VOLUME 279 (2004) PAGES 33438–33446For Fig. 1B, the second, third, and fifth panels were mistakenly duplicated during article preparation as no yeast colonies were observed in these conditions. The corrected images are presented in the revised Fig. 1B. This correction does not affect the results or conclusions of the work. The authors apologize for the error.jbc;295/50/17382/F1F1F1Figure 1B.

Understanding which patients with human epidermal growth factor receptor 2 (HER2)–negative or –low metastatic breast cancer (MBC) benefit from HER2-targeted strategies is urgently needed. We assessed the whole-body heterogeneity of HER2 expression on ⁸⁹Zr-trastuzumab PET (HER2 PET) and the diagnostic performance of HER2 PET in a large series of patients, including HER2-negative and -low MBC. Methods: In the IMPACT-MBC study, patients with newly diagnosed and nonrapidly progressive MBC of all subtypes were included. Metastasis HER2 status was determined by immunohistochemistry and in situ hybridization.⁸⁹Zr-trastuzumab uptake was quantified as SUV_max and SUV_mean. HER2 immunohistochemistry was related to the quantitative ⁸⁹Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, uptake heterogeneity, and qualitative scan evaluation. A prediction algorithm for HER2 immunohistochemistry positivity based on uptake was developed. Results: In 200 patients, ⁸⁹Zr-trastuzumab uptake was quantified in 5,163 metastases, including 186 biopsied metastases. With increasing HER2 immunohistochemistry status, uptake was higher (geometric mean SUV_max of 7.0, 7.6, 7.3, and 17.4 for a HER2 immunohistochemistry score of 0, 1, 2, or 3+, respectively; P < 0.001). High uptake exceeding 14.6 (90th percentile) was observed in one third of patients with a HER2-negative or -low metastasis biopsy. The algorithm performed best when lesion site and size were incorporated (area under the curve, 0.86; 95% CI, 0.79–0.93). Conclusion: HER2 PET had good diagnostic performance in MBC, showing considerable whole-body HER2 heterogeneity and uptake above background in HER2-negative and -low MBC. This provides novel insights into HER2-negative and -low MBC compared with standard HER2 immunohistochemistry on a single biopsy.

Actress Megan Fox and musician Machine Gun Kelly are expecting a child together.

Looking to infuse more connection into your time with friends and family? Facilitator Priya Parker urges us to approach gathering with intention and creativity. Diving into the evolving significance of coming together both in-person and virtually, she demystifies the role of a host, outlines mistakes we should avoid and shares the potential of thoughtfully designed get-togethers to bring lasting change to communities, workplaces and personal relationships. (This conversation was hosted by TED's Cloe Shasha Brooks. Visit ted.com/membership to support TED today and join more exclusive events like this one.)

Roger Dooley, international keynote speaker and author, just launched a new, three-minute speaker reel video featuring highlights of his Neuro-Loyalty speech based on the ideas in his award-winning book, FRICTION.

The post Neuro-Loyalty: New Speaker Reel For Roger Dooley appeared first on Neuromarketing.

Collaboration doesn’t require turning parents into math experts, classroom teachers say.

Prithviraj Rajebhosale
Oct 23, 2024; 44:e0063242024-e0063242024
Cellular

Evdokia Menelaou
Aug 8, 2012; 32:10925-10939
BehavioralSystemsCognitive

Danilo De Gregorio
Feb 3, 2021; 41:891-900
Symposium and Mini-Symposium

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by -secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V₃₂₁L) in the Nrg1 transmembrane domain that disrupts nuclear back signaling with minimal effects on forward signaling or local back signaling and was previously found to be associated with psychosis (Walss-Bass et al., 2006). We combined RNA sequencing, retroviral fate mapping of neural stem cells, behavioral analyses, and various network analyses of transcriptomic data to investigate the effect of disrupting Nrg1 nuclear back signaling in the dentate gyrus (DG) of male and female mice. The V₃₂₁L mutation impairs nuclear translocation of the Nrg1 ICD and alters gene expression in the DG. V₃₂₁L mice show reduced stem cell proliferation, altered cell cycle dynamics, fate specification defects, and dendritic dysmorphogenesis. Orthologs of known schizophrenia (SCZ)-susceptibility genes were dysregulated in the V₃₂₁L DG. These genes coordinated a larger network with other dysregulated genes. Weighted gene correlation network analysis and protein interaction network analyses revealed striking similarity between DG transcriptomes of V₃₂₁L mouse and humans with SCZ.

