of recognizing/transporting pyridoxine, favoring acidic conditions for operation, and suggest a possible role for these transporters in pyridoxine transport mainly in tissues with an acidic environment like the small intestine, which has an acidic surface microclimate.

Pathogenic mutations in the Leucine-rich repeat kinase 2 (LRRK2) are the predominant genetic cause of Parkinson's disease (PD). They increase its activity, resulting in augmented Rab10-Thr73 phosphorylation and conversely, LRRK2 inhibition decreases pRab10 levels. Currently, there is no assay to quantify pRab10 levels for drug target engagement or patient stratification. To meet this challenge, we developed an high accuracy and sensitivity targeted mass spectrometry (MS)-based assay for determining Rab10-Thr73 phosphorylation stoichiometry in human samples. It uses synthetic stable isotope-labeled (SIL) analogues for both phosphorylated and nonphosphorylated tryptic peptides surrounding Rab10-Thr73 to directly derive the percentage of Rab10 phosphorylation from attomole amounts of the endogenous phosphopeptide. The SIL and the endogenous phosphopeptides are separately admitted into an Orbitrap analyzer with the appropriate injection times. We test the reproducibility of our assay by determining Rab10-Thr73 phosphorylation stoichiometry in neutrophils of LRRK2 mutation carriers before and after LRRK2 inhibition. Compared with healthy controls, the PD predisposing mutation carriers LRRK2 G2019S and VPS35 D620N display 1.9-fold and 3.7-fold increased pRab10 levels, respectively. Our generic MS-based assay further establishes the relevance of pRab10 as a prognostic PD marker and is a powerful tool for determining LRRK2 inhibitor efficacy and for stratifying PD patients for LRRK2 inhibitor treatment.

Despite the continued analysis of HDAC inhibitors in clinical trials, the heterogeneous nature of the protein complexes they target limits our understanding of the beneficial and off-target effects associated with their application. Among the many HDAC protein complexes found within the cell, Sin3 complexes are conserved from yeast to humans and likely play important roles as regulators of transcriptional activity. The presence of two Sin3 paralogs in humans, SIN3A and SIN3B, may result in a heterogeneous population of Sin3 complexes and contributes to our poor understanding of the functional attributes of these complexes. Here, we profile the interaction networks of SIN3A and SIN3B to gain insight into complex composition and organization. In accordance with existing data, we show that Sin3 paralog identity influences complex composition. Additionally, chemical cross-linking MS identifies domains that mediate interactions between Sin3 proteins and binding partners. The characterization of rare SIN3B proteoforms provides additional evidence for the existence of conserved and divergent elements within human Sin3 proteins. Together, these findings shed light on both the shared and divergent properties of human Sin3 proteins and highlight the heterogeneous nature of the complexes they organize.

Specific E3 ligases target tumor suppressors for degradation. Inhibition of such E3 ligases may be an important approach to cancer treatment. RNF146 is a RING domain and PARylation-dependent E3 ligase that functions as an activator of the β-catenin/Wnt and YAP/Hippo pathways by targeting the degradation of several tumor suppressors. Tankyrases 1 and 2 (TNKS1/2) are the only known poly-ADP-ribosyltransferases that require RNF146 to degrade their substrates. However, systematic identification of RNF146 substrates have not yet been performed. To uncover substrates of RNF146 that are targeted for degradation, we generated RNF146 knockout cells and TNKS1/2-double knockout cells and performed proteome profiling with label-free quantification as well as transcriptome analysis. We identified 160 potential substrates of RNF146, which included many known substrates of RNF146 and TNKS1/2 and 122 potential TNKS-independent substrates of RNF146. In addition, we validated OTU domain-containing protein 5 and Protein mono-ADP-ribosyltransferase PARP10 as TNKS1/2-independent substrates of RNF146 and SARDH as a novel substrate of TNKS1/2 and RNF146. Our study is the first proteome-wide analysis of potential RNF146 substrates. Together, these findings not only demonstrate that proteome profiling can be a useful general approach for the systemic identification of substrates of E3 ligases but also reveal new substrates of RNF146, which provides a resource for further functional studies.

