Barbara J. Vilen & team now identify defective late endosomes and lysosomes (LELs) in patients with active lupus and show reduced LEL function promotes SLE through chronic PI3k activity and SHP-1/SHIP-1 defects:
The figure shows bone marrow-derived macrophages from lupus prone mice (MRL/lpr) have decreased recruitment of pSHIP-1Y1022 (green) to the plasma membrane, indicated by cholera toxin-stained lipid rafts (blue), compared with control mice (B6).
1Department of Microbiology and Immunology and.
2Division of Rheumatology, Allergy, and Immunology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
3Division of Rheumatology and Immunology, Duke University Medical Center, Durham, North Carolina, USA.
Neurodegenerative diseases form a tangled biological web with overlapping molecular signatures and symptoms. To decode this complexity, a multi-institute collaboration led by St. Jude Children’s Research Hospital scientists developed the pan-neurodegeneration atlas (PanNDA). The atlas is a comprehensive survey of neurodegenerative disease “proteomes” containing information about protein levels, modifications, and interactions. This resource, published today in Cell, provides a wide-ranging protein-based outlook to better understand the origins of neurodegenerative diseases and to aid in their diagnosis and treatment.
Neurodegenerative diseases often stem from protein misfolding or accumulation. These errors also disrupt binding partners, upstream and downstream effectors, and any connected pathways. By combining multiple proteomic strategies, co-corresponding authors Junmin Peng, Ph.D., St. Jude Departments of Structural Biology and Developmental Neurobiology, and Bin Zhang, Ph.D., Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, created PanNDA to understand and explore this network and how it is disrupted in these diseases.
Human papillomavirus (HPV), a DNA virus, is a well-documented causative agent of several cancers, including cervical, vulvar, vaginal, penile, anal, and head & neck cancers. Major factors contributing to HPV-related cancers include persistent infection and the oncogenic potential of particular HPV genotypes. High-risk HPV strains, particularly HPV-16 and HPV-18, are responsible for over 70% of cervical cancer cases worldwide, as well as a significant proportion of other genital and head and neck cancers. At the molecular level, the oncogenic activity of these viruses is driven by the overexpression of E6 and E7 oncoproteins. These oncoproteins dysregulate the cell cycle, inhibit apoptosis, and promote the accumulation of DNA damage, ultimately transforming normal cells into cancerous ones. This review aims to provide a comprehensive overview of the recent advances in HPV-related cancer biology and epidemiology. The review highlights the molecular pathways of HPV-driven carcinogenesis, focusing on the role of viral oncoproteins in altering host cell targets and disrupting cellular signalling pathways. The review explores the therapeutic potential of these viral proteins, and discusses current diagnostic and treatment strategies for HPV-associated cancers. Furthermore, the review highlights the critical role of HPV in the development of various malignancies, emphasizing the persistent challenges in combating these cancers despite advancements in vaccination and therapeutic strategies. We also emphasize recent breakthroughs in utilizing biomarkers to monitor cancer therapy responses, such as mRNAs, miRNAs, lncRNAs, proteins, and genetic markers. We hope this review will serve as a valuable resource for researchers working on HPV, providing insights that can guide future investigations into this complex virus, which continues to be a major contributor to global morbidity and mortality.
This interview is an episode from The Well, our publication about ideas that inspire a life well-lived, created with the John Templeton Foundation.
Watch Seager’s next interview ► What if intelligent life exists, but we can’t recognize it? • What if intelligent life exists, but we ca…
Sara Seager, a planetary scientist, astrophysicist, and leading researcher in the search for life beyond Earth, examines how discovering life elsewhere would represent a Copernican-level shift in human understanding.
Research into Mars, Venus, and the icy moons of Jupiter and Saturn has revealed complex molecules and liquid environments that could support life. Independent origins of life would imply that the galaxy is rich with living individuals, challenging long-held cultural, religious, and philosophical assumptions. The acceptance of major scientific discoveries — and the unexpected practical contributions to pure science — impact how the search for extraterrestrial life may benefit society over time.
https://doi.org/10.1172/JCI195189 Dolores Hambardzumyan & team develop mouse models of germline and somatic MMR-deficient high-grade gliomas, finding a role for MMR genes in tumor growth and temozolomide resistance, and presenting KL-50 as a therapeutic avenue.
The figure demonstrates a potent anti-tumor effect from KL-50 treatment in glioblastoma models.
1Departments of Oncological Sciences and Neurosurgery, The Tisch Cancer Institute and.
2Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
3Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, New York, USA.
The ToxFree Life for All project analysed 81 headphone models (180 material samples) across Central Europe and online marketplaces like Temu and Shein. 100% of products contained hazardous substances, including bisphenols, phthalates, and flame retardants. While these products do not pose an acute or “imminent” danger, the cumulative and synergistic effects of chronic exposure to these chemical classes pose a long-term risk to public health, therefore having a negative impact on sovereign consumer choice. The individual consumer has limited power to choose a safe product. Consumer protection is a systemic problem that cannot be solved by individual choice; it must be addressed at the institutional level.
Dr. Joscha Bach is a renowned cognitive scientist, AI researcher, and philosopher of mind known for his work on synthetic intelligence and the computational foundations of the soul. He is currently the founding director of the California Institute for Machine Consciousness (CIMC) and a strategic advisor at Liquid AI.
