August 2015 Blog with Durk and Sandy

— Voltaire

— William Burroughs, 1992

— Mark Twain (Mark Twain Speeches, 1996; speech made in 1900)

— Mae West 
From same source: Mae West’s advice on how to keep a man: “You have to keep your eye on the balls. If you don’t take good care of your man, someone will.” Quoted in The Penguin Book of Interviews, ed. C. Silvester, 1993

— H. L. Mencken

— Helen Rowland (from Love, A Book of Quotations, ed. Ann Braybrooks, Dover Publications, 2012)

Reversal of Androgen Inhibition of Estrogen-Activated Sexual Behavior by Cholinergic Agents

We have previously written about the interaction of the cholinergic nervous system and estrogens in our hypothesis (also shared by others) that it is the decline in the cholinergic nervous system with age that is largely responsible for the fact that restoration of estrogen in ovariectomized animals after a certain period of time no longer provides the cognitive advantages of estrogen that occur when it is given right after ovariectomy (Hammond, 2011).

Now, we have come across a relatively early paper from 1989 (Dohanich, 1989) that reports that the inhibition by androgens of estrogen-induced sexual activity in ovariectomized female rats can be reversed by cholinergic agonists, which included in this study carbachol and the acetylcholinesterase inhibitor physostigmine. The nutrient choline also increases cholinergic activity (Mike, 2000) and, of course, galantamine (an acetylcholinesterase inhibitor) would be expected to act in a similar manner as the acetylcholinesterase inhibitor physostigmine.

This is a very interesting study that shows that the decline of the cholinergic system is likely to play a major role in the decline in sexual activity with age in post-menopausal women. Both testosterone and its 5-alpha reductase product dihydrotestosterone have been shown to inhibit diverse responses regulated by estrogens, including functions of the female reproductive system such as ovarian growth, follicular development, and progestin receptor induction, as well as inhibiting estrogen-activated female sexual behavior (such as lordosis) in female rats, mice, and hamsters. Cholinergic antagonists have been found to inhibit sexual behavior in ovariectomized females treated with estrogen and progesterone.

The cholinergic agonists that activate lordosis in the animals are mediated by the muscarinic type cholinergic receptors and lordosis is prevented by blockers of these receptors (Dohanich, 1989). Note that muscarinic cholinergic antagonists are very widely used for treating urinary urgency and incontinence in older women and these drugs may be impairing the libido of these older women.

Thus, the purpose of this study was to test the ability of cholinergic agents to reverse the inhibitory effects of dihydrotestosterone on estrogen-induced lordosis in female Long-Evans rats.

Interestingly, the acetylcholinesterase inhibitor physostigmine was more effective in increasing the incidence of lordosis in the rats than the cholinergic receptor agonist carbachol. Both physostigmine and carbachol were administered via intracerebral intraventricular infusion but these agents pass through the blood-brain barrier so this may have been done to ensure that a specific dose was received in the target tissue, whereas with oral treatment, there is not as much certainty on how much of the ingested treatment reaches the target tissue, especially when it is in the brain.

References

• Hammond and Gibbs. GPR30 is positioned to mediate estrogen effects on basal forebrain cholinergic neurons and cognitive performance. Brain Res. 1379:53-60 (2011).

• Dohanich and Cada. Reversal of androgen inhibition of estrogen-activated sexual behavior by cholinergic agents. Horm Behav. 23:503-13 (1989).

• Mike, Castro, Albuquerque. Choline and acetylcholine have similar kinetic properties of activation and desensitization on the alpha7 nicotinic receptors in rat hippocampal neurons. Brain Res. 882:155-68 (2000).

