aci Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic acid programmable protein arrays [11. Microarrays/Combinatorics/Display Technology] By feedproxy.google.com Published On :: 2010-02-01T14:51:46-08:00 Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases. Full Article
aci Belarusians Left Facing COVID-19 Alone By feedproxy.google.com Published On :: Thu, 16 Apr 2020 15:19:10 +0000 16 April 2020 Ryhor Astapenia Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @ryhorastapenia LinkedIn Anaïs Marin Associate Fellow, Russia and Eurasia Programme LinkedIn The way the epidemic is being mismanaged creates a risk of political destabilisation and leaves the country exposed to external influence. 2020-04-16-Belarus-COVID-Football Playing accordion in front of dummy football fans in Brest, Belarus as the country's championship continues despite the COVID-19 outbreak. Photo by SERGEI GAPON/AFP via Getty Images. Since the World Health Organisation (WHO) declared COVID-19 a pandemic, few countries have chosen to ignore social distancing recommendations. But, even among those states which have, the Belarusian official response to its epidemic remains unique.President Aliaksandr Lukashenka’s statements that vodka, sauna and tractors are protecting Belarusians from coronavirus attracted amused attention in international media. Lukashenka also described other societies’ response to COVID-19 as ‘a massive psychosis’.Although Lukashenka is notorious for his awkward style of public communication, the fact that Belarus is refusing to impose comprehensive confinement measures is of concern. Belarusians continue to work, play football and socialise.Lukashenka, himself playing ice hockey in front of state cameras, claims it is the best way to stay healthy. Belarusian authorities clearly appear to be in denial – and this could have dire humanitarian consequences.From denial to half measuresBelarus actually has one of the largest numbers of hospital beds in the world per 1,000 of the population. But in the absence of quarantine measures its health system, already crippled by corruption and embezzlement, is likely to be overwhelmed.Patients being treated for pneumonia in hospitals have suggested medical staff are uninformed and inadequately equipped. It is claimed doctors are not reporting COVID-19 as the suspected cause of death, either through a lack of testing or for fear of reprisals.Observers believe the real mortality rate is already well above official figures (40 deaths as of 16 April). Based on an Imperial College London model, between 15,000 and 32,000 people could die under the current mild confinement regime – and such a high death toll would hugely impact the country’s political stability. Citing personal data protection, the Ministry of Health has imposed a total news blackout; the only cluster officially acknowledged so far is the city of Vitsebsk.Although specific Belarusian cities and some individuals started changing their approach – by extending school vacations or cancelling weddings – such measures remain half-hearted.Clearly a major reason for such an apparently irresponsible reaction is that Belarus cannot afford a massive lockdown that would freeze its already underdeveloped economy and drive it deeper into recession. Unlike many other nations, Belarus lacks budgetary resources for a sizable stimulus package. But a delayed response might backfire on the economy.Economic recession has been forecast to amount to at least 10% of GDP. For Lukashenka, who openly challenged conventional wisdom regarding the need for quarantine and isolation, such an economic downturn would harm his confidence rating in the eyes of Belarusian voters, mindful of the state’s mismanagement of the crisis. And it could create doubt within the ruling elite itself, with Lukashenka seeking re-election for a sixth mandate in late August.Against this backdrop, a radicalization of the opposition-minded part of society is also to be expected, with greater reliance on social networks in the face of official secrecy and disinformation. The expected response of the regime is then likely to be pre-emptive repression. Evidence is emerging that law enforcement agencies have already stepped up judicial and paralegal harassment of dissenters, notably independent journalists and bloggers.Russia’s initial reluctance to address the coronavirus crisis may also have influenced Belarus. Lukashenka and his administration often react to public health challenges by the Soviet rulebook, reminiscent of the Soviet authorities’ mismanagement of the Chernobyl disaster in 1986.Russia has unilaterally closed its borders with Belarus and, as bilateral relations continue to deteriorate, this casts further doubt on the viability of the Union State of Belarus and Russia. Pro-Russian media forecast Moscow will be unwilling to alleviate the expected socio-economic crisis, as it continues to reject Minsk’s demands regarding subsidised oil deliveries. Yet the Kremlin might use the crisis as an opportunity to resume its integrationist pressure on Belarus.China, with which Belarus engaged in a seemingly privileged strategic partnership in the 2010s, was actually the first country to dispatch humanitarian aid to beef up Belarusian capacity to fight the virus.But Minsk should not expect Beijing to rescue its economy and, unless it commits to more internal reforms, Belarus is not likely to receive much from the EU either. The regime has already applied to the IMF for emergency financial support, but conditions are attached and, even if successful, the funds would amount to no more than $900m.The government’s decision to take only half measures so far is rooted in the hope COVID-19 is not as bad as foreign experts fear. But, unless the leadership acknowledges the public health crisis and mitigates its economic impact, COVID-19 will accelerate Belarus’s slide back into international self-isolation. If combined with a humanitarian crisis, this will put the Belarusian regime under considerable stress.This crisis does risk a new ‘Chernobyl moment’ for the authorities, but the population could react more vocally this time. As volunteers self-organise to fight the epidemic, it might become more difficult for the authorities to say that it is efficient in running the country. But the bottom line is Belarus desperately needs money. Whoever steps up to support Belarus financially will also be able to heavily influence its politics. Full Article
