if Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression By feedproxy.google.com Published On :: 1996-05-01 K SchoonjansMay 1, 1996; 37:907-925Reviews Full Article
if Direct transesterification of all classes of lipids in a one-step reaction By feedproxy.google.com Published On :: 1986-01-01 G LepageJan 1, 1986; 27:114-120Articles Full Article
if Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI By feedproxy.google.com Published On :: 1990-03-01 JE HixsonMar 1, 1990; 31:545-548Articles Full Article
if Latin America’s COVID-19 Moment: Differences and Solidarity By feedproxy.google.com Published On :: Thu, 30 Apr 2020 11:37:25 +0000 30 April 2020 Dr Christopher Sabatini Senior Research Fellow for Latin America, US and the Americas Programme @ChrisSabatini LinkedIn There has been no better example of the political diversity in Latin America than the varying responses of governments to the coronavirus crisis. 2020-04-30-Chile-Covid.jpg A municipal cleaning worker disinfects the central market in Santiago, Chile on 7 April 2020 amid the coronavirus pandemic. Photo: Getty Images. Differing approaches across the hemisphere have had different impacts on presidential popularity and, at least in one case, on democratic institutions and human rights. Yet, even within that diversity, South America’s Southern Cone countries (Argentina, Chile, Paraguay and Uruguay) have shown a sign of solidarity: protecting and facilitating trade flows, sponsoring cross-border research and ensuring citizens’ return to their home countries. The response from populist leadersOn the extreme have been the responses of presidents of Brazil, Nicaragua and Mexico, all of whom have ignored the science of the virus and of experts and refused to implement isolation policies. President Jair Bolsonaro of Brazil fired his health minister, Luis Henrique Mandetta on 16 April for contradicting him and earlier had claimed that the pandemic was a hoax or little more than a ‘measly cold.' Meanwhile, Nicaraguan president Daniel Ortega has resisted closing businesses and schools. After a mysterious 34-day absence, Ortega appeared on television on 15 April reinforcing his refusal to close businesses saying that Nicaraguans must work or they will die and claiming that the virus was ‘imported.’ Mexico’s Andres Manuel Lopez Obrador (AMLO) has also resisted the call for strict stay-at-home policies, though with his Deputy Health Minister, Hugo López-Gatell, has closed schools – recently extending the closure to the 1st of June and urging non-essential businesses to close – but focusing primarily on social distancing. In contrast to his deputy health minister and Foreign Minister Marcelo Ebrard – who had declared the situation a health emergency on 30th March, later than many neighbouring countries – AMLO has largely attempted to avoid discussion of the pandemic, claiming that in his case he has lucky charms that prevent him from contracting the virus. And both Bolsonaro and AMLO have participated in large public rallies, doing all the things that politicians love, shaking hands and hugging babies, and in the case of the former even wiping his nose before embracing an elderly woman.The Nicaraguan, Brazilian and Mexican presidents make an odd grouping since one (Bosonaro) is considered of the extreme populist right and the others (Ortega and AMLO) of the populist left. What unites them is good old-fashioned populism, a belief in a leader who represents the amorphous popular will and should be unfettered by checks and balances on his power, including something like… science. An eclectic groupAt the other extreme have been the quick responses by governments in Peru, Argentina, Chile, El Salvador and Colombia which put quarantine measures in place in mid-March. In these cases, governments have even banned outdoor activities and in the case of Peru and Colombia (in the large cities) have imposed alternating days for when women and men can leave the house so as to better control outside movement. This too, though, is an eclectic group. It includes a Peronist president Alberto Fernández in Argentina, conservative presidents Sebastian Piñera in Chile and Ivan Duque in Colombia, interim president and relative political neophyte Martin Vizcarra in Peru and outsider president Nayib Bukele in El Salvador. El Salvador’s strict quarantine measures have led to rising concerns that Bukele is using the crisis to consolidate personal power, using the national police and the armed forces to enforce the quarantine and ignoring three rulings by the Supreme Court urging the president to end the abuses. In Argentina, Peronist Fernández has shown a surprising commitment to containment even as it hurts his party’s working-class base, not something typically expected of the populist Peronist Party. In all of these cases, the quick, strong responses by the presidents shored up their popularity. Peru’s Vizcarra saw his popularity shoot up 35 points in a week to 82 per cent according to surveys taken in March. In late March 2020, Fernández in Argentina saw his approval ratings swell to 79.2 per cent with 94.7 percent of citizens approving of the government’s strict shelter-at-home policies. Even presidents Piñera and Duque who had struggled with low approval ratings throughout 2019 and saw those numbers sink even lower after the social protests that ended the year have seen their numbers rise. According to an 20th April poll, Piñera’s popular approval rating swelled from 13 percent in March 18th at the start of the crisis to 25 per cent by 20th April; while hardly a sweeping popular mandate, even that level was unthinkable only a few months ago when administration was battered by social protests. In Colombia, after a series of political missteps and the popular protests, Duque’s popular approval rating had slumped to 26 per cent; by April 2nd, 62 percent of Colombians supported the once-beleaguered president. (No recent surveys were available for Bukele in El Salvador.)In contrast, Bolsonaro’s in Brazil has only nudged up. Before the crisis hit, the president’s popularity had been in steady decline from a high of 49 per cent in January 2019 to 30 per cent by early December 2019. But by the first week in April, in the midst of a crisis in which other presidents saw their approval ratings increase by double digits, after his public disagreements with the health minister, Bolsonaro’s had sunk to 33 per cent while the soon-to-be-fired Mandetta’s stood at 76 per cent. AMLO in Mexico has fared no better. The populist leftist scored a high 86 per cent approval rating in February 1, 2019. By March 28, 2020 with concerns over his weak and flippant COVID-19 response and a severe contraction in economic growth, AMLO’s approval rating had sunk 26 points to 60 per cent and his disapproval stood at 37 per cent. In the midst of disharmony, coordinationDespite these differences, many countries in the region have shown the solidarity they often speak of but rarely follow in policy or practice. Peru, Chile and other countries have collaborated in repatriating