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.

The molecular mechanisms of reduced frataxin (FXN) expression in Friedreich's ataxia (FRDA) are linked to epigenetic modification of the FXN locus caused by the disease-associated GAA expansion. Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target. Using a human FXN–GAA–Luciferase repeat expansion genomic DNA reporter model of FRDA, we screened the Structural Genomics Consortium epigenetic probe collection. We found that pharmacological inhibition of the SUV4-20 methyltransferases by the tool compound A-196 increased the expression of FXN by ∼1.5-fold in the reporter cell line. In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells, A-196 increased FXN expression by up to 2-fold, an effect not seen in WT cells. SUV4-20 inhibition was accompanied by a reduction in H4K20me2 and H4K20me3 and an increase in H4K20me1, but only modest (1.4–7.8%) perturbation in genome-wide expression was observed. Finally, based on the structural activity relationship and crystal structure of A-196, novel small molecule A-196 analogs were synthesized and shown to give a 20-fold increase in potency for increasing FXN expression. Overall, our results suggest that histone methylation is important in the regulation of FXN expression and highlight SUV4-20 H1 as a potential novel therapeutic target for FRDA.

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Histone recognition by “reader” modules serves as a fundamental mechanism in epigenetic regulation. Previous studies have shown that Spindlin1 is a reader of histone H3K4me3 as well as “K4me3-R8me2a” and promotes transcription of rDNA or Wnt/TCF4 target genes. Here we show that Spindlin1 also acts as a potent reader of histone H3 “K4me3-K9me3/2” bivalent methylation pattern. Calorimetric titration revealed a binding affinity of 16 nm between Spindlin1 and H3 “K4me3-K9me3” peptide, which is one to three orders of magnitude stronger than most other histone readout events at peptide level. Structural studies revealed concurrent recognition of H3K4me3 and H3K9me3/2 by aromatic pockets 2 and 1 of Spindlin1, respectively. Epigenomic profiling studies showed that Spindlin1 colocalizes with both H3K4me3 and H3K9me3 peaks in a subset of genes enriched in biological processes of transcription and its regulation. Moreover, the distribution of Spindlin1 peaks is primarily associated with H3K4me3 but not H3K9me3, which suggests that Spindlin1 is a downstream effector of H3K4me3 generated in heterochromatic regions. Collectively, our work calls attention to an intriguing function of Spindlin1 as a potent H3 “K4me3-K9me3/2” bivalent mark reader, thereby balancing gene expression and silencing in H3K9me3/2-enriched regions.

E. A. Rakhmanov and S. P. Suetin
Trans. Moscow Math. Soc. 83 (), 269-290.
Abstract, references and article information

A. P. Starovoitov and N. V. Ryabchenko
Trans. Moscow Math. Soc. 83 (), 15-31.
Abstract, references and article information

Korea's New Energy Policy and Implications for LNG Imports 3 October 2018 — 9:00AM TO 10:30AM Anonymous (not verified) 17 September 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

The new energy policy of Moon Jae-In’s administration aims to swing radically from coal and nuclear towards renewables and LNG for power generation. During the last 12 months the priority given to the expansion of renewable energy has been overwhelming and the support for the expansion of gas not as strong as many observers had expected. The 13th gas supply and demand plan announced in Spring 2018 confirmed the trend. Based on this projection, Professor K. Paik will discuss how this new energy policy will affect Korea’s LNG imports strategy and what are the implications of Korea’s northern policy towards this LNG supply strategy and pipeline gas imports to the Korean Peninsula.

Attendance at this event is by invitation only.

The Global Implications of China's Energy Revolution 4 March 2019 — 9:00AM TO 10:30AM Anonymous (not verified) 7 February 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Ten years ago, it would have been difficult to believe that China – the world’s largest greenhouse gas emitter – would be one of the global leaders in some elements of clean energy development and deployment. With increasing air pollution and predominantly coal-fired power generation fueled by a booming economy and population, China has had to rethink its approach to environmental protection and climate mitigation.

Strong government signalling and national policies have led to the construction of the world’s largest fleets, wind farms and solar photovoltaic arrays in an effort to reduce national GDP intensities of energy and CO2 emissions. How has the availability of large amounts of capital, and the number of state-owned companies with soft budgetary constraints, helped contribute to this?

Against this backdrop, this event will consider how China must re-evaluate its approach to energy security – coal made up the majority of the country’s energy in 2016, followed by oil, of which 65 per cent had to be imported – despite the country being one of the pioneers of renewable energy. This event will look at how, in delivering on its clean energy objectives, China could redefine the traditional energy security paradox and in fact become more resilient to previously overlooked vulnerabilities.

Plant-based 'Meat' and Cultured Meat: Revolutionizing the Livestock Sector 10 April 2019 — 4:00PM TO 5:30PM Anonymous (not verified) 14 March 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Consensus is building across the scientific, environmental and public health communities that a radical shift away from excessive meat-eating patterns is urgently needed to tackle the unsustainability of the livestock sector. Recognizing the scale of the challenge ahead, public policymakers, civil society and innovators have increasingly sought to prompt shifts in consumer food choices – away from the most resource-intensive meat products and towards more sustainable alternatives.