En fonction de leurs causes, les douleurs du côté droit peuvent se manifester de différentes manières. Les symptômes de ces douleurs peuvent également varier d’une personne à une autre. Certaines personnes décrivent les douleurs du côté comme des sensations de crampes, de brûlures ou de piqûres. D’autres en revanche parlent de douleurs sourdes ou lancinantes qui irradient […]

L’article Douleurs côté droit sous les côtes : comment les soulager naturellement est apparu en premier sur Ortho Doc France.

Gêne constant, difficulté à respirer : avez-vous une impression de glaires coincées dans la gorge actuellement ? Cette impression peut être due à plusieurs facteurs parfois bénignes mais aussi graves. Fort heureusement, il existe quelques astuces naturelles qui vous permettront d’avoir un soulagement en attendant de consulter un médecin ORL. Mais avant, l’impression de glaires coincées dans la gorge est […]

L’article Comment se débarrasser des glaires coincées dans la gorge ? est apparu en premier sur Ortho Doc France.

En France, environ 2 à 4 % de la population, souvent des femmes, est touchée par la fibromyalgie. Mais en réalité, qu’est-ce que la fibromyalgie ? Quelles sont les astuces naturelles permettant de soulager les patients qui présentent des symptômes de cette maladie ? Quels sont les symptômes de la fibromyalgie ? La fibromyalgie, ou syndrome fibromyalgique, […]

L’article Quelques remèdes de grand-mère pour soulager les symptômes de la fibromyalgie est apparu en premier sur Ortho Doc France.

L’utilisation du féminin dans les titres de professions dans le domaine de la santé a beaucoup évolué ces dernières années. Cela reflète une prise de conscience croissante de certaines réalités des métiers de la santé et la reconnaissance de la présence de plus en plus importante des femmes dans le domaine. Vous demandez-vous quand mettre les professions au féminin […]

L’article Quand mettre les professions au féminin dans le domaine de la santé ? est apparu en premier sur Ortho Doc France.

Les troubles gastro-intestinaux peuvent avoir un impact significatif sur la qualité de vie des patients. Ils engendrent en effet des symptômes variés et inconfortables allant de douleurs abdominales et nausées à des troubles plus graves comme les maladies inflammatoires chroniques de l’intestin. Quelles sont les principales pathologies rencontrées dans cette spécialité de la médecine ? À quel […]

L’article Quelles sont les principales pathologies en gastroentérologie ? est apparu en premier sur Ortho Doc France.

Pour de nombreuses personnes, perte de poids rime obligatoirement avec privations. Et si vous appreniez aujourd’hui que vous pouvez perdre efficacement vos kilos en trop sans pour autant vous priver excessivement ? De nombreux programmes minceur et de rééquilibrage, notamment Croq’kilos offrent ce genre d’alternative. Mais de quoi s’agit-il réellement ? C’est quoi Croq’Kilos ? Croq’Kilos […]

L’article Croq’Kilos : programme minceur, rééquilibrage alimentaire est apparu en premier sur Ortho Doc France.

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Colorectal cancer (CRC) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor, and thus is an useful model for studying metabolic shift. In the present study, we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC. Colonic tissues including tumor, polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors were elevated, suggesting higher energy needs for increased cellular proliferation. In contrast, significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis. In addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric acid concentration, suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC. Further, there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors. It appears that to gain a growth advantage, cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment.

The histidine kinase Hik33 plays important roles in mediating cyanobacterial response to divergent types of abiotic stresses including cold, salt, high light (HL), and osmotic stresses. However, how these functions are regulated by Hik33 remains to be addressed. Using a hik33-deficient strain (hik33) of Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found that Hik33 depletion induces differential protein expression highly similar to that induced by divergent types of stresses. This typically includes downregulation of proteins in photosynthesis and carbon assimilation that are necessary for cell propagation, and upregulation of heat shock proteins, chaperons, and proteases that are important for cell survival. This observation indicates that depletion of Hik33 alone mimics divergent types of abiotic stresses, and that Hik33 could be important for preventing abnormal stress response in the normal condition. Moreover, we found the majority of proteins of plasmid origin were significantly upregulated in hik33, though their biological significance remains to be addressed. Together, the systematically characterized Hik33-regulated cyanobacterial proteome, which is largely involved in stress responses, builds the molecular basis for Hik33 as a general regulator of stress responses.