citizens back to their home countries in the midst of the crisis. Even the countries of the Southern Cone common market, MERCOSUR, have pulled together on a number of fronts. The trade bloc had effectively been ruled a dead-man-walking after its failed efforts to integrate Venezuela into the bloc, lowering its standards to let in the petroleum dependent semi-authoritarian government of then President Hugo Chávez. Even on the basics of internal cooperation, the block was struggling, unable to coordinate monetary policies and non-tariff trade barriers between the original founding member states, Argentina, Brazil, Paraguay and Uruguay.The 35-year-old customs union seemed to get a breath a new life with the announcement that it had concluded 20-year-long negotiations with the EU for a free trade deal. Ratification of that deal, however, ran aground on the political differences between the recently elected governments of Bolsonaro in Brazil and the Peronist Fernández in Argentina. Bolsonaro refused to attend the Fernández December 2019 inauguration, in protest of the newly elected president’s leftist leanings. And this was well before their sharply divergent reactions to the COVID-19 virus. How surprising then that Mercosur has served as an effective coordination mechanism for these different and once opposed governments. The trade body is collaborating among member states to ensure the repatriation of citizens and has agreed to coordinate to ensure that trade flows, especially of medical supplies, are not interrupted by shutdown measures. Mercosur has even gone one step further than several other bodies have failed to take. In early April the bloc’s governing body, based in Montevideo, Uruguay created a $16 million (12 million pound) fund to augment country research and assist in the purchase of supplies needed to combat the virus. Now if Brazil, Argentina and the others could only coordinate their domestic coronavirus responses and economic policy. In late March Fernández announced he was pulling Argentina out of a possible Mercosur-EU trade deal. Full Article
if Latin America’s COVID-19 Moment: Differences and Solidarity By feedproxy.google.com Published On :: Thu, 30 Apr 2020 11:37:25 +0000 30 April 2020 Dr Christopher Sabatini Senior Research Fellow for Latin America, US and the Americas Programme @ChrisSabatini LinkedIn There has been no better example of the political diversity in Latin America than the varying responses of governments to the coronavirus crisis. 2020-04-30-Chile-Covid.jpg A municipal cleaning worker disinfects the central market in Santiago, Chile on 7 April 2020 amid the coronavirus pandemic. Photo: Getty Images. Differing approaches across the hemisphere have had different impacts on presidential popularity and, at least in one case, on democratic institutions and human rights. Yet, even within that diversity, South America’s Southern Cone countries (Argentina, Chile, Paraguay and Uruguay) have shown a sign of solidarity: protecting and facilitating trade flows, sponsoring cross-border research and ensuring citizens’ return to their home countries. The response from populist leadersOn the extreme have been the responses of presidents of Brazil, Nicaragua and Mexico, all of whom have ignored the science of the virus and of experts and refused to implement isolation policies. President Jair Bolsonaro of Brazil fired his health minister, Luis Henrique Mandetta on 16 April for contradicting him and earlier had claimed that the pandemic was a hoax or little more than a ‘measly cold.' Meanwhile, Nicaraguan president Daniel Ortega has resisted closing businesses and schools. After a mysterious 34-day absence, Ortega appeared on television on 15 April reinforcing his refusal to close businesses saying that Nicaraguans must work or they will die and claiming that the virus was ‘imported.’ Mexico’s Andres Manuel Lopez Obrador (AMLO) has also resisted the call for strict stay-at-home policies, though with his Deputy Health Minister, Hugo López-Gatell, has closed schools – recently extending the closure to the 1st of June and urging non-essential businesses to close – but focusing primarily on social distancing. In contrast to his deputy health minister and Foreign Minister Marcelo Ebrard – who had declared the situation a health emergency on 30th March, later than many neighbouring countries – AMLO has largely attempted to avoid discussion of the pandemic, claiming that in his case he has lucky charms that prevent him from contracting the virus. And both Bolsonaro and AMLO have participated in large public rallies, doing all the things that politicians love, shaking hands and hugging babies, and in the case of the former even wiping his nose before embracing an elderly woman.The Nicaraguan, Brazilian and Mexican presidents make an odd grouping since one (Bosonaro) is considered of the extreme populist right and the others (Ortega and AMLO) of the populist left. What unites them is good old-fashioned populism, a belief in a leader who represents the amorphous popular will and should be unfettered by checks and balances on his power, including something like… science. An eclectic groupAt the other extreme have been the quick responses by governments in Peru, Argentina, Chile, El Salvador and Colombia which put quarantine measures in place in mid-March. In these cases, governments have even banned outdoor activities and in the case of Peru and Colombia (in the large cities) have imposed alternating days for when women and men can leave the house so as to better control outside movement. This too, though, is an eclectic group. It includes a Peronist president Alberto Fernández in Argentina, conservative presidents Sebastian Piñera in Chile and Ivan Duque in Colombia, interim president and relative political neophyte Martin Vizcarra in Peru and outsider president Nayib Bukele in El Salvador. El Salvador’s strict quarantine measures have led to rising concerns that Bukele is using the crisis to consolidate personal power, using the national police and the armed forces to enforce the quarantine and ignoring three rulings by the Supreme Court urging the president to end the abuses. In Argentina, Peronist Fernández has shown a surprising commitment to containment even as it hurts his party’s working-class base, not something typically expected of the populist Peronist Party. In all of these cases, the quick, strong responses by the presidents shored up their popularity. Peru’s Vizcarra saw his popularity shoot up 35 points in a week to 82 per cent according to surveys taken in March. In late March 2020, Fernández in Argentina saw his approval ratings swell to 79.2 per cent with 94.7 percent of citizens approving of the government’s strict shelter-at-home policies. Even presidents Piñera and Duque who had struggled with low approval ratings throughout 2019 and saw those numbers sink even lower after the social protests that ended the year have seen their numbers rise. According to an 20th April poll, Piñera’s popular approval rating swelled from 13 percent in