aci Erratum: FTY720/fingolimod decreases hepatic steatosis and expression of fatty acid synthase in diet-induced nonalcoholic fatty liver disease in mice [Errata] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 Full Article
aci Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 Bile acids (BAs) serve multiple biological functions, ranging from the absorption of lipids and fat-soluble vitamins to serving as signaling molecules through the direct activation of dedicated cellular receptors. Synthesized by both host and microbial pathways, BAs are increasingly understood as participating in the regulation of numerous pathways relevant to metabolic diseases, including lipid and glucose metabolism, energy expenditure, and inflammation. Quantitative analyses of BAs in biological matrices can be problematic due to their unusual and diverse physicochemical properties, making optimization of a method that shows good accuracy, precision, efficiency of extraction, and minimized matrix effects across structurally distinct human and murine BAs challenging. Herein we develop and clinically validate a stable-isotope-dilution LC/MS/MS method for the quantitative analysis of numerous primary and secondary BAs in both human and mouse biological matrices. We also utilize this tool to investigate gut microbiota participation in the generation of structurally specific BAs in both humans and mice. We examine circulating levels of specific BAs and in a clinical case-control study of age- and gender-matched type 2 diabetes mellitus (T2DM) versus nondiabetics. BAs whose circulating levels are associated with T2DM include numerous 12α-hydroxyl BAs (taurocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid, and 3-ketodeoxycholic acid), while taurohyodeoxycholic acid was negatively associated with diabetes. The LC/MS/MS-based platform described should serve as a robust, high-throughput investigative tool for studying the potential involvement of structurally specific BAs and the gut microbiome on both physiological and disease processes. Full Article
aci A human-like bile acid pool induced by deletion of hepatic Cyp2c70 modulates effects of FXR activation in mice [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Bile acids (BAs) facilitate intestinal absorption of lipid-soluble nutrients and modulate various metabolic pathways through the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5. These receptors are targets for therapy in cholestatic and metabolic diseases. However, dissimilarities in BA metabolism between humans and mice complicate translation of preclinical data. Cytochrome P450 family 2 subfamily c polypeptide 70 (CYP2C70) was recently proposed to catalyze the formation of rodent-specific muricholic acids (MCAs). With CRISPR/Cas9-mediated somatic genome editing, we generated an acute hepatic Cyp2c70 knockout mouse model (Cyp2c70ako) to clarify the role of CYP2C70 in BA metabolism in vivo and evaluate whether its activity modulates effects of pharmacologic FXR activation on cholesterol homeostasis. In Cyp2c70ako mice, chenodeoxycholic acid (CDCA) increased at the expense of βMCA, resulting in a more hydrophobic human-like BA pool. Tracer studies demonstrated that, in vivo, CYP2C70 catalyzes the formation of βMCA primarily by sequential 6β-hydroxylation and C7-epimerization of CDCA, generating αMCA as an intermediate metabolite. Physiologically, the humanized BA composition in Cyp2c70ako mice blunted the stimulation of fecal cholesterol disposal in response to FXR activation compared with WT mice, predominantly due to reduced stimulation of transintestinal cholesterol excretion. Thus, deletion of hepatic Cyp2c70 in adult mice translates into a human-like BA pool composition and impacts the response to pharmacologic FXR activation. This Cyp2c70ako mouse model may be a useful tool for future studies of BA signaling and metabolism that informs human disease development and treatment. Full Article
aci Is CYP2C70 the key to new mouse models to understand bile acids in humans? [Commentary] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Full Article
aci Erratum: Unequivocal evidence for endogenous geranylgeranoic acid biosynthesized from mevalonate in mammalian cells [Errata] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 Full Article
aci Development of a sensitive and quantitative method for the identification of two major furan fatty acids in human plasma [Methods] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 This article focuses on the establishment of an accurate and sensitive quantitation method for the analysis of furan fatty acids. In particular, the sensitivity of GC/MS and UPLC/ESI/MS/MS was compared for the identification and quantification of furan fatty acids. Different methylation methods were tested with respect to GC/MS analysis. Special attention needs to be paid to the methylation of furan fatty acids, as acidic catalysts might lead to the degradation of the furan ring. GC/MS analysis in full-scan mode demonstrated that the limit of quantitation was 10 μM. UPLC/ESI/MS/MS in multiple reaction monitoring mode displayed a higher detection sensitivity than GC/MS. Moreover, the identification of furan fatty acids with charge-reversal derivatization was tested in the positive mode with two widely used pyridinium salts. Significant oxidation was unexpectedly observed using N-(4-aminomethylphenyl) pyridinium as a derivatization agent. The formed 3-acyl-oxymethyl-1-methylpyridinium iodide derivatized by 2-bromo-1-methylpyridinium iodide and 3-carbinol-1-methylpyridinium iodide improved the sensitivity more than 2,000-fold compared with nonderivatization in the negative mode by UPLC/ESI/MS/MS. This charge-reversal derivatization enabled the targeted quantitation of furan fatty acids in human plasma. Thus, it is anticipated that this protocol could greatly contribute to the clarification of pathological mechanisms related to furan fatty acids and their metabolites. Full Article
