In 1991, after a three-year investigation, US and UK authorities announced indictments against two Libyan intelligence officials in connection with the 1988 bombing of Pan Am Flight 103 over Lockerbie, Scotland, which killed 270 people. During a trial held a decade later in the Netherlands, one of the defendants was found guilty and sentenced to life imprisonment. Whose presence on board the airplane has given rise to a number of conspiracy theories about the motivations behind the bombing? Discuss

Eastwood takes measured aim at the American justice system in a film that centers on a murder trial — and a juror who realizes he may be implicated in the crime.

(Official Washington Examiner editorial, Nov. 11)  Year after year, presidential administration after administration, people across the political spectrum agree that U.S. military veterans deserve better treatment. Alas, despite genuinely good […]

The post Two major reforms can improve the VA appeared first on Quin Hillyer.

Over the past year, Aya and Khalid have been filming their lives for a BBC documentary.

Israel says its targets are legitimate, but critics say it is aiming at Hezbollah's social base.

West Indies fast bowler Alzarri Joseph is suspended for two matches after storming off against England following an argument with captain Shai Hope.

Body camera footage shows the moment a boy was saved from his home in Texas after his mother couldn't reach him in the fire.

World champions South Africa are aiming to have "the two best teams in the world", according to centre Andre Esterhuizen.

When it comes to heating your home or enjoying a cozy evening by the fireplace, the type of firewood you choose can make a significant difference in both the efficiency and quality of your fire. One critical distinction in the world of firewood is whether it is hardwood or softwood. While the terms “hardwood” and […]

The post How To Tell Hardwood From Softwood Firewood? appeared first on Patriot Outdoor News.

The prime minister was in Paris, while Sophie, the Duchess of Edinburgh led events at the National Memorial Arboretum.

Is the Premier League title race down to two teams after just 11 games? BBC Sport looks at the chances of the top four.

Ukraine has said that the toll from a Russian strike on the hometown of President Volodymyr Zelensky had risen to four people, identifying the dead as a mother and her three children, including a newborn.

It’s time to hang your winter jacket in the closet and change your wardrobe to warmer clothes, because “Spring Is Coming” to the Avangate Affiliate Network. Our spring contest will make your sales bloom and may even fulfill your Amazon wishlist. (Feel free to think “beyond the wall” with creative promotions!)

2FA, the common abbreviation for two-factor authentication is a word often spoken about when one is setting up a website or account where security is vital. With more and more confidential information being uploaded on the net, it makes sense to add additional measures to prevent hackers from gaining access to an account. In terms […]

The post Enabling Two-Factor Authentication (2FA) for a PayPal Account appeared first on Tips and Tricks HQ.

Cape Town police have arrested two suspects in connection with the murder of Noem My Skollie actor David Manuel and his friend, Alfonso Fisher, in Gugulethu last month.

Three years ago, Chris Wallace walked away from Fox News over concerns that those at the “Fair and Balanced” network were beginning to, as he put it, “question the truth.” […]

The post CNN Host Reportedly Leaving Network After Short-Lived Stay: His Career Change Is Completely Absurd appeared first on The Western Journal.

Labour Party Conference – International affairs networking brunch 24 September 2024 — 11:00AM TO 12:00PM Anonymous (not verified) 16 September 2024 Labour – Grace 1 Suite, Hilton Hotel, Liverpool

Hosted by Sir Simon Fraser, Chairman of Chatham House.

This event is taking place at the Hilton Hotel, Grace 1 Suite, Liverpool.

You are warmly invited to join us for an exclusive networking brunch at the 2024 Labour Party Conference.

Sir Simon Fraser, Chairman of Chatham House, and Olivia O’Sullivan, Director of Chatham House’s UK in the World Programme, will deliver opening remarks, followed by an interactive networking session where you will have the chance to engage with a wide range of stakeholders. Join us to connect with key senior parliamentary, corporate and media attendees at the Labour Party Conference.

This event will be taking place outside of the secure zone.

Network Power in the Asia-Pacific: Making Sense of the New Regionalism and Opportunities for Cooperation 7 February 2020 — 9:45AM TO 5:30PM Anonymous (not verified) 17 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

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.