Throughout his career, Joscha has held research positions at some of the world’s most prestigious institutions, including the MIT Media Lab, the Harvard Program for Evolutionary Dynamics, and Intel Labs. He is the architect behind MicroPsi, a cognitive architecture that models how agents think, act, and feel based on internal motivations.
Are minds just processes? Can AI become conscious, morally wiser, or even part of a larger collective intelligence? Anders Sandberg and Joscha Bach discuss consciousness, AGI, hybrid minds, moral uncertainty, collective agency and the future of the cyborg Leviathan. It’s a deep and winding discussion with so many interesting topics covered!
0:00 Intro. 0:37 What is consciousness? Phenomenology — functionalism & panpsychism. 1:54 Causal boundaries — the mind is a causally organised process with a non-arbitrary functional boundary, sustained through time by feedback, control, and internal continuity. 3:20 Minds are not states — they are processes. We don’t see causal filtering in tables. 5:54 Epiphenomenalism is self-undermining if it has no causal role, and taking causation seriously pushes towards functionalism. 9:49 Methodological humility about armchair philosophy of mind. 12:41 Putnam-style Brain-in-a-vat — and why standard objections to AI minds fall flat. 16:37 Is sentience required (or desired) for not just moral competence in AI, but moral motivation as well? 22:35 Why stepping outside yourself is powerful — seeing. 25:12 Are AIs born enlightened? 26:25 Are LLMs AGI yet? What’s still missing. 28:16 AI, hybrid minds, and the limits of human augmentation. 32:32 Can minds be extended — in humans, dogs, and cats? 36:19 Why human language may not be open-ended enough. 39:41 Why AI is so data-hungry — and why better algorithms must exist. 43:39 Why better representations matter more than raw compute (grokking was surprising) 48:46 How babies build a world model from touch and perception. 51:05 What comes after copilots: agent teams, multimodality and new AI workflows. 55:32 Can AI help us discover new forms of taste and aesthetics. 59:49 Using AI to learn art history and invent a transhumanist aesthetic. 1:01:47 When AI helps everyone looks professional, what still counts as real skill? 1:03:56 What happens when the self starts to merge with AI 1:05:43 How AI changes the way we think and create. 1:08:10 What happens when AI starts shaping human relationships. 1:11:18 Why feeling in control can matter more than being right. 1:12:58 Why intelligence without wisdom is very dangerous. 1:17:45 AI via scaling statistical pattern matching vs symbolic (& causal) reasoning. Can LLMs learn causality or just correlation? 1:23:00 Will multimodal AI replace LLMs or use them as glue everywhere. 1:24:02 10 years to the singularity? 1:25:27 AI, coordination and the corruption problem. 1:29:47 Can AI become more moral than us (humans)? and if so, should it? 1:34:31 Why pluralism still leaves moral collisions unresolved. 1:34:31 Traversing the landscape of norms (value) 1:38:14 Can ethics work across nested levels of existence? (from the person-effecting-view to the matrioshka-effecting-view) 1:43:08 Moral realism, evolution & game-theoretic symmetries. 1:48:01 Is there a global optimum of moral coordination? Is that god? 1:55:12 Metaphors of the body-politic, the body of Christ, Omega Point theory, Leviathan. 1:59:36 Will superintelligences converge into a cosmic singleton?
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THANK-YOU to M. Howard, M. Metts, M. Provost, S. Shardool, M. Bueche, M. Williams, M. Morrow, R. Borbidge, M. Everest, M. Vystoropskyi, M. Bryant, M. Nimmerjahn, M. Schreiner, M. Canning, M. Stewart, M. Cartmell, M. Brooks, M. Smith, E. Garland, M. Borisoff, M. Danielson, M. Adler, M. Sanford, M. Smith, M. Larter, M. Devermont, M. Chaffee, M. Rockett, M. Aron, M. Daniluk, M. Corwin, M. Bylinsky, C. Fitzgerald, M. Kingston, M. Ortiz, M. Venzor, B. Gaalen, M. Muriuki, M. Schoen, M. Popovski, M. Frederick, M. Kruger, M. Bottaccini, M. Johnston, M. Huch, M. Singh, M. Sattler, M. McMillan, M. Brownlee, M. Armstrong, M. Williams, M. Souter, M. OBrien, M. Shamp, M. Kochkov, M. Schiff, M. Fitzsimmons, G. Belsak, M. Johnston, M. Gillette, M. Murphy, M. Gonzalez, M. Hedlund, M. Seay, M. Zajonc, M. Morrison, N. Offor, M. Alley, M. Hoffman, M. Ross-Lee, M. Haan, M. Elliott, M. Lovely, M. Donkin, M. Cunningham, M. Bassnett, M. Hansen, M. Vaal, M. Langley, M. Reese, W. Ruf, M. Ford, M. Herman, M. Fullwood, M. Edris, M. Czirr, M. Patterson, L. Deacon, M. Saint, M. Lee, M. Murray, M. Kennedy, M. Stevenson, M. Thomsen, M. Daughaday, M. Farabee & M. Matters.