 

In the News: Women’s Dementia Worsens Faster Than Men’s

So says a headline in the July 22, 2015 The Wall Street Journal. According to the study (398 subjects who participated in the Alzheimer’s Disease Neuroimaging Initiative), women’s cognitive decline took place about twice as fast as men’s. The good news is that it is very likely, based on scientific studies showing that women need more choline than men do (Fischer, 2007), and that, as choline has been identified as a nutrient important to cognition (Poly, 2011) a deficiency of choline is one cause of this vulnerability to dementia in women. Not only does estrogen play an important role in the cholinergic nervous system (Fischer, 2007, Craig, 2010)—estrogen that declines rapidly following menopause—but it is known that in older people, choline is taken up less effectively into the brain (Cohen, 1995). In addition, women are much more susceptible to autoimmune diseases than men are and the cholinergic nervous system is a major antiinflammatory system (Tracey, 2007).

Add it all up and the evidence points to a need for additional choline in older women. The amount of choline recommended by the Institute of Medicine (IOM) for non-pregnant women, 425 mg a day, is (in our judgment) too low to supply adequate amounts of choline to older women when you consider the reduced ability to transport choline into the brain, the loss of estrogen, and also the variation (dietary composition (van Wijk, 2012), choline consumption, genetic and epigenetic differences in the ability to absorb choline from the diet, get it into the brain, and then convert it to phospatidylcholine via biochemical pathways) between individuals suggests that the amount that may be adequate for much of the population per the IOM recommendation may not be adequate for YOU.

In short, choline is a major nutrient for keeping your cognitive function in good condition as you get older. We ourselves take 2 grams a day of choline in the form of choline dihydrogen citrate.

References

• Fischer, daCosta, Kwock, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr. 85(5):1275-85 (2007).

• Poly, Massaro, Seshadri, et al. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Am J Clin Nutr. 94:1584-91 (2011).

• Craig, Brammer, Maki, et al. The interactive effect of acute ovarian suppression and the cholinergic system on visuospatial working memory in young women. Psychoneuroendocrinology. 35:987-1000 (2010).

• Cohen, Renshaw, Stoll, et al. Decreased brain choline uptake in older adults. An in vivo proton magnetic resonance spectroscopy study. JAMA. 274(11):902-7 (1995).

• Tracey. Physiology and immunology of the cholinergic antiinflammatory pathway.J Clin Invest. 117(2):289-96 (2007).

• van Wijk, Watkins, Bohlke, et al. Plasma choline concentration varies with different dietary levels of vitamins B6, B12 and folic acid in rats maintained on choline-adequate diets. Br J Nutr. 107:1408-12 (2012)

 

Battle of the Sexes: 
Here, There, and Everywhere 
Horses, Cattle, Baboons, Bonobos, And Humans, Now and 2000 
Years Ago In the Roman Empire

by Sandy Shaw

Many of you may have heard of what happened to Nobel Prize Winner Tim Hunt, 72, who was reported (for example, see pg. 1294 in the 19 June 2015 Science) to have been “punished” for making purportedly “sexist” statements about women scientists in the lab (resigning from his post as an honorary researcher at University College London and from the European Research Council’s Scientific Council, as well as from the Royal Society’s Biological Sciences Award Committee, presumably under pressure from these organizations to do so). Dr. Hunt had declared his statements to be “funny” and the response to be “extreme and unfair.” He had been reported to have said that he favored one-gender scientific labs in part because female scientists fall in love with their male associates in the lab and cry when criticized. One wonders why Dr. Hunt would have said this if he hadn’t actually observed such behavior in scientific labs, but of course we weren’t there so we can’t say.

Dr. Hunt has gone on to apologize for his “inexcusable” statements though, as noted above, he was reported to have thought the response extreme and unfair. You can’t be sure whether Dr. Hunt really thought his statements “inexcusable” or whether this is all a political ploy to recover his former status with the feminist scientists (mostly women) who wield much power these days in organized science. Too bad such games have become a very sad and frequent event, enough to make you wonder how the hell did this pathetic view of male/female “equality” (e.g., the genders behave the same and therefore should be treated the same) come about in the first place.

