Hyperbaric Oxygen Therapy (HBOT) is a medical treatment that involves breathing pure oxygen in a pressurized environment. This unique treatment method has shown effectiveness in healing various conditions, from complex wound healing to treating decompression sickness in divers. HBOT works on the principle of increasing oxygen concentration in the body, which can enhance the body’s ... Read more

The post How Much Does Hyperbaric Oxygen Therapy Cost? Price Tips appeared first on Star Two.

In the 1700s, an enslaved man named Onesimus shared a novel way to stave off smallpox during the Boston epidemic. Here’s his little-told story, and how the Atlantic slave trade and Indigenous medicine influenced early modern science.

Stories of brilliant innovations and inventions by the world’s greatest minds.

In Louisiana, more than 100,000 students are using an AI tutor that is helping to raise reading scores.

If you’re like most business owners, you probably think of your website as an online brochure. It’s a...

The post How to Make Your Website a Lead-Generating Machine appeared first on Ignition Media.

From the horror of the Holocaust to the struggles that the cousins face in the modern day, the movie is about the overall pains of life, film star Jennifer Grey iterated.

The man was pronounced dead at the scene after CPR efforts from cabin crew

The following article, Not Looking Good for Kamala Harris or Democrats in General, was first published on The Black Sphere.

Republicans have picked up a Senate seat, and will likely add 2 more. But the best news will come in just a few hours...

Continue reading Not Looking Good for Kamala Harris or Democrats in General ...

The FEMA official who was just fired for telling workers to avoid homes impacted by the hurricanes in Florida if they had Trump signs says that it was not “isolated” and that FEMA workers were instructed to do it in the Carolinas too. (X) The American people must get justice. Indict and convict. So, apparently this …

England have a "generational" crop of talent that has more potential than the squad that reached the 2019 World Cup final, says Rugby Football Union director of performance Conor O'Shea.

A UK law allowing gene-edited food has been paused and some British scientists fear being overtaken.

Mohamed Bin Salman was speaking at the opening of a summit of Muslim and Arab leaders in Riyadh.

But Israel says it has greatly increased deliveries since being warned of cuts to military assistance.

Latino, black and younger voters once helped Obama win power - Trump made gains with all three groups this election. Why?

Generative AI Is Your Ally for Smart Staging, Selling

2 ‘Moody’ Home Design Trends Generating Buzz

England prop Ellis Genge admits last year's World Cup semi-final defeat by South Africa is something he will carry for the rest of his career.

A general election in the Republic of Ireland has officially been called for Friday 29 November.

After growing speculation, the Irish prime minister has called a general election.

Nineteen years and 10 miles separated Zambia's football team from a lost, golden generation on a fateful night in Libreville.

BBC MOTD2 pundit and former Arsenal forward Theo Walcott explains why Newcastle striker Alexander Isak's all-round game makes him a player who could get in any team.

Israel's parliament, the Knesset, has suspended lawmaker Ofer Cassif for six months due to comments he made about the IDF, the war in Gaza, and his support for South Africa accusing his country of genocide against Palestinians.

Apple Intelligence is here on Mac, iPhone, and iPad, and while the system requirements are strict, the Apple devices that are new and powerful enough to use the AI tools now gain some really fantastic features. We’re going to show you six helpful Apple Intelligence features and uses that you’ll find beneficial to your workflow, ... Read More

When my job announced we were returning to the office, I was able to quit and rely on my emergency fund while job searching. I still wish I had saved more.

This article describes the current findings on phonics and phonological awareness instruction. It uses a question & answer format to explore 10 common questions that teachers ask about teaching phonics and phonemic awareness. Here are a few key questions addressed in the article: What are phonics and phonemic awareness? Should phonemic awareness be paired with print and taught together? Should phonological awareness be coordinated with phonics instruction? What is the best sequence for teaching phonics?

Tuesday 12 November 2024 – Best Wallet ($BEST) sold out its first presale stage in just six hours, raising $162,000… Continue reading Best Wallet’s Presale Generates $162K in 6 Hours, Sells Out on Launch Day

The post Best Wallet’s Presale Generates $162K in 6 Hours, Sells Out on Launch Day appeared first on ReadWrite.

The Atlantic is out with a delicious piece of doomerism: It’s The End of the Web As We Know It. Were it not for the authors, Judith Donath and Bruce Schneier, I’d have passed right on by, because well-respected publications have been proclaiming the death of the Web for more than a decade. By and … Continue reading "Will GenAI Kill The Web?"