aci Of mice and men: murine bile acids explain species differences in the regulation of bile acid and cholesterol metabolism [Research Articles] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 Compared with humans, rodents have higher synthesis of cholesterol and bile acids (BAs) and faster clearance and lower levels of serum LDL-cholesterol. Paradoxically, they increase BA synthesis in response to bile duct ligation (BDL). Another difference is the production of hydrophilic 6-hydroxylated muricholic acids (MCAs), which may antagonize the activation of FXRs, in rodents versus humans. We hypothesized that the presence of MCAs is key for many of these metabolic differences between mice and humans. We thus studied the effects of genetic deletion of the Cyp2c70 gene, previously proposed to control MCA formation. Compared with WT animals, KO mice created using the CRISPR/Cas9 system completely lacked MCAs, and displayed >50% reductions in BA and cholesterol synthesis and hepatic LDL receptors, leading to a marked increase in serum LDL-cholesterol. The doubling of BA synthesis following BDL in WT animals was abolished in KO mice, despite extinguished intestinal fibroblast growth factor (Fgf)15 expression in both groups. Accumulation of cholesterol-enriched particles ("Lp-X") in serum was almost eliminated in KO mice. Livers of KO mice were increased 18% in weight, and serum markers of liver function indicated liver damage. The human-like phenotype of BA metabolism in KO mice could not be fully explained by the activation of FXR-mediated changes. In conclusion, the presence of MCAs is critical for many of the known metabolic differences between mice and humans. The Cyp2c70-KO mouse should be useful in studies exploring potential therapeutic targets for human disease. Full Article
aci Hepatic monoamine oxidase B is involved in endogenous geranylgeranoic acid synthesis in mammalian liver cells [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:28-07:00 Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from 13C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation. Full Article
aci Slc43a3 is a regulator of free fatty acid flux [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, increased about 2.5-fold after bariatric surgery. Further investigation demonstrated that Slc43a3 is highly expressed in murine adipose tissue and induced during adipocyte differentiation in primary preadipocytes and in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated FA efflux, while also increasing FA uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased FA uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate FA flux in adipocytes, functioning as a positive regulator of FA efflux and as a negative regulator of FA uptake. Full Article
aci Commentary on SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect fatty acid translocation [Commentaries] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Full Article
aci Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects with Hepatic Steatosis By diabetes.diabetesjournals.org Published On :: 2020-01-23T08:19:19-08:00 Glucagon secretion is regulated by circulating glucose, but it has turned out that amino acids also play an important role, and that hepatic amino acid metabolism and glucagon are linked in a mutual feed-back cycle, the liver-alpha cell axis. On this background, we hypothesized that hepatic steatosis might impair glucagon’s action on hepatic amino acid metabolism and lead to hyperaminoacidemia and hyperglucagonemia.We subjected 15 healthy lean and 15 obese steatotic male participants to a pancreatic clamp with somatostatin and evaluated hepatic glucose and amino acid metabolism during basal and high physiological levels of glucagon. The degree of steatosis was evaluated from liver biopsies.Total RNA sequencing of liver biopsies revealed perturbations in the expression of genes predominantly involved in amino acid metabolism in the obese steatotic individuals. This group was also characterized by fasting hyperglucagonemia, hyperaminoacidemia and an absent lowering of amino acid levels in response to high levels of glucagon. Endogenous glucose production was similar between lean and obese individuals.Our results suggest that hepatic steatosis causes resistance to the effect of glucagon on amino acid metabolism resulting in increased amino acid concentrations as well as increased glucagon secretion providing a likely explanation of fatty liver-associated hyperglucagonemia. Full Article
aci Branched-Chain Amino Acids Exacerbate Obesity-Related Hepatic Glucose and Lipid Metabolic Disorders via Attenuating Akt2 Signaling By diabetes.diabetesjournals.org Published On :: 2020-04-24T14:07:36-07:00 Branched chain amino acids (BCAAs) are associated with the progression of obesity-related metabolic disorders, including T2DM and non-alcoholic fatty liver disease. However, whether BCAAs disrupt the homeostasis of hepatic glucose and lipid metabolism remains unknown. In this study, we observed that BCAAs supplementation significantly reduced high-fat (HF) diet-induced hepatic lipid accumulation while increasing the plasma lipid levels and promoting muscular and renal lipid accumulation. Further studies demonstrated that BCAAs supplementation significantly increased hepatic gluconeogenesis and suppressed hepatic lipogenesis in HF diet-induced obese (DIO) mice. These phenotypes resulted from severe attenuation of Akt2 signaling via mTORC1- and mTORC2-dependent pathways. BCAAs/branched-chain α-keto acids (BCKAs) chronically suppressed Akt2 activation through mTORC1 and mTORC2 signaling and promoted Akt2 ubiquitin-proteasome-dependent degradation through the mTORC2 pathway. Moreover, the E3 ligase Mul1 played an essential role in BCAAs/BCKAs-mTORC2-induced Akt2 ubiquitin-dependent degradation. We also demonstrated that BCAAs inhibited hepatic lipogenesis by blocking Akt2/SREBP1/INSIG2a signaling and increased hepatic glycogenesis by regulating Akt2/Foxo1 signaling. Collectively, these data demonstrate that in DIO mice, BCAAs supplementation resulted in serious hepatic metabolic disorder and severe liver insulin resistance: insulin failed to not only suppress gluconeogenesis but also activate lipogenesis. Intervening BCAA metabolism is a potential therapeutic target for severe insulin-resistant disease. Full Article