March 18th at the start of the crisis to 25 per cent by 20th April; while hardly a sweeping popular mandate, even that level was unthinkable only a few months ago when administration was battered by social protests. In Colombia, after a series of political missteps and the popular protests, Duque’s popular approval rating had slumped to 26 per cent; by April 2nd, 62 percent of Colombians supported the once-beleaguered president. (No recent surveys were available for Bukele in El Salvador.)In contrast, Bolsonaro’s in Brazil has only nudged up. Before the crisis hit, the president’s popularity had been in steady decline from a high of 49 per cent in January 2019 to 30 per cent by early December 2019. But by the first week in April, in the midst of a crisis in which other presidents saw their approval ratings increase by double digits, after his public disagreements with the health minister, Bolsonaro’s had sunk to 33 per cent while the soon-to-be-fired Mandetta’s stood at 76 per cent. AMLO in Mexico has fared no better. The populist leftist scored a high 86 per cent approval rating in February 1, 2019. By March 28, 2020 with concerns over his weak and flippant COVID-19 response and a severe contraction in economic growth, AMLO’s approval rating had sunk 26 points to 60 per cent and his disapproval stood at 37 per cent. In the midst of disharmony, coordinationDespite these differences, many countries in the region have shown the solidarity they often speak of but rarely follow in policy or practice. Peru, Chile and other countries have collaborated in repatriating citizens back to their home countries in the midst of the crisis. Even the countries of the Southern Cone common market, MERCOSUR, have pulled together on a number of fronts. The trade bloc had effectively been ruled a dead-man-walking after its failed efforts to integrate Venezuela into the bloc, lowering its standards to let in the petroleum dependent semi-authoritarian government of then President Hugo Chávez. Even on the basics of internal cooperation, the block was struggling, unable to coordinate monetary policies and non-tariff trade barriers between the original founding member states, Argentina, Brazil, Paraguay and Uruguay.The 35-year-old customs union seemed to get a breath a new life with the announcement that it had concluded 20-year-long negotiations with the EU for a free trade deal. Ratification of that deal, however, ran aground on the political differences between the recently elected governments of Bolsonaro in Brazil and the Peronist Fernández in Argentina. Bolsonaro refused to attend the Fernández December 2019 inauguration, in protest of the newly elected president’s leftist leanings. And this was well before their sharply divergent reactions to the COVID-19 virus. How surprising then that Mercosur has served as an effective coordination mechanism for these different and once opposed governments. The trade body is collaborating among member states to ensure the repatriation of citizens and has agreed to coordinate to ensure that trade flows, especially of medical supplies, are not interrupted by shutdown measures. Mercosur has even gone one step further than several other bodies have failed to take. In early April the bloc’s governing body, based in Montevideo, Uruguay created a $16 million (12 million pound) fund to augment country research and assist in the purchase of supplies needed to combat the virus. Now if Brazil, Argentina and the others could only coordinate their domestic coronavirus responses and economic policy. In late March Fernández announced he was pulling Argentina out of a possible Mercosur-EU trade deal. Full Article
if Social media and the visibility of horrific violence By feedproxy.google.com Published On :: Thu, 07 May 2020 08:53:25 +0000 7 May 2020 , Volume 96, Number 3 Constance Duncombe Read Online Images are central to social media communication. Billions of images are shared across different social media platforms every day: photos, cartoons, GIFs and short video clips are exchanged by users, facilitating or framing discourse on participatory sites such as Twitter, Facebook and Instagram. Many of these images depict events of extreme violence, which circulate uninhibited by the conventional constraints associated with traditional news media censorship. A question arises here as to how such images mobilize public and policy-making responses to atrocities. This article examines the political dynamics of violent social media images. I argue that the particular qualities of social media can play an important role in how the digital visibility of horrific violence influences policy-making as a response to such atrocities. There is an important connection between the properties of social media platforms that allow user images to reach a global audience in real time and the emotional responses that this level of circulation generates. In turn, the pressure created by events made globally visible through the circulation of violent images and the audience responses to those images puts governments in a position where they are forced to act, which has significant implications for policy-making. Full Article
if Undercurrents: Episode 10 - Artificial Intelligence in International Affairs, and Women Drivers in Saudi Arabia By feedproxy.google.com Published On :: Fri, 15 Jun 2018 00:00:00 +0100 Full Article
if Undercurrents: Episode 21 - EU-US Relations after the Midterms, and Tackling the Illegal Wildlife Trade in Africa By feedproxy.google.com Published On :: Fri, 09 Nov 2018 00:00:00 +0000 Full Article
if Power Shift: The Rise of Asia and the Decline of the West? By feedproxy.google.com Published On :: Tue, 28 May 2019 00:00:00 +0100 Full Article
if Artificial Intelligence and the Public: Prospects, Perceptions and Implications By feedproxy.google.com Published On :: Fri, 28 Jun 2019 00:00:00 +0100 Full Article
if Undercurrents: Summer Special - Allison Gardner on Artificial Intelligence By feedproxy.google.com Published On :: Thu, 08 Aug 2019 00:00:00 +0100 Full Article
if Plaintiff in Chief: President Trump and the American Legal System By feedproxy.google.com Published On :: Wed, 30 Oct 2019 00:00:00 +0000 Full Article
if Podcast: International Law, Security and Prosperity in the Asia-Pacific By feedproxy.google.com Published On :: Fri, 01 Nov 2019 00:00:00 +0000 Full Article
if Undercurrents: Episode 40 - Illicit Financial Flows, and Geopolitics in the Indo-Pacific By feedproxy.google.com Published On :: Thu, 14 Nov 2019 00:00:00 +0000 Full Article