A quick note to point you toward this piece I wrote for P&G’s Signal publication. Since its inception, I’ve been co-editor of the monthly outlet, which covers innovation in large enterprise. This month I went in search of proof that the hype around generative AI – fueled in large part by both Google and Microsoft … Continue reading "Can GenAI Change Big Companies?"

A.F. Branco Cartoon – Democrats, the party of child genital mutilation and late-term abortion, are outraged at Trump for his comments alluding to..

Republicans have solidified their control of Washington by retaining control of the House of Representatives. President-elect Donald Trump’s overwhelming victory in the presidential race, coupled with GOP control of the […]

The post Breaking: Republicans Retain Control Over House of Representatives, Handing Trump the Keys to His Agenda appeared first on The Western Journal.

Sir Kenny Dalglish hailed nine-time Major champion Gary Player and expressed his delight at Liverpool's position at the top of the Premier League during his visit to South Africa this weekend.

Bafana Bafana coach Hugo Broos has welcomed the number of young players who are given a chance and backed in the premier division, but has warned that to build on their progress, agents must prioritise players' development over their personal enrichment.

Former Kaizer Chiefs legend Brian Baloyi says that holding the Kaizer Chiefs No 1 jersey requires a hardened mentality, but he is upbeat over Amakhosi's chances this season.

Total media ad spend in Russia to drop nearly 50%   March 30, 2022 (New York, NY) – Insider Intelligence expects the ongoing war in Ukraine to have a significant […]

Heterotrimeric G-proteins are signaling switches broadly divided into four families based on the sequence and functional similarity of their Gα subunits: Gs, Gi/o, Gq/11, and G12/13. Artificial mutations that activate Gα subunits of each of these families have long been known to induce oncogenic transformation in experimental systems. With the advent of next-generation sequencing, activating hotspot mutations in Gs, Gi/o, or Gq/11 proteins have also been identified in patient tumor samples. In contrast, patient tumor-associated G12/13 mutations characterized to date lead to inactivation rather than activation. By using bioinformatic pathway analysis and signaling assays, here we identified cancer-associated hotspot mutations in Arg-200 of Gα13 (encoded by GNA13) as potent activators of oncogenic signaling. First, we found that components of a G12/13-dependent signaling cascade that culminates in activation of the Hippo pathway effectors YAP and TAZ is frequently altered in bladder cancer. Up-regulation of this signaling cascade correlates with increased YAP/TAZ activation transcriptional signatures in this cancer type. Among the G12/13 pathway alterations were mutations in Arg-200 of Gα13, which we validated to promote YAP/TAZ-dependent (TEAD) and MRTF-A/B-dependent (SRE.L) transcriptional activity. We further showed that this mechanism relies on the same RhoGEF-RhoGTPase cascade components that are up-regulated in bladder cancers. Moreover, Gα13 Arg-200 mutants induced oncogenic transformation in vitro as determined by focus formation assays. In summary, our findings on Gα13 mutants establish that naturally occurring hotspot mutations in Gα subunits of any of the four families of heterotrimeric G-proteins are putative cancer drivers.

G protein–coupled receptors (GPCRs) initiate signaling cascades via G-proteins and beta-arrestins (βarr). βarr-dependent actions begin with recruitment of βarr to the phosphorylated receptor tail and are followed by engagement with the receptor core. βarrs are known to act as adaptor proteins binding receptors and various effectors, but it is unclear whether in addition to the scaffolding role βarrs can allosterically activate their downstream targets. Here we demonstrate the direct allosteric activation of proto-oncogene kinase Src by GPCR–βarr complexes in vitro and establish the conformational basis of the activation. Whereas free βarr1 had no effect on Src activity, βarr1 in complex with M2 muscarinic or β2-adrenergic receptors reconstituted in lipid nanodiscs activate Src by reducing the lag phase in Src autophosphorylation. Interestingly, receptor–βarr1 complexes formed with a βarr1 mutant, in which the finger-loop, required to interact with the receptor core, has been deleted, fully retain the ability to activate Src. Similarly, βarr1 in complex with only a phosphorylated C-terminal tail of the vasopressin 2 receptor activates Src as efficiently as GPCR–βarr complexes. In contrast, βarr1 and chimeric M2 receptor with nonphosphorylated C-terminal tail failed to activate Src. Taken together, these data demonstrate that the phosphorylated GPCR tail interaction with βarr1 is necessary and sufficient to empower it to allosterically activate Src. Our findings may have implications for understanding more broadly the mechanisms of allosteric activation of downstream targets by βarrs.

National security and transatlantic unity top Biden’s agenda Expert comment NCapeling 1 February 2023

The timing of the State of the Union address is significant as Joe Biden tries to maintain focus on Ukraine and China while navigating partisanship at home.