Cullin RING E3 Ligases (CRLs) ubiquitylate hundreds of important cellular substrates. Here we have assembled and purified the Ankyrin repeat and SOCS Box protein 9 CUL5 RBX2 Ligase (ASB9-CRL) in vitro and show how it ubiquitylates one of its substrates, CKB. CRLs occasionally collaborate with RING between RING E3 ligases (RBRLs) and indeed, mass spectrometry analysis showed that CKB is specifically ubiquitylated by the ASB9-CRL-ARIH2-UBE2L3 complex. Addition of other E2s such as UBE2R1 or UBE2D2 contribute to polyubiquitylation but do not alter the sites of CKB ubiquitylation. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis revealed that CUL5 neddylation allosterically exposes its ARIH2 binding site, promoting high affinity binding, and it also sequesters the NEDD8 E2 (UBE2F) binding site on RBX2. Once bound, ARIH2 helices near the Ariadne domain active site are exposed, presumably relieving its autoinhibition. These results allow us to propose a model of how neddylation activates ASB-CRLs to ubiquitylate their substrates.

China's Regions in an Era of Globalization Book sysadmin 14 May 2018

The rise of China has been shaped and driven by its engagement with the global economy. This engagement cannot be understood at the level of national policymaking alone, but requires analysis of the differences in participation in the global economy across China’s regions.

China is a continent-sized economy and society with substantial diversity across its different regions. This book traces the evolution of regional policy in China and its implications in a global context.

Detailed chapters examine the trajectory of what is now becoming known as the Greater Bay Area in southern China, the inland mega-city of Chongqing, and the role of China’s regions in the globally focused Belt and Road Initiative launched by the Chinese government in late 2013.

It will be of interest to practitioners and scholars engaging with contemporary China’s political economy and international relations.

This book is published as part of the Insights series.

Praise for China’s Regions in an Era of Globalization

About the author

Tim Summers works on the political economy and international relations of contemporary China. He is a Lecturer at the Centre for China Studies, The Chinese University of Hong Kong, and a (non-resident) Senior Consulting Fellow on the Asia-Pacific Programme at Chatham House. He was British consul general in Chongqing from 2004 to 2007.

This book is published in collaboration with Routledge.

Purchase

• Worldwide (via Routledge)
• Students (via Browns Books)

In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11–13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24–32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis. We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.

Homologous recombination (HR) repairs DNA double-strand breaks using intact homologous sequences as template DNA. Broken DNA and intact homologous sequences form joint molecules (JMs), including Holliday junctions (HJs), as HR intermediates. HJs are resolved to form crossover and noncrossover products. A mismatch repair factor, MLH3 endonuclease, produces the majority of crossovers during meiotic HR, but it remains elusive whether mismatch repair factors promote HR in nonmeiotic cells. We disrupted genes encoding the MLH3 and PMS2 endonucleases in the human B cell line, TK6, generating null MLH3−/− and PMS2−/− mutant cells. We also inserted point mutations into the endonuclease motif of MLH3 and PMS2 genes, generating endonuclease death MLH3DN/DN and PMS2EK/EK cells. MLH3−/− and MLH3DN/DN cells showed a very similar phenotype, a 2.5-fold decrease in the frequency of heteroallelic HR-dependent repair of restriction enzyme–induced double-strand breaks. PMS2−/− and PMS2EK/EK cells showed a phenotype very similar to that of the MLH3 mutants. These data indicate that MLH3 and PMS2 promote HR as an endonuclease. The MLH3DN/DN and PMS2EK/EK mutations had an additive effect on the heteroallelic HR. MLH3DN/DN/PMS2EK/EK cells showed normal kinetics of γ-irradiation–induced Rad51 foci but a significant delay in the resolution of Rad51 foci and a 3-fold decrease in the number of cisplatin-induced sister chromatid exchanges. The ectopic expression of the Gen1 HJ re-solvase partially reversed the defective heteroallelic HR of MLH3DN/DN/PMS2EK/EK cells. Taken together, we propose that MLH3 and PMS2 promote HR as endonucleases, most likely by processing JMs in mammalian somatic cells.

