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China Paves Its Way in New Areas of International Law Expert comment sysadmin 31 March 2017

China is looking to increase its capacity and influence in international legal matters – and it is particularly in frontier areas of the law that China is likely to take a proactive stance.

Foreign Minister Wang Yi called China a staunch defender and builder of the international rule of law in his speech to the UN General Assembly in October 2014. He promised that as China grew stronger, it would make a greater contribution to the maintenance and promotion of international rule of law, and would work with other countries to build a fairer and more reasonable international political and economic order.

For many in China, that time has now come: there is a sense that China deserves a much stronger and more respected voice in discussions surrounding the future of the international system. The recent speeches of Xi Jinping in Davos and Geneva in January 2017 suggest that China is now seizing the initiative and fighting for a voice and influence commensurate with its status and power as the number two economy in the world.

But there is an interesting divide in the areas in which China chooses to assert itself. In traditional areas of international law – such as the law of the sea and international human rights law – China continues to harbour reservations about the fairness of the existing international order. Its misgivings are fuelled by a perception that it did not play a significant part in the creation of the post-Second World War international order, and that those rules operate mainly in the interests of Western powers.

There is also a sense that traditional areas of international law do not offer a level playing field for China, since Western states have far more experience at operating in those. We know from Chinese experts that in the South China Sea case, one background issue that played into China’s refusal to engage in litigation with the Philippines and other interested states (which were represented by leading Western international lawyers) was a lack of experience before international courts and tribunals.

Contrast this with newer areas of international law– such as the regimes governing cyber, space, climate change and deep sea mining issues. In these areas, the rules are still in the process of being developed and tested, and the influence of the existing powers is not so firmly established or accepted, so there is more opportunity for China’s voice to be heard and heeded.

On climate change, China has become a champion of the Paris Agreement, which it worked hard with the Obama administration to secure. China is also active in some of the processes related to cyber rule-making, both as a member of the UN Group of Governmental Experts on cyber issues and through bilateral dialogues with a number of states. China has taken a keen interest in the regime applicable to the mining of the international seabed, making submissions to the International Tribunal on the Law of the Sea about the procedure for settling disputes. In international economic law, another relatively new area, China has been assiduously cultivating expertise, and is a major player in the negotiation of the ‘mega regional’ trade deal, the Regional Comprehensive Economic Partnership.

In time, the development of China’s much heralded Belt and Road Initiative may provide an opportunity for China to be further involved in international norm-setting, through the creation of a system of economic and political interaction that is built and run more along Chinese determined lines. The emergence of the Asian Infrastructure Investment Bank may offer an early indicator of China’s attempts to shape global governance, although in this context China has so far scrupulously observed international standards and has made no open attempt to challenge them.

So far, China’s practical input to international norm-setting has been limited. While China is prone to making wide-ranging statements of principle, it finds it more challenging to engage in the nitty gritty of specific rule making. But as is clear from its membership of the WTO, China can adapt quickly. While initially it was a reluctant adherent to the WTO dispute settlement mechanism, China is now adept at making active and effective use of its rules to promote China’s interests, including launching a legal challenge regarding the contested issue of its non-market economy status. Overall, there is strong leadership backing for a more activist approach to its engagement with the international legal system.

China sees international law as an important instrument in the “toolbox” of international diplomacy. It will increasingly be seeking to leverage international law to promote its own interests, particularly in newer areas, as it seeks to strengthen its wider soft power and influence.

Webinar: Hong Kong: Dissent in the Age of Coronavirus 17 April 2020 — 12:00PM TO 1:00PM Anonymous (not verified) 8 April 2020

Street protests demanding greater autonomy and democratization in Hong Kong upended the city for seven months last year. However, with the outbreak of the coronavirus in China in late January, the protests quickly died out. What does this mean for the city’s protest movement?

The speaker will argue that, despite the lack of high-profile street rallies, protest in the city is continuing. It is building on and evolving from last year’s protest movement albeit in different forms. At the same time, the Hong Kong authorities, emboldened by a hard line from Beijing, have begun cracking down on activists and protesters in the city as they seek to put a lid on dissent ahead of important Legislative Council elections scheduled for this September.

In this webinar, the speaker will look at the current state of dissent in Hong Kong and prospects for Hong Kong’s future.

This event will be held on the record.

