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morganism

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morganisms
« on: May 29, 2021, 11:00:41 PM »
Prenatal exposure to paracetamol associated with ADHD and autism symptoms in childhood

"In total, the researchers analysed 73,881 children for whom data were available on prenatal or postnatal exposure to paracetamol, at least one symptom of ASC or ADHD, and main covariates. Depending on the cohort, 14% to 56% of the mothers reported taking paracetamol while pregnant.

The study found that children exposed to paracetamol before birth were 19% more likely to develop ASC symptoms and 21% more likely to develop ADHD symptoms than children who were not exposed.

"Our findings are consistent with previous research," explained ISGlobal researcher Sílvia Alemany, lead author of the study. "We also found that prenatal exposure to paracetamol affects boys and girls in a similar way, as we observed practically no differences."

https://www.eurekalert.org/pub_releases/2021-05/bifg-pet052521.php

"The sample is large," she added, "and it includes cohorts from multiple European countries: the United Kingdom, Denmark, the Netherlands, Italy, Greece and Spain. We also used the same criteria for all of the cohorts, thereby reducing the heterogeneity of criteria that has hampered previous studies."

morganism

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morganisms
« Reply #1 on: September 27, 2021, 09:07:17 PM »

"Conclusions: In a large and diverse international sample of older adults, the current study found that abstinence from alcohol is associated with an increased risk for all-cause dementia. Among current drinkers, there was no consistent evidence to suggest that the amount of alcohol consumed in later life was significantly associated with dementia risk. "

The relationship between alcohol use and dementia:

https://psyarxiv.com/7835k/

word doc availible on-site
« Last Edit: October 04, 2021, 04:32:16 PM by be cause »

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Paracetamol use during pregnancy — a call for precautionary action

https://www.nature.com/articles/s41574-021-00553-7

"In this Consensus Statement, we summarize the epidemiological research and animal studies that have examined neurological, urogenital and reproductive outcomes that have been associated with maternal and perinatal use of APAP (Figs 1,2). Based on this research, we believe we know enough to be concerned about the potential developmental risks associated with prenatal APAP exposure and therefore call for precautionary action

APAP is an endocrine disruptor

Chemicals that disrupt the endocrine system are concerning because they can interfere with the activity of endogenous hormones that are essential for healthy neurological, urogenital and reproductive development2,47,48. APAP is known to readily cross the placenta and blood–brain barrier49,50. During pregnancy, changes occur in APAP metabolism, which might make pregnant women and their fetus more vulnerable to toxic effects. For instance, the molar dose fraction of APAP that is converted to the oxidative metabolite N-acetyl-p-benzoquinone imine might be increased during pregnancy51,52.

The analgesic and antipyretic properties of APAP are still not fully understood. However, several lines of evidence suggest that APAP acts both in the periphery and centrally through several mechanisms. For example, one of the ways APAP is believed to relieve pain is through inhibition of prostaglandin signalling53. Furthermore, APAP inhibits serotonergic mechanisms in clinical studies54. APAP also acts as a prodrug for analgesic metabolites55; in experimental studies, these metabolites activate serotonergic, opioidergic, vanilloid and cannabinoid receptors, as well as transient receptor potential channels53,56. Prostaglandins are lipid compounds with physiologically important roles in the development of the gonads in both sexes and the development of the brain57,58,59; therefore, some of the disrupting effects of APAP are probably mediated through this pathway. Moreover, increasing clinical evidence suggests that the action of APAP in inhibiting prostaglandin signalling in the third trimester can lead to ductus arteriosus constriction, a condition that might result in fetal loss or life-threatening cardiac failure in the newborn60.

In vivo, in vitro and ex vivo studies have shown that APAP directly perturbs hormone-dependent processes, including inhibition of androgen production and increased oestrogen production, disruption of steroidogenesis, depletion of sulfated sex hormones, perturbation of immune function, induction of oxidative stress and indirect activation of the endocannabinoid system1,2,61,62,63,64,65. Independently of APAP, these processes have been implicated as mechanisms related to the development of neurodevelopmental66,67,68,69,70,71,72,73,74,75,76 and reproductive disorders2. In addition to potential effects on neuronal and reproductive development, a combination of clinical studies together with experimental work in animal models and cell lines has also suggested that APAP exposure during pregnancy might decrease fetal haematopoietic stem cell numbers alter steroidogenesis in the placenta and induce placental damage"


Acetaminophen use during pregnancy and offspring attention deficit hyperactivity disorder – a longitudinal sibling control study

https://acamh.onlinelibrary.wiley.com/doi/10.1002/jcv2.12020

"Both the exposed and the unexposed children of mothers with long-term use of acetaminophen in one of the pregnancies had increased risk of receiving an ADHD diagnosis. This indicates that the observed association between long-term acetaminophen use during pregnancy and ADHD in the child may at least partly be confounded by unobserved family factors."

"All children (both exposed and unexposed) born to a mother with long-term use of acetaminophen in one pregnancy, had increased risk of receiving an ADHD diagnosis compared to children of mothers who did not use acetaminophen in any pregnancy (aHR = 2.77, 95% bootstrap C.I. = 1.48–5.05) (rightmost column in Table 2). The two leftmost columns in Figure 3 show the unadjusted and adjusted dose-response associations between number of days of acetaminophen exposure and risk of ADHD. The third column shows that the association between long-term exposure and ADHD was no longer present in the sibling control model. The rightmost column shows the family effect in the sibling control model."

"Children prenatally exposed to acetaminophen for 28 days or less, did not have increased risk of receiving an ADHD diagnosis, compared to unexposed children. Long-term exposure (29 days or more) was associated with a two-fold increase in risk. A substantial family effect in the sibling control model suggested that unmeasured familial confounding factors may explain at least part of the observed association between maternal long-term acetaminophen use and ADHD in the child.

morganism

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« Reply #3 on: October 12, 2021, 12:32:15 AM »
Urban mining by flash Joule heating

https://www.nature.com/articles/s41467-021-26038-9

The sample temperature ramps to ~3400 K in milliseconds by the ultrafast electrical thermal process. Such a high temperature enables the evaporative separation of precious metals from the supporting matrices, with the recovery yields >80% for Rh, Pd, Ag, and >60% for Au. The heavy metals in electronic waste, some of which are highly toxic including Cr, As, Cd, Hg, and Pb, are also removed, leaving a final waste with minimal metal content, acceptable even for agriculture soil levels. Urban mining by flash Joule heating would be 80× to 500× less energy consumptive than using traditional smelting furnaces for metal-component recovery and more environmentally friendly."

https://www.spacedaily.com/reports/Urban_mining_for_metals_flashes_forward_999.html

"    
TECH SPACE
Urban mining for metals flashes forward
by Staff Writers
Houston TX (SPX) Oct 05, 2021

The flash Joule heating process developed at Rice University has been adapted to recover valuable and toxic metals from electronic waste. The process allows for "urban mining" of resources that could be a win for the environment as well as for manufacturers. Video: Flash Joule heating by Rice lab recovers precious metals from electronic waste in seconds

In what should be a win-win-win for the environment, a process developed at Rice University to extract valuable metals from electronic waste would also use up to 500 times less energy than current lab methods and produce a byproduct clean enough for agricultural land.

The flash Joule heating method introduced last year to produce graphene from carbon sources like waste food and plastic has been adapted to recover rhodium, palladium, gold and silver for reuse.

A report in Nature Communications by the Rice lab of chemist James Tour also shows highly toxic heavy metals including chromium, arsenic, cadmium, mercury and lead are removed from the flashed materials, leaving a byproduct with minimal metal content.

Instantly heating the waste to 3,400 Kelvin (5,660 degrees Fahrenheit) with a jolt of electricity vaporizes the precious metals, and the gases are vented away for separation, storage or disposal. Tour said that with more than 40 million tons of e-waste produced globally every year, there is plenty of potential for "urban mining."

"Here, the largest growing source of waste becomes a treasure," Tour said. "This will curtail the need to go all over the world to mine from ores in remote and dangerous places, stripping the Earth's surface and using gobs of water resources. The treasure is in our dumpsters."

He noted an increasingly rapid turnover of personal devices like cell phones has driven the worldwide rise of electronic waste, with only about 20% of landfill waste currently being recycled.

"We found a way to get the precious metals back and turn e-waste into a sustainable resource," he said. "The toxic metals can be removed to spare the environment."

The lab found flashing e-waste requires some preparation. Guided by lead author and Rice postdoctoral research associate Bing Deng, the researchers powdered circuit boards they used to test the process and added halides, like Teflon or table salt, and a dash of carbon black to improve the recovery yield.

Once flashed, the process relies on "evaporative separation" of the metal vapors. The vapors are transported from the flash chamber under vacuum to another vessel, a cold trap, where they condense into their constituent metals. "The reclaimed metal mixtures in the trap can be further purified to individual metals by well-established refining methods," Deng said.

The researchers reported that one flash Joule reaction reduced the concentration of lead in the remaining char to below 0.05 parts per million, the level deemed safe for agricultural soils. Levels of arsenic, mercury and chromium were all further reduced by increasing the number of flashes.

"Since each flash takes less than a second, this is easy to do," Tour said.

The scalable Rice process consumes about 939 kilowatt-hours per ton of material processed, 80 times less energy than commercial smelting furnaces and 500 times less than laboratory tube furnaces, according to the researchers. It also eliminates the lengthy purification required by smelting and leaching processes."

morganism

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« Reply #4 on: October 18, 2021, 07:46:44 PM »
Severe pain control without opiods using brain wire implants

3D microelectrode cluster and stimulation paradigm yield powerful analgesia without noticeable adverse effects

" Stimulation of brainstem pain control systems can trigger powerful analgesia, but their complex network organization frequently prevents separation of analgesia from side effects. To overcome this long-standing challenge, we developed a biocompatible gelatin-embedded cluster of ultrathin microelectrodes that enables fine-tuned, high-definition three-dimensional stimulation in periaqueductal gray/dorsal raphe nucleus in awake rats. Analgesia was assessed from both motor reactions and intracortical signals, corresponding to pain-related signals in humans. We could select an individual-specific subset of microelectrodes in each animal that reliably provided strong pain inhibition during normal and hyperalgesia conditions, without noticeable behavioral side effects. Gait, spontaneous cortical activity at rest, and cortical tactile responses were minimally affected, indicating a highly selective action. In conclusion, our developed biocompatible microelectrode cluster and stimulation paradigm reliably enabled powerful, fine-tuned, and selective analgesia without noticeable side effects."