if Proteomic Analysis of Salmonella-modified Membranes Reveals Adaptations to Macrophage Hosts [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Systemic infection and proliferation of intracellular pathogens require the biogenesis of a growth-stimulating compartment. The gastrointestinal pathogen Salmonella enterica commonly forms highly dynamic and extensive tubular membrane compartments built from Salmonella-modified membranes (SMMs) in diverse host cells. Although the general mechanism involved in the formation of replication-permissive compartments of S. enterica is well researched, much less is known regarding specific adaptations to different host cell types. Using an affinity-based proteome approach, we explored the composition of SMMs in murine macrophages. The systematic characterization provides a broader landscape of host players to the maturation of Salmonella-containing compartments and reveals core host elements targeted by Salmonella in macrophages as well as epithelial cells. However, we also identified subtle host specific adaptations. Some of these observations, such as the differential involvement of the COPII system, Rab GTPases 2A, 8B, 11 and ER transport proteins Sec61 and Sec22B may explain cell line-dependent variations in the pathophysiology of Salmonella infections. In summary, our system-wide approach demonstrates a hitherto underappreciated impact of the host cell type in the formation of intracellular compartments by Salmonella. Full Article
if Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Acute myeloid leukemia (AML) is a clonal disorder arising from hematopoietic myeloid progenitors. Aberrantly activated tyrosine kinases (TK) are involved in leukemogenesis and are associated with poor treatment outcome. Kinase inhibitor (KI) treatment has shown promise in improving patient outcome in AML. However, inhibitor selection for patients is suboptimal. In a preclinical effort to address KI selection, we analyzed a panel of 16 AML cell lines using phosphotyrosine (pY) enrichment-based, label-free phosphoproteomics. The Integrative Inferred Kinase Activity (INKA) algorithm was used to identify hyperphosphorylated, active kinases as candidates for KI treatment, and efficacy of selected KIs was tested. Heterogeneous signaling was observed with between 241 and 2764 phosphopeptides detected per cell line. Of 4853 identified phosphopeptides with 4229 phosphosites, 4459 phosphopeptides (4430 pY) were linked to 3605 class I sites (3525 pY). INKA analysis in single cell lines successfully pinpointed driver kinases (PDGFRA, JAK2, KIT and FLT3) corresponding with activating mutations present in these cell lines. Furthermore, potential receptor tyrosine kinase (RTK) drivers, undetected by standard molecular analyses, were identified in four cell lines (FGFR1 in KG-1 and KG-1a, PDGFRA in Kasumi-3, and FLT3 in MM6). These cell lines proved highly sensitive to specific KIs. Six AML cell lines without a clear RTK driver showed evidence of MAPK1/3 activation, indicative of the presence of activating upstream RAS mutations. Importantly, FLT3 phosphorylation was demonstrated in two clinical AML samples with a FLT3 internal tandem duplication (ITD) mutation. Our data show the potential of pY-phosphoproteomics and INKA analysis to provide insight in AML TK signaling and identify hyperactive kinases as potential targets for treatment in AML cell lines. These results warrant future investigation of clinical samples to further our understanding of TK phosphorylation in relation to clinical response in the individual patient. Full Article
if Identification of an Unconventional Subpeptidome Bound to the Behcet's Disease-associated HLA-B*51:01 that is Regulated by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Human leukocyte antigen (HLA) B*51:01 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly genetically associated with Behcet's disease (BD). Previous studies have defined two subgroups of HLA-B*51 peptidome containing proline (Pro) or alanine (Ala) at position 2 (P2). Little is known about the unconventional non-Pro/Ala2 HLA-B*51-bound peptides. We aimed to study the features of this novel subpeptidome, and investigate its regulation by ERAP1. CRISPR-Cas9 was used to generate an HLA-ABC-triple knockout HeLa cell line (HeLa.ABC-KO), which was subsequently transduced to express HLA-B*51:01 (HeLa.ABC-KO.B51). ERAP1 was silenced using lentiviral shRNA. Peptides bound to HLA-B*51:01 were eluted and analyzed by mass spectrometry. The characteristics of non-Pro/Ala2, Pro2, and Ala2 peptides and their alteration by ERAP1 silencing were investigated. Effects of ERAP1 silencing on cell surface expression of HLA-B*51:01 were studied using flow cytometry. More than 20% of peptides eluted from HLA-B*51:01 lacked Pro or Ala at P2. This unconventional group of HLA-B*51:01-bound peptides was relatively enriched for 8-mers (with relatively fewer 9-mers) compared with the Pro2 and Ala2 subpeptidomes and had similar N-terminal and C-terminal residue usages to Ala2 peptides (with the exception of the less abundant leucine at position ). Knockdown of ERAP1 increased the percentage of non-Pro/Ala2 from 20% to ~40%, increased the percentage of longer (10-mer and 11-mer) peptides eluted from HLA-B*51:01 complexes, and abrogated the predominance of leucine at P1. Interestingly knockdown of ERAP1 altered the length and N-terminal residue usage of non-Ala2&Pro2 and Ala2 but not the Pro2 peptides. Finally, ERAP1 silencing regulated the expression levels of cell surface HLA-B*51 in a cell-type-dependent manner. In conclusion, we have used a novel methodology to identify an unconventional but surprisingly abundant non-Pro/Ala2 HLA-B*51:01 subpeptidome. It is increased by knockdown of ERAP1, a gene affecting the risk of developing BD. This has implications for theories of disease pathogenesis. Full Article
if An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have further evaluated and optimized our recent boosting to amplify signal with isobaric labeling (BASIL) approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of proteins in single cells. This improved BASIL (iBASIL) approach enables reliable quantitative single-cell proteomics analysis with greater proteome coverage by carefully controlling the boosting-to-sample ratio (e.g. in general <100x) and optimizing MS automatic gain control (AGC) and ion injection time settings in MS/MS analysis (e.g. 5E5 and 300 ms, respectively, which is significantly higher than that used in typical bulk analysis). By coupling with a nanodroplet-based single cell preparation (nanoPOTS) platform, iBASIL enabled identification of ~2500 proteins and precise quantification of ~1500 proteins in the analysis of 104 FACS-isolated single cells, with the resulting protein profiles robustly clustering the cells from three different acute myeloid leukemia cell lines. This study highlights the importance of carefully evaluating and optimizing the boosting ratios and MS data acquisition conditions for achieving robust, comprehensive proteomic analysis of single cells. Full Article
if The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange and can be accessed at https://www.ebi.ac.uk/pride/ with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium. Full Article
if Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015 [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms. Full Article
if Quantification of the affinities of CRISPR-Cas9 nucleases for cognate protospacer adȷacent motif (PAM) sequences [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency. Full Article