Constantin Carle and Marlis Hochbruck
Math. Comp. 93 (), 2611-2641.
Abstract, references and article information

Kazuhiro Ishige, Paolo Salani and Asuka Takatsu
Trans. Amer. Math. Soc. 377 (), 5705-5748.
Abstract, references and article information

firehouse.ie posted a photo:

firehouse.ie posted a photo:

Benjamin Jaye and Manasa N. Vempati
Proc. Amer. Math. Soc. 152 (), 5105-5116.
Abstract, references and article information

Roland Donninger
Bull. Amer. Math. Soc. 61 (), 659-685.
Abstract, references and article information

Family, friends, and community members gathered on Saturday at the Falmouth First Assembly Church to celebrate the life of 15-year-old Jahmarie Reid, a William Knibb High student who tragically lost his life at sea on August 27 in what is believed...

With tears streaming down his face and his voice trembling, a windshield wiper made a declaration that he would rather live in the cemetery than with his relatives. "A the cemetery me ago live. Unnu wicked to me," Ramarieo Bailey declared. Bailey...

Knockout mouse models have been extensively used to study the antiviral activity of IFIT (interferon-induced protein with tetratricopeptide repeats). Human IFIT1 binds to cap0 (m7GpppN) RNA, which lacks methylation on the first and second cap-proximal nucleotides (cap1, m7GpppNm, and cap2, m7GpppNmNm, respectively). These modifications are signatures of “self” in higher eukaryotes, whereas unmodified cap0-RNA is recognized as foreign and, therefore, potentially harmful to the host cell. IFIT1 inhibits translation at the initiation stage by competing with the cap-binding initiation factor complex, eIF4F, restricting infection by certain viruses that possess “nonself” cap0-mRNAs. However, in mice and other rodents, the IFIT1 orthologue has been lost, and the closely related Ifit1b has been duplicated twice, yielding three paralogues: Ifit1, Ifit1b, and Ifit1c. Although murine Ifit1 is similar to human IFIT1 in its cap0-RNA–binding selectivity, the roles of Ifit1b and Ifit1c are unknown. Here, we found that Ifit1b preferentially binds to cap1-RNA, whereas binding is much weaker to cap0- and cap2-RNA. In murine cells, we show that Ifit1b can modulate host translation and restrict WT mouse coronavirus infection. We found that Ifit1c acts as a stimulatory cofactor for both Ifit1 and Ifit1b, promoting their translation inhibition. In this way, Ifit1c acts in an analogous fashion to human IFIT3, which is a cofactor to human IFIT1. This work clarifies similarities and differences between the human and murine IFIT families to facilitate better design and interpretation of mouse models of human infection and sheds light on the evolutionary plasticity of the IFIT family.

Systemic antibody light chains (AL) amyloidosis is characterized by deposition of amyloid fibrils derived from a particular antibody light chain. Cardiac involvement is a major risk factor for mortality. Using MAS solid-state NMR, we studied the fibril structure of a recombinant light chain fragment corresponding to the fibril protein from patient FOR005, together with fibrils formed by protein sequence variants that are derived from the closest germline (GL) sequence. Both analyzed fibril structures were seeded with ex-vivo amyloid fibrils purified from the explanted heart of this patient. We find that residues 11-42 and 69-102 adopt β-sheet conformation in patient protein fibrils. We identify arginine-49 as a key residue that forms a salt bridge to aspartate-25 in the patient protein fibril structure. In the germline sequence, this residue is replaced by a glycine. Fibrils from the GL protein and from the patient protein harboring the single point mutation R49G can be both heterologously seeded using patient ex-vivo fibrils. Seeded R49G fibrils show an increased heterogeneity in the C-terminal residues 80-102, which is reflected by the disappearance of all resonances of these residues. By contrast, residues 11-42 and 69-77, which are visible in the MAS solid-state NMR spectra, show 13Cα chemical shifts that are highly like patient fibrils. The mutation R49G thus induces a conformational heterogeneity at the C terminus in the fibril state, whereas the overall fibril topology is retained. These findings imply that patient mutations in FOR005 can stabilize the fibril structure.

27 July 2020

Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

COP27: Navigating a difficult road to Sharm El-Sheikh Expert comment NCapeling 6 July 2022

Against a backdrop of rising urgency, COP27 in Egypt will bring all aspects of climate action into the spotlight – but especially the role of the host country.

As COP26 drew to a close in Glasgow, Egyptian officials announced their priorities for COP27, emphasizing climate finance and climate adaptation – a new approach given previous COPs mainly focused on mitigation, reducing emissions to limit climate damage.

This was followed by the COP27 presidency outlining its vision at MENA Climate Week 2022 to achieve ‘substantive and equal progress’ on all aspects of the negotiations, and Egypt emphasizing its intention to focus on implementing existing carbon reduction targets rather than pushing for further carbon cuts.

