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A better flu shot may be coming: How epitope targeting could widen protection

Doctors recommend getting your flu shot annually, since the specific influenza strain it targets varies from year to year. But what if the shot could be more effective while protecting against more strains? Researchers from the University of Missouri School of Medicine are one step closer to making this happen. When the immune system sees a new strain of a familiar virus, it typically focuses on the parts it “remembers” most, even if those regions have changed. “Epitope-spanning antigenic variation reprograms immunodominance and broadens immunity in sequential influenza vaccination” was recently published in Nature Communications.

“In our vaccine model, we targeted specific but distinct regions of the protein on the surface of the influenza virus. These regions are called epitopes,” said study author Henry Wan. “The model included different versions of epitopes in hopes of redirecting how the immune system responds. We found that the vaccine approach helped the immune system target more variants of the virus, leading to broader protection.”

Wan says the epitopes help the immune system see the flu virus differently, and it learns to respond with more coordination between the different types of immune cells. Some of the epitopes are also not as likely to change, which could make flu vaccines more reliable or even help create a universal flu vaccine.

Abstract: Implications for protecting against cognitive impairment following HeadInjury👇

Here, Michael T. Heneka & team find the inflammasome adaptor ASC drives long-lasting brain inflammation and cognitive problems after mild head injury in a closed-head injury model.

The figure shows skeletonized activated microglia (Iba1+ cells) following closed head injury, with mice lacking ASC show showing preservation of morphological features, particularly at later time points.


3Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg.

4German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

5Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, PR China.

How do cancer cells ‘learn’ to resist treatment?

Researchers at NYU Langone Health propose a model that could explain how cancer cells adapt to environmental stress, an approach that may lead to new therapies. Published online April 15 as the cover story of the journal Nature, the perspective article centers on a family of proteins called AP-1, which are quickly activated in cells in response to stressful situations—like being exposed to chemotherapy.

While AP-1 proteins have been studied for many decades, the authors propose they are part of a previously overlooked molecular mechanism in which cells survive by learning to rewire their circuitry. This process depends not on permanent changes to a cell’s DNA code, but rather on the cell’s ability to turn genes on or off, and then “remember” the changes that improve its survival chances.

The work suggests that cancer cells use this plasticity to explore gene expression patterns until they find a combination that helps them survive. Once a successful survival state is discovered, it can be locked in and passed down to future cell generations, leading to drug-resistant tumors.

Eosinophil extracellular traps: heterogeneity of their stimuli, components, and functions

Like neutrophil extracellular traps, eosinophil extracellular trap formation also involves two distinct processes: suicidal EETosis and vital eosinophil extracellular trap release.

Eosinophil extracellular trap contains chromatin and/or mitochondrial DNA, granular proteins, nuclear histone variants, cytosolic mediators, cytoskeletal proteins, organelle proteins, and cell membrane proteins.

There are at least four major classes of stimuli that contribute to eosinophil extracellular trap formation via NADPH induced reactive oxygen species generation and/or peptidylarginine deiminase4-dependent histone citrullination pathways.

Cell necrosis, autophagy, and apoptosis, disease status and severity, and eosinophil subtypes all affect eosinophil extracellular trap formation.

The diversities of DNA sources and granule protein types in eosinophil extracellular trap all determine eosinophil extracellular trap’s functional heterogeneity, depending on stimulation environments and disease status. sciencenewshighlights ScienceMission https://sciencemission.com/Eosinophil-extracellular-traps


Eosinophils participate in immune regulation through their granule proteins and cytokines. Recent studies demonstrate eosinophil functional versatility through the mechanism of eosinophil extracellular traps (EETs). EET formation occurs via suicidal eosinophil extracellular trap cell death (EETosis) and vital EET release. EETs contain chromatin-or mitochondrial-derived DNA, granule proteins, nuclear proteins, and cytosolic components that vary depending on the type and intensity of stimuli. Synthetic compounds, pathogenic microorganisms, endogenous molecules, and co-stimulatory factors stimulate EET formation via diverse signaling pathways through receptors that rely on or operate independently of NADPH oxidase-mediated reactive oxygen species production and peptidylarginine deiminase-4-dependent histone modification.

Fields as Formal Causes, with David Bentley Hart

In this conversation, Rupert Sheldrake and David Bentley Hart delve into the concept of fields in physics, discussing their nature as non-material formative causes and their historical context in scientific thought. They explore the idea that fields, such as gravitational and electromagnetic, act as top-down causes, aligning with Aristotle’s formal and final causes, and argue for a re-evaluation of these ancient concepts in modern science.

