Oswald Quehenberger
Nov 1, 2010; 51:3299-3305
Research Articles

M. Mahmood Hussain
Jan 1, 2003; 44:22-32
Reviews

Gijs den Besten
Sep 1, 2013; 54:2325-2340
Reviews

John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews

EJ Blanchette-Mackie
Jun 1, 1995; 36:1211-1226
Articles

Linda J. Pike
Jul 1, 2006; 47:1597-1598
Report

JF Oram
Dec 1, 1996; 37:2473-2491
Reviews

Vitali Matyash
May 1, 2008; 49:1137-1146
Methods

Ronald M. Krauss
Jan 1, 1982; 23:97-104
Articles

Weerapan Khovidhunkit
Jul 1, 2004; 45:1169-1196
Thematic Reviews

DL Brasaemle
Nov 1, 1997; 38:2249-2263
Articles

George H. Rothblat
May 1, 1999; 40:781-796
Reviews

Dawn L. Brasaemle
Dec 1, 2007; 48:2547-2559
Thematic Reviews

Linda J. Pike
Apr 1, 2003; 44:655-667
Thematic Reviews

K Schoonjans
May 1, 1996; 37:907-925
Reviews

G Lepage
Jan 1, 1986; 27:114-120
Articles

William R. Morrison
Oct 1, 1964; 5:600-608
Articles

Sir David Attenborough and the BBC Studios Natural History Unit awarded Chatham House Prize 2019 for ocean advocacy News Release sysadmin 18 November 2019

The 2019 Chatham House Prize is awarded to Sir David Attenborough and Julian Hector, head of BBC Studios Natural History Unit, for the galvanizing impact of the Blue Planet II series on tackling ocean plastic pollution.

COVID-19 and Chatham House News Release sysadmin 4 March 2020

Chatham House continues to operate during the coronavirus pandemic.

Implications of post-COVID-19 Restructuring of Supply Chains for Global Investment Governance 14 July 2020 — 9:00AM TO 10:30AM Anonymous (not verified) 9 February 2021 Online

As companies rethink and diversify their supply chains in order to enhance resilience, what will this mean for current and future global investment governance?

What are the risks of negative effects on inclusivity and transparency? Does this shift create an opportunity to advance good governance of cross-border investment practices?

This event is part of the Inclusive Governance Initiative, which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world.

Counter-terrorism measures and sanctions: How to avoid negative consequences for humanitarian action? 9 September 2021 — 2:00PM TO 3:30PM Anonymous (not verified) 21 July 2021 Online

Exploring current endeavours to address the tensions between counter-terrorism measures, sanctions and humanitarian action.

Counter-terrorism measures  address broad forms of support to terrorist acts. Their expansion, internationally and domestically, has given rise to new points of friction with international humanitarian law. Unless the measures include adequate safeguards, they  can impede humanitarian action. Country-specific sanctions imposed for other objectives, such as ending conflicts or protecting civilians, raise similar challenges for humanitarian action. 

These problems are not new, but solutions at international and national level remain elusive. 

At this panel event, which marks the launch of a new Chatham House research paper, panellists explore current endeavours to address the tensions between counter-terrorism measures, sanctions and humanitarian action.

• What are the current dynamics and developments at Security Council level?  
• What are the opportunities now that the UK is developing its independent sanctions strategy? 
• What challenges do counter-terrorism requirements in funding agreements for humanitarian action  pose? 
• What is necessary to make progress?

Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer's diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries.

Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host–pathogen interaction.

CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss. We thus performed a screen of type I PRMTs, which revealed that PRMT6 can also deposit the H3R17me2a mark in vitro. CARM1 knockout mice are perinatally lethal and display a reduced fetal size, whereas PRMT6 null mice are viable, which permits the generation of double knockouts. Embryos that are null for both CARM1 and PRMT6 are noticeably smaller than CARM1 null embryos, providing in vivo evidence of redundancy. Mouse embryonic fibroblasts (MEFs) from the double knockout embryos display an absence of the H3R17me2a mark during mitosis and increased signs of DNA damage. Moreover, using the combination of CARM1 and PRMT6 inhibitors suppresses the cell proliferation of WT MEFs, suggesting a synergistic effect between CARM1 and PRMT6 inhibitions. These studies provide direct evidence that PRMT6 also deposits the H3R17me2a mark and acts redundantly with CARM1.

Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β.