aci Motifs of Three HLA-DQ Amino Acid Residues ({alpha}44, {beta}57, {beta}135) Capture Full Association with the Risk of Type 1 Diabetes in DQ2 and DQ8 Children By diabetes.diabetesjournals.org Published On :: 2020-04-24T20:01:59-07:00 HLA-DQA1 and -DQB1 are strongly associated with type 1 diabetes (T1D), and DQ8.1 and DQ2.5 are major risk haplotypes. Next generation targeted sequencing of HLA-DQA1 and -DQB1 in Swedish newly diagnosed 1-18 year-old patients (n=962) and controls (n=636) was used to construct abbreviated DQ haplotypes, converted into amino acid (AA) residues, and assessed for their associations with T1D. A hierarchically-organized haplotype (HOH) association analysis, allowed 45 unique DQ haplotypes to be categorized into seven clusters. The DQ8/9 cluster included two DQ8.1 risk and the DQ9 resistant haplotypes, and the DQ2 cluster, included the DQ2.5 risk and DQ2.2 resistant haplotypes. Within each cluster, HOH found residues α44Q (OR 3.29, p=2.38*10-85 ) and β57A (OR 3.44, p=3.80*10-84) to be associated with T1D in the DQ8/9 cluster representing all ten residues (α22, α23, α44, α49, α51, α53, α54, α73, α184, β57) due to complete linkage-disequilibrium (LD) of α44 with eight such residues. Within the DQ2 cluster and due to LD, HOH analysis found α44C and β135D to share the risk for T1D (OR 2.10, p=1.96*10-20). The motif "QAD" of α44, β57, and β135 captured the T1D risk association of DQ8.1 (OR 3.44, p=3.80*10-84), the corresponding motif "CAD" captured the risk association of DQ2.5 (OR 2.10, p=1.96*10-20). Two risk associations were related to GADA and IA-2A, but in opposite directions. "CAD" was positively associated with GADA (OR 1.56; p=6.35*10-8) but negatively with IA-2A (OR 0.59, p= 6.55*10-11). "QAD" was negatively associated with GADA (OR 0.88; p= 3.70*10-3) but positively with IA-2A (OR 1.64; p= 2.40*10-14), despite a single difference at α44. The residues are found in and around anchor pockets 1 and 9, as potential TCR contacts, in the areas for CD4 binding and putative homodimer formation. The identification of three HLA-DQ AA (α44, β57, β135) conferring T1D risk should sharpen functional and translational studies. Full Article
aci Lactation vs Formula Feeding: Insulin, Glucose and Fatty Acid Metabolism During the Postpartum Period By diabetes.diabetesjournals.org Published On :: 2020-05-08T10:11:46-07:00 Milk production may involve a transient development of insulin resistance in non-mammary tissues to support redistribution of maternal macronutrients to match the requirements of the lactating mammary gland. In the present study, adipose and liver metabolic responses were measured in the fasting state and during a 2-step (10 and 20 mU/m2/min) hyperinsulinemic-euglycemic clamp with stable isotopes, in 6-week postpartum women who were lactating (n=12) or formula-feeding (n=6) their infants and who were closely matched for baseline characteristics (e.g., parity, body composition, intrahepatic lipid). When controlling for the low insulin concentrations of both groups, the lactating women exhibited a fasting rate of endogenous glucose production (EGP) that was 2.6-fold greater, and a lipolysis rate that was 2.3-fold greater than the formula-feeding group. During the clamp, the groups exhibited similar suppression rates of EGP and lipolysis. In the lactating women only, higher prolactin concentrations were associated with greater suppression rates of lipolysis, lower intrahepatic lipid and plasma triacylglycerol concentrations. These data suggest that whole-body alterations in glucose transport may be organ specific and facilitate nutrient partitioning during lactation. Recapitulating a shift toward noninsulin-mediated glucose uptake could be an early postpartum strategy to enhance lactation success in women at risk for delayed onset of milk production. Full Article
aci Genetic lineage tracing with multiple DNA recombinases: A user's guide for conducting more precise cell fate mapping studies [Methods and Resources] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Site-specific recombinases, such as Cre, are a widely used tool for genetic lineage tracing in the fields of developmental biology, neural science, stem cell biology, and regenerative medicine. However, nonspecific cell labeling by some genetic Cre tools remains a technical limitation of this recombination system, which has resulted in data misinterpretation and led to many controversies in the scientific community. In the past decade, to enhance the specificity and precision of genetic targeting, researchers have used two or more orthogonal recombinases simultaneously for labeling cell lineages. Here, we review the history of cell-tracing strategies and then elaborate on the working principle and application of a recently developed dual genetic lineage-tracing approach for cell fate studies. We place an emphasis on discussing the technical strengths and caveats of different methods, with the goal to develop more specific and efficient tracing technologies for cell fate mapping. Our review also provides several examples for how to use different types of DNA recombinase–mediated lineage-tracing strategies to improve the resolution of the cell fate mapping in order to probe and explore cell fate–related biological phenomena in the life sciences. Full Article
aci Amino Acid Metabolism, {beta}-Cell Function, and Diabetes By diabetes.diabetesjournals.org Published On :: 2006-12-01 Philip NewsholmeDec 1, 2006; 55:S39-S47Section II: The Muscle and Liver Connections Full Article
aci Effect of a Sustained Reduction in Plasma Free Fatty Acid Concentration on Intramuscular Long-Chain Fatty Acyl-CoAs and Insulin Action in Type 2 Diabetic Patients By diabetes.diabetesjournals.org Published On :: 2005-11-01 Mandeep BajajNov 1, 2005; 54:3148-3153Metabolism Full Article
aci Sugar, Uric Acid, and the Etiology of Diabetes and Obesity By diabetes.diabetesjournals.org Published On :: 2013-10-01 Richard J. JohnsonOct 1, 2013; 62:3307-3315Perspectives in Diabetes Full Article
aci Covid-19: Lack of capacity led to halting of community testing in March, admits deputy chief medical officer By feeds.bmj.com Published On :: Wednesday, May 6, 2020 - 12:25 Full Article
aci Covid-19: Allow pharmacists to dispense controlled drugs without prescription, urge specialists By feeds.bmj.com Published On :: Thursday, May 7, 2020 - 16:31 Full Article
aci Belarusians Left Facing COVID-19 Alone By feedproxy.google.com Published On :: Thu, 16 Apr 2020 15:19:10 +0000 16 April 2020 Ryhor Astapenia Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @ryhorastapenia LinkedIn Anaïs Marin Associate Fellow, Russia and Eurasia Programme LinkedIn The way the epidemic is being mismanaged creates a risk of political destabilisation and leaves the country exposed to external influence. 