if 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
if China's ivory bans: enhancing soft power through wildlife conservation By feedproxy.google.com Published On :: Wed, 06 Nov 2019 09:20:21 +0000 6 November 2019 , Volume 95, Number 6 Jonas Gamso Read online China has been a major market for elephant ivory for centuries. However, the Chinese government recently enacted bans on imports and exports of ivory (2015) and on the domestic ivory trade (2017). These bans appear to have come in response to intensive influence campaigns and public shaming from domestic and foreign activists, who cited declining elephant populations and highlighted China's role. However, this shaming-narrative is at odds with conventional wisdom regarding Chinese policy-making: China typically resists international pressures and its authoritarian government is thought to be largely insulated from domestic efforts by civil society groups. This article reconciles Beijing's ivory policy with these conventional beliefs about policy-making in China. I argue that the Chinese government saw unique benefits to banning the ivory trade, under growing international scrutiny, as doing so enhanced Chinese soft power while having very little impact on its sovereignty or development. Non-government organizations (NGOs) operating both inside and outside of China played a role as well: NGOs in China helped to shift Chinese public opinion towards favouring the bans, while those operating abroad led public relations efforts to publicize Chinese demand for ivory to foreign audiences. Efforts by the latter group of NGOs intensified pressure on the Chinese government to rein in the ivory market, while increasing the soft power benefits that banning ivory would bring to Beijing. Full Article
if 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
if 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
if Episode 32: Pacific Rim By feedproxy.google.com Published On :: Sun, 21 Jul 2013 23:23:00 +0000 Pacific Rim ReviewWorld War Z mini-reviewWhat We Watched: The Lone Ranger, Breaking Bad, Mad Men, Celeste and Jesse Forever, Despicable Me 2, Ruby Sparks, Melancholia, Do The Right Thing, ESPN 30 for 30: Broke, etc.You can download the episode here. (right click to save) Next Episode: The Conjuring Full Article
if Myeloid-specific deficiency of pregnane X receptor decreases atherosclerosis in LDL receptor-deficient mice [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXRMyeLDLR–/–) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXRMyeLDLR–/– mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXRMyeLDLR–/– mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management. Full Article
if Tariffs on Germany a card Trump seems willing to play, analyst says By feedproxy.google.com Published On :: Tue, 21 Jan 2020 14:34:30 +0000 Source CNBC URL https://www.cnbc.com/video/2019/12/03/tariffs-on-germany-a-card-trump-seems-will... Release date 03 December 2019 Expert Dr Lindsay Newman In the news type Op-ed Hide date on homepage Full Article
if Long noncoding RNA pncRNA-D reduces cyclin D1 gene expression and arrests cell cycle through RNA m6A modification [RNA] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 pncRNA-D is an irradiation-induced 602-nt long noncoding RNA transcribed from the promoter region of the cyclin D1 (CCND1) gene. CCND1 expression is predicted to be inhibited through an interplay between pncRNA-D and RNA-binding protein TLS/FUS. Because the pncRNA-D–TLS interaction is essential for pncRNA-D–stimulated CCND1 inhibition, here we studied the possible role of RNA modification in this interaction in HeLa cells. We found that osmotic stress induces pncRNA-D by recruiting RNA polymerase II to its promoter. pncRNA-D was highly m6A-methylated in control cells, but osmotic stress reduced the methylation and also arginine methylation of TLS in the nucleus. Knockdown of the m6A modification enzyme methyltransferase-like 3 (METTL3) prolonged the half-life of pncRNA-D, and among the known m6A recognition proteins, YTH domain-containing 1 (YTHDC1) was responsible for binding m6A of pncRNA-D. Knockdown of METTL3 or YTHDC1 also enhanced the interaction of pncRNA-D with TLS, and results from RNA pulldown assays implicated YTHDC1 in the inhibitory effect on the TLS–pncRNA-D interaction. CRISPR/Cas9-mediated deletion of candidate m6A site decreased the m6A level in pncRNA-D and altered its interaction with the RNA-binding proteins. Of note, a reduction in the m6A modification arrested the cell cycle at the G0/G1 phase, and pncRNA-D knockdown partially reversed this arrest. Moreover, pncRNA-D induction in HeLa cells significantly suppressed cell growth. Collectively, these findings suggest that m6A modification of the long noncoding RNA pncRNA-D plays a role in the regulation of CCND1 gene expression and cell cycle progression. Full Article
if RNA helicase-regulated processing of the Synechocystis rimO-crhR operon results in differential cistron expression and accumulation of two sRNAs [Gene Regulation] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts. Full Article
if Unified approach to critical-contrast homogenisation with explicit links to time-dispersive media By www.ams.org Published On :: Fri, 10 Apr 2020 08:09 EDT K. D. Cherednichenko, Yu. Yu. Ershova, A. V. Kiselev and S. N. Naboko Trans. Moscow Math. Soc. 80 (2020), 251-294. Abstract, references and article information Full Article
if Spectral analysis and representation of solutions of integro-differential equations with fractional exponential kernels By www.ams.org Published On :: Fri, 10 Apr 2020 08:09 EDT V. V. Vlasov and N. A. Rautian Trans. Moscow Math. Soc. 80 (2020), 169-188. Abstract, references and article information Full Article
if Spectral Properties of Differential Operators with Oscillating Coefficients By www.ams.org Published On :: Fri, 10 Apr 2020 08:09 EDT N. F. Valeev, Ya. T. Sultanaev and É. A. Nazirova Trans. Moscow Math. Soc. 80 (2020), 153-167. Abstract, references and article information Full Article
if Ordinary differential operators and the integral representation of sums of certain power series By www.ams.org Published On :: Fri, 10 Apr 2020 08:09 EDT K. A. Mirzoev and T. A. Safonova Trans. Moscow Math. Soc. 80 (2020), 133-151. Abstract, references and article information Full Article
if What happens to a fund that is listed pursuant to a product specific rule filing once the fund is eligible to operate under Rule 6c-11 and elects to list on Nasdaq under Rule 5704? By feedproxy.google.com Published On :: Publication Date: Apr 10 2020 The SEC will withdraw the existing approval order and the fund will become subject to the requirements of Rule 6c-11 and Nasdaq Rule 5704.... Full Article
if What happens if an ETF is no longer compliant with Rule 6c-11? By feedproxy.google.com Published On :: Publication Date: Apr 10 2020 On or before December 22, 2020, all ETFs that meet the definition of "Exchange Traded Fund" in Nasdaq Rule 5704(a)(1)(A) will need to be compliant with Rule 6c-11. If it is determined that an ETF no longer complies with Rule 6c-11 and therefore no longer complies Nasdaq Rule 5704, Nasdaq will generally issue a letter of deficiency. The ETF will generally be given 45 days to submit a plan to regain compliance. If the plan is accepted, Nasdaq Staff can grant an... Full Article