By embedding the microelectrodes in needle-shaped, hard gelatin that expands and then dissolves during implantation, highly flexible microelectrodes could be implanted and spread out as a cluster in deep brain targets.

Stimulation of different neuron types in the PAG/DRN induces different circuit effects. For example, dopamine neurons in this region have been shown to produce analgesia without anxiety (19). In addition, different microcircuits of γ-aminobutyric acid (GABA) and glutamate neurons with divergent end targets can produce competing behaviors (20). One function of this powerful control may be to prevent pain-related reactions from interfering with other, more urgent, and behaviorally appropriate actions.

We compared the effects of PAG/DRN stimulation with the analgesia induced by morphine (1 mg/kg, subcutaneously) in the same animals (n = 8) during weeks 4 to 5 PS to benchmark the analgesic efficacy of PAG/DRN cluster stimulation. The analgesia induced by morphine was less powerful than PAG/DRN stimulation (Fig. 4, A and B). Moreover, morphine caused obvious signs of behavioral sedation. For example, the rats usually appeared to fall asleep with slower breathing and closed eyes."


https://www.science.org/doi/10.1126/sciadv.abj2847

morganism

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« Reply #5 on: October 25, 2021, 07:46:05 AM »
Hardened wood as a renewable alternative to steel and plastic

"Cellulose itself is a remarkably strong material, whose strength relative to its density is "higher than almost all the metals and alloys in the world," said Li.

But cellulose comprises only 40 to 50 per cent of wood. So the first step in developing a higher-density wood-based material was to reduce the components that weren't cellulose. In particular they targeted lignin, which acts like a kind of glue in normal wood, binding fibres together.

"We use chemicals to partially remove lignin. And after the first step the wood becomes soft, flexible and somewhat squishy," said Li.

"So the second step is that we apply pressure. We also increase the temperature. The purpose of that is to really densify the natural wood and also remove the water, reducing its thickness to around 20 per cent of the original natural wood."


https://www.cbc.ca/radio/quirks/oct-23-vikings-in-newfoundland-new-rocks-from-the-moon-making-wood-better-and-more-1.6219865/scientists-have-found-a-way-to-harden-wood-to-make-a-knife-that-rivals-steel-1.6219874

https://www.sciencedirect.com/science/article/abs/pii/S2590238521004653


morganism

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« Reply #6 on: October 29, 2021, 11:08:27 PM »
The fluoride wars rage on

"Den Besten has spent her career trying to work out the systemic effects of swallowing this anion. The fact that fluoride can affect ameloblasts, the cells that produce and deposit tooth enamel, suggests that it could affect other cells of the body. In fact, she notes, studies in animals and humans show that, in addition to fluorosis, cellular effects of fluoride also include inflammation and altered neurodevelopment. That, in turn, suggests that it could make its way into the brain. Den Besten says that means researchers should be looking into whether fluoride has potential effects on the central nervous system. “It should be a high priority to answer these questions. And yet, it’s not.” These potential effects of fluoride are important for individuals at all ages, she says.

The possibility of neurological effects is part of what Connett is trying to draw attention to in his lawsuit against the EPA. The finding that has garnered the most attention is a 2019 study in JAMA Pediatrics6, in which researchers compared the IQ of children who were born to women living in fluoridated areas and non-fluoridated areas. The data, which came from 512 mother–child pairs in 6 cities in Canada, indicated that, depending on how fluoride intake was assessed, exposure during fetal development was associated with as much as a five-point drop in IQ. A second study, led by public-health physician and epidemiologist Howard Hu at the Keck School of Medicine at the University of Southern California in Los Angeles, found a correlation between increased maternal urinary fluoride and decreased IQ in children born in Mexico City7.

“It’s not disputed that fluoride is toxic at high levels,” says Christine Till, a neuropsychologist at York University in Toronto, Canada, and lead researcher of the JAMA Pediatrics study. But what happens at lower levels, such as the 0.7 milligrams of fluoride per litre recommended in US fluoridation, is contested. That’s what Till and her colleagues have been working to tease out. “You have some weaker studies saying there’s no effect. And then you have our study, and the Mexico study, that are high quality, saying there is an effect,” she says.

On the basis of these two studies, Philippe Grandjean, a physician and environmental medicine researcher at the University of Southern Denmark in Odense, put together a benchmark-dose study on fluoride to document concentrations at which fluoride begins to have detectable adverse effects on IQ. According to the report, published in June8, that level is 0.2 milligrams per litre. That’s less than one-third of the recommended level for US water supplementation and one-twentieth of the US maximum allowable level of 4 mg l−1 (a level originally intended to prevent skeletal fluorosis). These numbers are just the beginning. More cohort studies are under way, and toxicologists and epidemiologists hope they’ll help to bring clarity to the fraught debate."

https://www.nature.com/articles/d41586-021-02924-6

morganism

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« Reply #7 on: November 04, 2021, 11:22:00 AM »
Elements may have been forged on Earth, as well as in space

" But he claims that the presence of subatomic particles known as neutral pions can increase the nuclear attraction to the point where fusion occurs. Those pions, he says, would be generated by electrons excited by the rapid fracturing and sliding of carbonate crystals – caused by volcanic eruptions. Alongside the excited electrons would be neutrinos, captured as they stream through the Earth in large numbers from the Sun or other stars, or alternatively from nuclear reactions in the Earth’s core.

The latest work builds on this research by showing how such catalyzed fusion reactions could explain the production not only of nitrogen, oxygen and water, but all of the 25 lightest elements. To demonstrate the plausibility of this mechanism, the researchers calculated the minimum energy required to initiate the reaction in each case and then analyzed the crystal structure of a mineral found in the mantle that contains the reacting elements.

https://physicsworld.com/a/elements-may-have-been-forged-on-earth-as-well-as-in-space/

https://iopscience.iop.org/article/10.1088/2399-6528/abb2e6

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« Reply #8 on: November 07, 2021, 07:58:22 PM »
the history of microbiology, a personal interpetation

https://www.annualreviews.org/doi/pdf/10.1146/annurev-micro-033020-020648

"Microbiology began as a unified science using the principles of chemistry tounderstand living systems. The unified view quickly split into the subdisci-plines of medical microbiology, molecular biology, and environmental mi-crobiology. The advent of a universal phylogeny and culture-independentapproaches has helped tear down the boundaries separating the subdisci-plines. The vision for the future is that the study of the fundamental rolesof microbes in ecology and evolution will lead to an integrated biology withno boundary between microbiology and macrobiology."

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« Reply #9 on: November 11, 2021, 07:17:00 AM »
Penn Researchers Show ‘Encrypted’ Peptides Could be Wellspring of Natural Antibiotics


The algorithm searched the proteome, the complete set of proteins in the body, and returned 43,000 peptides of 8 to 50 amino acids in length, many of which were found in a new region of the proteome all together. This wide scope of potential antimicrobials was then filtered to 2,603 peptides based on their fitness function inclusive of all the parameters.

To validate the antimicrobial properties of these algorithm-derived peptides, 55 were synthesized and exposed to eight different pathogens including E. coli and bacteria that cause staph infection and pneumonia.

“We found that 63.6% of these 55 encrypted peptides displayed antimicrobial activity,” says de la Fuente. “Interestingly, these peptides not only fought off infection by some of the most harmful bacteria in the world, they also targeted gut and skin commensal organisms that are beneficial to us. We speculate that this could be indicative of a microbiota modulating role that these peptides may possess as well.”

The team also tested the ability of the peptides to act synergistically and found that cocktails of peptides derived from the same biogeographic area within the body were able to potentiate their individual ability to fight off infection by 100-fold.

“This synergistic effect is likely already happening in our bodies,” says de la Fuente. “Some of the peptides discovered by our algorithm exhibited antimicrobial activity at levels that are physiologically relevant. These molecules are found throughout the body, including the immune system. A surprising finding was that these peptides were not only encoded in the immune system but were also found in the digestive, circulatory, and nervous systems, for example, indicating that fighting off infections caused by invading organisms may be a more holistic approach than previously thought.”

https://blog.seas.upenn.edu/penn-researchers-show-encrypted-peptides-could-be-wellspring-of-natural-antibiotics/

Mining for encrypted peptide antibiotics in the human proteome

https://www.nature.com/articles/s41551-021-00801-1

morganism

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« Reply #10 on: November 19, 2021, 11:04:17 PM »
Planetary Biosecurity: Applying Invasion Science to Prevent Biological Contamination from Space Trave

"To address the science and management of invasive alien species, a highly productive interdisciplinary field has emerged over the past few decades: invasion science (also known as invasion biology but embracing nonbiological disciplines)—the study of the causes and consequences of the introduction of organisms beyond their natural evolutionary ranges, with emphasis on the role of humans in these introductions. Research in invasion science has produced novel insights for epidemiology, rapid evolution, the relationship between biodiversity and community stability, and the dynamics of predator–prey and parasite–host interactions, among many other concepts (Hui and Richardson 2017). These insights are being increasingly integrated into biosecurity frameworks "

https://academic.oup.com/bioscience/advance-article/doi/10.1093/biosci/biab115/6413826

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« Reply #11 on: November 23, 2021, 12:18:17 AM »
‘Dancing molecules’ successfully repair severe spinal cord injuries
After single injection, paralyzed animals regained ability to walk within four weeks

"By sending bioactive signals to trigger cells to repair and regenerate, the breakthrough therapy dramatically improved severely injured spinal cords in five key ways: (1) The severed extensions of neurons, called axons, regenerated; (2) scar tissue, which can create a physical barrier to regeneration and repair, significantly diminished; (3) myelin, the insulating layer of axons that is important in transmitting electrical signals efficiently, reformed around cells; (4) functional blood vessels formed to deliver nutrients to cells at the injury site; and (5) more motor neurons survived.
After the therapy performs its function, the materials biodegrade into nutrients for the cells within 12 weeks and then completely disappear from the body without noticeable side effects. This is the first study in which researchers controlled the collective motion of molecules through changes in chemical structure to increase a therapeutic’s efficacy."

The secret behind Stupp’s new breakthrough therapeutic is tuning the motion of molecules, so they can find and properly engage constantly moving cellular receptors. Injected as a liquid, the therapy immediately gels into a complex network of nanofibers that mimic the extracellular matrix of the spinal cord. By matching the matrix’s structure, mimicking the motion of biological molecules and incorporating signals for receptors, the synthetic materials are able to communicate with cells.