2020-04-16-Belarus-COVID-Football Playing accordion in front of dummy football fans in Brest, Belarus as the country's championship continues despite the COVID-19 outbreak. Photo by SERGEI GAPON/AFP via Getty Images. Since the World Health Organisation (WHO) declared COVID-19 a pandemic, few countries have chosen to ignore social distancing recommendations. But, even among those states which have, the Belarusian official response to its epidemic remains unique.President Aliaksandr Lukashenka’s statements that vodka, sauna and tractors are protecting Belarusians from coronavirus attracted amused attention in international media. Lukashenka also described other societies’ response to COVID-19 as ‘a massive psychosis’.Although Lukashenka is notorious for his awkward style of public communication, the fact that Belarus is refusing to impose comprehensive confinement measures is of concern. Belarusians continue to work, play football and socialise.Lukashenka, himself playing ice hockey in front of state cameras, claims it is the best way to stay healthy. Belarusian authorities clearly appear to be in denial – and this could have dire humanitarian consequences.From denial to half measuresBelarus actually has one of the largest numbers of hospital beds in the world per 1,000 of the population. But in the absence of quarantine measures its health system, already crippled by corruption and embezzlement, is likely to be overwhelmed.Patients being treated for pneumonia in hospitals have suggested medical staff are uninformed and inadequately equipped. It is claimed doctors are not reporting COVID-19 as the suspected cause of death, either through a lack of testing or for fear of reprisals.Observers believe the real mortality rate is already well above official figures (40 deaths as of 16 April). Based on an Imperial College London model, between 15,000 and 32,000 people could die under the current mild confinement regime – and such a high death toll would hugely impact the country’s political stability. Citing personal data protection, the Ministry of Health has imposed a total news blackout; the only cluster officially acknowledged so far is the city of Vitsebsk.Although specific Belarusian cities and some individuals started changing their approach – by extending school vacations or cancelling weddings – such measures remain half-hearted.Clearly a major reason for such an apparently irresponsible reaction is that Belarus cannot afford a massive lockdown that would freeze its already underdeveloped economy and drive it deeper into recession. Unlike many other nations, Belarus lacks budgetary resources for a sizable stimulus package. But a delayed response might backfire on the economy.Economic recession has been forecast to amount to at least 10% of GDP. For Lukashenka, who openly challenged conventional wisdom regarding the need for quarantine and isolation, such an economic downturn would harm his confidence rating in the eyes of Belarusian voters, mindful of the state’s mismanagement of the crisis. And it could create doubt within the ruling elite itself, with Lukashenka seeking re-election for a sixth mandate in late August.Against this backdrop, a radicalization of the opposition-minded part of society is also to be expected, with greater reliance on social networks in the face of official secrecy and disinformation. The expected response of the regime is then likely to be pre-emptive repression. Evidence is emerging that law enforcement agencies have already stepped up judicial and paralegal harassment of dissenters, notably independent journalists and bloggers.Russia’s initial reluctance to address the coronavirus crisis may also have influenced Belarus. Lukashenka and his administration often react to public health challenges by the Soviet rulebook, reminiscent of the Soviet authorities’ mismanagement of the Chernobyl disaster in 1986.Russia has unilaterally closed its borders with Belarus and, as bilateral relations continue to deteriorate, this casts further doubt on the viability of the Union State of Belarus and Russia. Pro-Russian media forecast Moscow will be unwilling to alleviate the expected socio-economic crisis, as it continues to reject Minsk’s demands regarding subsidised oil deliveries. Yet the Kremlin might use the crisis as an opportunity to resume its integrationist pressure on Belarus.China, with which Belarus engaged in a seemingly privileged strategic partnership in the 2010s, was actually the first country to dispatch humanitarian aid to beef up Belarusian capacity to fight the virus.But Minsk should not expect Beijing to rescue its economy and, unless it commits to more internal reforms, Belarus is not likely to receive much from the EU either. The regime has already applied to the IMF for emergency financial support, but conditions are attached and, even if successful, the funds would amount to no more than $900m.The government’s decision to take only half measures so far is rooted in the hope COVID-19 is not as bad as foreign experts fear. But, unless the leadership acknowledges the public health crisis and mitigates its economic impact, COVID-19 will accelerate Belarus’s slide back into international self-isolation. If combined with a humanitarian crisis, this will put the Belarusian regime under considerable stress.This crisis does risk a new ‘Chernobyl moment’ for the authorities, but the population could react more vocally this time. As volunteers self-organise to fight the epidemic, it might become more difficult for the authorities to say that it is efficient in running the country. But the bottom line is Belarus desperately needs money. Whoever steps up to support Belarus financially will also be able to heavily influence its politics. Full Article
aci Tonga Energy Road Map: Energy Security, the Aid Paradigm, and Pacific Geostrategy By feedproxy.google.com Published On :: Thu, 23 May 2013 13:00:07 +0000 Research Event 3 June 2013 - 2:00pm to 4:00pm Chatham House, London Event participants Lord Tu'ivakano, Prime Minister of the Kingdom of Tonga Lord Tu'ivakano, will deliver a keynote address on the development of the Tonga Energy Road Map (TERM), which plans for 50% of the country's energy to come from renewable energy sources by 2020. The Kingdom of Tonga is highly susceptible to both climate change as well as changes in global energy prices due to its high dependency on imported oil. The TERM has required both ground-breaking whole-of-sector institutional changes in Tonga as well as innovative coordination across a range of development partners, including the World Bank, ADB and the UN. Key players in the international community have closely watched the development and implementation of the TERM as it presents a complete change in the aid paradigm that is not just specific to Tonga, or the energy sector. Registration for this event has now closed. Department/project Energy, Environment and Resources Programme Full Article
aci Mark Ricketts | A nation with a capacity for caring, but much more is needed By jamaica-gleaner.com Published On :: Sun, 22 Mar 2020 00:25:29 -0500 The global pandemic is real, with almost 8,000 deaths worldwide and nearly 200,000 persons having contracted the virus in 155 affected countries. What is particularly comforting for this country, amid pain and the not knowing, is the bedside and... Full Article