Q: Ambassador, how did the Programme Committee in its recent session judge FAO's contribution to the eradication of hunger, food insecurity and malnutrition?

Ambassador Hoogeveen: [...]

Nearly 300,000 people gather every Memorial Day to witness the legendary Indianapolis 500, one of the greatest spectacles in U.S. racing

Two comb jellies can merge their digestive and nervous systems and even sync their bodily functions, according to new research. The discovery could have implications for human medicine

The Montreal English Theatre Awards ceremony is being held this evening at Le Gesù theatre. For the community, it's a time to celebrate their achievements and resilience coming out of the pandemic, together.

Fourteen young people participated in a month-long outreach within in their country. The result: unity.

OM Hungary works alongside partner organisations to bring comfort and Jesus’ love to refugees in Budapest.

Softball ministry in Hungary shows hospitality, international influence by hosting the 2016 Danube Cup

Various OM ministries partner with the Irish Evangelistic Band to share the good news at Ireland's National Ploughing Championship.

OM Hong Kong celebrates the annual Mid-Autumn Festival with South Asian friend and meets other families to learn about their needs.

A new approach to mathematics teaching helps English learners and others develop mathematics reasoning and language skills simultaneously.

Two small churches in a mountain area of Albania are isolated by geography, so meeting together for Christmas lunch was a great encouragement to both.

This week, SA Money Report focuses on the controversy around the appointment of Arrie Rautenbach as Absa CEO.

Riverboat community members took to the city centre for an afternoon and–to their surprise–met people who spoke their heart languages.

Elon Musk, alongside Indian-American entrepreneur Vivek Ramaswamy, will lead the 'Department of Government Efficiency' in the Donald Trump-led US government.

Rohit Shetty shared that it was his conscious choice to not cast Ranveer and Deepika together in a scene, as it might have received backlash

The caption accompanying the pictures read, "Sending all my love to my artist younger sister Farhat"

Experienced healthcare management strategist hired after lengthy national search Insurance Commissioner Trinidad Navarro welcomed Cristine Vogel to the Delaware Department of Insurance as its Director of Value-Based Health Care Delivery this week after a lengthy national search to fill the role. As the inaugural Director, Vogel will lead efforts that relate to value-based care, primary […]

डोनाल्ड ट्रंप ने ऐतिहासिक जीत के बाद चुनाव के दौरान दिए 'सेव अमेरिका' के नारे में जमीन पर उतारने की तैयारी शुरू कर दी है. लगातार वह बाइडेन सरकार (Biden Government) पर फिजूलखर्ची के आरोप लगाते चले आ रहे थे. ट्रंप ने बाइडेन सरकार की कई नीतियों की आलोचना भी की थी. साथ ही अवैध इमीग्रेशन के विरोध में सख्त कदम उठाने का भी लोगों से वादा किया है. अब सरकार ने बनने वाली और डोनाल्ड ट्रंप सरकार गठन की प्रक्रिया पूरी कर रहे हैं. उन्होंने सबसे पहले यह बता दिया है कि उनकी सरकार के काम करने का थीम क्या होगा. 

Delaware was the first state to ratify the Constitution but possibly the last state to settle its boundaries. Delaware has the distinction of the being the only state with a round border and the only state that lies completely east of the Mason-Dixon Line. Roger E. Nathan’s work discusses how Delaware’s territory changed during the […]

ing with Palladium”, running February 3-24, 2023. Guests are invited to attend a Meet-the-Artist Reception on Friday, February 3 from 5:00-7:00 p.m. Roger Matsumoto has […]

Governor Carney has ordered the Delaware flag to be lowered September 9, 2020 to honor the many years of public service of former Milford mayor Joseph Ronald “Ronnie” Rogers who passed away on Sunday, August 30, 2020. Mr. Rogers began his political career in Milford by running for city council representing the 1st ward in […]