In fact, the status of males and females can differ rather surprisingly in animal relationships. See next paragraph for Durk’s observations on cattle and wild horses. The two of us are ranchers of “natural beef” in central Nevada and have what is considered a medium sized herd. Our cattle wander freely over hundreds of thousands of acres of lush pasture and eat nothing but these natural grasses, supplemented with the occasional natural wheat plus some minerals that are lacking locally, such as copper, and drink water from springs or that has flowed down mountains from natural sources.

We have several bulls that can mate with whoever they want to, assuming the lady cow is willing and if in heat she is certainly likely to be, so the cows and bulls are pretty much masters of their own lives for however long they live before some of them—mostly steers that are not going to be breeding or old females past their prime breeding age—are sold for human consumption. For the rest, it is a pretty easy life.)

Among wild horses, the alpha female is the one who knows where the water holes and forage are located and she is followed by the entire group, including the big, bad alpha stallion, when leading the group to both food and water. The stallions are there to provide protection of the group from predators and, of course, to maintain their monopoly on mating with the female horses in the group. Then, there are cattle. The alpha female knows where the food and water are located and leads the group to it, including the big masterful bulls with their large intimidating balls, who are there (once again) to protect the group from predators and to ensure that they retain complete control of sexual access to the females in the group. (As a cow, you aren’t supposed to lift your tails for those other bulls over there, but it probably does happen now and again, so the bulls that “own” you have to be vigilant.)

Maybe this picture of who runs the herd is a little different than you might have thought. How have things changed among humans so that there is an ongoing virtual war over who controls the group’s resources in common (the human political process where decisions are made for the use of your tax money by vote—one person one vote (except when corruption occurs, but that is another story) and somehow or other political incorrectness has made the feminist view so powerful. Horses and cattle don’t vote, so maybe the picture you see there is a bit better model for considerations of gender control under “natural” conditions among mammals that are fairly close to humans in terms of having similar genomes.

In human hunter-gatherer groups, it is plausible that females might have a better map of local sources of water and plant food than men, who might know more about more distant sources of water and animal food. This would lead perhaps to a more “egalitarian” type society by providing for a division of labor with distinct trade goods and services between the males and females.

Our current society of huge numbers of humans under rules established within much smaller numbers of humans has led to dysfunctional societies as the genders have learned to use the guns of political power to set the rules and control the division of the public goods to a considerable extent to the benefit of one gender or another. Men seemed to have started out with a greater share of the political power in the U.S. and that has now been taken over by females after a long “war” between the genders. Women now to a considerable extent are able to reproduce by virtue of political resources extracted from men by government coercion, whereas in earlier days women had to find willing husbands to support their reproductive urges.

A recent paper on group decision making in olive baboons (19 June 2015 Science, pp. 1358-1361) suggests that, despite the large intimidating jaws of male baboons and their vital role in defending the group from predators and (of course) in rationing out sexual access to female baboons between the more dominant males and the subordinate ones, when it comes to day-to-day decisions about where the group is to move to next, unless there is a large difference between the alternatives, the group makes its choice on an individual basis, with the minority following the majority. Whereas if the alternatives are very different, then the decision is delayed but still takes place by a minority following a majority to the new location. Dominant males appear to have nothing to do with these day-to-day movement patterns. This probably came as quite a surprise to most scientists reading the paper, as it did to me. Method: The researchers obtained their data on patterns of movement among the olive baboons by fitting approximately 80% of the study troop’s adult and subadult members with a custom-designed global positioning system collar that recorded the location of each individual fitted with one every second.

The gender practices in place in bonobo society are the ones I like best. There, sexual activity is used to displace aggression, leading to an unusually peaceful sort of society with a lot of consensual sex. Though it is not clear why this doesn’t seem to have been a very successful model for gender relations, I imagine that there is a large reproductive fitness benefit in place when force is part of the picture, where males benefit (generally) from greater strength and size and can impose their sexual desires upon females. What would be particularly interesting would be to find out how the bonobos developed their unusual pattern of gender relationship in the first place.