if The recalibration of Chinese assertiveness: China's responses to the Indo-Pacific challenge By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:14:26 +0000 8 January 2020 , Volume 96, Number 1 Read online Feng Liu In response to the changing geopolitical landscape in Asia, both China and the United States attempt to alter the regional order in their own favour, both in the economic and security realms. This article shows how diverging views on future arrangements are leading to strategic shifts and increasing tension between these two Great Powers. As part of its quest for Great-Power status, China has been actively pushing its regional initiatives such as the Belt and Road Initiative (BRI) and the Asian Infrastructure Investment Bank (AIIB), as well as adopting assertive security policies towards its neighbours. In contrast, in order to counter China's growing influence America's regional strategy is undergoing a subtle shift from ‘rebalancing to Asia’ to focusing on the ‘Indo-Pacific’ region. However, amid an intensifying trade war and other challenges facing the region, China has chosen to moderate its proactive foreign policy-orientation in the past few years. In particular, China has made attempts to downplay its domestic rhetoric, rebuild strategic relationship with India and Japan, and to reassure ASEAN states in the South China Sea. In response to the Indo-Pacific strategy, it would be more effective for China to articulate a more inclusive regional vision and promote an institutional framework that also accommodates a US presence in the region. Full Article
if Non-traditional security cooperation between China and south-east Asia: implications for Indo-Pacific geopolitics By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:17:30 +0000 8 January 2020 , Volume 96, Number 1 Read online Xue Gong The ‘free and open Indo-Pacific’ (FOIP) strategy, actively promoted by the United States with support from its allies and partners, is a significant geopolitical response to China's growing power and expanding influence in Asia and beyond. Beijing has adopted various new strategies to cope with the challenges related to FOIP. One of these strategies is to secure a robust relationship with south-east Asia in order to make these regional states either neutral to or less supportive of the Indo-Pacific vision. In addition to economic statecraft and soft power, Beijing believes that it can also tap into the domain of non-traditional security (NTS) to strengthen relations with this region to position itself better in the intensifying regional geopolitical competition. The article addresses the following question: what is the impact of China's NTS cooperation with south-east Asia on Beijing's geopolitical rivalry with other major powers in the Indo-Pacific region? The article argues that China's NTS cooperation with south-east Asian countries may help China maintain its geopolitical standing in the region, but it is unlikely to lead to any dramatic increase of China's strategic influence in the region. This essentially means that Beijing may be able to prevent ASEAN or most ASEAN member states from lending substantive and strong support to the Indo-Pacific construct, but it will not be able to stop ASEAN states from supporting some elements of the FOIP. Full Article
if Japan's ‘Indo-Pacific’ question: countering China or shaping a new regional order? By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:19:14 +0000 8 January 2020 , Volume 96, Number 1 Read online Kei Koga Japan's primary objective of the ‘free and open Indo-Pacific’ (FOIP) strategy is to shape and consolidate regional order in the Indo-Pacific region based on the existing rules-based international order. The concept initially aimed to achieve two different objectives—shaping a regional order in the Indo-Pacific and ensuring the defence of Japan; however, Japan has gradually shifted its strategic focus onto the former, separating national defence from the FOIP concept, which reflects a change in the degree of its commitment to the two objectives. On the one hand, as its overall security strategy, Japan has determined to steadily enhance its national defence by increasing its own defence capabilities and strengthening the US–Japan alliance, while transforming its partnerships with like-minded states, such as Australia and India, into a diplomatic, and potentially military, alignment. This has been brought about by shifts in the regional balance of power, particularly the rise of China and the relative decline of the United States. On the other hand, as part of its FOIP strategy, Japan's attempts to build a new regional order in the Indo-Pacific region aim to defend the existing rules-based order established by the United States from challengers, particularly China. Yet, given the strategic uncertainty over Japan's international coalition-building efforts to create a new regional order, Japan has made its approach flexible; Tokyo is using its ambiguous FOIP concept to gauge other states' responses, understand their perspectives, and change its strategic emphases accordingly—so-called ‘tactical hedging’. Japan has pursued similar means to achieve the two key objectives. Nevertheless, the country's core interest, the defence of Japan, is more imperative than building a regional order in the Indo-Pacific region, and Japan faces different types of challenges in the future. Full Article
if Evasive balancing: India's unviable Indo-Pacific strategy By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:37:22 +0000 8 January 2020 , Volume 96, Number 1 Read online Rajesh Rajagopalan India has adopted the Indo-Pacific concept with uncharacteristic speed. This article examines India's Indo-Pacific strategy, which evolved out of its earlier ‘Look East’ and ‘Act East’ policies but is much more focused on strategic concerns than on trade or connectivity. As such, the strategy is subset of its China policy, and includes contradictory elements of balancing China by building partnerships with the United States as well as with regional powers, while simultaneously pursuing a reassurance strategy to convince Beijing that India is not really balancing China. The combination of these contradictory elements is characterized as evasive balancing, which is a more useful concept than either pure balancing or hedging for understanding the policies of India and of many other countries in the region that are trying to manage China's rise. However, reassurance strategies rarely work and the combination of balancing and reassurance is even less likely to be viable. Full Article
