#Warburg Effect

[optimisticgalaxydreamland]

Cancer treatments | Traitements du cancer | Tratamientos contra el cáncer | Tratamentos oncológicos

[blueoaknx]

Mitochondrial Dysfunction in Endometriosis

 A Technical Overview of Cellular Mechanisms

Endometriosis, a common gynecological condition affecting approximately 10% of women during their reproductive years, is characterized by the presence of endometrial-like tissue outside the uterine cavity, most frequently in the ovaries, fallopian tubes, and peritoneal cavity. This ectopic tissue leads to a chronic inflammatory environment, pain, and infertility. While the pathophysiology of endometriosis is not fully understood, recent studies have increasingly highlighted mitochondrial dysfunction as a central feature of the disease. This technical article provides a detailed exploration of the role of mitochondria in endometriosis, examining the molecular and cellular mechanisms through which mitochondrial dysfunction contributes to disease progression.

Mitochondrial Function and Metabolism

Mitochondria are dynamic organelles responsible for numerous vital cellular processes, most notably ATP production through oxidative phosphorylation (OXPHOS). ATP is generated within the mitochondrial matrix by the electron transport chain (ETC), which involves the transfer of electrons from NADH and FADH2 to oxygen molecules, ultimately producing ATP. In addition to ATP production, mitochondria are involved in the regulation of calcium signaling, the maintenance of cellular redox balance, apoptosis, and the synthesis of key metabolites, including lipids and steroids. Mitochondria also contain their own genome (mitochondrial DNA or mtDNA), which encodes essential components of the ETC and mitochondrial protein synthesis machinery.

Mitochondria maintain their function through a balance of fusion and fission, processes that help ensure the organelle's shape, distribution, and response to stress. Mitochondrial dysfunction can arise from an imbalance in these processes, as well as from damage to mitochondrial DNA (mtDNA), excessive reactive oxygen species (ROS) production, and impaired bioenergetic functions. In the context of endometriosis, these disruptions have profound implications for cellular homeostasis and tissue function.

Mitochondrial Dysfunction in Endometriosis

In endometriosis, altered mitochondrial function contributes significantly to the disease's pathology. The following mechanisms are central to understanding how mitochondrial dysfunction drives the progression of endometriosis:

1. Altered Metabolic Shifts: The Warburg Effect

A hallmark of cancerous and proliferative cells is a shift in cellular metabolism, often referred to as the Warburg effect, in which cells preferentially utilize glycolysis over oxidative phosphorylation for ATP production, even in the presence of oxygen. This metabolic reprogramming is also observed in endometriotic cells, particularly in ectopic lesions, where cells exhibit increased glycolytic activity. In these lesions, endometrial cells rely less on mitochondrial OXPHOS and instead preferentially use glycolysis for ATP production, generating lactate as a byproduct.

This metabolic shift supports enhanced cell proliferation and survival under suboptimal conditions, characteristic of the hyperplastic nature of endometriosis. Glycolysis is less efficient in terms of ATP production compared to OXPHOS, yet it provides the necessary metabolic intermediates for cell division and biosynthesis. Additionally, the accumulation of lactate in the extracellular space lowers the local pH, which can exacerbate tissue inflammation and create a microenvironment conducive to the growth and persistence of ectopic lesions.

2. Mitochondrial DNA Damage and Instability

Mitochondria are highly susceptible to damage due to their proximity to ROS-producing processes in the electron transport chain. ROS, which are byproducts of cellular respiration, can damage mitochondrial lipids, proteins, and most notably, mitochondrial DNA (mtDNA). Unlike nuclear DNA, mtDNA is not protected by histones, making it particularly vulnerable to oxidative damage. In endometriosis, there is compelling evidence that mtDNA is significantly damaged in ectopic endometrial tissue. Studies have shown mtDNA deletions, mutations, and increased levels of mtDNA fragmentation in these tissues, which suggest a breakdown in the integrity of mitochondrial function.

The damaged mtDNA further exacerbates mitochondrial dysfunction, impairing the ability of mitochondria to generate ATP through OXPHOS. This, in turn, results in an increased reliance on anaerobic glycolysis, fueling the Warburg effect. Furthermore, mtDNA mutations can impair mitochondrial protein synthesis, leading to dysfunctional mitochondrial complexes and altered cellular bioenergetics, perpetuating a cycle of cellular dysfunction in endometriotic lesions.

3. Oxidative Stress and Inflammation

One of the critical roles of mitochondria is the regulation of cellular redox balance. Under normal conditions, mitochondria produce ROS as part of the electron transport chain. However, when mitochondrial function is compromised—whether due to damage, oxidative stress, or metabolic reprogramming—excess ROS are produced, leading to a state of oxidative stress. In endometriosis, ectopic endometrial tissue exhibits elevated levels of ROS, contributing to a persistent inflammatory environment.

Oxidative stress in endometriotic lesions is amplified by mitochondrial dysfunction and is further exacerbated by the Warburg effect, which generates additional ROS during glycolysis. ROS directly activate inflammatory pathways, particularly through the nuclear factor-kappa B (NF-κB) signaling pathway, leading to the production of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α. These cytokines perpetuate the inflammatory response, recruiting immune cells to the site of ectopic lesions, which leads to pain, fibrosis, and the development of adhesions.