Egypt argues it is hosting COP27 on behalf of African nations and that, while it is promoting the interests of the developing world, it will be an impartial arbiter. However it is also useful to consider its priorities from the Egyptian government’s perspective.

Agenda drivers

Egypt has long prioritized climate finance and adaptation because it remains in need of technical and financial support to adapt, especially in agriculture and tourism.

It plans to expand its access to climate funding and investment, an area in which Egypt has been relatively successful as it currently receives 27 per cent of all multilateral climate finance in the MENA region and has issued the region’s first sovereign green bonds.

With public debt currently 94 per cent of GDP, Egyptian officials have also called for debt relief for Egypt and other developing countries.

Egypt’s Climate Change Strategy reflects this approach, aiming to enhance Egypt’s rank on the Climate Change Performance Index in order to ‘attract more investments and acquire more climate funding’.

Limiting the mitigation scope and the focus on finance also echoes Egypt’s own reluctance to make carbon reduction commitments. The Egyptian nationally determined contribution (NDC) – its 2030 pledge under the Paris Agreement – does not include any quantifiable emission reduction targets.

Egypt is one of only a few countries which failed to submit an updated NDC in 2021 and its upcoming update will not include an economy-wide carbon reduction target.

Egypt has also never published a long-term strategy and has no decarbonization plans despite independent estimates it should cut rising emissions by one-quarter by 2030, and by two-thirds by 2050 to be aligned with the Paris Agreement. This partly explains why observers rate Egypt’s climate action as highly insufficient.

Furthermore, Egypt’s championing of ‘moving from pledges to implementation’ without having quantifiable carbon reduction pledges of its own effectively exempts it from both pledging and implementation.

As a developing country, Egypt’s negotiating position is supported by UNFCCC provisions which recognize differentiated responsibilities and respective capabilities of nations.

Its proposal to focus COP27 on the implementation of climate action and finance pledges is important in consolidating progress. But not pushing for more emission reductions at this critical moment risks derailing global decarbonization momentum and undermining global climate action.

According to optimistic estimates, if current climate pledges were implemented the world would still remain on track for 2°C of warming by the end of the century, with far worse impacts than if warming was curbed at 1.5°C.

Under a 2°C scenario, 37 per cent of the global population could regularly be exposed to extreme heat waves compared to 14 per cent in a 1.5°C warmer world, with developing countries expected to be worst-affected.

A 2°C trajectory also runs the risk of tipping points such as the melting of ice sheets in Antarctica and Greenland, triggering runaway climate change. Time to change the warming trajectory is running out as the latest IPCC assessment warns the window of opportunity is now ‘brief and rapidly closing’, and the UN Secretary General recently called for faster carbon cuts by the end of 2022 to avoid a ‘climate catastrophe’.

A different energy transition

Egypt opted not to join any of the voluntary sectoral coalitions at COP26 on reducing methane, clean energy transition, transition to zero-emissions vehicles, or moving beyond oil and gas.

This position is explained by its growing role as an exporter and advocate for fossil gas in the energy transition. Egypt is the second-largest producer of natural gas in Africa and is emerging as a fossil gas hub for the eastern Mediterranean, which is shaping its domestic energy policy.

Its 59GW electricity generation capacity is almost double the peak demand and is dominated by gas-powered electricity generation, which currently represents 42 per cent of all Africa’s gas generation.

Egypt’s climate policy is also shaped by fossil gas, and its national Climate Change Strategy encourages the expansion of gas use by promoting a transition to compressed natural gas for vehicles, the expansion of its domestic natural gas network – despite having universal access to electricity – and shifting to a gas-fuelled shipping sector.

Egypt also voiced support for other African countries to extract and deploy fossil gas and oil resources, making it one of the protagonists of the ‘great fossil gas pushback’. These advocates defend the right of developing countries to deploy fossil gas as a ‘transition fuel’ and champion its necessity to solve energy poverty.

But their position is not shared by all African and developing countries, and is rejected by some civil society groups, who argue it risks locking in greenhouse gases and local emissions for decades as well as delaying future development of low carbon energy systems.

Egypt’s huge spare generation capacity has contributed to a slowdown in renewable energy projects over the past two years. With renewables representing just 6GW, Egypt is expected to miss its renewable energy target for 2022, set at 20 per cent of generating capacity.