Although primarily a domestic affair, the president’s remarks in the annual State of the Union (SOTU) telegraph the US’s foreign policy priorities to the rest of the world. They reveal the prism through which the US understands its national security and its role in the world.

The 2023 address comes as the first anniversary of the Ukraine invasion rapidly approaches, and the US is also trying to build international support for tough economic measures towards China. Domestically, Republican control of the House of Representatives will exert new pressure on US foreign policy choices. Electoral pressures are also around the corner and Joe Biden should announce soon whether he plans to run for president in 2024.

Alliances and partnerships are a driving force for Biden. As pressure to end the war in Ukraine intensifies, maintaining transatlantic unity on Ukraine will be a key priority for the president. And as US electoral politics rise to the fore, ensuring the visibility of Europe’s role as a security provider in its own backyard will be essential.

For a US president who sees China and the Indo-Pacific as America’s most significant long-term geopolitical challenge – and the only peer competitor to the US – transatlantic unity on China will also come under pressure.

Ukraine, China, and controlling domestic division

Republican leaders who now chair key committees in the House of Representatives continue to signal support for Ukraine, and polling shows a majority of US public opinion (54 per cent) favours sending either weapons or air defence systems.

But recent polls also reveal a growing gap between Democrat and Republican supporters with a slight majority of Republicans (52 per cent) now opposing further support for Ukraine.

Biden’s ability to demonstrate that America and its European partners remain unified in their policy towards Ukraine and Russia will help him ward off partisanship at home. Congressional approval of $45 billion for Ukraine in its end of year spending budget will help the president remain above the fray of partisan politics for now. But if there is an absence of clear signs Ukraine is succeeding in its war aims, the challenge of maintaining domestic support could become more difficult.

A greater US focus on China, India, and on the Indo-Pacific in 2023 is also likely. Bipartisanship is strong on China, Republicans are more singular and hawkish in their approach to China than the US president, and the public support tough measures. At a time of war in Europe, the president will place great emphasis on the need to maintain transatlantic unity and to work with a broader coalition of partners in the Indo-Pacific.

The groundwork for focus on China has already been laid. Throughout 2022, the Biden administration worked steadily, but quietly, to set out its China policy. Just before Russia’s invasion of Ukraine in February 2022, the US released its new US-Indo Pacific Strategy stressing regional partnerships – especially the Quad and ASEAN – and it’s determination to shape essential norms for the region.

It stated boldly – albeit in a document which was largely unnoticed – that the objective is not to change China but to ‘shape the strategic environment in which it operates’, a policy which signifies a clear departure from the more ideological approach pursued by the US during Donald Trump’s final year in office. And in May, the US announced its economic strategy for the region, the Indo-Pacific Economic Framework.

Now the terrain for competition with China and alignment with US partners and allies is heavily focused on technology and the daylight between national security and economic strategy in US China policy is rapidly disappearing. Biden’s policy focus of ‘invest (at home), align (with allies and partners), and compete (with China)’ has overshadowed earlier talk of cooperation between the US and China.

But as China opens its doors and Europe looks to bolster its economies, the US will have to work far harder to maintain transatlantic unity. Japan and the Netherlands embracing the US adoption of export controls on semiconductor chips is a positive sign, but the US’s economic strategy towards China may present harder choices to come for Europe. If China leans into its diplomacy, the pressure on transatlantic unity will also grow.

The new US Congress will only sharpen the president’s tough stance on China. Some Republican leaders still deny climate change and have demonstrated little interest in cooperating with China on debt relief for developing countries. The prospects for addressing critical global challenges appear dim without China’s collaboration, and the UK and Europe should work with the US president and Congress to correct this.

President Biden has clearly recognized that diplomacy will be critical in the months ahead. At a time of growing tensions, the potential for misperceptions or misunderstandings to create conflict will also increase, and so a US – and also European – commitment to broadening and deepening diplomacy with China is urgent but it also needs to be patient and sustained.

A new American industrial policy?

Those listening carefully to the State of the Union and who have followed US policy will also note the unchallenged hegemony of neoliberalism is rapidly vanishing. The American state appeared to be disturbingly absent in the early months of the US pandemic response – but now it is back and, in a surprising turn of events, is being cast as a solution not a problem.