Moreover, ROS play a critical role in sensitizing nociceptors, contributing to the chronic pain experienced by women with endometriosis. The interplay between oxidative stress and inflammation forms a vicious cycle that fuels the progression of endometriosis and promotes the growth and persistence of ectopic lesions.

4. Impaired Mitochondrial Dynamics: Fragmentation and Dysfunction

Mitochondria undergo constant fusion and fission, processes that regulate mitochondrial morphology, quality control, and function. Fusion allows for the mixing of mitochondrial contents, which can help dilute damaged components, while fission helps eliminate dysfunctional mitochondria through mitophagy. In endometriosis, there is evidence of disrupted mitochondrial dynamics, particularly an increase in mitochondrial fragmentation. Fragmented mitochondria are less efficient at ATP production and more prone to accumulating damaged proteins and lipids, which further impairs mitochondrial function.

The imbalance between mitochondrial fusion and fission in endometriosis is linked to altered expression of key proteins such as mitofusins (MFN1/2) and dynamin-related protein 1 (DRP1). DRP1-mediated mitochondrial fission is upregulated in endometriotic lesions, contributing to the generation of fragmented mitochondria. These fragmented organelles are associated with increased oxidative stress, apoptosis resistance, and enhanced cell proliferation—features that contribute to the pathogenesis of endometriosis.

5. Apoptosis Resistance and Cell Survival

Mitochondria play a pivotal role in regulating apoptosis through the release of pro-apoptotic factors, such as cytochrome c, from the mitochondrial intermembrane space. These factors initiate the caspase cascade, leading to cell death. However, in endometriosis, ectopic endometrial cells exhibit resistance to apoptosis, allowing them to survive and proliferate abnormally.

Mitochondrial dysfunction in endometriosis leads to alterations in key apoptotic proteins, including Bcl-2 family members, which regulate mitochondrial outer membrane permeabilization (MOMP). The overexpression of anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, and the downregulation of pro-apoptotic proteins, such as Bax and Bak, result in the persistence of damaged cells. This resistance to apoptosis allows for the survival of endometriotic lesions in hostile environments, contributing to the chronic nature of the disease and complicating treatment strategies.

Therapeutic Implications: Targeting Mitochondrial Dysfunction

Given the central role of mitochondrial dysfunction in endometriosis, therapeutic approaches targeting mitochondrial function hold promise for improving disease management. Several potential strategies include:

Antioxidant Therapies: Reducing oxidative stress through antioxidants such as N-acetylcysteine (NAC), Coenzyme Q10 (CoQ10), and vitamin E could help restore mitochondrial function and reduce inflammation in endometriotic tissues.

Modulation of Mitochondrial Dynamics: Targeting proteins involved in mitochondrial fusion and fission, such as DRP1 and MFN2, may help restore mitochondrial morphology and improve bioenergetic function in endometriotic lesions.

Inhibition of Glycolysis: Given the shift toward glycolysis in endometriotic cells, inhibiting key glycolytic enzymes, such as hexokinase or lactate dehydrogenase, may help reduce lesion growth and metabolic reprogramming.

Mitochondrial Biogenesis Stimulation: Activators of PGC-1α, a central regulator of mitochondrial biogenesis, could promote the generation of healthy mitochondria and improve overall cellular metabolism in endometriotic tissue.

Conclusion

Mitochondrial dysfunction is a key contributor to the pathogenesis of endometriosis. Alterations in mitochondrial metabolism, oxidative stress, mitochondrial DNA damage, and impaired apoptotic regulation are central to the disease's progression. Understanding the molecular mechanisms underlying mitochondrial dysfunction in endometriosis provides novel insights into potential therapeutic strategies. Targeting mitochondrial function and bioenergetics could lead to more effective treatments for endometriosis, alleviating its symptoms and improving outcomes for affected women.

[justforbooks]

Sir John Nott

Defence secretary in Margaret Thatcher’s cabinet during the Falklands war

The reputation of John Nott, who has died aged 92, will for ever be linked with the Falklands war of 1982. Nott was the defence secretary in Margaret Thatcher’s first administration and was extremely fortunate politically to survive one of Britain’s gravest postwar crises – yet it effectively ended his ministerial career.

Although the British taskforce retook the islands from Argentina after just 10 weeks’ occupation, Nott could not escape responsibility for his part in the government’s earlier decisions to reduce the islands’ protection, which had convinced the generals in Buenos Aires that they could launch their attack with impunity. Nor did he ever live down his ill-disguised pessimism about the taskforce’s chances of success. From being one of the Tories’ rising rightwing hopes and a prospective future chancellor, he left parliament for good a year after the war, with a knighthood; he was never awarded a peerage.

Nott was a somewhat forbidding figure with the air of a disapproving bank manager, a waspish tongue and a self-righteous and partisan manner – none of them attributes likely to inspire either the nation or its armed forces in time of national emergency. He had in fact calculated on an intermittent political career, sandwiching stints as an MP and minister between spells making money in business. Instead, his political career was over by the time he was 51 and he retired to the City, becoming chairman and chief executive of the merchant bank Lazard Brothers.

In that sense, his most memorable television appearance, a live interview with Robin Day in 1982 when he flounced out in an undignified huff on being referred to as a “here today, gone tomorrow” politician, was apposite. Indeed, 20 years later he entitled his autobiography Here Today, Gone Tomorrow (2002).