Engaging Egypt better

But these positions are more malleable than they seem, and Egypt is open to dialogue – not just on refining the COP27 agenda but also on reviewing its own climate priorities and leveraging its energy sector for a more ambitious transition.

Sylwia Struk
Dec 28, 2020; 0:RA119.001766v1-mcp.RA119.001766
Research

Mingkun Yang
Nov 24, 2020; 0:RA120.002144v1-mcp.RA120.002144
Research

Elisa Vidal
Dec 1, 2020; 61:1733-1746
Research Articles

Carlota Oleaga
Nov 17, 2020; 0:jlr.RA120000964v1-jlr.RA120000964
Research Articles

In SAS Customer Intelligence Studio, you can choose to create a new calculated variable in the Edit Value dialog box when you populate a treatment custom detail. Following creation of the new calculated

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism by inducing the degradation of hepatic low-density lipoprotein receptor (LDLR). Plasma PCSK9 has two main molecular forms: a 62-kDa mature form (PCSK9_62) and a 55-kDa, furin-cleaved form (PCSK9_55). PCSK9_55 is considered less active than PCSK9_62 in degrading LDLR. We aimed to identify the site of PCSK9_55 formation (intra- vs. extracellular) and to further characterize the LDLR-degradative function of PCSK9_55 relative to PCSK9_62. Co-expressing PCSK9_62 with furin in cell culture induced formation of PCSK9_55, most of which was found in the extracellular space. Under the same conditions we found that: i) adding a cell-permeable furin inhibitor preferentially decreased the formation of PCSK9_55 extracellularly; ii) using pulse-chase, we observed the formation of PCSK9_55 exclusively extracellularly in a time-dependent manner. A recombinant form of PCSK9_55 was efficiently produced but displayed impaired secretion that resulted in its intracellular trapping. However, the non-secreted PCSK9_55 was able to induce degradation of LDLR, though with 50% lower efficiency compared with PCSK9_62. Collectively, our data show that PCSK9_55 is generated in the extracellular space, and that intracellular PCSK9_55 is not secreted but retains the ability to degrade the LDLR through an intracellular pathway.

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

Voltage-gated Cav1 and Cav2 Ca2+ channels are comprised of a pore-forming α1 subunit (Cav1.1-1.4, Cav2.1-2.3) and auxiliary β (β1-4) and α2δ (α2δ−1−4) subunits. The properties of these channels vary with distinct combinations of Cav subunits and alternative splicing of the encoding transcripts. Therefore, the impact of disease-causing mutations affecting these channels may depend on the identities of Cav subunits and splice variants. Here, we analyzed the effects of a congenital stationary night blindness type 2 (CSNB2)-causing mutation, I745T (IT), in Cav1.4 channels typical of those in human retina: Cav1.4 splice variants with or without exon 47 (Cav1.4+ex47 and Cav1.4Δex47, respectively), and the auxiliary subunits, β2X13 and α2δ-4. We find that IT caused both Cav1.4 splice variants to activate at significantly more negative voltages and with slower deactivation kinetics than the corresponding WT channels. These effects of the IT mutation, along with unexpected alterations in ion selectivity, were generally larger in channels lacking exon 47. The weaker ion selectivity caused by IT led to hyperpolarizing shifts in the reversal potential and large outward currents that were evident in channels containing the auxiliary subunits β2X13 and α2δ-4 but not in those with β2A and α2δ-1. We conclude that the IT mutation stabilizes channel opening and alters ion selectivity of Cav1.4 in a manner that is strengthened by exclusion of exon 47 and inclusion of β2X13 and α2δ-4. Our results reveal complex actions of IT in modifying the properties of Cav1.4 channels, which may influence the pathological consequences of this mutation in retinal photoreceptors.

The dominant role of CaV2 voltage-gated calcium channels for driving neurotransmitter release is broadly conserved. Given the overlapping functional properties of CaV2 and CaV1 channels, and less so CaV3 channels, it is unclear why there have not been major shifts toward dependence on other CaV channels for synaptic transmission. Here, we provide a structural and functional profile of the CaV2 channel cloned from the early-diverging animal Trichoplax adhaerens, which lacks a nervous system but possesses single gene homologues for CaV1–CaV3 channels. Remarkably, the highly divergent channel possesses similar features as human CaV2.1 and other CaV2 channels, including high voltage–activated currents that are larger in external Ba2+ than in Ca2+; voltage-dependent kinetics of activation, inactivation, and deactivation; and bimodal recovery from inactivation. Altogether, the functional profile of Trichoplax CaV2 suggests that the core features of presynaptic CaV2 channels were established early during animal evolution, after CaV1 and CaV2 channels emerged via proposed gene duplication from an ancestral CaV1/2 type channel. The Trichoplax channel was relatively insensitive to mammalian CaV2 channel blockers ω-agatoxin-IVA and ω-conotoxin-GVIA and to metal cation blockers Cd2+ and Ni2+. Also absent was the capacity for voltage-dependent G-protein inhibition by co-expressed Trichoplax Gβγ subunits, which nevertheless inhibited the human CaV2.1 channel, suggesting that this modulatory capacity evolved via changes in channel sequence/structure, and not G proteins. Last, the Trichoplax channel was immunolocalized in cells that express an endomorphin-like peptide implicated in cell signaling and locomotive behavior and other likely secretory cells, suggesting contributions to regulated exocytosis.