if Is Australia's Indo-Pacific strategy an illusion? By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:39:40 +0000 8 January 2020 , Volume 96, Number 1 Read online Brendan Taylor Australia has been among the most prominent advocates of the increasingly popular Indo-Pacific concept. This article argues that Canberra's enthusiasm for the concept stems from its appeal to the two dominant traditions of Australian foreign policy—a ‘dependent ally’ tradition and a ‘middle power’ approach. While these two traditions are typically seen as being in tension, the Indo-Pacific concept provides a rare point of convergence between them. The article begins by outlining the appeal of the Indo-Pacific concept to each of these traditions. Using a case-study of recent Australian policy toward the South China Sea disputes, however, the article then demonstrates that Australia has in practice implemented its stated Indo-Pacific strategy far less consistently than its very vocal support would appear to suggest. This disjuncture is attributed to the growing influence of a third, generally understudied, ‘pragmatic’ Australian foreign policy tradition. Because Australia has been such a prominent champion of the Indo-Pacific concept, the article concludes that this divergence between the rhetoric and the reality of Australia's Indo-Pacific strategy threatens to have a negative impact on the concept's broader international appeal and sustainability, particularly among Australia's south-east Asian neighbours. Full Article
if Indonesia and the ASEAN outlook on the Indo-Pacific By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:44:49 +0000 8 January 2020 , Volume 96, Number 1 Read online Dewi Fortuna Anwar Indonesia has taken a leadership role within the Association of Southeast Asian Nations (ASEAN) in drafting a common outlook on the Indo-Pacific concept. The widening of Indonesia's geostrategic canvas from the Asia–Pacific to the Indo-Pacific is in line with President Joko Widodo's intent to make Indonesia a Global Maritime Fulcrum (GMF). In view of the rivalry between the US and China and the emergence of various Indo-Pacific initiatives from other countries, Indonesia believes that ASEAN must try to maintain its centrality. The draft of Indonesia's perspective for an ASEAN outlook on the Indo-Pacific: towards a peaceful, prosperous, and inclusive region was submitted for considerations by ASEAN, and after 18 months of intensive lobbying by Indonesia the concept was finally adopted at the ASEAN Summit in June 2019. The ASEAN outlook promotes the principles of openness, inclusiveness, transparency, respect for international law and ASEAN centrality in the Indo-Pacific region. It proposes a building-block approach, seeking commonalities between existing regional initiatives in which ASEAN-led mechanisms will act as a fulcrum for both norm-setting and concrete cooperation. Rather than creating a new regional architecture, the East Asia Summit (EAS) is proposed as the platform for advancing the Indo-Pacific discourse and cooperation. Indonesia's ASEAN outlook on the Indo-Pacific marks its renewed foreign policy activism as a middle power and underlines the continuing importance that Indonesia places on ASEAN as the cornerstone of its foreign policy, emphasising ASEAN's centrality as the primary vehicle for managing relations with the major powers in the Indo-Pacific region. Full Article
if Consigned to hedge: south-east Asia and America's ‘free and open Indo-Pacific’ strategy By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:47:11 +0000 8 January 2020 , Volume 96, Number 1 Read online See Seng Tan This article assesses how south-east Asian countries and the Association of Southeast Asian Nations (ASEAN) have responded to the ‘free and open Indo-Pacific’ (FOIP) strategies promoted by the United States and the other countries in the Quadrilateral Security Dialogue (the ‘Quad’: US, Japan, Australia and India). Their nuanced ripostes imply a persistent commitment to hedging and shifting limited alignments in the face of growing great rivalry and the lack of a clear FOIP vision among Quad members. In the face of external pressure to take sides, the ASEAN states are likely to keep hedging through working selectively with China and the United States. Given the United States' apparent preference to balance China and Trump's disregard for multilateralism, ASEAN's ability to maintain its centrality in the evolving regional architecture is in doubt—despite the Quad countries' (belated) accommodation of ASEAN in their FOIP strategies. However, the success of the US strategy depends on Washington's ability to build and sustain the requisite coalition to balance Beijing. ASEAN has undertaken efforts to enhance bilateral security collaboration with China and the United States respectively. In doing so, ASEAN is arguably seeking to informally redefine its centrality in an era of Great Power discord and its ramifications for multilateralism. Full Article
if The institutionalization of the Indo-Pacific: problems and prospects By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:49:12 +0000 8 January 2020 , Volume 96, Number 1 Read online Kai He and Huiyun Feng Although the term ‘Indo-Pacific’ has become popular in the foreign policy discourse of some countries, we have yet to see any significant institution-building in the Indo-Pacific region. Borrowing insights from functional institutionalism and political leadership studies of international regimes, we introduce a ‘leadership–institution’ model to explore the problems and prospects of institutionalizing the Indo-Pacific. Through a comparative case study of the institutionalization of the Asia–Pacific vs the Indo-Pacific, we argue that two crucial factors contributed to the slow institutionalization of the Indo-Pacific as a regional system in world politics: the lack of ideational leadership from an epistemic community and the weak executive leadership from a powerful state. While ideational leaders can help states identify and expand common interests in cooperation, executive leadership will facilitate states to overcome operational obstacles in cooperation, such as the ‘collective action’ problem and the ‘relative gains’ concern. The future of institution-building in the Indo-Pacific will depend on whether and how these two leadership roles are played by scholars and states in the region. In the conclusion, we discuss the challenges of institutionalizing the Indo-Pacific and highlight China as a wild card in the future of Indo-Pacific regionalism. Full Article