“Receptors in neurons and other cells constantly move around,” Stupp said. “The key innovation in our research, which has never been done before, is to control the collective motion of more than 100,000 molecules within our nanofibers. By making the molecules move, ‘dance’ or even leap temporarily out of these structures, known as supramolecular polymers, they are able to connect more effectively with receptors.”

Once connected to the receptors, the moving molecules trigger two cascading signals, both of which are critical to spinal cord repair. One signal prompts the long tails of neurons in the spinal cord, called axons, to regenerate. Similar to electrical cables, axons send signals between the brain and the rest of the body. Severing or damaging axons can result in the loss of feeling in the body or even paralysis. Repairing axons, on the other hand, increases communication between the body and brain.

Alvarez spinal cord injuries
Zaida Álvarez

The second signal helps neurons survive after injury because it causes other cell types to proliferate, promoting the regrowth of lost blood vessels that feed neurons and critical cells for tissue repair. The therapy also induces myelin to rebuild around axons and reduces glial scarring, which acts as a physical barrier that prevents the spinal cord from healing.

“The signals used in the study mimic the natural proteins that are needed to induce the desired biological responses. However, proteins have extremely short half-lives and are expensive to produce,” said Zaida Álvarez, the study’s first author. “Our synthetic signals are short, modified peptides that — when bonded together by the thousands — will survive for weeks to deliver bioactivity. The end result is a therapy that is less expensive to produce and lasts much longer.”

Stupp believes the underlying discovery — that “supramolecular motion” is a key factor in bioactivity — can be applied to other therapies and targets.

“The central nervous system tissues we have successfully regenerated in the injured spinal cord are similar to those in the brain affected by stroke and neurodegenerative diseases, such as ALS, Parkinson’s disease and Alzheimer’s disease,” Stupp said. “Beyond that, our fundamental discovery about controlling the motion of molecular assemblies to enhance cell signaling could be applied universally across biomedical targets.”

https://news.northwestern.edu/stories/2021/11/dancing-molecules-successfully-repair-severe-spinal-cord-injuries/

Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury

https://www.science.org/doi/10.1126/science.abh3602

morganism

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« Reply #12 on: December 07, 2021, 09:32:07 PM »
 Giant Study Finds Viagra Is Linked to Almost 70% Lower Risk of Alzheimer's

"Out of over 1,600 such medications already approved by the FDA, sildenafil turned out to be one of the most promising candidates.

That might sound baffling – given the drug is so far used in the main only for treating erectile dysfunction and pulmonary hypertension – in the research community, there were already signs the sildenafil compound might have other kinds of health benefits, given its interactions with the amyloid and tau proteins implicated in Alzheimer's pathology.

"Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer's than either by itself," Cheng says.

"We hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success… Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate."

The hypothesis appears to be borne out by the health insurance data, with the team finding sildenafil users had a 69 percent reduced risk of Alzheimer's disease compared to non-users – a reduction that was notably stronger than other kinds of medications also investigated in the study, including losartan, metformin, diltiazem, and glimepiride.

Of course, the researchers emphasize that none of this establishes causality, but on that front there may be other promising leads.

In separate experiments studying human brain cells in vitro to explore how sildenafil might confer protection against Alzheimer's cognitive decline, the researchers observed that neurons treated with the drug showed elevated growth and reduced tau accumulation."

https://www.sciencealert.com/giant-study-finds-viagra-is-linked-to-almost-70-lower-risk-of-alzheimer-s

insurance record data mining identifies sildenafil as a candidate drug for Alzheimer’s disease

https://www.nature.com/articles/s43587-021-00138-z

morganism

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« Reply #13 on: December 18, 2021, 11:12:54 PM »
google analytics requires a plugin to block it, or opt out.

https://tools.google.com/dlpage/gaoptout/eula.html?hl=en

i use NoScript on firefox, but you can fight with it a bit to get it to work well for you. Works great for me!

(after opening a youtube video "i bought 1k meters of wire to test a physics question", post button wouldn't work)
even after dis-abling and removing plugin)
« Last Edit: December 19, 2021, 01:20:51 AM by morganism »

morganism

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« Reply #14 on: December 22, 2021, 04:39:27 PM »
"By the end of this article, you’ll have all the steps needed to develop film at home with instant coffee and water softener."

https://www.fieldmag.com/articles/how-to-develop-film-with-coffee-caffenol-guide

https://www.caffenol.org/

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« Reply #15 on: December 24, 2021, 08:39:38 PM »
Precision cooking for printed foods via multiwavelength lasers

Additive manufacturing of food is a method of creating three-dimensional edible products layer-by-layer. While food printers have been in use since 2007, commercial cooking appliances to simultaneously cook and print food layers do not yet exist. A key challenge has been the spatially controlled delivery of cooking energy. Here, we explore precision laser cooking which offers precise temporal and spatial control over heat delivery and the ability to cook, broil, cut and otherwise transform food products via customized software-driven patterns, including through packaging. Using chicken as a model food, we combine the cooking capabilities of a blue laser (λ = 445 nm), a near-infrared (NIR) laser (λ = 980 nm), and a mid-infrared (MIR) laser (λ = 10.6 μm) to broil printed chicken and find that IR light browns more efficiently than blue light, NIR light can brown and cook foods through packaging, laser-cooked foods experience about 50% less cooking loss than foods broiled in an oven, and calculate the cooking resolution of a laser to be ~1 mm"

https://www.nature.com/articles/s41538-021-00107-1Precision cooking for printed foods via multiwavelength lasers

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« Reply #16 on: December 27, 2021, 03:44:42 AM »
Transport in the emergent Bose liquid: Bad metal, strange metal, and weak insulator, all in one system

"Non-saturating high-temperature resistivity ("bad metal"), T-linear low-temperature resistivity ("strange metal"), and a crossover to activation-free growth of the resistivity in the low-temperature limit ("weak insulator") are among the most exotic behaviors widely observed in many strongly correlated materials for decades that defy the standard Fermi liquid description of solids. Here we investigate these puzzling behaviors by computing temperature-dependent optical conductivity of an emergent Bose liquid and find that it reproduces all the unexplained features of the experiments, including a featureless continuum and a well-known mid-infrared peak. Amazingly and with physically intuitive mechanisms, the corresponding doping- and temperature-dependent resistivity displays the bad metal and strange metal simultaneously and sometimes weak insulating behaviors as well. The unification of all these non-Fermi liquid behaviors in a single model suggests that a new quantum state of matter, namely the emergent Bose liquid, will guide the development of the next generation of solid state physics."

https://arxiv.org/abs/2112.05747

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« Reply #17 on: December 27, 2021, 09:14:20 PM »
Practical transformer winding

"In the good old times it was a matter of fact that every electronic hobbyist or technician would wind himself any power transformers he needed, and rewind any that burned out. Unfortunately, nowadays transformer winding is fast becoming a lost art, and I have seen many people despair about where to find some very specific transformer, or pull their hair out about the cost of having one professionally wound to specifications.

Since I started in electronics, as a 12 year old boy, I have always wound my own transformers. I started using the basic, but useful instructions provided in The Radio Amateur's Handbook of the time, and later I came to better understand how transformers work, which enabled me to optimize a given transformer for the intended application.

Following a request by many readers of my web site, I've added this page, which is complementary to the previously published Transformers and coils. You should first read (and understand!) that page, before trying to design any transformer. Then come to this more practically-oriented page, to learn some tricks and hints about the design process, and about hands-on winding.

This page addresses mainly single-phase power transformers in the power range from about 1 watt to 10,000 watts, operating at line frequencies, but much of what's described here can be applied to a wide range of other transformers too."

https://ludens.cl/Electron/trafos/trafos.html

https://ludens.cl/Electron/Magnet.html

"The next step is calculating how many turns per volt you need on this core. To this end, you have to decide how much flux density you will put through your core, and then you can apply the equations from Transformers and coils. The optimal flux density might be anything from 0.8 to 1.6 Tesla, and sometimes even outside this range! General rules of thumb are these:

- Larger transformers use lower flux densities.

- Better core material uses higher flux densities.

- Transformers that are always energized, but rarely used at full power, use lower flux densities.

- Likewise, transformers that work at full power whenever energized, use very high flux density.

- Forced air cooled transformers use higher flux density.

- Oil-immersed transformers use even higher flux density!

- Higher flux density produces better voltage regulation.

- Lower flux density produces less base loss.

- Lower flux density is less likely to produce humming noise, and magnetic stray fields.

- Lower flux density produces lower iron loss, but higher copper loss.

 

I have seen many text books giving design equations that result in a flux density of 1 Tesla in each and every transformer you calculate by them, like if that were a sacred rule! If you come across any such book, BURN IT! It's nonsense! While 1 Tesla indeed tends to produce a workable transformer in most cases, in at least 70% of all situations it's far enough from the optimal value to warrant some effort toward optimization! Specially in small transformers, and in those using the better core materials."

morganism

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« Reply #18 on: December 30, 2021, 11:16:14 AM »
Experimental depression treatment is nearly 80% effective in controlled study

In a double-blind controlled study, high doses of magnetic brain stimulation, given on an accelerated timeline and individually targeted, caused remission in 79% of trial participants with severe depression.

The treatment, known as Stanford accelerated intelligent neuromodulation therapy (SAINT) or simply Stanford neuromodulation therapy, is an intensive, individualized form of transcranial magnetic stimulation. In the study, remission typically occurred within days and lasted months. The only side effects were temporary fatigue and headaches. “It works well, it works quickly and it’s noninvasive,”

n the study, the researchers first used MRI to locate the best location to target within each participant’s dorsolateral prefrontal cortex, which regulates executive functions, such as problem solving and inhibiting unwanted responses. They applied the stimulation in a subregion that has the strongest relationship with the subgenual cingulate, a part of the brain that is overactive in people experiencing depression. The transcranial magnetic stimulation strengthens the connection between the two regions, facilitating dorsolateral prefrontal cortex control of the activity in the subgenual cingulate.

The researchers also used 1,800 pulses per session instead of 600. (The larger amount has been used safely in other forms of brain stimulation for neurological disorders such as Parkinson’s disease.) And instead of providing one treatment a day, they gave participants 10 10-minute treatments, with 50-minute breaks in between.

Within four weeks after treatment, 12 of the 14 participants who had received the treatment improved, and 11 of them met FDA criteria for remission. In contrast, only two of the 15 participants who had received the placebo met the criteria for remission.