Delaware Attorney General Kathy Jennings, alongside a bipartisan coalition of thirty state attorneys general, announced today the completion of the $1.37 billion settlement agreement with Kroger, addressing the grocery chain’s role in the opioid crisis. Delaware will receive over $2.7 million for opioid abatement, all of which will be overseen by the Prescription Opioids Settlement Distribution Commission. Payments are […]

1. Elon Musk, Vivek Ramaswamy to lead DOGE to clean up US bureaucracy: Trump  India Today
2. Trump’s 'Manhattan Project' of government reform: Musk and Ramaswamy to lead efficiency crusade  The Times of India
3. Democrat Senator's 'efficient' dig at Elon Musk-Vivek Ramaswamy heading DOGE  India Today
4. Donald Trump picks Elon Musk, Vivek Ramaswamy to lead newly formed Department of Government Efficiency (DOGE)  The Hindu
5. A dope for DOGE (and Dogecoin): Trump taps Musk in efficiency team, crypto fans rejoice  The Economic Times

Canadian utilities giant ATCO was struck by Australia’s unique ability to make green hydrogen by harnessing its abundant sunshine. This capacity, combined with the country’s can-do attitude and commitment to the development of renewable energies, compelled the company to invest in Australia’s first Clean Energy Innovation Hub to fast-track sustainable solutions for future energy needs.

They met at eight years old, married, and died together in a Ukrainian trench

Cities are engines of economic growth, generating over 80% of the global gross domestic product. As centers of innovation and technological development, they play a crucial role in creating jobs, driving commerce, and providing social services.

Migration may reinforce less productive forms of informal employment in rural Nepal.

Scientists have known for centuries that sunflowers wobble in seemingly random ways as they grow – but it seems that those movements actually optimise how much light each plant gets

The physicist Peter Higgs quietly revolutionised quantum field theory, then lived long enough to see the discovery of the Higgs boson he theorised. Despite receiving a Nobel prize, he remained in some ways as elusive as the particle that shares his name

The Impossible Man by Patchen Barss salutes Roger Penrose's groundbreaking work in physics and mathematics while challenging the idea that a genius should be exempt from ordinary obligations

Geologists think there may be vast natural stores of hidden hydrogen gas within Earth, but no one is sure how much there is or how much could be recovered for energy

A well in Nebraska is the first in the world to have been drilled in search of naturally occurring geologic hydrogen, but tests to determine how much of the gas it might supply are on hold because of a broken pump

Companies are searching all over the world for deposits of geologic hydrogen that could be used as clean fuel, and a mine in Albania could give them clues about where to look

The Impossible Man by Patchen Barss salutes Roger Penrose's groundbreaking work in physics and mathematics while challenging the idea that a genius should be exempt from ordinary obligations

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As a major type of structural variants, tandem duplication plays a critical role in tumorigenesis by increasing oncogene dosage. Recent work has revealed that noncoding enhancers are also affected by duplications leading to the activation of oncogenes that are inside or outside of the duplicated regions. However, the prevalence of enhancer duplication and the identity of their target genes remains largely unknown in the cancer genome. Here, by analyzing whole-genome sequencing data in a non-gene-centric manner, we identify 881 duplication hotspots in 13 major cancer types, most of which do not contain protein-coding genes. We show that the hotspots are enriched with distal enhancer elements and are highly lineage-specific. We develop a HiChIP-based methodology that navigates enhancer–promoter contact maps to prioritize the target genes for the duplication hotspots harboring enhancer elements. The methodology identifies many novel enhancer duplication events activating oncogenes such as ESR1, FOXA1, GATA3, GATA6, TP63, and VEGFA, as well as potentially novel oncogenes such as GRHL2, IRF2BP2, and CREB3L1. In particular, we identify a duplication hotspot on Chromosome 10p15 harboring a cluster of enhancers, which skips over two genes, through a long-range chromatin interaction, to activate an oncogenic isoform of the NET1 gene to promote migration of gastric cancer cells. Focusing on tandem duplications, our study substantially extends the catalog of noncoding driver alterations in multiple cancer types, revealing attractive targets for functional characterization and therapeutic intervention.