if The Belt and Road Initiative: geo-economics and Indo-Pacific security competition By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:58:35 +0000 8 January 2020 , Volume 96, Number 1 Read online Mingjiang Li The Belt and Road Initiative (BRI) has been regarded by international society as a major policy tool in China's geo-economic strategy. Under this policy platform, Beijing has pledged to invest billions of dollars in the infrastructure and industrial sectors across Eurasia and in the Indo-Pacific nations. It is widely believed that such huge amount of investment will inevitably generate significant geostrategic repercussions in these regions. In response to the BRI, the United States and other powers have come up with a ‘free and open Indo-Pacific’ strategy. This article attempts to address the following question: what impact is the BRI likely to have on the security ties between China and the other major players in the Indo-Pacific? The author finds that the BRI may significantly transform China's international security policy and the expansion of Beijing's security influence may further intensify the security competition between China and other major powers in the Indo-Pacific region. The article also proposes a new analytical angle for the study of geo-economics that unpacks the role of economic activities and processes in generating geopolitical intentions and catalysing geopolitical competition. Full Article
if Developmental peace in east Asia and its implications for the Indo-Pacific By feedproxy.google.com Published On :: Wed, 08 Jan 2020 12:01:42 +0000 8 January 2020 , Volume 96, Number 1 Read online Ling Wei This article adopts a constructive approach to examining the problem of the Indo-Pacific construct. Through reflection on the east Asian experience, it proposes an analytical framework of developmental peace as a constellation of international practices, which means that the more economic development is prioritized by states in regional processes, the more likely it is that a sustainable peace will be achieved. States participating in regional integration comprise a community of practice. On the basis of a shared understanding that development is of overriding importance and underpins security and state legitimacy, the community takes economic development as the anchoring practice; this practice embodies and enacts constitutive rules and fundamental norms for a broader set of practices in regional processes, such as peaceful coexistence and non-interference. The more economic development is prioritized on domestic and regional agendas, the more likely it is that conflicts in the security realm will be relaxed or even resolved to protect security interests. The author draws some useful implications from the developmental peace in east Asia for the Indo-Pacific construct, among which the most important include building shared understandings on the prioritization of economic development, taking advantage of the Regional Comprehensive Economic Partnership (RCEP), Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) and the Asian Infrastructure Investment Bank, and using the code of conduct process as a vehicle and best practice to facilitate rule-making for the maritime order. Finally, the author briefly discusses the contributions of the study and limitations of the model. Full Article
if Understanding the dynamics of the Indo-Pacific: US–China strategic competition, regional actors, and beyond By feedproxy.google.com Published On :: Wed, 08 Jan 2020 21:20:01 +0000 6 November 2019 , Volume 96, Number 1 The first issue of International Affairs in 2020 explores the geopolitics of the 'Indo-Pacific' region. Read online Kai He and Mingjiang Li As a geographical concept, ‘Indo-Pacific’ has existed for decades. As a political and strategic concept, it has since 2010 gradually become established in the foreign policy lexicon of some countries, especially Australia, India, Japan and the United States. However, China seems to be reluctant to identify itself as part of the Indo-Pacific; Chinese leaders believe that the US-led Indo-Pacific strategy aims to contain China's rise. While the battle between the two geographical concepts ‘Indo-Pacific’ and ‘Asia–Pacific’ may be fairly easily settled in the future, US–China strategic competition has just begun. Will the Indo-Pacific become a battlefield for US–China rivalry? How will China cope with the US ‘free and open Indo-Pacific’ (FOIP) strategy? How will other regional actors respond to the US–China strategic competition in the Indo-Pacific? What are the strategic implications of the ‘Indo-Pacific’ concept for regional order transformation? How will the Indo-Pacific be institutionalized, economically, politically and strategically? This article introduces the January 2020 special issue of International Affairs, which aims to address those questions, using both country-specific and regional perspectives. Seven articles focus on the policy responses of major players (Australia, China, India, Indonesia, Japan and ASEAN) to the US FOIP strategy and related US–China rivalry in the region. A further three articles examine the profound implications of Indo-Pacific dynamics for regional institution-building and for geopolitical and geo-economic architecture. Full Article
if 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
if Network Power in the Asia-Pacific: Making Sense of the New Regionalism and Opportunities for Cooperation By feedproxy.google.com Published On :: Fri, 17 Jan 2020 16:00:01 +0000 Research Event 7 February 2020 - 9:45am to 5:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Agenda - Network Power in the Asia-Pacific.pdfpdf | 118.01 KB The Asia-Pacific region continues to increase in geopolitical and geoeconomic importance. The rise of China and tensions with the US are affecting bilateral relationships and traditional alliances in the region. Whether seen from the perspective of the Quad – Australia, India, Japan and the US – or the Indo-Pacific concept embraced by a wide range of countries but with no shared consensus on scope and objectives or with ASEAN who insists on the importance of its own centrality, the region is redefining and reconceptualising itself.With a diverse range of initiatives – including the Regional Comprehensive Economic Partnership (RCEP) and Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) – there are a plethora of regional agreements and institutional groupings that add further complexity.As the Bretton Woods architecture continues to be dominated by Western powers, China is also spearheading parallel governance initiatives such as the Asian Infrastructure Investment Bank (AIIB), the Belt and Road Initiative and the Shanghai Cooperation Organization (SCO) as a means of enhancing its geopolitical and geoeconomic influence.This one-day conference will focus on how such networks and alliances have been built, and sustained, in the Asia-Pacific region. In order to understand how new regional initiatives might open up opportunities for new forms of international cooperation, the conference will focus on the themes of cyber-technology and innovation, sustainable development and mitigating the impacts of climate change and new infrastructure initiatives. It will assess whether there is a zero-sum conflict between competing networks and agendas or whether a common approach can be developed. Department/project Asia-Pacific Programme, Geopolitics and Governance, Sustainable and Inclusive Growth, Technology and Society, Trade, Investment and Economics Lucy Ridout Programme Administrator, Asia-Pacific Programme +44 (0) 207 314 2761 Email Full Article
if 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