Because the study participants typically felt better within days of starting SAINT, the researchers are hoping it can be used to quickly treat patients who are at a crisis point. Patients who start taking medication for depression typically don’t experience any reduction of symptoms for a month.

“We want to get this into emergency departments and psychiatric wards where we can treat people who are in a psychiatric emergency,”

https://med.stanford.edu/news/all-news/2021/10/depression-treatment.html

https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2021.20101429

morganism

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« Reply #19 on: January 13, 2022, 10:19:43 PM »
Making animations the easy way

Welcome to  Animatize

Make an animation by dragging a character around the screen

Once you drag the character onto the canvas, the animation will start recording.

Once your finished, you can download the code and add it to your own site!

https://animatize.com/

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« Reply #20 on: January 15, 2022, 06:43:35 AM »
Epstein-Barr virus may be leading cause of multiple sclerosis

the researchers conducted a study among more than 10 million young adults on active duty in the U.S. military and identified 955 who were diagnosed with MS during their period of service.

The team analyzed serum samples taken biennially by the military and determined the soldiers’ EBV status at time of first sample and the relationship between EBV infection and MS onset during the period of active duty. In this cohort, the risk of MS increased 32-fold after infection with EBV but was unchanged after infection with other viruses. Serum levels of neurofilament light chain, a biomarker of the nerve degeneration typical in MS, increased only after EBV infection. The findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.

Ascherio says that the delay between EBV infection and the onset of MS may be partially due the disease’s symptoms being undetected during the earliest stages and partially due to the evolving relationship between EBV and the host’s immune system, which is repeatedly stimulated whenever latent virus reactivates. "

https://www.eurekalert.org/news-releases/939873



Strong new evidence suggests a virus triggers multiple sclerosis

Besides MS, the virus has also been linked to a variety of cancers and other autoimmune diseases such as lupus.

“Understanding the detailed mechanism of how EBV triggers MS is more of an academic question,” said Wilson. “For a public vaccination campaign, we just have to show that it reduces cases of MS, even if we don’t understand exactly how it’s happening.”
Related:
Researchers shatter the speed record for diagnosing rare genetic diseases with DNA sequencing

There are precedents for such a campaign. In 2006, regulators approved a vaccine to prevent spread of four strains of human papillomavirus, or HPV, which raise risks of developing cervical cancers that kill thousands of women in the U.S. each year. Although Americans were slow to get immunized, uptake in the U.K. was sky-high. A recent analysis found the vaccines have already nearly eliminated cervical cancer in young women there.

“If EBV is causing MS then this could shift the focus of research into trying to find a cure for MS as well as motivate vaccine development,” said Bjornevik. The study might also shift research priorities for other neurological conditions. For years, scientists have found evidence that Alzheimer’s disease might be driven by inflammation triggered by viral infections, including other herpes viruses. But these outsiders’ research has repeatedly been met with ridicule, their projects left unfunded and their hypotheses unexplored.

“Our findings are very specific for MS, but we expect it may spark interest in reexamining infectious causes of other diseases,” said Bjornevik.

https://www.statnews.com/2022/01/13/strong-new-evidence-suggests-virus-triggers-multiple-sclerosis/
« Last Edit: January 15, 2022, 07:02:49 AM by morganism »

morganism

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« Reply #21 on: January 22, 2022, 11:45:09 AM »
black holes and bathtub vortices

Analogical thinking is a valuable tool in theoretical physics, since it allows us to take the understanding we have developed in one system and apply it to another. In this thesis, we study the analogy between two seemingly unlikely systems: rotating black holes, elusive cosmic entities that push our theoretical understanding of modern physics to its limits, and bathtub vortices, an occurrence so common that they can be observed on a day-to-day basis in almost any household. Despite the clear difference between these two systems, we argue that lessons from each can be used to learn something about the other.
We investigate the equivalence between surface wave propagation in shallow water and the propagation of a massless scalar field on an effective spacetime, focussing in particular on the rotating black hole geometry sourced by a rotating draining vortex flow. Using this analogy, we verify for the first time that three effects predicted to occur around rotating black holes also occur in a laboratory experiment. These are superradiance, an energy enhancement process whereby waves extract rotational energy from the system, quasi-normal ringing, describing the relaxation of the system toward equilibrium, and the backreaction, which mediates the exchange of energy between fluctuations and the background they experience.

https://arxiv.org/abs/2009.02133

morganism

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« Reply #22 on: February 12, 2022, 07:40:22 PM »
Accidental discovery could be game changer for stem cell research

An unexpected observation by researchers exploring the development of heart cells could have enormous implications in the understanding of how embryonic stem cells become an adult cell. The removal of a single gene in heart cell precursors somehow caused the cells to morph into brain cell precursors, something never before seen or believed possible, according to a recent study from the Gladstone Institutes of Cardiovascular Disease in San Francisco.

Stem Cell Mystery Unravels

Embryonic stem cells are known to be plurioplonic, meaning they are able to convert into and become any type of cell in an adult body. Before they are fully transformed into a specific type of cell in the body, stem cells must go through a number of complicated steps along the way. While the precise mechanisms that cause a stem cell to become a heart or bone cell, for example, are unclear, it has been accepted that once a cell is marked to become a specific type of cell, there’s no turning back.

After 10 days of differentiation, normal cells are beating rhythmically; they’re clearly heart cells. But without Brahma, there was just a mass of inert cells. No beating at all,” explains first author, Swetansu Hotz.

Not only that, but the deactivation of Brm seemed to simultaneously activate other genes required for stem cells to become brain cells. This caused the transformation of the heart cell precursors directly into brain cell precursors, according to the study, something scientists didn’t know was possible beforehand.

The fact that a single genetic alteration can shift the seemingly predetermined path of a stem cell is an exhilarating discovery, which could lead to a greater understanding of overall cell health and development. Additionally, since genetic mutations of Brm have been linked to certain diseases and cancers, the unexpected results could lead to further insight on how certain cells are altered by those maladies."

https://www.braintomorrow.com/2022/02/08/mutant-stem-cell-research-discovery/


Brahma safeguards canalization of cardiac mesoderm differentiation

https://www.nature.com/articles/s41586-021-04336-y

Differentiation proceeds along a continuum of increasingly fate-restricted intermediates, referred to as canalization1,2. Canalization is essential for stabilizing cell fate, but the mechanisms that underlie robust canalization are unclear. Here we show that the BRG1/BRM-associated factor (BAF) chromatin-remodelling complex ATPase gene Brm safeguards cell identity during directed cardiogenesis of mouse embryonic stem cells. Despite the establishment of a well-differentiated precardiac mesoderm, Brm−/− cells predominantly became neural precursors, violating germ layer assignment. Trajectory inference showed a sudden acquisition of a non-mesodermal identity in Brm−/− cells. Mechanistically, the loss of Brm prevented de novo accessibility of primed cardiac enhancers while increasing the expression of neurogenic factor POU3F1, preventing the binding of the neural suppressor REST and shifting the composition of BRG1 complexes. The identity switch caused by the Brm mutation was overcome by increasing BMP4 levels during mesoderm induction. Mathematical modelling supports these observations and demonstrates that Brm deletion affects cell fate trajectory by modifying saddle–node bifurcations2. In the mouse embryo, Brm deletion exacerbated mesoderm-deleted Brg1-mutant phenotypes, severely compromising cardiogenesis, and reveals an in vivo role for Brm. Our results show that Brm is a compensable safeguard of the fidelity of mesoderm chromatin states, and support a model in which developmental canalization is not a rigid irreversible path, but a highly plastic trajectory.



Biohybrid fish made from human cardiac cells swims like the heart beats
Device offers insights into artificial muscular pumps, a step toward building an artificial heart


https://www.seas.harvard.edu/news/2022/02/biohybrid-fish-made-human-cardiac-cells-swims-heart-beats

In this research, the team built the first autonomous biohybrid device made from human stem-cell derived cardiomyocytes. This device was inspired by the shape and swimming motion of a zebrafish. Unlike previous devices, the biohybrid zebrafish has two layers of muscle cells, one on each side of the tail fin. When one side contracts, the other stretches. That stretch triggers the opening of a mechanosensitive protein channel, which causes a contraction, which triggers a stretch and so on and so forth, leading to a closed loop system that can propel the fish for more than 100 days.

“By leveraging cardiac mechano-electrical signaling between two layers of muscle, we recreated the cycle where each contraction results automatically as a response to the stretching on the opposite side,


“Because of the two internal pacing mechanisms, our fish can live longer, move faster and swim more efficiently than previous work,” said Sung-Jin Park, a former postdoctoral fellow in the Disease Biophysics Group at SEAS and co-first author of the study. “This new research provides a model to investigate mechano-electrical signaling as a therapeutic target of heart rhythm management and for understanding pathophysiology in sinoatrial node dysfunctions and cardiac arrhythmia."
« Last Edit: February 12, 2022, 10:21:48 PM by morganism »

morganism

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« Reply #23 on: March 07, 2022, 11:51:57 AM »
How to Slice a Bagel into Two Linked Halves

The cutting surface is a two-twist Mobius strip; it has two sides, one for each half.
After being cut, the two halves can be moved but are still linked together, each passing through
the hole of the other.   (So when you buy your bagels, pick ones with the biggest holes.)

http://www.georgehart.com/bagel/bagel.html

SteveMDFP

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Re: morganisms
« Reply #24 on: March 08, 2022, 01:15:32 PM »
How to Slice a Bagel into Two Linked Halves

The cutting surface is a two-twist Mobius strip; it has two sides, one for each half.
After being cut, the two halves can be moved but are still linked together, each passing through
the hole of the other.   (So when you buy your bagels, pick ones with the biggest holes.)

http://www.georgehart.com/bagel/bagel.html
The next challenge in this realm is slicing a bagel into a Klein Bottle.


morganism

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« Reply #25 on: March 25, 2022, 12:01:32 AM »
Artificial Sweeteners Are Associated With Increased Cancer Risk, Finds Large-Scale Cohort Study
Published: March 24, 2022

The researchers found that participants consuming larger amounts of artificial sweeteners (particularly aspartame and acesulfame-K), had an increased overall risk of cancer compared to non-consumers. In relation to this finding, Debras emphasizes that “aspartame and acesulfame-K were by far the most frequently consumed artificial sweeteners. Thus, the fact that associations were observed for these two (and not for sucralose, for instance) should be considered with caution since it may only be due to the fact that aspartame and acesulfame-K were the most commonly consumed.”


