Gα proteins promote dynamic adjustments of cell shape directed by actin-cytoskeleton reorganization via their respective RhoGEF effectors. For example, Gα13 binding to the RGS-homology (RH) domains of several RH-RhoGEFs allosterically activates these proteins, causing them to expose their catalytic Dbl-homology (DH)/pleckstrin-homology (PH) regions, which triggers downstream signals. However, whether additional Gα proteins might directly regulate the RH-RhoGEFs was not known. To explore this question, we first examined the morphological effects of expressing shortened RH-RhoGEF DH/PH constructs of p115RhoGEF/ARHGEF1, PDZ-RhoGEF (PRG)/ARHGEF11, and LARG/ARHGEF12. As expected, the three constructs promoted cell contraction and activated RhoA, known to be downstream of Gα13. Intriguingly, PRG DH/PH also induced filopodia-like cell protrusions and activated Cdc42. This pathway was stimulated by constitutively active Gαs (GαsQ227L), which enabled endogenous PRG to gain affinity for Cdc42. A chemogenetic approach revealed that signaling by Gs-coupled receptors, but not by those coupled to Gi or Gq, enabled PRG to bind Cdc42. This receptor-dependent effect, as well as CREB phosphorylation, was blocked by a construct derived from the PRG:Gαs-binding region, PRG-linker. Active Gαs interacted with isolated PRG DH and PH domains and their linker. In addition, this construct interfered with GαsQ227L's ability to guide PRG's interaction with Cdc42. Endogenous Gs-coupled prostaglandin receptors stimulated PRG binding to membrane fractions and activated signaling to PKA, and this canonical endogenous pathway was attenuated by PRG-linker. Altogether, our results demonstrate that active Gαs can recognize PRG as a novel effector directing its DH/PH catalytic module to gain affinity for Cdc42.

After successful completion of the Human Genome Project (HGP), HUPO has recently officially launched a global Human Proteome Project (HPP) which is designed to map the entire human protein set. Given the presence of about 30% undisclosed proteins out of 20,300 protein gene products, a systematic global effort is necessary to achieve this goal with respect to protein abundance, distribution, subcellular localization, interaction with other biomolecules, and functions at specific time points. As a general experimental strategy, HPP groups employ the three working pillars for HPP: mass spectrometry, antibody capture, and bioinformatics tools and knowledge base. The HPP participants will take advantage of the output and cross-analyses from the ongoing HUPO initiatives and a chromosome-based protein mapping strategy, termed C-HPP with many national teams currently engaged. In addition, numerous biologically-driven projects will be stimulated and facilitated by the HPP. Timely planning with proper governance of HPP will deliver a protein parts list, reagents and tools for protein studies and analyses, and a stronger basis for personalized medicine. HUPO urges each national research funding agency and the scientific community at large to identify their preferred pathways to participate in aspects of this highly promising project in a HPP consortium of funders and investigators.

The Director’s Annual Lecture 2023 10 January 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 17 November 2022 Chatham House and Online

Bronwen Maddox looks ahead to the challenges of the year and sets out Chatham House’s recommendations for change.

Read a transcript of the event

A lecture and discussion on the year ahead in international relations with Bronwen Maddox, director and chief executive of Chatham House.

Although Russia’s war on Ukraine rightly dominated headlines in 2022, other challenges also grew, the climate became warmer, US/China competition intensified, deglobalization became a much-analysed theme, and the global economy suffered significant blows.

The UK has its third prime minister in less than one year as it grapples with its changing place in the world. And the world is still living in the shadow of COVID-19 and what the pandemic revealed about strengths and vulnerabilities, global inequity, and North/South divides.

This event examines how the forces that shaped 2022 may manifest in 2023, and what that means for progress in international relations:

• What will progress look like on the climate agenda?
• How will the new US Congress reposition America’s role in the world?
• What does the North/South divergence on Russia’s war in Ukraine tell us about shared values and prospects for working together?
• After a turbulent year, how will the UK recover its standing in Europe and beyond?

Director’s breakfast briefing: Shifts in European foreign policy since 9/11 14 October 2021 — 8:00AM TO 9:15AM Anonymous (not verified) 4 October 2021 Chatham House

Former MI6 chief, Sir Alex Younger, discusses shifts in European foreign policy since 9/11.

Former MI6 chief Sir Alex Younger, discusses shifts in European foreign policy since 9/11.