Born in Bromley. south-east London, John was the son of Phyllis (nee Francis) and Richard Nott, a rice broker from a West Country military family. On leaving Bradfield college, Berkshire, he served as a subaltern with the Gurkha Rifles during the Malayan emergency and was for a period the ADC to the commander-in-chief of British far east forces, before going to Trinity College, Cambridge, to study law and economics. He became president of the Cambridge Union and, on graduation, was called to the Bar, although he never practised as a lawyer. Instead he joined SG Warburg, the merchant bank, and remained there for eight years.

At Cambridge he met Miloska Sekol, a Slovenian refugee, who was studying English. The story went that Nott told her at their first meeting, in 1959, that he intended to marry her – a remarkable gesture from such an apparently staid and undashing figure, and an approach that appears to have taken her by surprise. She wrote in her diary that night: “What a cheek, how preposterous!” They married the same year.

Nott entered the Commons at the 1966 general election as MP for St Ives in Cornwall. He spent the rest of his life living in the county and promoting what he saw as its interests, calling for improved rail links west of Plymouth, and opposing incursions by French fishermen and the Anglo-French Concorde project. But it was as a bone-dry, rightwing economist, suspicious of the EU and pro-Commonwealth, that he made his mark: serving as an opposition economics spokesman and, after the Conservatives returned to power in 1970, becoming a junior Treasury minister, focusing on matters such as tax reform.

After Edward Heath’s 1974 defeat, however, he refused to become an opposition spokesman. He returned to the City as a consultant and to his Cornish estate, where he grew flowers commercially. Thatcher’s leadership was more to his liking and the rising Tory tide in favour of monetarism more ideologically congenial. “The party has almost found its soul again,” he told readers of the Daily Telegraph. He returned to the opposition frontbench, harrying the chancellor Denis Healey with a sharp wit.

Thatcher saw him as a kindred spirit, identified him as a rising star and, when the Tories returned to power in 1979, rewarded him by making him trade secretary. He naturally enthusiastically supported cuts in public spending, but also supported the expansion of London’s airports: a fourth terminal at Heathrow, a second runway at Gatwick and expansion at Stansted formed his most tangible legacy.

Then, in 1981, as the prime minister turned against the wets, Nott was moved to defence, to shake up the department and cut without squeamishness. He quickly decided that the priority was defence against the Soviet Union, not the promotion of worldwide, post-imperial pretensions, which was unfortunate in the light of what was to happen the following year in the South Atlantic. “Our first priority had to be credible deterrence from Soviet aggression on mainland Europe, decidedly not equipping ourselves for another Suez or post-colonial war,” he wrote later, and he proceeded to strengthen the army at the expense of the Royal Navy, targeting the service’s last aircraft carrier for closure.

Among the lesser cuts was a plan to scrap the gunboat Endurance, which guarded the Falklands. That, and the ruminations of his fellow rightwinger and Thatcherite rising star Nicholas Ridley that the islands were dispensable, sent a clear message to the junta. Had the Argentinian generals been a little more patient, Nott might single-handedly have made the taskforce that was subsequently launched impossible. As it was, he lost the navy minister to resignation and earned the lasting hostility of the first sea lord, Sir Henry Leach, who later wrote that he despised Nott’s performance.

Accordingly, when some Argentinian scrap metal merchants landed on South Georgia Island, sparking conflict, the government was taken by surprise. Nott later confessed that he had to look up where the Falkland Islands were on the globe in his office and he was immediately pessimistic of the chances of recovering them: it was Leach who seized the initiative to prove the navy’s worth and urged the prime minister, against her defence secretary’s advice and instincts, to mobilise an immediate taskforce to retake the islands. Nott’s insistence to MPs during that weekend’s emergency Commons debate that “no other country could have reacted so fast and the preparations have been in progress for several weeks. We were not unprepared” was therefore at best being economical with the truth.

When, 10 weeks later, the islands were retaken, albeit at considerable human cost, Nott received little of the credit and none of the glory within the party – that all went to Thatcher – or in the country, which was more inclined to credit the bravery and resilience of the troops than the triumphalism of politicians. His pretensions to succeed Howe as chancellor, or indeed any ambitions he might have harboured one day to follow Thatcher as prime minister, a possibility that had been occasionally mooted by some of the party’s zealouts, were at an end.

Before Thatcher’s post-Falklands general election landslide victory the following year, Nott chose to stand down as an MP. He could see the way the wind was blowing: the naval cuts were reversed. “The admirals have got their fucking gin palaces back,” he told friends. There was a certain degree of bitterness, too, even towards the prime minister herself. “The full cabinet was never more than a rubber stamp,” he said in a later BBC interview, accusing Thatcher of fostering a cult of personality: “Like all ambitious women, she thinks all men are feeble and that gentlemen are even more feeble.”

Back in the City, he accumulated directorships and money: chairman of Lazard, director of Royal Insurance, chairman of the food company Hillsdown Holdings, and of the clothing retailer Etam, and an adviser to the law firm Freshfields. He only occasionally intervened in politics: vociferously opposing the euro from an early stage and calling for early intervention in the 1990s Balkans crisis.

And he continued his battle with the pretensions of the navy: “Today’s defence policy has not been assisted by the Falklands experience,” he wrote in the Daily Telegraph in 2012. “It is still designed to prepare the Royal Navy for another Falklands … when technology, particularly air power, has moved into a new era … The Royal Navy’s future lies in a substantial number of well-armed modern frigates and destroyers, not two carriers, which are far too expensive to build, service and protect.”

He is survived by his wife and their children, Julian, William and Sasha.