Aspartame was specifically associated with an increased risk of breast and obesity-related cancers.

https://www.technologynetworks.com/cancer-research/news/artificial-sweeteners-are-associated-with-increased-cancer-risk-finds-large-scale-cohort-study-359968

https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003950


SteveMDFP, i have a klein beer stein that is pretty sweet...)

morganism

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« Reply #26 on: April 18, 2022, 08:27:41 PM »
Bacterial soundtracks revealed by graphene membrane

 If we could listen to bacteria, we would be able to know whether they are alive or not. When bacteria are killed using an antibiotic, those sounds would stop – unless of course the bacteria are resistant to the antibiotic.

 “What we saw was striking! When a single bacterium adheres to the surface of a graphene drum, it generates random oscillations with amplitudes as low as a few nanometers that we could detect. We could hear the sound of a single bacterium!”

Punching a graphene drum with a bacterium
The extremely small oscillations are a result of the biological processes of the bacteria with main contribution from their flagella (tails on the cell surface that propel bacteria). “To understand how tiny these flagellar beats on graphene are, it’s worth saying that they are at least 10 billion times smaller than a boxer’s punch when reaching a punch bag. Yet, these nanoscale beats can be converted to sound tracks and listened to - and how cool is that,” Alijani says.


https://www.eurekalert.org/news-releases/949784

Probing nanomotion of single bacteria with graphene drums

Motion is a key characteristic of every form of life1. Even at the microscale, it has been reported that colonies of bacteria can generate nanomotion on mechanical cantilevers2, but the origin of these nanoscale vibrations has remained unresolved3,4. Here, we present a new technique using drums made of ultrathin bilayer graphene, where the nanomotion of single bacteria can be measured in its aqueous growth environment. A single Escherichia coli cell is found to generate random oscillations with amplitudes of up to 60 nm, exerting forces of up to 6 nN to its environment. Using mutant strains that differ by single gene deletions that affect motility, we are able to pinpoint the bacterial flagella as the main source of nanomotion. By real-time tracing of changes in nanomotion on administering antibiotics, we demonstrate that graphene drums can perform antibiotic susceptibility testing with single-cell sensitivity. These findings deepen our understanding of processes underlying cellular dynamics, and pave the way towards high-throughput and parallelized rapid screening of the effectiveness of antibiotics in bacterial infections with graphene devices.

https://www.nature.com/articles/s41565-022-01111-6

kassy

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Re: morganisms
« Reply #27 on: April 19, 2022, 01:57:43 PM »
Flagella drumming. Nice story.  :)
Þetta minnismerki er til vitnis um að við vitum hvað er að gerast og hvað þarf að gera. Aðeins þú veist hvort við gerðum eitthvað.

SteveMDFP

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« Reply #28 on: April 20, 2022, 12:30:23 AM »
Flagella drumming. Nice story.  :)

Waiting for a band that has E. coli on drums, pseudomonas on piano...

morganism

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« Reply #29 on: April 23, 2022, 11:03:26 PM »





Windows to the Soul: Pupils Reveal ‘Aphantasia’ – The Absence of Visual Imagination

Summary: People who experience visual imagination have pupillary responses that optimize the amount of light hitting the retina and change in response to imagined items. This pupillary response does not occur in those with aphantasia.

Source: University of New South Wales

The study, led by researchers from UNSW Sydney and published in eLife, found that the pupils of people with aphantasia did not respond when asked to imagine dark and light objects, while those without aphantasia did.

To first gauge the pupillary reflex of non-aphantasic people, the researchers sought 42 study participants, self-reported as having a visual imagination, and fitted them with glasses to track their eye movements and pupil sizes.

Participants were then exposed to bright or dark shapes against a grey background, which predictably evoked pupillary constriction in response to bright shapes (comparable to looking up at a bright sky) and pupillary dilation in response to dark shapes (after switching a light off).

Next, to test visual imagery – the mind’s capacity to visualise objects – participants were asked to simply imagine those same light or dark shapes (with their eyes open, for their pupils to be tracked) and subsequently report the ‘vividness’ of that imagery.

The researchers found that even in response to imagined bright and dark shapes, the participants’ pupils still constricted and dilated appropriately, a pupillary response that was larger in those reporting greater imagery vividness.

“The pupillary reflex is an adaption that optimises the amount of light hitting the retina,” says Professor Joel Pearson, senior author on the paper.

“And while it was already known that imagined objects can evoke so-called ‘endogenous’ changes in pupil size, we were surprised to see more dramatic changes in those reporting more vivid imagery. This really is the first biological, objective test for imagery vividness.”

Testing for a lack of imagination

Finally, with the link between visual imagery and pupillary response established, the researchers sought to test the effect in aphantasic individuals. The researchers repeated the study with 18 participants self-reporting aphantasia.

Exposing participants to bright and dark shapes, the researchers found that aphantasic individuals exhibited the same pupillary response as the general population: constriction to bright, dilation to dark.

However, during the study’s second component where participants were asked to visualise those same shapes, the pupillary response of aphantasic individuals did not significantly differ in response to imagined dark versus imagined bright objects.

“One of the problems with many existing methods to measure imagery is that they are subjective, that is to say they rely on people being able to accurately assess their own imagery. Our results show an exciting new objective method to measure visual imagery,” says Prof Pearson, “and the first physiological evidence of aphantasia. With over 1.3 million Australians thought to have aphantasia, and 400 million more internationally, we are now close to an objective physiological test, like a blood test, to see if someone truly has it.”

To ensure the aphantasic participants were really attempting imagery, the researchers included a further experimental condition, requesting aphantasic individuals to visualise four shapes, instead of one.

While the pupils of those with aphantasia showed no difference when imagining light versus dark objects, they did show a difference imagining one versus four objects, suggesting more mental effort, thereby negating an explanation of non-participation by aphantasic individuals.

https://neurosciencenews.com/pupillary-response-aphantasia-20423/

morganism

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« Reply #30 on: April 26, 2022, 11:41:35 PM »



Conservatism in science
Some of the forces blocking really new ideas in science

How might you identify whether a scientific community blocks new ideas? Merely observing the absence of new ideas isn’t enough; it could be that there just aren’t any new ideas worth pursuing. But what if you could identify sets of scientific fields that are quite similar to each other? Next, imagine you suddenly and randomly exile the dominant researchers in half the fields in order to stymie their ability to block new research. You could then compare what happens in fields that lost these dominant researchers to ones that didn’t. In particular, do new people enter these fields and pursue new and novel ideas? If so, that suggests there were new ideas worth investigating, but the dominant researchers in the field were blocking investigation of them. Alternatively, if new people enter these fields but basically continue doing the same thing as the previous generation, that suggests the opposite; the dominant researchers were not blocking anything and everyone in the field was just pursuing what they thought were the best ideas available at the time."

You can’t really do this experiment because you’re not going to get IRB approval to exile dominant researchers. It’s a bad thing to do. But Azoulay, Fons-Rosen, and Graff Zivin (2019) try to learn something from the sad fact that we live in a world where bad things do happen all the time. They begin by identifying a large set of superstar researchers in the life sciences. It turns out, 452 of these superstars died in the midst of an active research career. This is going to be analogous to the “exile” I described above in this hypothetical idealized experiment, though applying only to one prominent researcher per field, rather than the full set of dominant ones. (Note – as I’ll discuss later, the findings discussed below should not be interpreted as implying these superstars were behaving unethically or something. It’s more complicated than that.)

Azoulay, Fons-Rosen and Graff Zivin next identify a large set of small microfields in which these deceased researchers were active in the five years before their deaths. Each of these microfields consists of about 75 papers on average. For each of these microfields, they find sets of matching microfields that are similar in various ways. Most importantly, these matched microfields are ones that include active participation by a superstar researcher who did not pass away. The idea is to compare what happens in a microfield where a superstar researcher passed away to what happens in similar microfields where a superstar researcher did not pass away.

The first thing that happens is new people do begin to enter the field. Following the death of a superstar researcher, there is a slight increase in the number of new articles published in that microfield by people other than the superstar, as compared to microfields where the superstar lives. These new papers are disproportionately written by people who were not previously publishing in the microfield, rather than by people who were active publishing more.

Most relevant for our inquiry today, these new researchers appear to bring new ideas and new approaches with them. They’re less likely to cite the existing work in this microfield, including the work of the superstar. And their work is assigned a greater share of novel scientific keywords from the MeSH lexicon (a standardized classification system used in biomedicine). Also important – the new work tends to be well cited. There’s a greater influx of highly cited work than low-citation work.

Can we say anything more about the specific mechanisms going on here?

Well, we can say it’s not simply a case of these dominant researchers vetoing grant proposals and publication from rival researchers. Only a tiny fraction of them were in positions of formal academic power, such as sitting on NIH grant review committees or serving as journal editors, when they passed away. So what else could it be? I’m going to tentatively suggest it’s about the dominance of the ideas the superstar researcher promoted."

Echoing what I said at the beginning, highly novel work seems desirable; it’s much more likely to become one of the top 1% most cited papers in its field.

But importantly, this isn’t really because people in the field quickly recognize it’s a breakthrough. In fact, this recognition disproportionately comes from other fields, and with a significant delay. Restricting attention to citations received from within the same field, novelty isn’t rewarded. And even looking across all fields, these citations come late. Restricting attention to citations received in just the first three years, again, novelty isn’t really rewarded.

Moreover, Wang, Veugelers, and Stephan also show moderately and highly novel papers are less likely to be published in the best journals (as measured by the journal impact factor). That suggests to me that highly novel work is also less likely to be published at all, and so the results we’re seeing might be over-estimating the citations received, since they rely on novel work that was good enough to clear skeptical peer review.
(snip, a lot)
But even if they aren’t personally blocking research, their ideas might be.

For one, the ability of researchers to enter with new ideas seems weaker when the superstar’s former collaborators retain positions of influence, sitting on more NIH grant review committees and editorships (though the latter can only be assessed really imperfectly). Second, Azoulay, Fons-Rosen, and Graff-Zivin provide some suggestive evidence that when the microfield has more firmly consolidated itself around the ideas promoted by the superstar, it remains hard for newcomers to enter even after the superstar has passed away. They attempt to measure this by looking at measures of closely connected coauthorship networks are, how intensely the field cites its own work, and how similar papers in the field are to each other according to an algorithm.