Meat analogues – plant-based ‘meat’ and cultured meat also known as ‘lab-grown’ meat – mark a departure from traditional meat alternatives. Both are intended to be indistinguishable from – and in the case of cultured meat biologically equivalent to – animal-derived meat and are marketed principally at meat-eaters. Innovation and investment in meat analogues have increased significantly, but the direction and pace of growth in the meat analogue industry will depend upon a multitude of factors, including public acceptance, civil society support and incumbent industry responses.

This event will explore the challenges of scaling up production and generating demand for meat alternatives. It will also look at the ways policymakers in the UK and EU can impact the direction of the industry while examining what factors will influence consumer acceptance of plant-based ‘meat’ and cultured meat as substitutes for animal-derived meat.

What's next for environmental peacebuilding? Lessons learned and opportunities from conflict-affected states 17 February 2021 — 3:00PM TO 4:00PM Anonymous (not verified) 8 February 2021 Online

 This event explores lessons and opportunities from conflict-affected states.

In the field of peacebuilding, scholars and policymakers increasingly recognize the importance of environmental restoration, afforestation and infrastructural renewal for creating the sustainable livelihoods necessary for successful peacebuilding efforts.

Featuring academics writing for International Affairs on environmental peacebuilding in Colombia, Yemen and the Sahel, this webinar discusses the policy implications of the turn to environmental peacebuilding.

This event is part of the Chatham House’s Environment and Society Discussion Series in which the Energy Environment and Resources Programme brings together leading academics and policymakers to discuss key issues in environmental policy.

In particular, this event focuses on the role of environmental peacebuilding in creating sustainable livelihoods. From the impact the destruction of infrastructure can have on poverty as a driver of conflict, to the role environmental peacebuilding can play in bringing communities together by creating sustainable shared spaces of employment, the importance of the environmental livelihood creation is difficult to overstate.

Panellists focus on how policymakers can best encourage inclusive and sustainable livelihood creation and on addressing the key challenges such approaches face in the context of environmental peacebuilding efforts.

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.

Webinar: Gandhi's Vision for India 15 June 2020 — 12:00PM TO 12:45PM Anonymous (not verified) 9 June 2020

In 1931, Mahatma Gandhi visited Chatham House as part of his campaign for Indian independence. Addressing an overflowing hall, he described the poverty and the religious conflict that plagued India at the time.

Today, India is the world’s fifth largest economy and more than 270 million people have been lifted out of poverty in just a decade. But poverty in India remains widespread and the outbreak of the COVID-19 pandemic is only expected to exacerbate the situation. Meanwhile, the communal violence that erupted in Delhi earlier this year reflects intensifying religious tensions under Prime Minister Narendra Modi.

In this webinar, the speakers discuss Gandhi’s global legacy and to what extent we are seeing a re-awakening of his principles across modern India.

This event is part of a series, held in the context of the Chatham House Centenary in 2020, bringing together historians, practitioners and current policymakers to discuss contemporary problems of international relations.

Torin Greenwood, Jonathan Kariv and Noah Williams
Math. Comp. 93 (), 2959-2983.
Abstract, references and article information

Time: 9:00 AM, Location: E1.028 (Hearing Room)

Soun-Hi Kwon
Trans. Amer. Math. Soc. 377 (), 6021-6022.
Abstract, references and article information

Tsz-Kiu Aaron Chow and Yangyang Li
Trans. Amer. Math. Soc. 377 (), 5993-6020.
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Yinji Li, Zhiwei Wang and Xiangyu Zhou
Trans. Amer. Math. Soc. 377 (), 5947-5992.
Abstract, references and article information

Otto Overkamp
Trans. Amer. Math. Soc. 377 (), 5863-5903.
Abstract, references and article information

firehouse.ie posted a photo:

firehouse.ie posted a photo:

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WendyHarris1955 posted a photo:

unbranded
plywood (basswood)
175 pieces
280 x 350 mm

TED: "I fink this lickle cat an' tiger pussle's cute. It's got pussycat wimsys an' it's shaped, so it's gonna be a keeper. The wobbly edj wuz a bit fiddly an' I 'ad to check the pikchur to make shure I 'ad it rite, but uvverwise it's a good'un.
That peece of cake I'm abowt to eat is Mum's 'ome-made froot cake spredd wiv butter - s'nice cuz she puts whisky in it. That's the cake, not the butter!"

AO-Koun posted a photo:

Bero Roos
Theor. Probability and Math. Statist. 111 (), 137-151.
Abstract, references and article information

Luiz Ricardo Abreu Melo
Proc. Amer. Math. Soc. 152 (), 5373-5380.
Abstract, references and article information

NEW YORK (AP): When it comes to the 2025 Grammy Award nominations, Cowboy Carter rules. Its superstar singer, Beyonce, leads the nods with 11, bringing her career total to 99 nominations. That makes her the most nominated artiste in Grammy history...

Long hailed as dancehall's most controversial figure, Vybz Kartel has always commanded the spotlight with his edgy lyrics and unfiltered persona. But since his release from prison in July, Kartel has begun to show a surprising transformation that'...