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research

Christian Tagwerker
Apr 1, 2006; 5:737-748
Research

Independent Thinking: Myanmar, the coup two years on Audio NCapeling 2 February 2023

Episode 13 of our weekly podcast focuses on the ongoing crisis in Myanmar, marking the two-year anniversary of the coup there by the Tatmadaw armed forces.

In February 2021 the Tatmadaw overthrew the democratically-elected government of Aung San Suu Kyi in Myanmar and, since then, the country has descended into a brutal and complex civil war.

Our panel analyses the state of the country and its people two years on. Can Myanmar hold together, can democracy ever be restored? And is the world ignoring a major humanitarian crisis in the making?

With Bronwen Maddox to discuss the issues are two journalists who have both covered Myanmar extensively. Sebastian Strangio is an author and the Southeast Asia editor at The Diplomat, and Ali Fowle is a freelance journalist with Al Jazeera and the BBC.

Joining them in the studio from Chatham House are Ben Bland, director of our Asia-Pacific programme, and Rashmin Sagoo, director of our International Law programme.

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

An Attack on the ‘One Country, Two Systems’ Principle in Hong Kong Expert comment sysadmin 11 January 2016

The disappearance of publisher Lee Bo may mark the beginning of the end of Beijing’s commitment to uphold the framework that provides the territory with a high degree of autonomy.

The disappearance of a publisher in Hong Kong, Lee Bo, who owns a well-known bookshop that sells books critical of Chinese leaders, is a landmark event and potentially a historical turning point for Hong Kong. It is not clear if this happened at the behest of the senior Chinese leadership. But if those responsible for the disappearing of Lee are not punished, it will be clear that their acts are condoned by the authorities.

This is deeply worrying as it gravely undermines the ‘one country, two systems’ framework, which provides Hong Kong with high degree of autonomy from Beijing. Under the Sino-British Agreement of 1984 and Hong Kong’s Basic Law, which govern relations between Hong Kong and China, the rights of Hong Kong citizens are meant to be protected within the territory. Mainland Chinese authorities do not have the legal power to arrest or detain an individual in, or remove anyone from, Hong Kong.

The Chinese know the limit of their legal authority in Hong Kong. Hence, Lee was quietly disappeared, rather than openly arrested. But that it happened at all may mark the beginning of the end of Beijing’s commitment to uphold the ‘one country, two systems’ framework – a relationship that requires Beijing to tolerate, if not respect, the judicial integrity and the way of life in Hong Kong.

Do we know for sure that Lee was ‘disappeared’ by China’s security apparatus? Before he disappeared, Lee said in an interview that he knew he had been watched and that his emails were accessed by Chinese agents, and that he would not travel to the mainland as a result. And we know that Lee’s travel documents are all in his home; yet he is now supposedly in China ‘assisting the authorities in an investigation’ into something unspecified. This explanation comes from a fax sent to Lee’s wife, probably intended by the Chinese authorities to put an end to speculation. But why would Chinese authorities work with Lee, a British citizen who carries no travel documents and would thus have broken the law by entering China? The circumstantial evidence is strong enough to show that whether he was taken by Chinese officers or someone else, his removal from Hong Kong to China must have received official endorsement.

Should the rest of the world be concerned about this? Hong Kong is a major financial center that services the world economy, and it can do so largely because it enjoys judicial independence and the high degree of autonomy under the ‘one country, two systems’ framework. It is also a shining example of how the rights and scope of development for individuals can be respected in a Chinese community. Should the ‘one country, two systems’ framework be undermined, Hong Kong as we know it will be no more.

Beijing’s quick response in requiring Lee to fax his family may come across as ham-fisted and callous, but it also demonstrates that it had not expected the strong backlash to Lee’s disappearance. A strong and well-articulated international response that brings the matter to Xi’s attention may persuade him that it is in China’s best interest to put a stop to this process of undermining the ‘one country, two systems’ framework. Given Hong Kong’s importance to the global economy, this should be a priority for the international community.

This article was originally published in the Diplomat.

