Speech by Mr Claudio Borio, Head of the Monetary and Economic Department of the BIS, at the OECD-G20 High Level Policy Seminar, Paris, 11 September 2019.

Keynote speech by Mr Agustín Carstens, General Manager of the BIS, at the 55th SEACEN Governors' Conference and High-level Seminar on "Data and technology: embracing innovation", Singapore, 14 November 2019.

Krabbe's disease is an infantile neurodegenerative disease, which is affected by mutations in the lysosomal enzyme galactocerebrosidase, leading to the accumulation of its metabolite psychosine. We have shown previously that the S1P receptor agonist fingolimod (FTY720) attenuates psychosine-induced glial cell death and demyelination both in vitro and ex vivo models. These data, together with a lack of therapies for Krabbe's disease, prompted the current preclinical study examining the effects of fingolimod in twitcher mice, a murine model of Krabbe's disease. Twitcher mice, both male and female, carrying a natural mutation in the galc gene were given fingolimod via drinking water (1 mg/kg/d). The direct impact of fingolimod administration was assessed via histochemical and biochemical analysis using markers of myelin, astrocytes, microglia, neurons, globoid cells, and immune cells. The effects of fingolimod on twitching behavior and life span were also demonstrated. Our results show that treatment of twitcher mice with fingolimod significantly rescued myelin levels compared with vehicle-treated animals and also regulated astrocyte and microglial reactivity. Furthermore, nonphosphorylated neurofilament levels were decreased, indicating neuroprotective and neurorestorative processes. These protective effects of fingolimod on twitcher mice brain pathology was reflected by an increased life span of fingolimod-treated twitcher mice. These in vivo findings corroborate initial in vitro studies and highlight the potential use of S1P receptors as drug targets for treatment of Krabbe's disease.

SIGNIFICANCE STATEMENT This study demonstrates that the administration of the therapy known as fingolimod in a mouse model of Krabbe's disease (namely, the twitcher mouse model) significantly rescues myelin levels. Further, the drug fingolimod also regulates the reactivity of glial cells, astrocytes and microglia, in this mouse model. These protective effects of fingolimod result in an increased life span of twitcher mice.

During differentiation, oligodendrocyte precursor cells (OPCs) extend a network of processes that make contact with axons and initiate myelination. Recent studies revealed that actin polymerization is required for initiation of myelination whereas actin depolymerization promotes myelin wrapping. Here, we used primary OPCs in culture isolated from neonatal rat cortices of both sexes and young male and female mice with oligodendrocyte-specific deletion of mechanistic target of rapamycin (mTOR) to demonstrate that mTOR regulates expression of specific cytoskeletal targets and actin reorganization in oligodendrocytes during developmental myelination. Loss or inhibition of mTOR reduced expression of profilin2 and ARPC3, actin polymerizing factors, and elevated levels of active cofilin, which mediates actin depolymerization. The deficits in actin polymerization were revealed in reduced phalloidin and deficits in oligodendrocyte cellular branching complexity at the peak of morphologic differentiation and a delay in initiation of myelination. We further show a critical role for mTOR in expression and localization of myelin basic protein (Mbp) mRNA and MBP protein to the cellular processes where it is necessary at the myelin membrane for axon wrapping. Mbp mRNA transport deficits were confirmed by single molecule RNA FISH. Moreover, expression of the kinesin family member 1B, an Mbp mRNA transport protein, was reduced in CC1+ cells in the mTOR cKO and in mTOR inhibited oligodendrocytes undergoing differentiation in vitro. These data support the conclusion that mTOR regulates both initiation of myelination and axon wrapping by targeting cytoskeletal reorganization and MBP localization to oligodendrocyte processes.

SIGNIFICANCE STATEMENT Myelination is essential for normal CNS development and adult axon preservation and function. The mechanistic target of rapamycin (mTOR) signaling pathway has been implicated in promoting CNS myelination; however, there is a gap in our understanding of the mechanisms by which mTOR promotes developmental myelination through regulating specific downstream targets. Here, we present evidence that mTOR promotes the initiation of myelination through regulating specific cytoskeletal targets and cellular process expansion by oligodendrocyte precursor cells as well as expression and cellular localization of myelin basic protein.