The Phillies acquired All-Star catcher J.T. Realmuto from the Marlins on Thursday for catcher Jorge Alfaro, right-hander Sixto Sanchez, left-hander Will Stewart and $250,000 in international bonus slot money, the latest move in a busy and ambitious offseason for a team eager to return to the postseason.

Phillies pitchers and catchers have their first workout Wednesday morning at Carpenter Complex. Almost anything can happen between Wednesday and Opening Day. That said, here is a very early prediction of the Phillies' Opening Day roster, knowing the Phillies remain in the hunt to sign Bryce Harper or Manny Machado.

Fans and analysts spend the entire offseason speculating where the top free agents could go, but sometimes an under-the-radar pickup can end up making a world of difference. As positional competitions begin to heat up at Spring Training camps this month, MLB.com's beat writers were asked to identify one potentially overlooked acquisition for each of the 30 clubs. Here's who they came up with.

The Phillies introduced J.T. Realmuto, their new All-Star catcher, in a news conference Tuesday at the team's Spring Training complex in Clearwater, Fla.

Aaron Nola established himself as one of the best pitchers in baseball in 2018. The Phillies ensured on Wednesday that he will be the ace in their rotation for possibly the next five seasons.

Phillies president Andy MacPhail opened a 28-minute press conference on Friday afternoon at Spectrum Field with facts and figures about investments the organization made the past few seasons as the team wallowed at the bottom of the National League. Then MacPhail talked a lot about Bryce Harper and Manny Machado as well as manager Gabe Kapler.

Maikel Franco followed the endless and often mind-numbing speculation the past few months from the Dominican Republic. Franco knows that Manny Machado could show up at Spectrum Field at any moment. The Phillies entertained him at Citizens Bank Park just before Christmas. They have made him at least one contract offer. If the Phillies sign him, Franco also knows he could be traded.

Who do the Phillies have in the pipeline? Get scouting reports, video, stats, projected ETAs and more for Philly's Top 30 Prospects on MLBPipeline.com's Prospect Watch.

The next five weeks will see lots of shuffling on Major League rosters. Here are the most intriguing positional battles on each of the 30 MLB clubs.

The Phillies have been the favorites in the Bryce Harper sweepstakes for months, and that speculation heated up over the weekend.

The Phillies list isn't quite as strong as it once was because of the Realmuto deal, but there's still some very good talent at the top and some exciting players on the rise.

Bryce Harper is the final superstar standing for the Phillies.

MLB.com looked at each team's two highest-ranked position players in WAR, according to the Steamer projections. Here are the top 10, but keep in mind that things could change once Manny Machado and Bryce Harper find homes.

It's almost time for Spring Training yet again, as Angels pitchers and catchers report to their Spring Training complex in Tempe, Ariz. on Feb. 12.

Our weekly series previewing each of baseball's six divisions begins with the American League West. Let's take a team-by-team look at the biggest questions this season.

Since debuting in 2011, center fielder Mike Trout has been far and away the best player in the Majors, but the Angels have reached the postseason just once in his eight-year career.

Brad Ausmus held his first media session of the spring on the day pitchers and catchers officially reported on Tuesday, giving updates on rehabbing players such as Shohei Ohtani, Albert Pujols and Zack Cozart.

MLB Network's countdown of baseball's best players at each position continued with the third installment of the "Top 10 Right Now!" series, featuring the game's top left and center fielders.

Shohei Ohtani remains a must-watch player for Angels fans in 2019, and his recovery from Tommy John surgery will be worth monitoring throughout the season as he prepares to pitch again in '20.

Fans and analysts spend the entire offseason speculating where the top free agents could go, but sometimes an under-the-radar pickup can end up making a world of difference. As positional competitions begin to heat up at Spring Training camps this month, MLB.com's beat writers were asked to identify one potentially overlooked acquisition for each of the 30 clubs. Here's who they came up with.

The Angels head to Spring Training with most of their roster set, but there will be competition for a few spots. Here's a look at the projected roster for the Angels, as they begin their first campaign under manager Brad Ausmus.

Who do the Angels have in the pipeline? Get scouting reports, video, stats, projected ETAs and more for the Halos' Top 30 Prospects on MLB Pipeline's Prospect Watch.

The next five weeks will see lots of shuffling on Major League rosters. Here are the most intriguing positional battles on each of the 30 MLB clubs.

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.

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.

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.

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.