The Roman Empire

A note on male/female relationships goes back to the Roman Empire and a fascinating look at how men at that time looked upon women who had qualities and attributes admirable to men.

On pg. 78 of his book Roman Women (Fonthill Media Limited, 2015) the author Paul Chrystal explains that “[w]omen, like slaves and children, were second class citizens, on the margins of society. They were—at least technically—always under the control of a man ...” They were seen as having no place outside the home. Yet there were Roman women who achieved positions of authority, respect, and admiration in the Roman Empire. Chrystal explains (pg 62) in his discussion of Fulvia, wife of Mark Antony and then, later of Octavian (later naming himself Augustus, the first of the Roman emperors after the Dictator Julius Caesar): “Valleius’s observation that Fulvia was devoid of basic female characteristics and, in doing what she did as a soldier, behaved as a man would, is significant. When she is defeminised in this way, Fulvia joins a tradition of notable women who were described more as men than as women by elite Roman writers. It seems clear that Roman men had a problem reconciling powerful virtues and qualities in women with their sex, with their femaleness—they thought that these eminent and successful women must really be men.” “Were women to break free of their traditional constrictions,” argued Philo of Alexandria (here in the book’s words), “it is not because they are women, but rather because they exhibit qualities more appropriate to men.”

Valerius Maximus in the later Roman Republic cites the case of Maesia Sentias, “who conducted her own defense before the praetor” (pg. 78) ... “and through her legal expertise, secured her own acquittal. Valerius ascribes this success to a masculine spirit ...”

The author, Paul Chrystal, took degrees in Classics at the Universities of Hull and Southampton, has written frequently for the BBC over 35 years, and has published forty or so books on classical social history and other subjects. This book, Roman Womenincludes a large number of references to primary literature as reported and cited in the book. Chrystal is said to be publishing In Bed with the Romans in 2015 and Sandy is looking forward to reading it, complete with revelations of fun in bed with men in the Roman Empire, whose opinions of women may or may not please her but she is (obviously) free to ignore or not as she chooses. Incidentally, being seen as having a “masculine spirit” or the attributes of a man is quite agreeable to Sandy, as she rather admires many attributes and qualities that she sees more frequently in men than in women and, moreover, she has no sense of a gender label defining her.

Women Live Longer Than Men: A Significant Factor in the “Battle Between the Sexes”

A recent review paper (Vina, 2010) describes the phenomenon of women living longer than men, with some discussion of possible mechanisms, and of the societal implications of larger numbers of dependent older women as compared to men.

The authors (two men) point out that the “difference in longevity between woman and men has occurred in all advanced as well as primitive societies.” They also provide data indicating that as human lifespan has increased, the difference between the lifespan of women as compared to men has become even greater. “... in 1900 (i.e. when the average lifespan [in Spain] was approximately 33 years), women lived only 3.8% longer than men. However in 1992, when average lifespan was around 75-80 years, the increased longevity between women and men increased to almost 10%. This is by no means a characteristic of a given country (i.e., Spain) but rather it is a general phenomenon.” The paper includes a figure showing that there is a significant increase in life expectancy of females vs. males in Sweden as well. The authors also state that in the Caucasians, well known to have long-lived individuals, women also live longer than men.

On the matter of age-dependent dependency, the authors show (in figure 2 of their paper) that in the European Community the proportion of persons over 65 years old who are dependent on others for their care was (in 2010) about 25%. However, they say, “the predicted proportion of population of 65 years that is dependent on others will be about 50% in 2050. (We do not know how they made this estimate, but it depends on extrapolation from conditions as they now exist, a highly questionable assumption.) Still, the outlook is grim even if they are only half right. This would lead to a situation where young men were being taxed to support a larger population of older dependent women, hardly the sort of thing to alleviate a battle between the sexes.