🔔 John William Frederic Nott, politician, born 1 February 1932; died 6 November 2024

Daily inspiration. Discover more photos at Just for Books…?

[dailyanarchistposts]

Footnotes - Part 2

[80] Graham Kemp and Douglas P. Fry (eds.), Keeping the Peace: Conflict Resolution and Peaceful Societies around the World, New York: Routledge, 2004, p. 163.

[81] All quotes and statistics on the Navajo come from Dennis Sullivan and Larry Tifft, Restorative Justice: Healing the Foundations of Our Everyday Lives, Monsey, NY: Willow Tree Press, 2001, pp. 53–59.

[82] www.harmfreezone.org (viewed November 24, 2006)

[83] Philly’s Pissed, www.phillyspissed.net [Viewed May 20, 2008]

[84] George R. Edison, MD, “The Drug Laws: Are They Effective and Safe?” The Journal of the American Medial Association. Vol. 239 No.24, June 16, 1978. A.W. MacLeod, Recidivism: a Deficiency Disease, Philadelphia: University of Pennsylvania Press, 1965.

[85] Jamie Bissonette, When the Prisoners Ran Walpole: A True Story in the Movement for Prison Abolition, Cambridge: South End Press, 2008, p. 201. Also consider the stories of John Boone and other bureaucrats presented in this story.

[86] Some mainstream sources still contest that the Makhnovists were behind anti-Semitic pogroms in Ukraine. In Nestor Makhno, Anarchy’s Cossack, Alexandre Skirda traces this claim to its roots in anti-Makhno propaganda, while citing unfriendly contemporary sources who acknowledged that the Makhnovists were the only military units not carrying out pogroms. He also references propaganda put out by the Makhnovists attacking anti-Semitism as a tool of the aristocracy, Jewish militias that fought among the Makhnovists, and actions against pogromists personally carried out by Makhno.

[87] Paul Avrich, The Russian Anarchists, Oakland: AK Press, 2005, p. 218.

[88] Makhno hoped that Lenin and Trotsky were motivated by a personal vendetta against him rather than an absolute desire to crush the free soviets, and would call off the repression if he left.

[89] Alexandre Skirda, Nestor Makhno, Anarchy’s Cossack: The Struggle for Free Soviets in the Ukraine 1917–1921, London: AK Press, 2005, p. 314.

[90] Amy Goodman, “Lakota Indians Declare Sovereignty from US Government,” Democracy Now!, December 26, 2007.

[91] From an anonymous illustrated pamphlet, “The ‘Oka Crisis’ ”

[92] Oscar Olivera, Cochabamba! Water War in Bolivia, Cambridge: South End Press, 2004.

[93] George Katsiaficas, The Subversion of Politics: European Autonomous Social Movements and the Decolonization of Everyday Life. Oakland: AK Press, 2006, p. 123

[94] Jaime Semprun, Apología por la Insurrección Argelina, Bilbao: Muturreko Burutazioak, 2002, p.34 (translated from French to Spanish by Javier Rodriguez Hidalgo; the translation to English is my own). The quotes in the next paragraphs are from p.18 and p.20.

[95] Jaime Semprun, Apología por la Insurrección Argelina, Bilbao: Muturreko Burutazioak, 2002, pp.73–74 (translated from French to Spanish by Javier Rodriguez Hidalgo; the translation to English is my own).

[96] Ditto, p.80 . Regarding the fourth point, in contrast to Western society and its various forms of pacifism, the peacefulness of the movement in Algeria does not preclude self-defense or even armed uprising, as evidenced by the preceding point regarding the martyrs. Rather, peacefulness indicates a preference for peaceful and consensual outcomes over coercion and arbitrary authority.

[97] Ditto, p.26.

[98] George Orwell, Homage to Catalonia, London: Martin Secker & Warburg Ltd., 1938, pp.26–28.

[99] There were 40,000 armed anarchist militants in Barcelona and the surrounding region alone. The Catalan government would have been effectively abolished had the CNT simply ignored it, rather than entering into negotiations. Stuart Christie, We, the Anarchists! A study of the Iberian Anarchist Federation (FAI) 1927–1937, Hastings, UK: The Meltzer Press, 2000, p. 106.

[100] Ditto, p. 101

[101] John Jordan and Jennifer Whitney, Que Se Vayan Todos: Argentina’s Popular Rebellion, Montreal: Kersplebedeb, 2003, p. 56.

[102] Natasha Gordon and Paul Chatterton, Taking Back Control: A Journey through Argentina’s Popular Uprising, Leeds (UK): University of Leeds, 2004.

[103] John Jordan and Jennifer Whitney, Que Se Vayan Todos: Argentina’s Popular Rebellion, Montreal: Kersplebedeb, 2003, p. 9.

[104] George Katsiaficas, “Comparing the Paris Commune and the Kwangju Uprising,” www.eroseffect.com. That the resistance was “well-organized” comes from a report from the conservative Heritage Foundation, Daryl M. Plunk’s “South Korea’s Kwangju Incident Revisited,” The Heritage Foundation, No. 35, September 16, 1985.

[105] Goods produced in environmentally friendly ways, by workers who receive a living wage in healthier labor conditions.

[106] Sam Dolgoff, The Anarchist Collectives, New York: Free Life Editions, 1974, p. 71.

[107] David Graeber, Fragments of an Anarchist Anthropology, Chicago: Prickly Paradigm Press, 2004, pp. 54–55.