aci Island Wedding: A racing romance all the way to ‘I do’ By jamaica-gleaner.com Published On :: Mon, 23 Mar 2020 00:20:19 -0500 Famous American poet and singer Maya Angelou shared this about matters pertaining to the heart: “Love recognises no barriers. It jumps hurdles, leaps fences, penetrates walls to arrive at its destination full of hope.” What started out as an... Full Article
aci Insulin-Deficient Diabetic Condition Upregulates the Insulin-Secreting Capacity of Human Induced Pluripotent Stem Cell-Derived Pancreatic Endocrine Progenitor Cells After Implantation in Mice By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 The host environment is a crucial factor for considering the transplant of stem cell–derived immature pancreatic cells in patients with type 1 diabetes. Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell–derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A+ NK6 homeobox 1+ cells and very few INS+ cells, were used. When the EPCs were implanted under the kidney capsule in immunodeficient mice, INS-deficient diabetes accelerated increase in plasma human C-peptide, a marker of graft-derived INS secretion. The acceleration was suppressed by INS infusion but not affected by partial attenuation of hyperglycemia by dapagliflozin, an INS-independent glucose-lowering agent. Immunohistochemical analyses indicated that the grafts from diabetic mice contained more endocrine cells including proliferative INS-producing cells compared with that from nondiabetic mice, despite no difference in whole graft mass between the two groups. These data suggest that INS-deficient diabetes upregulates the INS-secreting capacity of EPC grafts by increasing the number of endocrine cells including INS-producing cells without changing the graft mass. These findings provide useful insights into postoperative diabetic care for cell therapy using stem cell–derived pancreatic cells. Full Article
aci Davis embracing data, new approach to improve By mlb.mlb.com Published On :: Fri, 15 Feb 2019 17:07:20 EDT Looking to preempt questions about his work ethic in a nightmare 2018 season, Chris Davis reported to Spring Training in Florida more than a week before Orioles position players were required to. That's when his efforts to rebound hit their first minor snag. Full Article
aci Tackling racism in the NHS By feeds.bmj.com Published On :: Thu, 23 Jul 2015 10:45:44 +0000 For decades research has shown that discrimination, harassment, and exclusion are pervasive experiences for staff from black and minority ethnic (BME) backgrounds in the National Health Service. In this podcast, the authors of a recent analysis article in The BMJ talk about the evidence for discrimination, what the NHS has done and is doing, and... Full Article
aci The World Bank - the Global Financing Facility By feeds.bmj.com Published On :: Fri, 01 Sep 2017 09:05:03 +0000 The world bank was set up in 1944. In the aftermath of the second world war, the institution was there to give loans to countries rebuilding after the conflict. Their first loan went to France - but with stipulations about repayment that set a tone for future funds. A new series, authored by Devi Sridhar, and her team from the University of... Full Article
aci Yvonne Coghill is trying to fix racism in the NHS By feeds.bmj.com Published On :: Fri, 28 Feb 2020 11:59:19 +0000 In this week's special episode of Sharp Scratch, we've got something a little different for you! Last week the panel talked microaggressions, so this week we're hearing from an expert guest who is leading the work the NHS is doing to combat inequality in healthcare. If you like this special edition, let us know on Facebook, Instagram or Twitter... Full Article
aci High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells By diabetes.diabetesjournals.org Published On :: 2000-11-01 T InoguchiNov 1, 2000; 49:1939-1945Articles Full Article
aci Banting Lecture 2001: Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes By diabetes.diabetesjournals.org Published On :: 2002-01-01 J. Denis McGarryJan 1, 2002; 51:7-18Banting Lecture 2001 Full Article
aci Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade By diabetes.diabetesjournals.org Published On :: 1999-06-01 ME GriffinJun 1, 1999; 48:1270-1274Articles Full Article
aci Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM By diabetes.diabetesjournals.org Published On :: 1997-01-01 Guenther BodenJan 1, 1997; 46:3-10Perspectives in Diabetes Full Article
aci St Mary COVID crackdown - Health teams go house to house tracing virus as quarantine hits Dover, Annotto Bay, Enfield By jamaica-gleaner.com Published On :: Fri, 08 May 2020 00:26:31 -0500 Days after The Gleaner reported a clarion call from Port Maria Mayor Richard Creary for the quarantine of St Mary communities owing to growing concerns about the spread of COVID-19 in the parish, the Government responded with the lockdown of three... Full Article
aci L-Cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 Glucagon-like peptide 1 (GLP-1) mimetics are effective drugs for treatment of type 2 diabetes, and there is consequently extensive interest in increasing endogenous GLP-1 secretion and L-cell abundance. Here we identify G-protein–coupled bile acid receptor 1 (GPBAR1) as a selective regulator of intestinal L-cell differentiation. Lithocholic acid and the synthetic GPBAR1 agonist, L3740, selectively increased L-cell density in mouse and human intestinal organoids and elevated GLP-1 secretory capacity. L3740 induced expression of Gcg and transcription factors Ngn3 and NeuroD1. L3740 also increased the L-cell number and GLP-1 levels and improved glucose tolerance in vivo. Further mechanistic examination revealed that the effect of L3740 on L cells required intact GLP-1 receptor and serotonin 5-hydroxytryptamine receptor 4 (5-HT4) signaling. Importantly, serotonin signaling through 5-HT4 mimicked the effects of L3740, acting downstream of GLP-1. Thus, GPBAR1 agonists and other powerful GLP-1 secretagogues facilitate L-cell differentiation through a paracrine GLP-1–dependent and serotonin-mediated mechanism. Full Article
aci Bell facing tough decisions for OF alignment By mlb.mlb.com Published On :: Mon, 18 Feb 2019 18:45:48 EDT Reds manager David Bell has great corner outfield depth, but he doesn't have a regular center fielder. Determining who will get to play where and sorting out the log jam should be a challenge for Bell in his first season as a skipper in the big leagues. Full Article