Michal Bassani-Sternberg
Mar 1, 2015; 14:658-673
Research

Timothy J. Griffin
Apr 1, 2002; 1:323-333
Research

Qiang Tian
Oct 1, 2004; 3:960-969
Research

Ludovic C. Gillet
Jun 1, 2012; 11:O111.016717-O111.016717
Research

Ignat V. Shilov
Sep 1, 2007; 6:1638-1655
Technology

Linn Fagerberg
Feb 1, 2014; 13:397-406
Research

Philip L. Ross
Dec 1, 2004; 3:1154-1169
Research

This article is by Emma Lammers.

Author’s note: neurodivergent is term used to refer to people whose neurological functions differ from the norm because of an innate or acquired condition. Examples of these conditions include autism, learning disabilities, mood disorders, traumatic brain injuries, and more. People who do not have any neurodivergent conditions are considered neurotypical.

To the delight of many readers, more characters in fantasy literature reflect aspects of real-world people than ever before. Today’s heroes can be people of colour, people of any gender or sexual identity, people of nearly any age. Writers are answering the call for more diversity in their work, and oftentimes they do it well, portraying realistic, nuanced characters from marginalized communities.

Some people, however, aren’t as likely to see themselves accurately reflected in the pages of a fantasy story. I’ve searched long and hard to find literary characters who experience autism, anxiety, and sensory processing disorder as I do, and very few of these characters show up in fantasy – a detriment to my favourite genre. Villainous characters are often portrayed as neurodivergent because writers think that this will make them scarier, and you will encounter the occasional hero with post-traumatic stress disorder, but  these depictions tend to lack accuracy, diversity, and consideration for the people who actually have the conditions used in the story.

Continue reading Writing Neurodivergent Characters in Fantasy at Mythic Scribes.

Accumulation of the microtubule-associated protein tau is associated with Alzheimer's disease (AD). In AD brain, tau is abnormally phosphorylated at many sites, and phosphorylation at Ser-262 and Ser-356 plays critical roles in tau accumulation and toxicity. Microtubule affinity–regulating kinase 4 (MARK4) phosphorylates tau at those sites, and a double de novo mutation in the linker region of MARK4, ΔG316E317D, is associated with an elevated risk of AD. However, it remains unclear how this mutation affects phosphorylation, aggregation, and accumulation of tau and tau-induced neurodegeneration. Here, we report that MARK4ΔG316E317D increases the abundance of highly phosphorylated, insoluble tau species and exacerbates neurodegeneration via Ser-262/356–dependent and –independent mechanisms. Using transgenic Drosophila expressing human MARK4 (MARK4wt) or a mutant version of MARK4 (MARK4ΔG316E317D), we found that coexpression of MARK4wt and MARK4ΔG316E317D increased total tau levels and enhanced tau-induced neurodegeneration and that MARK4ΔG316E317D had more potent effects than MARK4wt. Interestingly, the in vitro kinase activities of MARK4wt and MARK4ΔG316E317D were similar. When tau phosphorylation at Ser-262 and Ser-356 was blocked by alanine substitutions, MARK4wt did not promote tau accumulation or exacerbate neurodegeneration, whereas coexpression of MARK4ΔG316E317D did. Both MARK4wt and MARK4ΔG316E317D increased the levels of oligomeric forms of tau; however, only MARK4ΔG316E317D further increased the detergent insolubility of tau in vivo. Together, these findings suggest that MARK4ΔG316E317D increases tau levels and exacerbates tau toxicity via a novel gain-of-function mechanism and that modification in this region of MARK4 may affect disease pathogenesis.

Synapse loss is associated with motor and cognitive decline in multiple neurodegenerative disorders, and the cellular redistribution of tau is related to synaptic impairment in tauopathies, such as Alzheimer's disease and frontotemporal dementia. Here, we examined the cellular distribution of tau protein species in human tau overexpressing line 66 mice, a transgenic mouse model akin to genetic variants of frontotemporal dementia. Line 66 mice express intracellular tau aggregates in multiple brain regions and exhibit sensorimotor and motor learning deficiencies. Using a series of anti-tau antibodies, we observed, histologically, that nonphosphorylated transgenic human tau is enriched in synapses, whereas phosphorylated tau accumulates predominantly in cell bodies and axons. Subcellular fractionation confirmed that human tau is highly enriched in insoluble cytosolic and synaptosomal fractions, whereas endogenous mouse tau is virtually absent from synapses. Cytosolic tau was resistant to solubilization with urea and Triton X-100, indicating the formation of larger tau aggregates. By contrast, synaptic tau was partially soluble after Triton X-100 treatment and most likely represents aggregates of smaller size. MS corroborated that synaptosomal tau is nonphosphorylated. Tau enriched in the synapse of line 66 mice, therefore, appears to be in an oligomeric and nonphosphorylated state, and one that could have a direct impact on cognitive function.