But when a field is not highly consolidated around the superstar’s ideas and there is still some active debate about the way a microfield might go, there appears to be a big effect on having a superstar active in the field prematurely pass away. After the superstar researcher passes away, clearly they aren’t around anymore to publish, thereby expanding and clarifying the idea. And indeed, the entry of newcomers is strongest in fields where the superstar had an outsized role in the microfield, as measured by the share of publications, citations, and research funding they garnered. But the death of a superstar has additional knock-on effects that might further shake the dominance of their ideas. Even the former collaborators of the superstar publish significantly less work after the superstar dies. And this effect is stronger for collaborators who work on more similar topics as the superstar.

Novel ideas do get published, they can attract attention, and old paradigms do fall. It just happens less often than we might like. Research has an inertia that is real, but not insurmountable.
 
https://www.newthingsunderthesun.com/pub/rogqzrma/release/7


(and a cool article about immigration bringing in innovation at the same site.)

Importing Knowledge
The knowledge immigrants bring with them takes root in receiving countries

https://www.newthingsunderthesun.com/pub/8d5ydc84/release/8

morganism

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« Reply #31 on: April 27, 2022, 12:01:19 AM »
Targeting a different pathway for pain relief could keep people off opioids from the outset.

Fortunately, scientists may have found the pain-relieving golden goose, according to a new study published Tuesday in the journal Science. Researchers at the University of São Paulo in Brazil have created a promising new drug that targets a pathway in the human body that triggers pain sensations. The drug, named TAT-pQYP, provided relief to mice suffering from inflammatory pain, and it may one day be the answer for many different kinds of chronic pain.

There can be a whole host of medical conditions behind pain like disease or physical injury, but the biological reason for those unpleasant twinges is nociceptors, or sensory neurons that detect damage in skin, muscle, bones, and other internal organs. When a nociceptor senses trauma—like when you scald your hand with a hot cup of coffee—it sends the information to the brain and spinal cord for further processing. In the case of burning your hand, as long as the injury isn’t severe and you received timely medical treatment, the raw burning sensation tends to go away on its own. But in some conditions like cancer, multiple sclerosis, arthritis, or serious physical trauma, the pain might not go away. This could be because the nociceptors are kept active by chemical signals like inflammation or there is some sort of damage to the nervous system.

Over the years, scientists have noticed one shady character cropping up whenever pain does: nerve growth factor (NGF), a protein important to the development and survival of neurons, especially those that transmit sensory information like temperature and pain. In certain conditions like osteoarthritis, NGF can keep nociceptors perpetually on and lead to persistent, chronic pain.

Some treatments tackling the protein head-on are still in development (like antibodies that hunt down NGF and sequester it before it can poke a neuron). But such treatments can have undesirable side effects like preventing neuron growth. Scientists like the University of São Paulo group are trying instead focus on other targets like TrkA, a receptor that’s found on the surface of some sensory neurons and activated by NGF. It can launch a domino effect inside the neuron of other proteins signaling pain.

The researchers looked at the genes of patients who have congenital insensitivity to pain as well as those with anhidrosis, a rare genetic disorder where people affected are unable to feel pain and temperature. The University of São Paulo team found that mutated forms of a gene in these patients prevented TrkA from interacting with another protein called PLCg, and setting off pain alarms.

This gave the research team the idea to build a decoy, dubbed TAT-pQYP, that looks like TrkA but doesn’t allow it to mingle with PLCg. When human embryonic kidney cells in Petri dishes were doused with the new drug, the pain relay wasn’t turned on. When it was injected into mice with inflammatory pain, it appeared to provide relief since the animals didn’t flinch when touched. The drug also didn’t seem to cause any nasty side effects in healthy mice like messing up their tactile perception.

There’s still much more work to be done, so the University of São Paulo researchers caution. TAT-pQYP needs to undergo more lab testing before it can reach clinical trials in humans. And if it does get to that stage, it may take a while for the drug to reach the commercial market if decades-long clinical trials for anti-NGF drugs are any indication. It’s a promising first step, though, in uncovering the why behind pain and spurring further research efforts into NGF. The drug may also provide an alternative to patients who still rely on opioids despite prescriptions in the U.S. tapering off in the past decade due to the ongoing and unprecedented epidemic.

https://www.thedailybeast.com/alternative-of-chronic-pain-medication-could-curb-the-opioid-crisis?source=articles&via=rss

Structural analysis of TrkA mutations in patients with congenital insensitivity to pain reveals PLCγ as an analgesic drug target

 One such target is the pathway mediated by tropomyosin receptor kinase A (TrkA) in response to its ligand, nerve growth factor (NGF). NGF-TrkA is essential for the survival and differentiation of sympathetic and sensory nociceptive neurons during development (2, 3). Upon injury, inflammatory cell–secreted NGF activates peptidergic TrkA-positive nociceptors that contribute to inflammatory and neuropathic pain (3, 4).
Several inflammatory pain models in rodents display an increase in NGF levels (5–10), as do humans with arthritis and chronic headache (2). NGF-knockout mice are deficient in sensory perception of mechanical and thermal stimuli (5, 6), and treatment with NGF-blocking antibodies, antibody derivatives, or antisense oligonucleotides has analgesic effects in rodent models of inflammatory pain (5–10). NGF-blocking antibodies have been used to treat osteoarthritis pain in humans, but side effects such as osteonecrosis were observed (10). This could be due to inhibition of bone remodeling due to overload, because NGF signaling is required for survival and sprouting of sensory and sympathetic nerve fibers during bone formation (10, 11).
Likewise, several inhibitors that target the kinase domain of TrkA have also been developed. However, because of the conservation of the adenosine triphosphate (ATP)–binding site of TrkA with several other kinases, these inhibitors are not particularly selective for TrkA and are likely to have unwanted side effects (12). A peptide inhibitor derived from a sequence of the activation loop of TrkA (IPTRK3) that binds the catalytic site of TrkA to mimic the intramolecular interactions of an inactive protein (thereby rendering the kinase inactive) has been reported to decrease pain sensitivity in animal models (13); however, because it abolishes TrkA activity, it would affect all TrkA signaling pathways. Therefore, inhibitors that could block only pain signaling–specific NGF-TrkA pathways might provide the analgesic effect with fewer side effects.

https://www.science.org/doi/10.1126/scisignal.abm6046

morganism

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« Reply #32 on: May 01, 2022, 08:23:43 AM »
Mapping the “catscape” formed by a population of pet cats with outdoor access

The domestic cat (Felis catus) is among the most popular companion animals and most abundant carnivores globally. It is also a pet with an immense ecological footprint because even non-feral and food-subsidized cats can be prolific predators. Whereas knowledge about the spatial behavior of individual domestic cats is growing, we still know little about how a local population of free-ranging pet cats occupies the landscape. Using a citizen science approach, we GPS-tagged 92 pet cats with outdoor access living in a residential area in southern Norway. The resulting position data allowed us to construct both individual home range kernels and a population-level utilization distribution. Our results reveal a dense predatory blanket that outdoor cats drape over and beyond the urban landscape. It is this population-level intensity surface—the “catscape”—that potential prey have to navigate. There were few gaps in the catscape within our residential study area and therefore few terrestrial refuges from potential cat predation. However, cats spent on average 79% of their outdoor time within 50 m to their owner’s home, which suggests that the primary impact is local and most acute for wildlife in the vicinity to homes with cats. We discuss the catscape as a conceptual and quantitative tool for better understanding and mitigating the environmental impact of domestic cats.

https://www.nature.com/articles/s41598-022-09694-9

be cause

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Re: morganisms
« Reply #33 on: May 02, 2022, 02:00:13 PM »
keep up the great work ! thanks .. b.c.
2007 + 5 = 2012 + 4 = 2016 + 3 = 2019 + 2 = 2021 + 1 .. it's 2022 !

  don't panic  ..   life's not organic !

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Re: morganisms
« Reply #34 on: May 02, 2022, 06:21:36 PM »
Mapping the “catscape” formed by a population of pet cats with outdoor access

The domestic cat (Felis catus) is among the most popular companion animals and most abundant carnivores globally. It is also a pet with an immense ecological footprint because even non-feral and food-subsidized cats can be prolific predators.

https://www.nature.com/articles/s41598-022-09694-9

The "catscape" should not be underestimated as an environmental quandary.  Wind turbines are commonly opposed for killing birds.  In reality, they kill very few birds, compared to other causes.



(from https://www.businessinsider.com/cats-kill-more-birds-than-wind-turbines-despite-trumps-claims-2020-10)

morganism

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« Reply #35 on: May 04, 2022, 12:05:09 AM »
Anarchist Collective Shares Instructions to Make DIY Abortion Pills

https://archive.org/details/FTVDIYA

In the video, Laufer explains that, besides being used to medically induce abortions, misoprostol is also used to treat ulcers in horses. This makes misoprostol powder relatively easy to acquire from veterinary sources. (This is reminiscent of ivermectin, which is used to control parasites in horses but also became a favored—but ineffective—COVID treatment among conspiracy theorists. Ivermectin’s use in horses made it easier for humans to get without a prescription.)

Laufer explains in the video how to dose misoprostol and how to press it into pills using a scale, corn syrup, powdered sugar, a spray bottle, and a pollen press. They explain that a three-dose regimen of misoprostol is 85 percent effective in inducing abortion. If taken with mifepristone, another abortion pill, that rate rises to 95 percent effectiveness, though raw mifepristone is harder to source.