aci Bariatric Surgery Rapidly Decreases Cardiac Dietary Fatty Acid Partitioning and Hepatic Insulin Resistance Through Increased Intra-abdominal Adipose Tissue Storage and Reduced Spillover in Type 2 Diabetes By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8–12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.75 (interquartile range 1.39–2.57) before to 1.09 (1.04–1.53) after surgery (P = 0.01) and systemic DFA spillover from 56.7 mmol before to 24.7 mmol over 6 h after meal intake after surgery (P = 0.01), with a significant increase in intra-abdominal adipose tissue DFA uptake from 0.15 (0.04–0.31] before to 0.49 (0.20–0.59) SUV after surgery (P = 0.008). Hepatic insulin resistance was significantly reduced in close association with increased DFA storage in intra-abdominal adipose tissues (r = –0.79, P = 0.05) and reduced DFA spillover (r = 0.76, P = 0.01). We conclude that bariatric surgery in subjects with T2D rapidly reduces cardiac DFA partitioning and hepatic insulin resistance at least in part through increased intra-abdominal DFA storage and reduced spillover. Full Article
aci n-3 Fatty Acid and Its Metabolite 18-HEPE Ameliorate Retinal Neuronal Cell Dysfunction by Enhancing Müller BDNF in Diabetic Retinopathy By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:29-07:00 Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H2O2) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H2O2 by high glucose, and H2O2 reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E–fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR. Full Article
aci Kelly already knows his way around ST facility By mlb.mlb.com Published On :: Thu, 14 Feb 2019 19:50:20 EDT Yes, catcher Carson Kelly is new to the D-backs this spring, but this wasn't the first time he's gotten to see what the inside of Salt River Fields looks like. Full Article
aci Facing forex shortage, productive sector appeals to BOJ for help By jamaica-gleaner.com Published On :: Fri, 08 May 2020 00:17:12 -0500 WITH THE productive sector experiencing a shortage of foreign exchange for the past two months, the Jamaican Manufacturers and Exporters Association, JMEA, says it has appealed to the Bank of Jamaica, BOJ, for direct access to US currency for three... Full Article
aci The Indo-Pacific: Geostrategic Outlook to 2024 - Workshop 4 By feedproxy.google.com Published On :: Thu, 09 Jan 2020 11:15:01 +0000 Invitation Only Research Event 26 November 2019 - 9:30am to 12:00pm Gateway House, Stevens Street, Colaba This closed-door roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024.Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence.The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga). Department/project Asia-Pacific Programme, Geopolitics and Governance, Sustainable and Inclusive Growth, Trade, Investment and Economics, Energy, Environment and Resources Programme Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Full Article
aci Belarusians Left Facing COVID-19 Alone By feedproxy.google.com Published On :: Thu, 16 Apr 2020 15:19:10 +0000 16 April 2020 Ryhor Astapenia Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @ryhorastapenia LinkedIn Anaïs Marin Associate Fellow, Russia and Eurasia Programme LinkedIn The way the epidemic is being mismanaged creates a risk of political destabilisation and leaves the country exposed to external influence. 2020-04-16-Belarus-COVID-Football Playing accordion in front of dummy football fans in Brest, Belarus as the country's championship continues despite the COVID-19 outbreak. Photo by SERGEI GAPON/AFP via Getty Images. Since the World Health Organisation (WHO) declared COVID-19 a pandemic, few countries have chosen to ignore social distancing recommendations. But, even among those states which have, the Belarusian official response to its epidemic remains unique.President Aliaksandr Lukashenka’s statements that vodka, sauna and tractors are protecting Belarusians from coronavirus attracted amused attention in international media. Lukashenka also described other societies’ response to COVID-19 as ‘a massive psychosis’.Although Lukashenka is notorious for his awkward style of public communication, the fact that Belarus is refusing to impose comprehensive confinement measures is of concern. Belarusians continue to work, play football and socialise.Lukashenka, himself playing ice hockey in front of state cameras, claims it is the best way to stay healthy. Belarusian authorities clearly appear to be in denial – and this could have dire humanitarian consequences.From denial to half measuresBelarus actually has one of the largest numbers of hospital beds in the world per 1,000 of the population. But in the absence of quarantine measures its health system, already crippled by corruption and embezzlement, is likely to be overwhelmed.Patients being treated for pneumonia in hospitals have suggested medical staff are uninformed and inadequately equipped. It is claimed doctors are not reporting COVID-19 as the suspected cause of death, either through a lack of testing or for fear of reprisals.Observers believe the real mortality rate is already well above official figures (40 deaths as of 16 April). Based on an Imperial College London model, between 15,000 and 32,000 people could die under the current mild confinement regime – and such a high death toll would hugely impact the country’s political stability. Citing personal data protection, the Ministry of Health has imposed a total news blackout; the only cluster officially acknowledged so far is the city of Vitsebsk.Although specific Belarusian cities and some individuals started changing their approach – by extending school vacations or cancelling weddings – such measures remain half-hearted.Clearly a major reason for such an apparently irresponsible reaction is that Belarus cannot afford a massive lockdown that would freeze its already underdeveloped economy and drive it deeper into recession. Unlike many other nations, Belarus lacks budgetary resources for a sizable stimulus package. But a delayed response might backfire on the economy.Economic recession has been forecast to amount to at least 10% of GDP. For Lukashenka, who openly challenged conventional wisdom regarding the need for quarantine and isolation, such an economic downturn would harm his confidence rating in the eyes of Belarusian voters, mindful of the state’s mismanagement of the crisis. And it could create doubt within the ruling elite itself, with