[108] John Jordan and Jennifer Whitney, Que Se Vayan Todos: Argentina’s Popular Rebellion, Montreal: Kersplebedeb, 2003, pp. 42–52.

[109] Ditto, pp. 43–44.

[110] Diana Denham and C.A.S.A. Collective (eds.), Teaching Rebellion: Stories from the Grassroots Mobilization in Oaxaca, Oakland: PM Press, 2008, interview with Yescka.

[111] Ditto, interview with Leyla.

[112] “Longo Maï,” Buiten de Orde, Summer 2008, p.38. My own translation.

[113] Natasha Gordon and Paul Chatterton, Taking Back Control: A Journey through Argentina’s Popular Uprising, Leeds (UK): University of Leeds, 2004.

[114] For those who cannot read French or Spanish, in 2004 Firestarter Press put out a good zine about this insurrection, called “You Cannot Kill Us, We Are Already Dead.” Algeria’s Ongoing Popular Uprising.

[115] Paul Avrich, The Russian Anarchists, Oakland: AK Press, p. 212–213.

[116] Harold Barclay, People Without Government: An Anthropology of Anarchy, London: Kahn and Averill, 1982, p. 57.

[117] “Pirate Utopias,” Do or Die, No. 8, 1999, pp. 63–78.

[118] To name just one example, “humanitarian” UN missions have been caught repeatedly setting up sex trafficking rings in the countries where they are stationed for peacekeeping. “But the problem goes beyond Kosovo and sex trafficking. Wherever the UN has established operations in recent years, various violations of women seem to follow.” Michael J. Jordan, “Sex Charges haunt UN forces,” Christian Science Monitor, 26 November 2004. What the mainstream press cannot go so far as to admit is that this reality is universal to militaries, whether they wear blue helmets or not.

[119] “About RAWA,” www.rawa.org Viewed June 22, 2007

[120] See the citation of van der Dennen and Rappaport in Chapter 1.

[121] Harold Barclay, People Without Government: An Anthropology of Anarchy, London: Kahn and Averill, 1982, p. 122.

[122] Haudennosaunne oral traditions always maintained this early date, but racist white anthropologists discounted this claim and estimated the league began in the 1500s. Some even hypothesized that the Five Nations constitution was written with European help. But recent archaeological evidence and the record of a coinciding solar eclipse backed up the oral histories, proving that the federation was their own invention. Wikipedia, “The Iroquois League,” http: //en.wikipedia.org/wiki/Iroquois_League Viewed 22 June 2007

[123] Stephen Arthur, “Where License Reigns With All Impunity:” An Anarchist Study of the Rotinonshón:ni Polity,” Northeastern Anarchist No. 12, Winter 2007 nefac.net

[124] See, for example, Dmitri M. Bondarenko and Andrey V. Korotayev, Civilizational Models of Politogenesis, Moscow: Russian Academy of Sciences, 2000.

[125] The argument that certain societies were able to take over the world because of geographic conditions rather than any inherent superiority is skillfully presented by Jared Diamond in Guns, Germs, and Steel: The Fates of Human Societies. New York: W.W. Norton, 1997.

[domitiaa]

Was Simonetta Vespucci really Botticelli's muse?

I know my answer will shock millions of people, but I absolutely have to disagree.

Unfortunately we have no source that certifies that Simonetta Vespucci was portrayed by Sandro Botticelli. In the fifteenth century each artist had his own repertoire of female and male figures, for this reason Botticelli's women are ALL THE SAME and this tells us that they are absolutely not portraits.

The fact is that it is a rather old idea, largely outdated in critical literature for over a century, but with an origin, it is painful to say, noble. This is the doctoral thesis of one of the greatest art historians: Aby Warburg. Warburg was a true pioneer, almost single-handedly creating an entire new field of study. We owe to him, among other things, the first serious consideration of Neoplatonism for the understanding of the Florentine Renaissance: without Warburg no Panofsky, Gombrich etc. Now, dealing with the topic he obviously studied the literature of the time regarding Simonetta, presented as an ideal of perfect Beauty and embodiment of a Platonic ideal. And this is absolutely true. What he added, and we cannot blame him in an era of pioneering studies (we are in 1892!), was that that ideal Beauty could be found in the works of Botticelli and that therefore Primavera and Venus had to depict Simonetta. Warburg had no source to support it, but it seemed to complement his vision so well that he supported it anyway. Even then it was immediately criticized, because it was not methodologically sustainable, and it was precisely its best followers who excluded it in the studies of the following decades. Among art historians the idea has effectively been abandoned, at least due to lack of evidence, for decades and decades. But it survives by repetition in texts of another nature and above all in popular imagination (with the addition of other completely invented details, such as Botticelli in love wanting to be buried at Simonetta's feet etc.)

To conclude, the historicity of Simonetta's character is undoubted. Although sources about her are scarce, we know that she was celebrated by poets such as Angelo Poliziano and the Medici brothers themselves. But her true face remains a mystery!

[artofthemindblog]

Karin Valis on Magic and Artificial Intelligence – The Secret History of Western Esotericism Podcast (SHWEP)

A House with Many Rooms Interview 2

We are delighted to speak with Karin Valis, machine-learning engineer and esoteric explorer, on the vast subject of how the fields of artificial intelligence and magic overlap, intertwine, and inform each other. We discuss:

The uncanny oracular effects and synchronistic weirdnesses exhibited by large language models,

Conversations with ChatGPT considered as invocation,

AI as the fulfilment of the dream of the homonculus (with the attendant ethical problems which arise),

AI as the fulfilment of esoteric alphanumeric cosmologies (and maybe, like the Sepher Yetsirah, this isn’t so esoteric after all; maybe it’s just science),

And much more.