Chapter List:

00:00 — Introduction.
01:14 — Exploring Fields as Causes in Nature.
02:08 — Magnetic Fields and Formative Processes.
04:19 — Gravitational Fields and Formative Effects.
06:10 — Aristotle’s Formal and Final Causes.
07:32 — Challenges in Understanding Fields.
09:09 — Fields as Top-Down Causes.
10:34 — Morphic Fields and Formative Causation.
12:23 — Information Theory vs. Form.
14:15 — Fields and Order in Physics.
17:15 — Semantic and Syntactic Information.
18:18 — Universal Gravitational Field.
19:44 — Strong and Weak Nuclear Fields.
21:18 — History of Field Theory and Ether.
23:14 — Gilbert’s Magnetic Theory.
24:46 — Mind-like Structure in Nature.
25:39 — Combination of Top-Down and Bottom-Up Theories.
27:07 — Mechanistic Models and Their Limitations.
28:52 — Recovering Aristotelian Causality.
31:39 — Conclusion and Reflection on Fields as Modern Souls.


Dr Rupert Sheldrake, PhD, is a biologist and author best known for his hypothesis of morphic resonance. At Cambridge University, as a Fellow of Clare College, he was Director of Studies in biochemistry and cell biology. As the Rosenheim Research Fellow of the Royal Society, he carried out research on the development of plants and the ageing of cells, and together with Philip Rubery discovered the mechanism of polar auxin transport. In India, he was Principal Plant Physiologist at the International Crops Research Institute for the Semi-Arid Tropics, where he helped develop new cropping systems now widely used by farmers. He is the author of more than 100 papers in peer-reviewed journals and his research contributions have been widely recognized by the academic community, earning him a notable h-index for numerous citations. On ResearchGate his Research Interest Score puts him among the top 4% of scientists.

https://www.sheldrake.org

Roger Penrose — Is the Universe Fine-Tuned for Life and Mind?

If the deep laws of the universe had been ever so slightly different human beings wouldn’t, and couldn’t, exist. All explanations of this exquisite fine-tuning, obvious and not-so-obvious, have problems or complexities. Natural or supernatural, that is the question.

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For much of history, many mathematicians—

Following thinkers like Aristotle—viewed infinity as a never-ending process rather than a completed object. In the late 19th century, Georg Cantor revolutionized this view by treating infinite sets as mathematical objects that could be compared and studied. His work showed that not all infinities are equal, and that there are infinitely many different sizes of infinity. While his ideas are foundational in modern mathematics, some philosophical schools, such as finitism and ultrafinitism, continue to question whether infinite objects meaningfully exist.

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  • TIMESTAMPS:

    • 00:00 — Potential vs. Actual Infinity
    • 03:12 — Cardinality and Aleph-Null
    • 06:12 — Diagonalization and Uncountability
    • 09:21 — ZFC and Logical Independence
    • 12:23 — Finitism and Ultrafinitism
    • 15:26 — Continuum Hypothesis Paradoxes
    • 16:00 — Foundational Mathematical Crisis

    LINKS MENTIONED:

    In Search of Ultimate-L [paper]: https://www.jstor.org/stable/44164514

    • Emily Riehl [TOE]: • Emily Riehl Makes Infinity Categories Elem…
    • Sir Roger Penrose [TOE]: • Roger Penrose: Quantum Theory Is Wrong, No…
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    TIMESTAMPS:
    00:00 — Potential vs. Actual Infinity.
    03:12 — Cardinality and Aleph-Null.
    06:12 — Diagonalization and Uncountability.
    09:21 — ZFC and Logical Independence.
    12:23 — Finitism and Ultrafinitism.
    15:26 — Continuum Hypothesis Paradoxes.
    16:00 — Foundational Mathematical Crisis.

    LINKS MENTIONED:
    The Most Abused Theorem in Math [TOE]: • The Most Abused Theorem in Math (Gödel’s I…
    Dror Bar Natan [TOE]: • Dror Bar Natan: Knot Theory & Quantum Fiel…
    Hilbert’s Problems: https://mathworld.wolfram.com/Hilbert
    The Independence of the Continuum Hypothesis [paper]: https://www.pnas.org/doi/pdf/10.1073/.
    Peano arithmetic: https://ncatlab.org/nlab/show/Peano+a
    Cantor’s Diagonal Argument: https://www.researchgate.net/publicat
    Hartog’s Construction: paultaylor.eu/trans/HartogsF-wellord.pdf.
    Cohen’s Forcing Method: https://timothychow.net/forcing.pdf.
    Norman Wildberger [TOE]: • Norman Wildberger: The Problem with Infini…
    Woodin’s lecture: • The Continuum Hypothesis and the search fo…
    In Search of Ultimate-L [paper]: https://www.jstor.org/stable/44164514
    Emily Riehl [TOE]: • Emily Riehl Makes Infinity Categories Elem…
    Sir Roger Penrose [TOE]: • Roger Penrose: Quantum Theory Is Wrong, No…
    Why Write? [article]: https://curtjaimungal.substack.com/p/.

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