Lukashenka seeking re-election for a sixth mandate in late August.Against this backdrop, a radicalization of the opposition-minded part of society is also to be expected, with greater reliance on social networks in the face of official secrecy and disinformation. The expected response of the regime is then likely to be pre-emptive repression. Evidence is emerging that law enforcement agencies have already stepped up judicial and paralegal harassment of dissenters, notably independent journalists and bloggers.Russia’s initial reluctance to address the coronavirus crisis may also have influenced Belarus. Lukashenka and his administration often react to public health challenges by the Soviet rulebook, reminiscent of the Soviet authorities’ mismanagement of the Chernobyl disaster in 1986.Russia has unilaterally closed its borders with Belarus and, as bilateral relations continue to deteriorate, this casts further doubt on the viability of the Union State of Belarus and Russia. Pro-Russian media forecast Moscow will be unwilling to alleviate the expected socio-economic crisis, as it continues to reject Minsk’s demands regarding subsidised oil deliveries. Yet the Kremlin might use the crisis as an opportunity to resume its integrationist pressure on Belarus.China, with which Belarus engaged in a seemingly privileged strategic partnership in the 2010s, was actually the first country to dispatch humanitarian aid to beef up Belarusian capacity to fight the virus.But Minsk should not expect Beijing to rescue its economy and, unless it commits to more internal reforms, Belarus is not likely to receive much from the EU either. The regime has already applied to the IMF for emergency financial support, but conditions are attached and, even if successful, the funds would amount to no more than $900m.The government’s decision to take only half measures so far is rooted in the hope COVID-19 is not as bad as foreign experts fear. But, unless the leadership acknowledges the public health crisis and mitigates its economic impact, COVID-19 will accelerate Belarus’s slide back into international self-isolation. If combined with a humanitarian crisis, this will put the Belarusian regime under considerable stress.This crisis does risk a new ‘Chernobyl moment’ for the authorities, but the population could react more vocally this time. As volunteers self-organise to fight the epidemic, it might become more difficult for the authorities to say that it is efficient in running the country. But the bottom line is Belarus desperately needs money. Whoever steps up to support Belarus financially will also be able to heavily influence its politics. Full Article
aci Geostrategic Outlook for the Indo-Pacific 2019-2024 By feedproxy.google.com Published On :: Mon, 09 Sep 2019 12:23:52 +0000 The project aims to broaden and deepen understanding of the geostrategic realities in, and outlook for, the Indo-Pacific region. Focusing on trade security, climate change disruptions and security cooperation, the project will develop scenarios exploring possible shifts in regional economic and security priorities from 2019-2024.Research staff from Chatham House will, in cooperation with local partners, convene expert roundtables in the United Kingdom, France, Japan, India, the United States and Tonga to enhance the discourse and understanding of the strategic relationships in the region, as well as the shared – or disparate – goals of the various countries.A podcast will be recorded and released in conjunction with each event. The project will culminate with a research paper, amalgamating the roundtable discussions with analyses and policy recommendations developed by the Chatham House team. Department contact Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Past events (3) Research Event The Indo-Pacific: Geostrategic Perspectives to 2024 - Workshop 3 17 October 2019 Research Event The Indo-Pacific: Geostrategic Perspectives 2019-24 – Workshop 2 24 September 2019 Research Event The Indo-Pacific: Geostrategic Perspectives 2019-20 – Workshop 1 11 September 2019 Full Article
aci The Indo-Pacific: Geostrategic Perspectives to 2024 - Workshop 3 By feedproxy.google.com Published On :: Mon, 14 Oct 2019 09:10:01 +0000 Invitation Only Research Event 17 October 2019 - 9:30am to 2:00pm Institut Francais des Relations Internationales, 27 rue de la Procession, 75740 Paris Cedex 15, France This closed-door roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024. Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence. The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga).Attendance at this event is by invitation only. Department/project Asia-Pacific Programme, Geopolitics and Governance, Sustainable and Inclusive Growth, Trade, Investment and Economics, Energy, Environment and Resources Programme, Geostrategic Outlook for the Indo-Pacific 2019-2024 Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Full Article
aci The Indo-Pacific: Geostrategic Outlook to 2024 - Workshop 4 By feedproxy.google.com Published On :: Thu, 09 Jan 2020 11:15:01 +0000 Invitation Only Research Event 26 November 2019 - 9:30am to 12:00pm Gateway House, Stevens Street, Colaba This closed-door roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024.Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence.The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga). Department/project Asia-Pacific Programme, Geopolitics and Governance, Sustainable and Inclusive Growth, Trade, Investment and Economics, Energy, Environment and Resources Programme Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Full Article
aci The Indo-Pacific: Geostrategic Outlook From Now to 2024 - Workshop 5 By feedproxy.google.com Published On :: Mon, 17 Feb 2020 14:25:01 +0000 Invitation Only Research Event 18 February 2020 - 12:00pm to 4:30pm Langafonua Centre This roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024. Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence. The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga). Department/project Asia-Pacific Programme, Sustainable and Inclusive Growth, Trade, Investment and Economics, Energy, Environment and Resources Programme Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Full Article
aci An older man with thoracic back pain By feeds.bmj.com Published On :: Wednesday, November 23, 2016 - 11:01 Full Article
aci Covid-19: Lack of capacity led to halting of community testing in March, admits deputy chief medical officer By feeds.bmj.com Published On :: Wednesday, May 6, 2020 - 12:25 Full Article