Interview Bio:

Karin Valis is a Berlin-based machine learning engineer and writer with a deep passion for everything occult and weird. Her work focuses mainly on combining technology with the esoteric, with projects such as Tarot of the Latent Spaces (visual extraction of the Major Arcana Archetypes) and Cellulare (a tool for exploring digital non-ordinary reality for the Foundation for Shamanic Studies Europe). She co-hosted workshops, talks and panel discussions such as Arana in the Feed (Uroboros 2021), Language in the Age of AI: Deciphering Voynich Manuscript (Trans-States 2022) and Remembering Our Future: Shamanism, Oracles and AI (NYU Shanghai 2022). She writes Mercurial Minutes and hosts monthly meetings of the occult and technology enthusiasts Gnostic Technology.

Works Cited in this Episode (roughly in the order cited):

The homonculus passage in the Pseudo-Clementines: Homilies 3.26; cf. Recognitions 2.9, 10, 13–15; 3.47.

On the Book of the Cow/Liber vaccæ: see e.g. Liana Saif. The Cows and the Bees: Arabic Sources and Parallels for Pseudo- Plato’s Liber Vaccæ (Kitab al-Nawams). Journal of the Warburg and Courtauld Institutes, LXXIX:147, 2016.

‘The Measure of a Man’, Star Trek: The Next Generation Season 2, Episode 9, first aired 13 February, 1989.

Doctor Strange, dir. Scott Derrickson, 2016 Marvel Studios.

Recommended Reading:

Karin has a substack where she posts interesting things. Her recent essay Divine Embeddings is particularly relevant to the discussion of alphanumericism in the interview.

[readingforever300]

This is the second book about cancer I’m reading. I haven’t started but I plan to read it soon.

Cancer is a huge world problem currently and I feel it is my duty to lend much of my mind and heart to the collective struggle against cancer. I’m hoping I can contribute to the intellectual progress towards eliminating cancer.

Tenets of Cancer Theory

• All cancer cells are derived from normal cells.

• humoral theory, lymph theory, then in 1838, blastema (cell) theory of cancer.

• cancer cells are more sensitive to damage by X-rays than normal tissue.

• cancer cells retain some features of the cell type the belong to. Breast cancer cells have estrogen progesterones receptors e.g.

•The eight hallmarks of cancer condensed into four: growth, replicative immortality, movement with immune evasion, and the warburg effect of goycolysis preference.

• Cancer cells prefer glycolysis over OxPhos. Need more glucose for same ATP prdctn.

[darkmaga-returns]

2nd Smartest Guy in the World

Oct 16, 2024

Peer reviewed Medical Evidence Unveiled

In a bold challenge to mainstream medicine, a new era in treating cancer and chronic disease has finally been discovered and disclosed…

BREAKING NEWS: First-in-the-World Ivermectin, Mebendazole and Fenbendazole Protocol in Cancer has been peer-reviewed and published Sep.19, 2024! The future of Cancer Treatment starts now.

2nd Smartest Guy in the World

·

Oct 13

For years now this Substack has been saving lives by promoting its cancer cure based on the original Joe Tippens protocol, and now brave doctors and researchers have finally caught up by publishing this very same treatment approach in a mainstream medical journal.

Read full story

Targeting the Mitochondrial-Stem Cell Connection in Cancer Treatment: A Hybrid Orthomolecular Protocol published in the Journal of Orthomolecular Medicine, is more than merely a research paper, it is a declaration of war against the profit-driven Iatrogenic Medical-Pharmaceutical Industrial Complex.

Gaining rapid traction across independent platforms like Substack and X (formerly Twitter), this paper heralds the dawn of a new era in oncology. This seminal work resurrects the Warburg Effect, emphasizing how cancer cells depend on glycolysis even when oxygen is present, and it positions metabolic therapies at the forefront of the fight against cancer.

As tens of thousands of success stories emerge on these platforms, the narrative of suppressed but effective treatments is becoming impossible to ignore; the time has come for a reckoning with regards to how the pharmaceutical industry has shaped public health: not for patient well-being, but for profit and depopulation.

[sisiad]

CMTM6 mediates the Warburg effect and promotes the liver metastasis of colorectal cancer

http://dlvr.it/TChhsP

[dominicspooner]

The Top 10 Private Equity Firms You Should Consider Partnering With

Private equity (PE) firms play a significant role in driving growth, innovation, and strategic transformation across various industries. Partnering with the right PE firm can provide businesses with access to capital, operational expertise, and industry networks necessary to achieve their growth objectives. This article highlights ten top PE firms renowned for their investment prowess, sector specialization, and track record of successful partnerships.

The Carlyle Group

Founded in 1987, The Carlyle Group is one of the largest and most diversified global investment firms. With extensive industry expertise across sectors such as aerospace, defense, healthcare, and technology, Carlyle focuses on growth capital, leveraged buyouts, and strategic investments. The firm's robust network and operational capabilities make it a preferred partner for businesses seeking to scale operations and expand their market presence.