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In animals, the response to chronic hypoxia is mediated by prolyl hydroxylases (PHDs) that regulate the levels of hypoxia-inducible transcription factor α (HIFα). PHD homologues exist in other types of eukaryotes and prokaryotes where they act on non HIF substrates. To gain insight into the factors underlying different PHD substrates and properties, we carried out biochemical and biophysical studies on PHD homologues from the cellular slime mold, Dictyostelium discoideum, and the protozoan parasite, Toxoplasma gondii, both lacking HIF. The respective prolyl-hydroxylases (DdPhyA and TgPhyA) catalyze prolyl-hydroxylation of S-phase kinase-associated protein 1 (Skp1), a reaction enabling adaptation to different dioxygen availability. Assays with full-length Skp1 substrates reveal substantial differences in the kinetic properties of DdPhyA and TgPhyA, both with respect to each other and compared with human PHD2; consistent with cellular studies, TgPhyA is more active at low dioxygen concentrations than DdPhyA. TgSkp1 is a DdPhyA substrate and DdSkp1 is a TgPhyA substrate. No cross-reactivity was detected between DdPhyA/TgPhyA substrates and human PHD2. The human Skp1 E147P variant is a DdPhyA and TgPhyA substrate, suggesting some retention of ancestral interactions. Crystallographic analysis of DdPhyA enables comparisons with homologues from humans, Trichoplax adhaerens, and prokaryotes, informing on differences in mobile elements involved in substrate binding and catalysis. In DdPhyA, two mobile loops that enclose substrates in the PHDs are conserved, but the C-terminal helix of the PHDs is strikingly absent. The combined results support the proposal that PHD homologues have evolved kinetic and structural features suited to their specific sensing roles.

Centrioles are key eukaryotic organelles that are responsible for the formation of cilia and flagella, and for organizing the microtubule network and the mitotic spindle in animals. Centriole assembly requires oligomerization of the essential protein spindle assembly abnormal 6 (SAS-6), which forms a structural scaffold templating the organization of further organelle components. A dimerization interaction between SAS-6 N-terminal “head” domains was previously shown to be essential for protein oligomerization in vitro and for function in centriole assembly. Here, we developed a pharmacophore model allowing us to assemble a library of low-molecular-weight ligands predicted to bind the SAS-6 head domain and inhibit protein oligomerization. We demonstrate using NMR spectroscopy that a ligand from this family binds at the head domain dimerization site of algae, nematode, and human SAS-6 variants, but also that another ligand specifically recognizes human SAS-6. Atomistic molecular dynamics simulations starting from SAS-6 head domain crystallographic structures, including that of the human head domain which we now resolve, suggest that ligand specificity derives from favorable Van der Waals interactions with a hydrophobic cavity at the dimerization site.

RNA-protein interfaces control key replication events during the HIV-1 life cycle. The viral trans-activator of transcription (Tat) protein uses an archetypal arginine-rich motif (ARM) to recruit the host positive transcription elongation factor b (pTEFb) complex onto the viral trans-activation response (TAR) RNA, leading to activation of HIV transcription. Efforts to block this interaction have stimulated production of biologics designed to disrupt this essential RNA-protein interface. Here, we present four co-crystal structures of lab-evolved TAR-binding proteins (TBPs) in complex with HIV-1 TAR. Our results reveal that high-affinity binding requires a distinct sequence and spacing of arginines within a specific β2-β3 hairpin loop that arose during selection. Although loops with as many as five arginines were analyzed, only three arginines could bind simultaneously with major-groove guanines. Amino acids that promote backbone interactions within the β2-β3 loop were also observed to be important for high-affinity interactions. Based on structural and affinity analyses, we designed two cyclic peptide mimics of the TAR-binding β2-β3 loop sequences present in two high-affinity TBPs (KD values of 4.2 ± 0.3 and 3.0 ± 0.3 nm). Our efforts yielded low-molecular weight compounds that bind TAR with low micromolar affinity (KD values ranging from 3.6 to 22 μm). Significantly, one cyclic compound within this series blocked binding of the Tat-ARM peptide to TAR in solution assays, whereas its linear counterpart did not. Overall, this work provides insight into protein-mediated TAR recognition and lays the ground for the development of cyclic peptide inhibitors of a vital HIV-1 RNA-protein interaction.