The dramatic events surrounding the withdrawal from Afghanistan demonstrates a profound shift in European security priorities since the beginning of the ‘war on terror’. Against the backdrop of the 20th anniversary of 9/11, former MI6 chief, Sir Alex Younger, discusses recent shifts in European foreign policy.

How has the focus on counterterrorism changed over the last two decades particularly in light of new and evolving strategic challenges? Why were many long-term objectives in Afghanistan left unachieved? Has the threat of terrorism changed across Europe? How has cooperation between security and intelligence services across the world changed particularly across the Atlantic? And, 20 years on, is the ‘war on terror’ really over?

This event is only open to Chatham House Partners and Major Corporate Members as well as selected giving circles of Chatham House. If you would like to attend, please RSVP to Linda Bedford at RSVP@chathamhouse.org.

C-X-C motif chemokine receptor 4 (CXCR4)–directed imaging has gained clinical interest in aiding clinical diagnostics in primary aldosteronism (PA). We retrospectively evaluated the feasibility of CXCR4-directed scintigraphy using the novel CXCR-4 ligand [^99mTc]Tc-pentixatec in patients with PA. Methods: Six patients (mean age ± SD, 49 ± 15 y) underwent CXCR4-directed scintigraphy (including planar imaging and SPECT/CT) 30, 120, and 240 min after injection of 435 ± 50 MBq of [^99mTc]Tc-pentixatec. Adrenal CXCR4 expression was analyzed by calculating lesion-to-contralateral ratios (LCRs). Imaging results were correlated to clinical information. Histopathology and clinical follow-up served as the standard of reference. Results: Three subjects showed lateralization of adrenal tracer accumulation, with a mean maximum lesion-to-contralateral ratio of 1.65 (range, 1.52–1.70), which correlated with morphologic findings on CT. One individual underwent adrenalectomy and presented with complete biochemical and clinical remission at follow-up. Histopathologic workup confirmed unilateral aldosterone-producing adenoma. Conclusion: [^99mTc]Tc-pentixatec scintigraphy with SPECT in patients with PA is feasible and might offer a valuable alternative to CXCR4-directed imaging with [⁶⁸Ga]Ga-pentixafor PET.

Turkey Needs Radical New Direction to Save the Economy Expert comment NCapeling 23 November 2020

Turkey should emulate the reformist approach it adopted after the 2001 crisis to prevent an economic and financial breakdown - but this looks highly unlikely.

Although Ankara has witnessed what appears to be an abrupt change of its top economic team with two fresh appointments to key positions – Naci Ağbal as governor of the central bank and Lütfi Elvan as finance and treasury minister – a cardinal rule of thumb in Turkish politics is that the more drama one sees, the less policy change there will actually be.

Financial markets reacted positively to the moves in the expectation they will signal a change of Turkey’s overall economic approach, but the reality is Turkish president Recep Tayyip Erdoğan is simply putting loyalists into key bureaucratic positions to help ensure the primary role of these functions becomes ‘selling’ his policies more effectively, rather than altering them.

The hope from the markets – which saw the beleaguered Turkish lira appreciate against the US dollar at the news – is that Turkey adopts substantial interest rate increases as well as measures to repress liquidity expansion in order to temper its controversial so-called ‘Triple C’ approach of using cheap credit to stimulate growth with an unsustainable consumption and construction boom.

But instead, Erdoğan’s declaration after the appointments were made indicates the new restrictions in which they will now operate, saying ‘we are in a historic struggle against those who want to force Turkey into modern capitulations through the shackles of interest rates, foreign exchange rates and inflation’.

Learn from past successes

To resolve its current underlying economic problems, Turkey should actually be looking to its recent past and aiming to emulate the approach pursued by former prime minister Bülent Ecevit during the 2001 financial crisis when he recruited Kemal Derviş, a senior World Bank official with extensive experience and international contacts in economic, financial, and monetary affairs.

As economy minister with a broad mandate to spearhead a durable economic recovery plan, Dervis established independent market regulatory agencies covering banking, telecommunications, energy, and other key sectors, and strengthened the competition authority.

He also either liquidated or merged insolvent banks, granted central bank autonomy to guarantee price stability, and ensured recruitment was based on competence, expertise, and meritocracy. Crucially, his productivity-enhancing restructuring blueprint was designed in Turkey rather than being imposed by the International Monetary Fund (IMF) or another external agency.