To determine whether Cav1.2 voltage-gated Ca²⁺ channels contribute to astrocyte activation, we generated an inducible conditional knock-out mouse in which the Cav1.2 α subunit was deleted in GFAP-positive astrocytes. This astrocytic Cav1.2 knock-out mouse was tested in the cuprizone model of myelin injury and repair which causes astrocyte and microglia activation in the absence of a lymphocytic response. Deletion of Cav1.2 channels in GFAP-positive astrocytes during cuprizone-induced demyelination leads to a significant reduction in the degree of astrocyte and microglia activation and proliferation in mice of either sex. Concomitantly, the production of proinflammatory factors such as TNFα, IL1β and TGFβ1 was significantly decreased in the corpus callosum and cortex of Cav1.2 knock-out mice through demyelination. Furthermore, this mild inflammatory environment promotes oligodendrocyte progenitor cells maturation and myelin regeneration across the remyelination phase of the cuprizone model. Similar results were found in animals treated with nimodipine, a Cav1.2 Ca²⁺ channel inhibitor with high affinity to the CNS. Mice of either sex injected with nimodipine during the demyelination stage of the cuprizone treatment displayed a reduced number of reactive astrocytes and showed a faster and more efficient brain remyelination. Together, these results indicate that Cav1.2 Ca²⁺ channels play a crucial role in the induction and proliferation of reactive astrocytes during demyelination; and that attenuation of astrocytic voltage-gated Ca²⁺ influx may be an effective therapy to reduce brain inflammation and promote myelin recovery in demyelinating diseases.

SIGNIFICANCE STATEMENT Reducing voltage-gated Ca²⁺ influx in astrocytes during brain demyelination significantly attenuates brain inflammation and astrocyte reactivity. Furthermore, these changes promote myelin restoration and oligodendrocyte maturation throughout remyelination.

In 2015 we celebrated the “International Year of Soils” and with good reason. Soil sustains all our agricultural and livestock food production, wood for fuel production, filters water so that we can drink it and fish can live in it. We also use it for construction - therefore it sustains our homes and infrastructure. As we approach the end of #IYS [...]

Mountains provide freshwater and biodiversity, and are a major source of food. By definition, they dominate their surroundings with towering height and protect valleys and their inhabitants. They play a critical part in moving the world towards sustainable economic growth and have a leading role as indicators of climate change. As we celebrate the International Mountain Day, see how much you [...]

10: EtymologyThe word pulse originates directly from the Latin puls meaning "thick gruel, porridge, mush.” 9: Pulses vs legumes, what’s the difference?The term "legume" refers to the plants whose fruit is enclosed in a pod. Pulses are a subgroup of the legume family, but the term “pulse” refers only to the dried seed. Dried beans, lentils and peas are the most commonly known and consumed types [...]

In 2016 we celebrated the International Year of Pulses and it is obvious why. Pulses are good for you, beneficial to farmers' livelihoods and have a positive impact on the environment. It is clear that even though dried beans, lentils and peas have been around for centuries, they will play a fundamental role in our sustainable future. Even though #IYP2016 has [...]

Over the past years, we have often been reminded that we must leave no one behind as we strive to cement our plans for a sustainable future. Most recent data indicate that many of the Small Island Developing States (SIDS) have achieved undernourishment levels of less than 5 percent. Good governance is perhaps the most essential factor in increasing food [...]

Autumn Ray's goal: 59 national parks before she turns 40 in four years

An independent survey finds that although NPS's annual budget is around $3 billion, Americans are willing to pay much more

Early conservation research and scientific expeditions laid the groundwork and helped to convince the public national parks were a good idea

These parks are less popular, but no less spectacular

For the first time, the indigenous community is allowed to gather the cherished plant on protected land

Some sites have closed completely, while others are making modifications to promote social distancing

The Internet Archive describes the downloadable collection of more than one million books as a library, but critics call it piracy

Coyotes, bears and more are enjoying areas usually reserved for crowds of human visitors

Items recovered include fossils, paintings, ancient coins, ceramics and jewelry

Catch the musical event, featuring Sting, Death Cab for Cutie front man Ben Gibbard and other artists, on YouTube tonight at 8 p.m. Eastern time

With Washington, D.C. COVID-19 state of emergency, Smithsonian officials say museums to close Saturday, March 14; events canceled through May 3

The 72-year-old animal was the third oldest in the North American population

A conversation about the challenges facing—and the resilience of—the largest reservation in the country, which has become a COVID-19 hotspot

Salt River First Nation in Fort Smith, N.W.T., is getting ready for a possible flood. 

Darin Isaac was elected on Wednesday as the new chief of the Selkirk First Nation in Yukon. Isaac also held the position for two terms from 2005 to 2011. He has also served as a councillor for three terms.