KKR (Kohlberg Kravis Roberts)

KKR, established in 1976, is a leading global investment firm known for its transformative approach to private equity and alternative investments. KKR's portfolio spans diverse industries, including energy, infrastructure, real estate, and technology. The firm leverages its deep industry knowledge, operational expertise, and global network to drive value creation and sustainable growth for portfolio companies.

Blackstone Group

Founded in 1985, Blackstone Group is a premier global investment firm specializing in private equity, real estate, credit, and hedge fund solutions. Blackstone's private equity division focuses on large-scale investments across sectors such as healthcare, financial services, consumer goods, and industrial manufacturing. The firm's strategic guidance and financial resources enable businesses to capitalize on growth opportunities and navigate complex market dynamics effectively.

TPG Capital

TPG Capital, established in 1992, is a leading global investment firm renowned for its expertise in private equity, growth equity, and credit investments. TPG's portfolio encompasses a wide range of industries, including healthcare, technology, media, and telecommunications. The firm's proactive approach to value creation, operational excellence, and sustainable growth makes it a preferred partner for businesses seeking strategic transformation and market leadership.

Bain Capital

Bain Capital, founded in 1984, is a prominent private equity firm with a strong focus on growth-oriented investments and operational improvement strategies. Bain's investment philosophy emphasizes partnership with management teams to drive long-term value creation and competitive advantage. The firm's sector expertise spans industries such as healthcare, consumer products, retail, and technology, positioning it as a trusted advisor and strategic partner for businesses worldwide.

Warburg Pincus

Warburg Pincus, established in 1966, is a leading global private equity firm known for its long-term investment approach and sector-focused strategies. Warburg Pincus invests across growth sectors such as healthcare, financial services, energy, and technology. The firm's deep industry knowledge, operational expertise, and global network enable portfolio companies to accelerate growth, enhance operational efficiency, and capitalize on market opportunities.

Apollo Global Management

Apollo Global Management, founded in 1990, is a diversified alternative investment firm specializing in private equity, credit, and real estate investments. Apollo's private equity arm focuses on investments in sectors such as chemicals, manufacturing, retail, and leisure. The firm's integrated platform, extensive resources, and strategic insights empower businesses to achieve operational excellence, execute transformative growth initiatives, and drive long-term value creation.

CVC Capital Partners

CVC Capital Partners, established in 1981, is a leading global investment firm specializing in private equity and credit investments across Europe, Asia, and the Americas. CVC's investment strategy emphasizes growth-oriented opportunities in sectors such as healthcare, technology, consumer goods, and financial services. The firm's collaborative approach, sector-specific expertise, and track record of successful investments make it a preferred partner for businesses seeking to achieve sustainable growth and market leadership.

Advent International

Advent International, founded in 1984, is a global private equity firm focused on investing in growth-oriented businesses across a wide range of industries. Advent's sector expertise includes healthcare, industrial, retail, and technology. The firm's partnership approach, operational support, and strategic guidance enable portfolio companies to accelerate growth, expand market reach, and enhance profitability in competitive global markets.

General Atlantic

General Atlantic, established in 1980, is a leading global growth equity firm providing capital and strategic support for growth-oriented businesses in sectors such as technology, healthcare, consumer, and financial services. General Atlantic's partnership approach emphasizes long-term value creation, innovation, and operational excellence. The firm's global network, sector-specific knowledge, and flexible investment approach make it a preferred partner for entrepreneurs and management teams seeking to scale their businesses and achieve sustainable growth.

Partnering with a top private equity firm can provide businesses with access to capital, strategic guidance, and operational expertise necessary to accelerate growth, enhance competitiveness, and achieve long-term success. Each of the firms highlighted in this article brings unique strengths, sector specialization, and a proven track record of driving value creation for portfolio companies. By carefully assessing their investment criteria, sector focus, and partnership approach, businesses can identify the right PE partner to support their growth objectives and navigate the complexities of today's global business landscape with confidence.

[optimisticgalaxydreamland]

The Warburg effect explained | L'effect Warburg expliqué | El effect Warburg explicado | O efeito Warburg explicado

[blueoaknx]

Mitochondria Combat Chronic Inflammation

Introduction

Chronic inflammation is a pathophysiological condition linked to numerous diseases, including obesity, diabetes, cardiovascular diseases, and neurodegenerative disorders. Mitochondria, the cellular powerhouses, are pivotal not only for ATP production but also for regulating cellular metabolism, redox balance, and apoptosis. Recent studies reveal that mitochondria play a crucial role in modulating inflammatory responses, and their dysfunction is often implicated in chronic inflammatory states. This article explores the intricate mechanisms by which mitochondria influence chronic inflammation and their potential as therapeutic targets.

Mitochondrial Structure and Function

Mitochondria possess a double-membrane structure that includes:

Outer Membrane: Contains porins that allow the passage of small molecules.

Inner Membrane: Rich in cardiolipin and contains the electron transport chain (ETC) complexes crucial for oxidative phosphorylation.

Matrix: Contains enzymes for the tricarboxylic acid (TCA) cycle, mitochondrial DNA (mtDNA), and ribosomes.

These structural features enable mitochondria to perform several essential functions, including ATP synthesis, calcium buffering, and reactive oxygen species (ROS) regulation.

Mitochondrial Dysfunction and Chronic Inflammation

Mitochondrial dysfunction is characterized by reduced ATP production, increased ROS generation, and impaired metabolic signaling. Key contributors to mitochondrial dysfunction include:

Oxidative Stress: Excessive ROS can damage mitochondrial components, leading to a vicious cycle of increased inflammation.