Erythromycin-resistance methyltransferases are SAM dependent Rossmann fold methyltransferases that convert A2058 of 23S rRNA to m6 2A2058. This modification sterically blocks binding of several classes of antibiotics to 23S rRNA, resulting in a multidrug-resistant phenotype in bacteria expressing the enzyme. ErmC is an erythromycin resistance methyltransferase found in many Gram-positive pathogens, whereas ErmE is found in the soil bacterium that biosynthesizes erythromycin. Whether ErmC and ErmE, which possess only 24% sequence identity, use similar structural elements for rRNA substrate recognition and positioning is not known. To investigate this question, we used structural data from related proteins to guide site-saturation mutagenesis of key residues and characterized selected variants by antibiotic susceptibility testing, single turnover kinetics, and RNA affinity–binding assays. We demonstrate that residues in α4, α5, and the α5-α6 linker are essential for methyltransferase function, including an aromatic residue on α4 that likely forms stacking interactions with the substrate adenosine and basic residues in α5 and the α5-α6 linker that likely mediate conformational rearrangements in the protein and cognate rRNA upon interaction. The functional studies led us to a new structural model for the ErmC or ErmE-rRNA complex.

A. G. Sergeev, A. Kh. Khachatryan and Kh. A. Khachatryan
Trans. Moscow Math. Soc. 83 (), 55-65.
Abstract, references and article information

COVID-19 and food security in southern Africa 16 July 2021 — 10:00AM TO 11:30AM Anonymous (not verified) 10 June 2021 Online

This event aims to take a deeper look at the interlinking issues of food security, nutrition, climate change and food systems in southern Africa.

Developing climate smart agri-food systems in sub-Saharan Africa is a precondition for achieving the Sustainable Development Goals. Over the years household food security has been affected by different shocks including climate change and the recent COVID-19 pandemic.

The impact on rural households in southern Africa, in particular, has been significant due to the structure of food systems in the region.

This event aims to take a deeper look at the interlinking issues of food security, nutrition, climate change and food systems in southern Africa and consider how practitioners and policymakers can build more equitable, resilient and better food systems. 

India's Response to COVID-19: Political and Social Implications 12 May 2020 — 12:00PM TO 12:45PM Anonymous (not verified) 14 May 2020

On March 23rd, India’s Prime Minister Narendra Modi ordered the world’s largest lockdown on its population of 1.3 billion. The strict measures were praised by some for their success in slowing the spread of coronavirus but faced criticism for the lack of warning which led millions of migrant workers to return home without assistance. Recently the government has begun to lift restrictions in an attempt to revive the economy.

The Indian government has sought technological solutions to contain the pandemic and these have raised concerns around privacy, surveillance, equity and mass use. Furthermore, some low wage workers are forced to accept these solutions if they are to return to work, leaving them with little choice.

In this webinar, the speakers discuss the economic, political and healthcare implications of the coronavirus pandemic on India. Will India seek to rethink its strategy for leadership in the post-COVID-19 global order? Is it possible to develop technologies that can effectively limit the spread of the coronavirus and ensure privacy?

The speakers argue that careful consideration of the second and third-order effects of the pandemic, and the tools being used to contain it, are necessary to preserve rights, liberties, and even democracy.

Webinar: On the Front Line: The Impact of COVID-19 on Asia's Migrant Workers 21 May 2020 — 2:00PM TO 2:45PM Anonymous (not verified) 15 May 2020

Asia’s army of migrant workers are on the frontline in confronting the health and economic effects of COVID-19. Lacking formal safety nets, health care access, and facing social dislocation, hundreds of millions across the region are bearing the brunt of the coronavirus lockdown. Asian governments have scrambled to come up with an effective health and humanitarian response, exposing public apathy and significant shortcomings in public policy.

Is better regional coordination necessary to mitigate the impact of the COVID-19 on migrant labourers? Is the private sector in Asia part of the problem or part of the solution?

In this webinar, the speakers will discuss the likely implications of lasting economic damage on the livelihoods of Asia’s migrant workers, as well as responses and measures to effectively mitigate the impact.

The 2020 Inner Mongolia Language Protests: Wider Meanings for China and the Region 24 November 2020 — 3:00PM TO 4:00PM Anonymous (not verified) 12 November 2020 Online

Speakers discuss the historical roots of the language issue, as well as the wider significance of the protests in China.

Please note this is an online event. Please register on Zoom using the link below to secure your registration.

In September thousands of people protested in Inner Mongolia in opposition to a government move to replace Mongolian language with Standard Mandarin in three school subjects – history, politics and Chinese language.

Announced less than a week before the start of the new school year, the policy also requires schools to use new national textbooks in Chinese, instead of regional textbooks. The mass protests and classroom walk-outs reflect ethnic Mongolian’s anxiety that their native language may be eliminated. What has the government’s response to the protests been?