RCMP say they were first called about the fires at 10 p.m. CST on May 7.

Retail stores in Fort William First Nation (FWFN) reopened to the general public on May 5, but they are under new operating requirements, the band council announced Friday. However, the residential area of the First Nation remains accessible only to people who live in the community.

Tensions are rising on Manitoulin Island because a First Nation is stopping travellers on provincial highways that go through the community. But opinions on M'Chigeeng's attempt to protect its people from COVID-19 are not divided along racial lines. 

The following is a guest post by Katherine Blood, Curator of Fine Prints, Prints & Photographs Division. As the Library of Congress marks its 220th year of serving the nation, the publication of a new guide tells two stories: how staff have for decades worked with art professionals to build the collections and how by […]

Using a cross-country sample of bank-dependent public fi rms we study the international spillovers of a change in banking regulation on corporate borrowing. For identi cation we examine how US rms' liabilities vis-a-vis banks, non-bank lenders and bond markets evolve after an increase in capital requirements implemented by the European Banking Authority (EBA) in 2011. We find that US firms experience a reduction in credit lines but not in term loans from EU banks.

This paper reviews post-crisis financial regulatory reforms, examines how they fit together and identifies open issues. Specifically, it takes stock of the salient new features of bank and CCP international standards within a unified analytical framework.

Recent literature has highlighted that international trade is mostly priced in a few key vehicle currencies, and is increasingly dominated by intermediate goods and global value chains (GVCs). Taking these features into account, this paper reexamines the business cycle dynamics of international trade and its relationship with monetary policy and exchange rates.

Our ongoing celebration of the Library of Congress National Book Festival continues with Poets Laureate Tracy K. Smith and Robert Hass discussing the making of poetry, the position of Poet Laureate and their new books, "American Journal: Fifty Poems for Our Time" (edited by Smith) and "A Little Book on Form: An Exploration into the Formal Imagination of Poetry" (Hass), on the Poetry & Prose stage at the 2018 Festival.

Our ongoing celebration of the Library of Congress National Book Festival continues with presidential scholar Annette Gordon-Reed discussing "The Hemingses of Monticello: An American Family" on the Special Programs stage at the 2015 Festival.

Our ongoing celebration of the Library of Congress National Book Festival continues with crime writer Patricia Cornwell discussing "Red Mist,” her 19th Kay Scarpetta novel, on the Fiction & Mystery stage at the 2012 Festival.

Our ongoing celebration of the Library of Congress National Book Festival continues with young adult and fantasy author Leigh Bardugo discussing "Crooked Kingdom" on the Genre Fiction stage at the 2018 Festival. This post includes prompts for writing and thinking that young readers, families and teachers can use to explore the author and the author’s work—recommended for ages 13+.

Our ongoing celebration of the Library of Congress National Book Festival continues with former Secretary of State Condoleezza Rice discussing "Democracy: Stories from the Long Road to Freedom" on the Main Stage at the 2017 Festival.

Our ongoing celebration of the Library of Congress National Book Festival continues with two-time Pulitzer Prize-winning novelist Colson Whitehead discussing "Zone One" on the Poetry & Prose stage at the 2012 Festival.

Our ongoing celebration of the Library of Congress National Book Festival continues with historian Michael Beschloss discussing “Presidents of War” on the Main Stage at the 2019 Festival.

Our ongoing celebration of the Library of Congress National Book Festival continues with crime and mystery writer Karin Slaughter discussing "Broken," part of her Will Trent series, on the Fiction & Mystery stage at the 2010 Festival.

Our ongoing celebration of the Library of Congress National Book Festival continues with actor and author Neil Patrick Harris discussing "The Magic Misfits: The Minor Third." The event, part of the new year-long National Book Festival Presents series, took place in the Library’s Coolidge Auditorium. This post includes prompts for writing and thinking that young readers, families and teachers can use to explore the author and the author’s work—recommended for ages 8+.

No global real estate market despite higher price synchronisation and growing role of international investors, central banks find (Press release, 18 February 2020)

Press release "Saudi G20 Presidency and the Bank for International Settlements (BIS) Innovation Hub invite global innovators to solve RegTech and SupTech challenges", 27 April 2020

Acute myeloid leukemia is an aggressive cancer of the blood-forming system. It affects the hematopoietic stem cells, or blood stem cells, of various white blood cells and of the red blood cells and platelets.