A recent study suggested that an abortion ban would lead to 21 percent increase in pregnancy-related deaths, and a 33 percent increase in pregnancy-related deaths among Black women."

https://www.vice.com/en/article/qjby4b/anarchist-collective-shares-instructions-to-make-diy-abortion-pills

morganism

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« Reply #36 on: May 05, 2022, 01:14:49 AM »
A Social Analgesic? Acetaminophen (Paracetamol) Reduces Positive Empathy  (2019)

Acetaminophen – a potent physical painkiller that also reduces empathy for other people’s suffering – blunts physical and social pain by reducing activation in brain areas (i.e. anterior insula and anterior cingulate) thought to be related to emotional awareness and motivation. Some neuroimaging research on positive empathy (i.e., the perception and sharing of positive affect in other people) suggests that the experience of positive empathy also recruits these paralimbic cortical brain areas. We thus hypothesized that acetaminophen may also impair affective processes related to the experience of positive empathy. We tested this hypothesis in a double-blind, placebo-controlled experiment. Specifically, we administered 1,000 mg acetaminophen or a placebo and measured effects on different measures of positive empathy while participants read scenarios about the uplifting experiences of other people. Results showed that acetaminophen reduced personal pleasure and other-directed empathic feelings in response to these scenarios. In contrast, effects on perceived positivity of the described experiences or perceived pleasure in scenario protagonists were not significant. These findings suggest that (1) acetaminophen reduces affective reactivity to other people’s positive experiences and (2) the experience of physical pain and positive empathy may have a more similar neurochemical basis than previously assumed. Because the experience of positive empathy is related to prosocial behavior, our findings also raise questions about the societal impact of excessive acetaminophen consumption."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455058/

morganism

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« Reply #37 on: May 05, 2022, 08:38:39 PM »
New Science's Report on the NIH

Our findings are complex and laden with opposing truths: Yes, the NIH has been the main driver of bioscience innovation for more than 80 years.  But the NIH, like all giant bureaucracies, suffers from structural problems that hinder its efficiency and leads to considerable, wasteful spending. The agency is risk-averse and excessively funds an aging cadre of scientists, likely at the cost of losing young scientists and missing out on ambitious, transformative ideas.
In this document, we break down the NIH’s history and bias, its triumphs and failures.

https://newscience.org/nih/

morganism

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« Reply #38 on: May 12, 2022, 08:42:21 PM »
Here’s another reason to donate blood: it reduces ‘forever chemicals’ in your body

They accumulate in the blood, bones and tissues of living things and do not degrade. PFAS impair human immune systems, making us more susceptible to diseases – even those we’ve been vaccinated against. Researchers associate the chemicals with liver disease, obesity, thyroid disorders, and certain cancers, among other health problems. These observations generally pertain to the relatively few PFAS we have researched, including PFOA and PFOS; PFAS belong to a massive family of chemicals, thousands of them unstudied and potentially harmful.

Now, for the first time, scientists have found a way to remove PFAS from the human body: by donating blood.

When you donate PFAS you are effectively pawning off your PFAS on the blood recipient. There’s something morally icky about that, though it’s important to remember that PFAS are already ubiquitous, and blood recipients generally need blood much more urgently than they need to worry about PFAS.

But the idea of offloading toxin-laced blood does raise health and ethical questions.



https://www.theguardian.com/commentisfree/2022/may/12/heres-another-reason-to-donate-blood-it-reduces-forever-chemicals-in-your-body

(There is some other papers out there that posit that donating blood in older folks, lowers the iron content, reducing oxidation targets, and saving the radicals for cellular processes.)


Effect of Plasma and Blood Donations on Levels of Perfluoroalkyl and Polyfluoroalkyl Substances in Firefighters in Australia

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790905?resultClick=1

morganism

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« Reply #39 on: May 14, 2022, 08:18:14 AM »

In Test Tubes, RNA Molecules Evolve Into a Tiny Ecosystem   (gene drive x risk, astrobiology)

When researchers gave a genetic molecule the ability to replicate, it evolved over time into a complex network of “hosts” and “parasites” that both competed and cooperated to survive.

Watch and Learn

After a lengthy experiment with tantalizing implications for origin-of-life studies, a research group in Japan has reported creating a test tube world of molecules that spontaneously evolved both complexity and, surprisingly, cooperation. Over hundreds of hours of replication, a single type of RNA evolved into five different molecular “species” or lineages of hosts and parasites that coexisted in harmony and cooperated to survive, like the beginning of a “molecular version of an ecosystem,”
...
“With what is shown here, the path ahead becomes a lot clearer, and one becomes a lot more optimistic that this can actually work out.”
...
Spiegelman’s work inspired decades of further study, much of which was foundational to research on life’s origins and provided fuel for the RNA world hypothesis that life sprang from self-replicating RNA molecules. But those studies left unanswered a crucial question: Could a single molecular replicator evolve into a complex network of multiple replicators?
...
Ichihashi and his team developed an RNA molecule that encoded a replicase, which can make copies of RNA. But for the molecule to translate its own code, the scientists needed to add something more: ribosomes and other gene translation machinery that they borrowed from the common gut bacteria Escherichia coli. They embedded the machinery inside droplets and added them to a mixture of RNAs and raw materials.
...
Their long-term experiment involved incubating their replication system at 37 degrees Celsius (the temperature of a human body or a hot summer’s day), adding new droplets with fresh translation systems, and stirring the mixture to induce replication. Every few days or so they analyzed RNA concentrations in the test tubes, and every week or so they froze samples from the latest mixture. Every half year or so, they sequenced large batches of the collected samples to see if the RNA had acquired new mutations and evolved into a new lineage.
...
But the researchers kept the experiments going, and by round 130, another host had evolved. By round 160, one of the parasites had disappeared; some rounds later, another parasite had appeared. By round 190, the researchers had hit on a new surprise: The huge dynamic swings in the population of each lineage had started giving way to smaller waves. This stabilization suggested that the lineages were no longer competing to replicate. Instead, they had started to interact as a network and cooperate in a state of quasi-stable coexistence"
...
Some of these results confirmed the predictions of earlier experimental studies of how complexity can arise in viruses, bacteria and eukaryotes, as well as some theoretical work. A study from Koonin’s lab, for instance, also suggested that parasites were inevitable in the emergence of complexity.

“Without parasites, this level of diversification is probably not possible,” Mizuuchi said. Evolutionary pressures that parasites and their hosts place on each other lead both sides to split into new lineages.

A more surprising fundamental principle that emerged was the critical role of cooperation. The five lineages belonged to different small networks of cooperation, and some were more cooperative than others. By round 228, for example, one of the three hosts had evolved into a “super cooperator” that could replicate itself and all the other lineages; the other two hosts could each replicate only themselves and one of the parasites.
...Meanwhile, the researchers have continued their main test tube experiments and are waiting to see whether their network will complexify further. They have also begun similar experiments that use DNA instead of RNA.

“We observed just the beginning” of how these communities of molecular replicators can evolve, Ichihashi said. “I think that they have a different destiny in the future — we cannot predict what happens.”

https://www.quantamagazine.org/in-test-tubes-rna-molecules-evolve-into-a-tiny-ecosystem-20220505/


Evolutionary transition from a single RNA replicator to a multiple replicator network

https://www.nature.com/articles/s41467-022-29113-x


Origin of life theory involving RNA–protein hybrid gets new support
Structure that links amino acids suggests that early organisms could have been based on an RNA–protein mix.


Carell’s team built a synthetic RNA molecule that included two such modified nucleosides by joining two pieces of RNA commonly found in living cells. At the first of the exotic sites, the synthetic molecule could bind to an amino acid, which then moved sideways to bind with the second exotic nucleoside adjacent to it. The team then separated their original RNA strands and brought in a fresh one, carrying its own amino acid. This was in the correct position to form a strong covalent bond with the amino acid previously attached to the second strand. The process continued step by step, growing a short chain of amino acids — a mini-protein called a peptide — that grew attached to the RNA. The formation of bonds between amino acids requires energy, which the researchers provided by priming the amino acids with various reactants in the solution.

“This is a very exciting finding,” says Martin, “not only because it maps out a new route to RNA-based peptide formation, but because it also uncovers new evolutionary significance to the naturally occurring modified bases of RNA.” The results point to an important part played by RNA at the origins of life, but without requiring RNA alone to self-replicate, Martin adds.

 “If the origins of RNA and the origins of protein are linked, and their emergence is not independent, then the math shifts radically in favour of an RNA–protein world and away from an RNA world,”

To show that this is a plausible origin of life, scientists must complete several further steps. The peptides that form on the team’s RNA are composed of a random sequence of amino acids, rather than one determined by information stored in the RNA. Carell says that larger RNA structures could have sections that fold into shapes that ‘recognize’ specific amino acids at specific sites, producing a well-determined structure. And some of these complex RNA–peptide hybrids could have catalytic properties, and be subject to evolutionary pressure to become more efficient. “If the molecule can replicate, you have something like a mini organism,” says Carell

https://www.nature.com/articles/d41586-022-01303-z

morganism

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« Reply #40 on: May 22, 2022, 09:36:24 PM »
We Are All Confident Idiots
The trouble with ignorance is that it feels so much like expertise. A leading researcher on the psychology of human wrongness sets us straight.

David Dunning Updated:Jun 14, 2017

 The American author and aphorist William Feather once wrote that being educated means “being able to differentiate between what you know and what you don’t.” As it turns out, this simple ideal is extremely hard to achieve. Although what we know is often perceptible to us, even the broad outlines of what we don’t know are all too often completely invisible. To a great degree, we fail to recognize the frequency and scope of our ignorance.

In 1999, in the Journal of Personality and Social Psychology, my then graduate student Justin Kruger and I published a paper that documented how, in many areas of life, incompetent people do not recognize—scratch that, cannot recognize—just how incompetent they are, a phenomenon that has come to be known as the Dunning-Kruger effect. Logic itself almost demands this lack of self-insight: For poor performers to recognize their ineptitude would require them to possess the very expertise they lack. To know how skilled or unskilled you are at using the rules of grammar, for instance, you must have a good working knowledge of those rules, an impossibility among the incompetent. Poor performers—and we are all poor performers at some things—fail to see the flaws in their thinking or the answers they lack.

What’s curious is that, in many cases, incompetence does not leave people disoriented, perplexed, or cautious. Instead, the incompetent are often blessed with an inappropriate confidence, buoyed by something that feels to them like knowledge.

snip:
 Because it’s so easy to judge the idiocy of others, it may be sorely tempting to think this doesn’t apply to you. But the problem of unrecognized ignorance is one that visits us all. And over the years, I’ve become convinced of one key, overarching fact about the ignorant mind. One should not think of it as uninformed. Rather, one should think of it as misinformed.

An ignorant mind is precisely not a spotless, empty vessel, but one that’s filled with the clutter of irrelevant or misleading life experiences, theories, facts, intuitions, strategies, algorithms, heuristics, metaphors, and hunches that regrettably have the look and feel of useful and accurate knowledge. This clutter is an unfortunate by-product of one of our greatest strengths as a species. We are unbridled pattern recognizers and profligate theorizers. Often, our theories are good enough to get us through the day, or at least to an age when we can procreate. But our genius for creative storytelling, combined with our inability to detect our own ignorance, can sometimes lead to situations that are embarrassing, unfortunate, or downright dangerous—especially in a technologically advanced, complex democratic society that occasionally invests mistaken popular beliefs with immense destructive power (See: crisis, financial; war, Iraq). As the humorist Josh Billings once put it, “It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so.” (Ironically, one thing many people “know” about this quote is that it was first uttered by Mark Twain or Will Rogers—which just ain’t so.)