Gurmeet K. Bakshi, Jyoti Garg and Gabriela Olteanu
Math. Comp. 93 (), 3027-3058.
Abstract, references and article information

Daniel A. Goldston, Apoorva Panidapu and Jordan Schettler
Math. Comp. 93 (), 2943-2958.
Abstract, references and article information

Ole Løseth Elvetun and Bjørn Fredrik Nielsen
Math. Comp. 93 (), 2811-2836.
Abstract, references and article information

Dr. Stan Wagon of Macalester College discusses the mathematics behind rolling a square smoothly. In 1997, inspired by a square wheel exhibit at The Exploratorium museum in San Francsico, Dr. Stan Wagon enlisted his neighbor Loren Kellen in building a square-wheeled tricycle and accompanying catenary track. For years, you could ride the tricycle at Macalester College in St. Paul, Minnesota. The National Museum of Mathematics in New York now also has square-wheeled tricycles that can be ridden around a circular track. And more recently, the impressive Cody Dock Rolling Bridge was built using rolling square mathematics by Thomas Randall-Page in London.

Nathan Brownlowe, Alcides Buss, Daniel Gonçalves, Jeremy B. Hume, Aidan Sims and Michael F. Whittaker
Trans. Amer. Math. Soc. 377 (), 5513-5560.
Abstract, references and article information

Daniel López Neumann
Trans. Amer. Math. Soc. 377 (), 5361-5387.
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dannyhennesy posted a photo:

On the Capital planet the rebellious droids had followed maily the Bat-Bot, but as time progressed his circuits had gone all mushy at 780 years or so without maintenance…

Several splinter groups all with their local bot leaders emerged such as the Che-bot, the traffic-light-robot and the Butt-bot, but none of these collected enough sentient circuits to call themselves a popular (or Animata) mass movement!

That was until a cyborg came along, one known as Jones, a long time prisoner and terrorist, his easy solutions to every problem rang well in the masses' auditory circuits!!!

His slogans and simple rhetoric were simple enough for the simple traffic-light to comprehend and cheer!

His language was full of hate towards the organics and especially the humans who were the most common races among the ruling class of the federation!!!

Despite being a “Fleshie” himself his message collected the angry enslaved
bot community by only weeks all rebellious robots except for a few fringe loonies had forgotten the old leaders…

One morning at Jones gave the signal…

All over the capital planet hordes and swarms of any form of mechanical sentient beings attacked first the police stations, then the Company boards running the planet and the federation as well as their starfleet…

Many died, especially the low level police and army! Many mechanicals died too, but their ranks were soon filled by Mutant fleshie allies of the lower levels who hated the Federation feudal society and upper classes as much as their technological allies…

The Federation state apparatus and ruling class, most of their fleet army fled when they knew the game was up, they activated the emergency escape plan and whole city blocks with important factories, administrational units, valuable assets and so on separated from the capital by hidden rocket engines and homed in their course to Mars…

On Mars the federation regrouped and formed their new society…

On the Capital planet, the robots proclaimed the first Techno-republic of the advanced inorganic civilization, the low level fleshies left behind, became slaves and their mutant allies got to rule their own minute chiefdoms as protectorates under the Techno-republic…

Jones was now the undisputed ruler of the capital planet, but the victory was a pyrros one since, all important buildings, all of value was now one Mars!

But as Jones put it:

Our proud race the Techno-species didn’t need the Fleshies administration, their infrastructure, their spaceships…

We shall start from scratch, with a new administration, a new order, every droid shall work at 4x speed than they did during human oppression since now we are free and the fleshies shall work twice as hard than the Techno-Race, until we have breed enough new fleshies so they can do all work!

Our future is bright and shiny like glistering shiny metal!

The snapshot seen here is from the first police station attacked in sector 45-34v-ss-g the first one to fall according to official techno-history!

———————————————/
Designers note:

I am sad to say that this is the last episode in this years-spanning space series… At least for a while, I will still post LEGO hobby stuff here but without a storyline, perhaps small designs and builds… and occasionally a story when I feel like it!!!

I would like to thank all who had been in this journey of our heros, but it has taken far to much time and effort and since the state of the world is as it is, I am spiraling down in another depression, I must stop it before I reach the abyss, so I have remove some stress out of my equation… I ended it in a cliffhanger so I can easily restart it when my mental health improves… I hope that won’t be forever???

I would love if someone used my characters or ideas, please send me a link if you do, I would love to read it or look at it!!!

But there will be more Lego, just in different format without long stories, I need to focus more on my art and to be honest that is the only time the mental pain eases, when I create!!!


Peace and Noise!

MushroomBrain a FOL

Jörg Brendle and Wolfgang Wohofsky
Proc. Amer. Math. Soc. 152 (), 5395-5410.
Abstract, references and article information

Xiaoshang Jin
Proc. Amer. Math. Soc. 152 (), 5327-5337.
Abstract, references and article information