To comment on this article, please contact Chatham House Feedback

Twenty Years After Hong Kong Handover, Does ‘One Country, Two Systems’ Still Work? Expert comment sysadmin 28 June 2017

This unique constitutional framework can endure – if Hong Kong society can reconcile its different visions of the future.

Twenty years after the handover of Hong Kong from British to Chinese sovereignty, the ‘one country, two systems’ arrangement – the main aim of which was to guarantee the continuity of Hong Kong’s open society and way of life – can be said to have worked well. Street protests remain a regular feature of Hong Kong’s political culture. Freedom of information and expression are alive and well. Hong Kong retains its ‘capitalist way of life’, its legal system based on common law and independent judiciary, and its status as an international financial centre. As a result the city remains one of the most open economies across Asia, with robust institutions and transparency which are hard to find anywhere else in the region.

Yet the 79-day ‘occupy’ protests of autumn 2014 showed that something is not quite right in the city of Hong Kong.

The protests themselves had a number of causes. Partly they reflected socioeconomic concerns, especially the rise in income inequality and lack of affordable housing. These might have been dealt with to some extent by better governance over the years, but they are also a feature of many societies in the current phase of globalization – a case, perhaps, of too much ‘capitalist way of life’.

Politically, the desire expressed by many in 2014 was for a form of ‘genuine universal suffrage’ for the selection of Hong Kong’s chief executive which went beyond a provision of Hong Kong’s mini constitution, the Basic Law, that candidates should be put forward by a ‘nominating committee’. It was on this point that the possibility of constitutional reform foundered in 2015, leaving Hong Kong no further ahead in its ‘gradual progress’ towards democracy.

But this episode also brought to the surface the tension between different visions for Hong Kong’s future. In particular, many in Hong Kong are still uncomfortable with the ‘one country’ part of the deal, rejected by some (especially young people) in the ways that they conceptualize Hong Kong identity – according to one recent survey, as little as 3.1% of Hong Kong youths identify themselves as ‘Chinese’. These issues are likely to constrain political development for some time to come.

At their sharpest, some of these visions are for some form of self-determination, or even independence, for Hong Kong. This is not just anathema to the national authorities in Beijing, but contradicts a basic tenet of Hong Kong’s handover in 1997, the return to Chinese sovereignty. This is not just something on which Beijing will never compromise, but will seek to challenge.

It is this which explains the sense in Hong Kong that the central government has been looking to become politically more involved since 2014. But the challenge of influencing Hong Kong society is great, and other than strengthening relations with the establishment camp, Beijing has not been able to tighten its grip. If anything, the centre of gravity of Hong Kong politics has continued to drift away from Beijing, not towards it.

How this will play out remains to be seen. Some amelioration of social tensions could help. But the fundamental divergence in visions of Hong Kong’s future will not be resolved so easily.

Looking forward therefore, the key to the continued success of ‘one country, two systems’ lies in Hong Kong society. If mainstream acceptance of the compromises involved can return, then this unique constitutional framework can still work for years to come.

Jan Goedgebeur, Jorik Jooken, On-Hei Solomon Lo, Ben Seamone and Carol T. Zamfirescu
Math. Comp. 93 (), 3059-3082.
Abstract, references and article information

T. De Ryck and S. Mishra
Math. Comp. 93 (), 2643-2677.
Abstract, references and article information

Recent studies have suggested that innate immune responses exhibit characteristics associated with memory linked to modulations in both vertebrates and invertebrates. However, the diverse evolutionary paths taken, particularly within the invertebrate taxa, should lead to similarly diverse innate immunity memory processes. Our understanding of innate immune memory in invertebrates primarily comes from studies of the fruit fly Drosophila melanogaster, the generality of which is unclear. Caenorhabditis elegans typically inhabits soil harboring a variety of fatal microbial pathogens; for this invertebrate, the innate immune system and aversive behavior are the major defensive strategies against microbial infection. However, their characteristics of immunological memory remains infantile. Here we discovered an immunological memory that promoted avoidance and suppressed innate immunity during reinfection with bacteria, which we revealed to be specific to the previously exposed pathogens. During this trade-off switch of avoidance and innate immunity, the chemosensory neurons AWB and ADF modulated production of serotonin and dopamine, which in turn decreased expression of the innate immunity-associated genes and led to enhanced avoidance via the downstream insulin-like pathway. Therefore, our current study profiles the immune memories during C. elegans reinfected by pathogenic bacteria and further reveals that the chemosensory neurons, the neurotransmitter(s), and their associated molecular signaling pathways are responsible for a trade-off switch between the two immunological memories.