Because of the way we are built, and because of the way we learn from our environment, we are all engines of misbelief. And the better we understand how our wonderful yet kludge-ridden, Rube Goldberg engine works, the better we—as individuals and as a society—can harness it to navigate toward a more objective understanding of the truth.


snip:
 But here is the real challenge: How can we learn to recognize our own ignorance and misbeliefs? To begin with, imagine that you are part of a small group that needs to make a decision about some matter of importance. Behavioral scientists often recommend that small groups appoint someone to serve as a devil’s advocate—a person whose job is to question and criticize the group’s logic. While this approach can prolong group discussions, irritate the group, and be uncomfortable, the decisions that groups ultimately reach are usually more accurate and more solidly grounded than they otherwise would be.

For individuals, the trick is to be your own devil’s advocate: to think through how your favored conclusions might be misguided; to ask yourself how you might be wrong, or how things might turn out differently from what you expect. It helps to try practicing what the psychologist Charles Lord calls “considering the opposite.” To do this, I often imagine myself in a future in which I have turned out to be wrong in a decision, and then consider what the likeliest path was that led to my failure. And lastly: Seek advice. Other people may have their own misbeliefs, but a discussion can often be sufficient to rid a serious person of his or her most egregious misconceptions.

The built-in features of our brains, and the life experiences we accumulate, do in fact fill our heads with immense knowledge; what they do not confer is insight into the dimensions of our ignorance. As such, wisdom may not involve facts and formulas so much as the ability to recognize when a limit has been reached. Stumbling through all our cognitive clutter just to recognize a true “I don’t know” may not constitute failure as much as it does an enviable success, a crucial signpost that shows us we are traveling in the right direction toward the truth.

https://psmag.com/social-justice/confident-idiots-92793

(lots deeper at link)

morganism

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« Reply #41 on: July 22, 2022, 12:38:36 AM »
Eggs can survive decades without signs of aging. Now, scientists may know why

"In the 1980s, Aitken uncovered a major cause of male infertility — free radicals attacking sperm DNA. Böke’s group demonstrated that for much of their early lives, oocytes are not protected from free radicals, as many scientists believed, but instead avoid generating these toxic molecules in the first place by a careful restructuring of their metabolism.

Mitochondria power the cell by taking electrons and using them to make a cellular fuel called ATP, through a process known as oxidative phosphorylation. It doesn’t happen all at once, but in a series of linked steps involving five protein complexes. Complex I is the largest of these molecular machines and the first to accept electrons.

“It’s considered to be the gatekeeper of this process,” Böke told STAT via email. So she was surprised to find that in studies of human and frog oocytes, the mitochondrial genes that produce Complex I were turned off. Only one other multicellular organism is known to be able to exist without it — the parasitic mistletoe.

By skipping Complex I, primordial oocytes are able to maintain a super-low energy state, kind of like standby mode, while removing a major source of electron leakage, and therefore damage from free radicals.

“The safeguards built here are more robust than those in many other systems, like the heart or liver, a testament to the importance of conserving reproduction,” said Johan Auwerx, a molecular biologist who studies metabolism and aging at École Polytechnique Fédérale in Switzerland. “Excellent functional oocytes allow reproduction, which is the most important act of our existence, from an evolutionary perspective, since it allows the continuation of the species.”

The trade-off though, is that this strategy only seems to be viable for about 35 years in humans. But now that they have a window into what’s happening mechanistically, Böke said fertility doctors could start testing for levels of Complex I subunits in oocytes of women with unexplained infertility to see whether an early exit from this quiescent state is causing the problem. The discovery also points the way toward possible treatments.

“If inhibition of Complex I is what drives these oocytes to stay safe in a quiescent state, then interventions that inhibit activity of Complex I may help extend reproductive lifespan,” said Hine.

One example of a drug that targets Complex I is metformin. Approved in the 1990s for treating diabetes, and since then prescribed to millions of people around the world, metformin has long been linked to longer, healthier lifespans. Researchers comparing the health of people on the drug to those taking other diabetes medications found that metformin-takers tended to get cancer less frequently, were less likely to suffer from age-related dementia, and, in general, just lived longer."

https://www.statnews.com/2022/07/20/why-eggs-can-survive-decades-without-signs-of-aging/


Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I


Mitochondrial ROS in early oocytes

Early human oocytes can be accessed only through invasive surgery into ovaries. Therefore, biochemical investigations into oocyte biology have historically been hindered by severe sample limitations. As a consequence, mitochondrial activity in primordial oocytes remains largely unstudied. Here we overcome challenges imposed by human oocytes by utilizing an improved human oocyte isolation protocol recently developed in our laboratory6, which we combine with a comparative evolutionary approach using more readily available Xenopus stage I oocytes (both referred to as early oocytes hereafter; Extended Data Fig. 1a,b). This approach allowed us to generate hypotheses using multi-species or Xenopus-alone analyses, and subsequently test those hypotheses in human oocytes.

We began our studies by imaging live early human and Xenopus oocytes labelled with various mitochondrial probes that quantify ROS levels. Neither Xenopus nor human early oocytes showed any detectable ROS signal, whereas mitochondria in somatic granulosa cells surrounding the oocytes exhibited ROS and served as positive controls (Fig. 1a–c and Extended Data Fig. 1c–g). ROS induction in oocytes also served as a positive control for live ROS probes.

To distinguish between the possibilities that low ROS probe levels resulted from low ROS production or, alternatively, a high scavenging capacity to eliminate ROS, we treated Xenopus oocytes with menadione and assessed their survival (Extended Data Fig. 1j). Mild treatment with menadione promotes the formation of ROS (ref. 10) but does not affect survival negatively in cell lines and fruit flies11,12. However, most early oocytes (78.3%) died when they were left to recover overnight after menadione treatment, in contrast to what was observed for late-stage oocytes (Fig. 1d and Extended Data Fig. 1j). Treatment with an antioxidant that quenches ROS was able to rescue oocyte survival (Fig. 1d). These results indicate that evasion of ROS damage in oocytes involves tight control of ROS generation, rather than a higher scavenging capacity of oocytes against ROS.
Mitochondrial respiration in oocytes

Using dyes that sense membrane potential (tetramethylrhodamine ethyl ester perchlorate (TMRE) and the cyanine dye JC-1), we found that mitochondria in human and Xenopus early oocytes exhibit lower membrane potentials compared to those of neighbouring granulosa cells, which served as positive controls (Fig. 2a,b and Extended Data Fig. 2a–d). Undetectable ROS levels and low membrane potential suggest that the mitochondrial electron transport chain (ETC) activity in early oocytes is either low or absent. To differentiate between these two possibilities, we measured respiration rate in Xenopus oocytes. Early oocytes stripped of granulosa cells exhibited a low basal respiration rate but a similar maximal respiration rate compared to those of growing oocytes (Fig. 2c and Extended Data Fig. 2e,f). This respiration was efficiently coupled to ATP synthesis, resulting in an undetectable proton leak (Extended Data Fig. 2e). Therefore, we conclude that mitochondria in early oocytes have a functional ETC, with low activity.

Mitochondrial proteome in oocytes

Mitochondria in early oocytes have an apparent lack of ROS, low membrane potential, low basal respiration rates and rotenone resistance in culture. We next investigated the mechanistic basis of this unusual mitochondrial physiology.

To do this, we purified mitochondria from early and late-stage Xenopus oocytes isolated from wild-type outbred animals, and performed proteomics using isobaric-tag-based quantification including muscle mitochondria as a somatic cell control (Extended Data Fig. 3a). Our efforts identified 80% of all known mitochondrial proteins (Extended Data Fig. 3b,c and Supplementary Table 1). Most ETC subunits showed a lower absolute abundance in early oocytes compared to that in late-stage oocytes (Fig. 3a), and to muscle (Extended Data Fig. 3d), which is expected owing to the presence of fewer cristae in mitochondria of early oocytes13,14,15 and compatible with their NADH levels16. In support of our findings with the ETC inhibitors (Fig. 2d and Extended Data Fig. 2g), the depletion of complex I in early oocytes was the most pronounced of all ETC complexes (Fig. 3a and Extended Data Fig. 3e). We reinforced this result by repeating proteomics with heart, liver and white adipose tissues.

Furthermore, among the most abundant proteins in the mitochondria of early oocytes were mitochondrial proteases and chaperones (Fig. 3b and Extended Data Figs. 3i,j and 4a). These proteins are upregulated after the activation of the mitochondrial unfolded protein response (UPRmt)17,18,19, which is often triggered by an imbalance of ETC subunits in mitochondria. Consistent with an active UPRmt (ref. 20), nuclear transcripts encoding complex I subunits were downregulated in early oocytes whereas mitochondrially encoded transcripts of complex I did not show significant changes compared to those of late-stage oocytes (Extended Data Fig. 3k,l).

We next examined whether complex I subunits were also depleted in human oocytes. Early oocytes and ovarian somatic cells were isolated from ovarian cortices of patients, and analysed by label-free proteomics. We identified 40% of all known mitochondrial proteins (Supplementary Table 3). The upregulation of proteins related to UPRmt was conserved in human early oocytes, and further confirmed with immunofluorescence (Fig. 3c and Extended Data Fig. 4b). An analysis of the OXPHOS machinery comparing oocytes and ovarian somatic cells revealed that, in line with the Xenopus data, many complex I subunits were either at very low levels or not identified in human oocytes (Fig. 3d,e and Extended Data Fig. 5a).

In conclusion, our proteomic characterization of mitochondria revealed an overall reduction of ETC subunits in early oocytes of human and Xenopus, with complex I levels exhibiting the strongest disproportionate depletion.
Absence of complex I in early oocytes

Taken together, the results of our proteomics and survival experiments suggest that both early human and Xenopus oocytes remodel their ETC to decrease complex I levels to an extent that complex I becomes unnecessary for survival. This result is unexpected, because no other animal cell type with functioning mitochondria has been shown to be able to dispense with complex I in physiological conditions, and only one other multicellular eukaryote, the parasitic plant mistletoe, is known to dispense with complex I entirely21. Therefore, we directly assayed complex I assembly status and function in early oocytes, using colorimetric, spectrophotometric and metabolic assays."

https://www.nature.com/articles/s41586-022-04979-5