Ecevit also turbocharged reforms motivated in part by a desire to join the EU with constitutional, political and legal modernization which widened personal freedom, significantly curtailed capital punishment, liberalized the cultural environment for Kurds, and fortified the rule of law. And one of his coalition partners in that work, the right-wing pro-Turkish National Action Party (MHP), is now allied with the current ruling Justice and Development Party (AKP).

His foreign minister Ismail Cem also enhanced Turkey’s relations with both Europe and the US, initiated the so-called ‘earthquake diplomacy’ with his Greek counterpart George Papandreou after twin tragedies struck both nations in 1999, and largely avoided entanglement in Middle Eastern conflicts.

The net result of all these actions was that Turkey emerged from the crisis with greater resilience, a more robust regulatory framework, upgraded political and economic institutions, rapidly decreasing inflation, a credible central bank, a stronger financial system, closer relations with the EU and US, and heightened domestic and foreign investor confidence.

But now that similar woes are engulfing Turkey anew, is Erdogan and the AKP/MHP alliance able – and willing – to repeat the Ecevit recipe? Present signs indicate they are highly unlikely to as they are too committed to entrenching the Triple C model.

Although this model will likely further consolidate their power, it will also empty the civil service of qualified professionals, restrict civil liberties and freedoms, and create more ideological politics, affecting Turkey’s foreign policy.

Such a stubborn refusal to shift direction is increasing the inevitability of a deep economic and financial breakdown and so, unless Turkey undertakes a serious policy departure instead of continuing to resort to the quick fix approach, there is real likelihood it will simply accelerate towards disaster.

What can be achieved using applications such as AI/ML, Deep Learning, and Big Data Analytics has been revolutionized by Magnum IO GPUDirect Storage’s capabilities. Agencies have invested in these solutions […]

The post Accelerating GPU Based Applications with NVIDIA Validated Magnum IO GPUDirect Storage and Pavilion appeared first on HPCwire.

Data centers are experiencing increasing power consumption, space constraints and cooling demands due to the unprecedented computing power required by today’s chips and servers. HVAC cooling systems consume approximately 40% […]

The post How Direct Liquid Cooling Improves Data Center Energy Efficiency appeared first on HPCwire.

Q-CTRL, the Australia-based start-up focusing on quantum infrastructure software, today announced that its performance-management software, Fire Opal, will be natively integrated into four of the world’s most advanced quantum computing […]

The post Quantum Software Specialist Q-CTRL Inks Deals with IBM, Rigetti, Oxford, and Diraq appeared first on HPCwire.

Jenni Farley discusses her directorial debut "Devon," streaming and on video-on-demand Tuesday, and how she applied her love of horror movies to making one.

President-elect Donald Trump announced his choice Tuesday for CIA Director, tapping his former intelligence chief John Ratcliffe, who he called a "warrior of truth."

The governors of Oklahoma and South Carolina have directed significant portions of their states' federal education relief aid to fund private school scholarships.

The state's decision indicates that U.S. Secretary of Education Betsy DeVos' push on COVID-19 and private school students is having an affect.

AP Georgopoulos
Nov 1, 1982; 2:1527-1537
Articles

Estimating the direction of functional connectivity (FC) can help further elucidate complex brain function. However, the estimation of directed FC at the voxel level in fMRI data, and evaluating its performance, has yet to be done. We therefore developed a novel directed seed-based connectivity analysis (SCA) method based on normalized pairwise Granger causality that provides greater detail and accuracy over ROI-based methods. We evaluated its performance against 145 cortical retrograde tracer injections in male and female marmosets that were used as ground truth cellular connectivity on a voxel-by-voxel basis. The receiver operating characteristic (ROC) curve was calculated for each injection, and we achieved area under the ROC curve of 0.95 for undirected and 0.942 for directed SCA in the case of high cell count threshold. This indicates that SCA can reliably estimate the strong cellular connections between voxels in fMRI data. We then used our directed SCA method to analyze the human default mode network (DMN) and found that dlPFC (dorsolateral prefrontal cortex) and temporal lobe were separated from other DMN regions, forming part of the language-network that works together with the core DMN regions. We also found that the cerebellum (Crus I-II) was strongly targeted by the posterior parietal cortices and dlPFC, but reciprocal connections were not observed. Thus, the cerebellum may not be a part of, but instead a target of, the DMN and language-network. Summarily, our novel directed SCA method, visualized with a new functional flat mapping technique, opens a new paradigm for whole-brain functional analysis.

FAO Director-General José Graziano da Silva today praised UN Secretary-General Ban Ki Moon for his support in the fight against hunger at a meeting with FAO member countries, the Committee [...]