RNase J enzymes are metallohydrolases that are involved in RNA maturation and RNA recycling, govern gene expression in bacteria, and catalyze both exonuclease and endonuclease activity. The catalytic activity of RNase J is regulated by multiple mechanisms which include oligomerization, conformational changes to aid substrate recognition, and the metal cofactor at the active site. However, little is known of how RNase J paralogs differ in expression and activity. Here we describe structural and biochemical features of two Staphylococcus epidermidis RNase J paralogs, RNase J1 and RNase J2. RNase J1 is a homodimer with exonuclease activity aided by two metal cofactors at the active site. RNase J2, on the other hand, has endonuclease activity and one metal ion at the active site and is predominantly a monomer. We note that the expression levels of these enzymes vary across Staphylococcal strains. Together, these observations suggest that multiple interacting RNase J paralogs could provide a strategy for functional improvisation utilizing differences in intracellular concentration, quaternary structure, and distinct active site architecture despite overall structural similarity.

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

R. Greg Stacey
Nov 4, 2020; 0:RA120.002275v1-mcp.RA120.002275
Research

Gle1 is a conserved, essential regulator of DEAD-box RNA helicases, with critical roles defined in mRNA export, translation initiation, translation termination, and stress granule formation. Mechanisms that specify which, where, and when DDXs are targeted by Gle1 are critical to understand. In addition to roles for stress-induced phosphorylation and inositol hexakisphosphate binding in specifying Gle1 function, Gle1 oligomerizes via its N-terminal domain in a phosphorylation-dependent manner. However, a thorough analysis of the role for Gle1 self-association is lacking. Here, we find that Gle1 self-association is driven by two distinct regions: a coiled-coil domain and a novel 10-amino acid aggregation-prone region, both of which are necessary for proper Gle1 oligomerization. By exogenous expression in HeLa cells, we tested the function of a series of mutations that impact the oligomerization domains of the Gle1A and Gle1B isoforms. Gle1 oligomerization is necessary for many, but not all aspects of Gle1A and Gle1B function, and the requirements for each interaction domain differ. Whereas the coiled-coil domain and aggregation-prone region additively contribute to competent mRNA export and stress granule formation, both self-association domains are independently required for regulation of translation under cellular stress. In contrast, Gle1 self-association is dispensable for phosphorylation and nonstressed translation initiation. Collectively, we reveal self-association functions as an additional mode of Gle1 regulation to ensure proper mRNA export and translation. This work also provides further insight into the mechanisms underlying human gle1 disease mutants found in prenatally lethal forms of arthrogryposis.

The glucagon receptor (GCGR) activated by the peptide hormone glucagon is a seven-transmembrane G protein–coupled receptor (GPCR) that regulates blood glucose levels. Ubiquitination influences trafficking and signaling of many GPCRs, but its characterization for the GCGR is lacking. Using endocytic colocalization and ubiquitination assays, we have identified a correlation between the ubiquitination profile and recycling of the GCGR. Our experiments revealed that GCGRs are constitutively ubiquitinated at the cell surface. Glucagon stimulation not only promoted GCGR endocytic trafficking through Rab5a early endosomes and Rab4a recycling endosomes, but also induced rapid deubiquitination of GCGRs. Inhibiting GCGR internalization or disrupting endocytic trafficking prevented agonist-induced deubiquitination of the GCGR. Furthermore, a Rab4a dominant negative (DN) that blocks trafficking at recycling endosomes enabled GCGR deubiquitination, whereas a Rab5a DN that blocks trafficking at early endosomes eliminated agonist-induced GCGR deubiquitination. By down-regulating candidate deubiquitinases that are either linked with GPCR trafficking or localized on endosomes, we identified signal-transducing adaptor molecule–binding protein (STAMBP) and ubiquitin-specific protease 33 (USP33) as cognate deubiquitinases for the GCGR. Our data suggest that USP33 constitutively deubiquitinates the GCGR, whereas both STAMBP and USP33 deubiquitinate agonist-activated GCGRs at early endosomes. A mutant GCGR with all five intracellular lysines altered to arginines remains deubiquitinated and shows augmented trafficking to Rab4a recycling endosomes compared with the WT, thus affirming the role of deubiquitination in GCGR recycling. We conclude that the GCGRs are rapidly deubiquitinated after agonist-activation to facilitate Rab4a-dependent recycling and that USP33 and STAMBP activities are critical for the endocytic recycling of the GCGR.