Pour beaucoup de personnes, la perte de poids rime obligatoirement avec une période de privation. Mais contrairement à ces idées reçues, il est bien possible d’observer un régime pour perdre du poids tout en vous faisant plaisir. Découvrez notre recette minceur de biscuits croquants sans beurre aux flocons d’avoine qui raviront vos papilles sans pour autant vous apporter […]

L’article Quelle est la meilleure recette minceur à base de biscuits aux flocons d’avoine ? est apparu en premier sur Ortho Doc France.

Aspergillus flavus (A. flavus), a pathogenic fungus, can produce carcinogenic and toxic aflatoxins that are a serious agricultural and medical threat worldwide. Attempts to decipher the aflatoxin biosynthetic pathway have been hampered by the lack of a high-quality genome annotation for A. flavus. To address this gap, we performed a comprehensive proteogenomic analysis using high-accuracy mass spectrometry data for this pathogen. The resulting high-quality dataset confirmed the translation of 8,724 previously-predicted genes, and identified 732 novel proteins, 269 splice variants, 447 single amino acid variants, 188 revised genes. A subset of novel proteins was experimentally validated by RT-PCR and synthetic peptides. Further functional annotation suggested that a number of the identified novel proteins may play roles in aflatoxin biosynthesis and stress responses in A. flavus. This comprehensive strategy also identified a wide range of post-translational modifications (PTMs), including 3,461 modification sites from 1,765 proteins. Functional analysis suggested the involvement of these modified proteins in the regulation of cellular metabolic and aflatoxin biosynthetic pathways. Together, we provided a high quality annotation of A. flavus genome and revealed novel insights into the mechanisms of aflatoxin production and pathogenicity in this pathogen.

The F-box protein MORE AXILLARY GROWTH 2 (MAX2) is a central component in the signaling cascade of strigolactones (SLs) as well as of the smoke derived karrikins (KARs) and the so far unknown endogenous KAI2 ligand (KL). The two groups of molecules are involved in overlapping and unique developmental processes, and signal-specific outcomes are attributed to perception by the paralogous α/β-hydrolases DWARF14 (D14) for SL and KARRIKIN INSENSITIVE 2/ HYPOSENSITIVE TO LIGHT (KAI2/HTL) for KAR/KL. Additionally, depending on which receptor is activated, specific members of the SUPPRESSOR OF MAX2 1 (SMAX1) – LIKE (SMXL) family control KAR/KL and SL responses. As proteins that function in the same signal transduction pathway often occur in large protein complexes, we aimed at discovering new players of the MAX2, D14 and KAI2 protein network by tandem affinity purification using Arabidopsis cell cultures. When using MAX2 as a bait, various proteins were co-purified among which general components of the Skp1-Cullin-F-box complex and members of the CONSTITUTIVE PHOTOMORPHOGENIC 9 signalosome. Here, we report the identification of a novel interactor of MAX2, a type 5 serine/threonine protein phosphatase, designated PHYTOCHROME-ASSOCIATED PROTEIN PHOSPHATASE 5 (PAPP5). Quantitative affinity purification pointed at PAPP5 as being more present in KAI2 rather than D14 protein complexes. In agreement, mutant analysis suggests that PAPP5 modulates KAR/KL-dependent seed germination in suboptimal conditions and seedling development. Additionally, a phosphopeptide enrichment experiment revealed that PAPP5 might dephosphorylate MAX2 in vivo independently of the synthetic strigolactone analog, rac-GR24. Together, by analyzing the protein complexes to which MAX2, D14 and KAI2 belong, we revealed a new MAX2 interactor, PAPP5, that might act through dephosphorylation of MAX2 to control mainly KAR/KL- related phenotypes and, hence, provide another link with the light pathway.