FAO Director-General José Graziano da Silva will be away from Rome during the next few weeks. During this period he will be involved in a range of [...]

Bagdad/Rome - FAO is scaling-up critical food and agriculture assistance to highly vulnerable rural households in Iraq thanks to a generous $14.7 million grant from Saudi Arabia. The donation is [...]

The [...]

FAO Director-General José Graziano da Silva today appointed Jacques Diouf as Special Envoy for the Horn of Africa and the Sahel.

In his new role, the former Director-General Jacques Diouf will [...]

FAO Director-General Graziano da Silva today opened the 150th session of the FAO Council, highlighting the successful conclusion of the Second International Conference on Nutrition (ICN2), held last month in [...]

5 December 2014, Rome – At the closure of the FAO Council held today, the [...]

Berlin- FAO Director-General José Graziano da Silva has highlighted some of the most important events on the organization’s 2015 calendar during meetings with agriculture ministers who attended the Global Forum [...]

Just announced by the Group of Latin America and the Caribbean Countries (GRULAC)

The Group of Latin American and Caribbean Countries (GRULAC) of FAO in Rome is pleased to endorse the [...]

Rome - José Graziano da Silva, the [...]

Rome, The Africa Regional Group of Ambassadors and Permanent Representatives accredited  to the Rome based UN Agencies have announced the endorsement of the candidature of Dr. José Graziano da Silva [...]

Rome, 02 March 2015 - In a letter addressed to the Director-General, the Chairperson of the Near East Regional Group has announced their endorsement of the candidature [...]

In a letter addressed to the Director-General, the Ambassador of Malaysia to FAO, on behalf of the Chair of the Asia Group, has announced the endorsement of the [...]

FAO Director-General José Graziano da Silva has been selected as one of the world's most influential Latin Americans for his work against hunger and malnutrition in the world. In its [...]

The Pre-Summit will bring together the global efforts to shape the transformation of agri-food systems.

Click here to access the presentation by QU Dongyu.

A statement by FAO Director-General QU Dongyu

FAO member nations to choose head of the UN specialized agency in July during the 43rd session of the FAO Conference

The Director of the Smithsonian's Hirshhorn Museum predicts what the museum's collections will hold in the next 40 years Read more at http://www.smithsonianmag.com/specialsections/40th-anniversary/Arts-Bold-New-Direction.html

David Lynch | Smithsonian Magazine’s 2016 American Ingenuity Award Winner for Education As a filmmaker, Lynch has a reputation for creating dark, surreal movies such as Eraserhead, Blue Velvet and Wild at Heart as well as the TV show “Twin Peaks.” In the education world, he's becoming known for something very different: promoting inner peace. Over the past decade, the David Lynch Foundation has sponsored Transcendental Meditation classes for half a million children in places as far-flung as the Bronx, Detroit, Los Angeles, Congo and the West Bank. The program, called Quiet Time, is now at the center of one of the largest-ever studies of meditation for children—a 6,800-pupil research project conducted by the Crime Lab at the University of Chicago and designed to learn if meditation can help kids in highly stressful environments fare better at home and in school. Read more about Lynch’s work: http://smithmag.co/9sHhtm | #IngenuityAwards And more about the American Ingenuity Awards: http://smithmag.co/77xPqy

By raising her son to be curious about the natural world, this mother helped shape the trajectory of the National Museum of Natural History

Waterloo region’s food landscape is more than farm stands and restaurants. There's a vast array of food producers, food makers and organizations that make up the food scene. And now, a new directory aims to make them easier to find. CBC KW's food columnist Jasmine Mangalaseril explored the directory.

Visual Effects Pioneer Will Share Stories of Overcoming Daunting Technical and Business Challenges

New Web destination lets visitors play with functionality, experience innovation, and influence product direction

Stephen Brandon takes on the role of national director for OM New Zealand after serving as OM’s International Web Manager for six years.

OM Director's Update from Lawrence Tong, International Director

OM Director's Update from Lawrence Tong, International Director

OM Director's Update from Lawrence Tong, International Director

OM Director's Update from Lawrence Tong, International Director

OM Director's Update from Lawrence Tong, International Director

OM Director's Update from Lawrence Tong, International Director

OM Director's Update from Lawrence Tong, International Director.

OM Director's Update from Lawrence Tong, International Director

OM Update from Lawrence Tong, International Director

OM Director's Update from Lawrence Tong, International Director