Montgomery Blencowe
Dec 23, 2020; 0:jlr.RA120000713v1-jlr.RA120000713
Research Articles

In SAS Customer Intelligence Studio,  when you add  Reply- node variable values in the Define Value dialog box, you might notice that two identically labeled data-grid variables are

Genome-wide association studies (GWAS) have implicated ~380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in ‘interferon signaling’, ‘autoimmune/immune activation’, ‘visual transduction’, and ‘protein catabolism’ were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g. APOH, APOA4, and ABCA1) and novel (e.g. F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

During Drosophila oogenesis, the localization and translational regulation of maternal transcripts relies on RNA-binding proteins (RBPs). Many of these RBPs localize several mRNAs and may have additional direct interaction partners to regulate their functions. Using immunoprecipitation from whole Drosophila ovaries coupled to mass spectrometry, we examined protein-protein associations of 6 GFP-tagged RBPs expressed at physiological levels. Analysis of the interaction network and further validation in human cells allowed us to identify 26 previously unknown associations, besides recovering several well characterized interactions. We identified interactions between RBPs and several splicing factors, providing links between nuclear and cytoplasmic events of mRNA regulation. Additionally, components of the translational and RNA decay machineries were selectively co-purified with some baits, suggesting a mechanism for how RBPs may regulate maternal transcripts. Given the evolutionary conservation of the studied RBPs, the interaction network presented here provides the foundation for future functional and structural studies of mRNA localization across metazoans.

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

The Discoidin, CUB, and LCCL domain-containing protein (DCBLD) family consists of two type-I transmembrane scaffolding receptors, DCBLD1 and DCBLD2, which play important roles in development and cancer. The nonreceptor tyrosine kinases FYN and ABL are known to drive phosphorylation of tyrosine residues in YXXP motifs within the intracellular domains of DCBLD family members, which leads to the recruitment of the Src homology 2 (SH2) domain of the adaptors CT10 regulator of kinase (CRK) and CRK-like (CRKL). We previously characterized the FYN- and ABL-driven phosphorylation of DCBLD family YXXP motifs. However, we have identified additional FYN- and ABL-dependent phosphorylation sites on DCBLD1 and DCBLD2. This suggests that beyond CRK and CRKL, additional DCBLD interactors may be regulated by FYN and ABL activity. Here, we report a quantitative proteomics approach in which we map the FYN- and ABL-regulated interactomes of DCBLD family members. We found FYN and ABL regulated the binding of several signaling molecules to DCBLD1 and DCBLD2, including members of the 14-3-3 family of adaptors. Biochemical investigation of the DCBLD2/14-3-3 interaction revealed ABL-induced binding of 14-3-3 family members directly to DCBLD2.