Aging: Aging is associated with mitochondrial dysfunction, contributing to the onset of chronic inflammatory diseases.

Environmental Toxins: Exposure to pollutants and toxins can induce mitochondrial damage.

Mitochondrial dysfunction is implicated in the activation of pro-inflammatory pathways, including:

NLRP3 Inflammasome Activation: Mitochondrial ROS and mtDNA release can activate the NLRP3 inflammasome, leading to the maturation and secretion of pro-inflammatory cytokines such as IL-1β and IL-18.

NF-κB Pathway: Mitochondrial stress can activate the NF-κB signaling pathway, promoting the expression of pro-inflammatory genes.

Mechanisms by Which Mitochondria Combat Chronic Inflammation

Energy Homeostasis and Immune Cell Function

Mitochondria are essential for the bioenergetic demands of immune cells, particularly during inflammatory responses. Immune cells like macrophages and T-cells switch from oxidative phosphorylation to glycolysis during activation, a process known as the Warburg effect. Mitochondria facilitate this metabolic flexibility by:

Providing substrates for glycolysis and subsequent oxidative phosphorylation.

Regulating ATP levels to support energy-intensive processes, such as cytokine production and phagocytosis.

Regulation of ROS and Redox Signaling

Mitochondria generate ROS as byproducts of the ETC. While excessive ROS can induce oxidative stress, physiological levels of ROS act as signaling molecules that modulate immune responses:

ROS can activate redox-sensitive transcription factors such as Nrf2, promoting the expression of antioxidant genes that mitigate oxidative stress.

Controlled ROS production aids in the differentiation of T-helper cells and enhances the immune response.

Apoptosis and Clearance of Damaged Cells

Mitochondria are central to the intrinsic apoptotic pathway, releasing cytochrome c and other pro-apoptotic factors that initiate caspase cascades. Effective apoptosis is crucial for:

Removing damaged or dysfunctional cells that could perpetuate inflammation.

Promoting an anti-inflammatory environment through the clearance of dead cells and debris, thereby preventing secondary necrosis and the associated inflammatory response.

Mitophagy: Mitochondrial Quality Control

Mitophagy is the selective autophagic degradation of damaged mitochondria, crucial for maintaining mitochondrial quality. Key mechanisms involved in mitophagy include:

PINK1/Parkin Pathway: PINK1 accumulates on damaged mitochondria, recruiting Parkin, which ubiquitinates mitochondrial proteins, signaling for degradation by the autophagy machinery.

Enhanced mitophagy reduces the release of pro-inflammatory factors and maintains cellular homeostasis.

Mitochondrial Biogenesis and Adaptation

Mitochondrial biogenesis is regulated by PGC-1α and other transcription factors. Increasing mitochondrial biogenesis can enhance cellular energy capacity and improve metabolic flexibility, which is particularly beneficial in inflammation. Strategies to promote mitochondrial biogenesis include:

Exercise: Physical activity enhances PGC-1α expression and mitochondrial function.

Nutritional Interventions: Certain bioactive compounds, like resveratrol and curcumin, have been shown to stimulate mitochondrial biogenesis.

Therapeutic Implications

Given their critical role in modulating inflammation, mitochondria represent promising therapeutic targets. Potential strategies include:

Nutraceuticals: Compounds like Coenzyme Q10 and α-lipoic acid may enhance mitochondrial function and reduce oxidative stress.

Exercise Interventions: Regular physical activity can improve mitochondrial health and reduce chronic inflammation.

Mitochondrial-targeted Therapies: Developing drugs that specifically target mitochondrial pathways could provide new treatment avenues for inflammatory diseases.

Conclusion

Mitochondria are integral to the regulation of chronic inflammation through their roles in energy metabolism, ROS management, apoptosis, mitophagy, and biogenesis. Understanding the complex interplay between mitochondrial function and inflammatory processes is essential for developing effective therapeutic strategies. By targeting mitochondrial health, we can potentially mitigate chronic inflammation and its associated diseases, paving the way for innovative approaches to improve public health outcomes. Continued research into mitochondrial biology will undoubtedly reveal further insights into their role in inflammation and disease.

[ribosome-papers]

Human tau promotes Warburg effect-like glycolytic metabolism under acute hyperglycemia conditions through modulating the homeostasis of protein-membrane association

bioRxiv: http://dlvr.it/T8Z6k3

[ouruncriticalmess]

Otto K. Werckmeister | Zitadellenkultur. Die schöne Kunst des Untergangs in der Kultur der achtziger Jahre | 1989

Cover Artist: Enki Bilal ("Le mur" | 1982)

Otto Karl Werckmeister, born in Berlin in 1934, began teaching at the University of Califormnia in 1965 after several years of research at the Warburg Institute in London and the German Archaeological Institute in Madrid. From 1984 he was professor of art history at Northwestern University in Evanston. From 2001 Werckmeister lived again in Berlin. He died on June 9, 2023, at the age of 89.

In Zitadellenkultur Werckmeister thematizes the citadel as a metaphor for a contemporary culture that turns to crises out of prosperity, but no longer intends their political rectification, but on the contrary has a stabilizing and normalizing effect. In Left Icons the author analyzes five works of art of the 20th century in their shift in meaning from the revolutionary to the transfiguration and functionalization.

Translated with www.DeepL.com/Translator (free version)