The EGFR tyrosine kinase inhibitor gefitinib is commonly used for lung cancer patients. However, some patients eventually become resistant to gefitinib and develop progressive disease. Here, we indicate that ecto-ATP synthase, which ectopically translocated from mitochondrial inner membrane to plasma membrane, is considered as a potential therapeutic target for drug-resistant cells. Quantitative multi-omics profiling reveals that ecto-ATP synthase inhibitor mediates CK2-dependent phosphorylation of DNA topoisomerase IIα (topo IIα) at serine 1106 and subsequently increases the expression of long noncoding RNA, GAS5. Additionally, we also determine that downstream of GAS5, p53 pathway, is activated by ecto-ATP synthase inhibitor for regulation of programed cell death. Interestingly, GAS5-proteins interactomic profiling elucidates that GAS5 associates with topo IIα and subsequently enhancing the phosphorylation level of topo IIα. Taken together, our findings suggest that ecto-ATP synthase blockade is an effective therapeutic strategy via regulation of CK2/phospho-topo IIα/GAS5 network in gefitinib-resistant lung cancer cells.

none

Biological functions emerge from complex and dynamic networks of protein-protein interactions. Because these protein-protein interaction networks, or interactomes, represent pairwise connections within a hierarchically organized system, it is often useful to identify higher-order associations embedded within them, such as multi-member protein complexes. Graph-based clustering techniques are widely used to accomplish this goal, and dozens of field-specific and general clustering algorithms exist. However, interactomes can be prone to errors, especially when inferred from high-throughput biochemical assays. Therefore, robustness to network-level noise is an important criterion for any clustering algorithm that aims to generate robust, reproducible clusters. Here, we tested the robustness of a range of graph-based clustering algorithms in the presence of noise, including algorithms common across domains and those specific to protein networks. Strikingly, we found that all of the clustering algorithms tested here markedly amplified noise within the underlying protein interaction network. Randomly rewiring only 1% of network edges yielded more than a 50% change in clustering results, indicating that clustering markedly amplified network-level noise. Moreover, we found the impact of network noise on individual clusters was not uniform: some clusters were consistently robust to injected noise while others were not. To assist in assessing this, we developed the clust.perturb R package and Shiny web application to measure the reproducibility of clusters by randomly perturbing the network. We show that clust.perturb results are predictive of real-world cluster stability: poorly reproducible clusters as identified by clust.perturb are significantly less likely to be reclustered across experiments. We conclude that graph-based clustering amplifies noise in protein interaction networks, but quantifying the robustness of a cluster to network noise can separate stable protein complexes from spurious associations.

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.

Exploring Public International Law and the Rights of Individuals with Chinese Scholars - Part Two Other resource sysadmin 30 October 2018

As part of a roundtable series, Chatham House and China University of Political Science and Law (CUPL) held a two-day roundtable meeting in Beijing on public international law and the rights of individuals.

The specific objectives were to:

• create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;
• build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China’s role within it;
• support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.

The roundtable forms part of a wider Chatham House project exploring China’s impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.

For CUPL, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.

The meeting in Beijing was hosted by CUPL and involved 20 participants, 10 Chinese (from universities and other academic institutions in Beijing) and 10 non-Chinese (from Australia, the Netherlands, South Africa, Switzerland, the United Kingdom and the United States).

To ensure continuity while also expanding the experts network being built, the second meeting included a mix of participants from the first meeting and some new participants.

All discussions were held in English under the Chatham House Rule.

MLB Network's countdown of baseball's best players at each position came to a conclusion with the final installment of the "Top 10 Right Now!" series, featuring the game's top relief pitchers and shortstops.

After Ohtani's nearly unprecedented two-way success during his American League Rookie of the Year campaign last year, more clubs are looking into the possibility of having players who can both pitch and play a position. Walsh fits that bill, as he has been a power-hitting first baseman and outfielder in the Minors, but he's made 10 pitching appearances over the past three seasons as well. The Angels are experimenting with him doing both this spring and this upcoming season.

CAMBRIDGE, England, Oct. 15, 2024 — Nu Quantum has announced a proof-of-principle prototype that advances the development of modular, distributed quantum computers by enabling connections across different qubit modalities and […]

The post Nu Quantum Unveils Qubit-Photon Interface to Enable Distributed Quantum Computing Networks appeared first on HPCwire.

Oct. 24, 2024 — The San Diego Supercomputer Center (SDSC), part of the School of Computing, Information and Data Sciences at UC San Diego, has been leading the Open Storage Network (OSN) program for years, and along […]

The post SDSC Leads Expansion of Open Storage Network to More Campus Computing Sites appeared first on HPCwire.