The authors propose that the difference in longevity between women and men could be related to differences in mitochondrial free radical production, as estrogens are protective against oxidative stress. They cite two studies showing that “estrogen replacement therapy can increase life expectancy in humans.” These researchers have done work on Wistar rats, finding that liver mitochondria from females produce approximately half the amount of peroxide produced by males. Ovariectomized Wistar rats were found to produce the same amount of peroxides as males and when the ovariectomized females were treated with estrogen replacement, they again produced the same amount of peroxide as normal female rats at the level much lower than males.

Moreover, the authors go on to describe a study (Ali, 2006) by another group that showed that in strains of mice such as the Black C57BL6 the other group was studying, males lived longer than females and it is the males that produce fewer oxidants than females. That study included the determination of oxidants not only by measuring dihydroethidium oxidation in the brain but also by electron paramagnetic resonance spectroscopy in brain mitochondria of these mice where the males outlived the females.

Finally, the authors (Vina, 2010) propose that estrogens do not act as chemical antioxidants, but rather induce the expression of antioxidant enzymes. In an attempt to test this hypothesis, they suggest the use of phytoestrogens, such as genistein, because (in the case of genistein) it binds almost exclusively to the estrogen receptor beta, thus avoiding the feminizing and potential cancer increasing effects of estrogen receptor alpha. They did not report in this paper on what they may have found in their phyto­estrogens/life extension studies.

References

• Vina and Borras. Women live longer than men: understanding molecular mechanisms offers opportunities to intervene by using estrogenic compounds. Antioxid Redox Signal. 13(3):269-77 (2010).

• Ali, Xiong, Lucero, et al. Gender differences in free radical homeostasis during aging: shorter-lived female C57BL6 mice have increased oxidative stress. Aging Cell. 5:565-74 (2006).

 

A Final Final Note on Male/Female Relationships SURPRISE: Men Really Do Choose Women on the Basis of Beauty

I don’t expect anyone to be surprised by this, but a scientific study (Todd, 2007) was performed to actually verify that men, when choosing potential mates, are highly attracted by female beauty as compared to other attributes, even including wealth, health, and social status.

Scientists got their subjects from a group of men and women who were participating in a “speed dating” event, where they met a number of different “dates” one after another for conversations just a few minutes each. The researchers had the 46 adult participants fill out a questionnaire in advance providing the stated preferences of the participants and then compared that to the actual choices. (Men and women could choose to meet a particular man or woman again or not to meet them again after interacting with them in the “speed dating” event.) Surprise, surprise, no matter what they had in their stated preferences before the event, men chose women based on their physical attractiveness, whereas women were more choosy, choosing men whose overall desirability as a mate matched the woman’s perceived physical attractiveness. In fact. women’s self perceived attractiveness was the only domain-specific self perception that was substantially correlated with the number of offers (to be met again) from men. The researchers put it this way: “They [the women] appeared to be aware of the importance to men of their own physical attractiveness, and they used their self-perception to adjust their aspiration level and picked only a few men with traits that matched their own desirability as a mate.”

So there you have it. The choices made by men and women in the speed-dating events closely match that predicted by the Darwinian principle of choosy females and competitive males, all in the name of reproductive fitness.

Our advice as concerns the Battle of the Sexes is to resign from it. However, this requires a considerable amount of introspection to keep track of the booby traps that reside inside your head and get you into trouble because the urges built in by your reproductive drive (such as falling in love, which famous rock star Ted Nugent described as having the effect of a “tire iron”) may not always match the choices of other drives that coinhabit your brain.

Reference

• Todd, Penke, Fasolo, Lenton. Different cognitive processes underlie human mate choices and mate preferences. Proc Natl Acad Sci U S A. 104(38):15011-6 (2007). Apparently the study was funded by FastDating, a company based in Munich, Germany, where participants were sucked into the study by being offered a discount on the regular price for their participation.

SENSITIVITY TO PUNISHMENT 
REQUIRES SEROTONIN SIGNALING

by Sandy Shaw

Here is a remarkable paper published in 2012 (Robinson, 2012) that shows that SEROTONIN IS CRITICAL FOR PUNISHMENT-INDUCED INHIBITION. This could relate to a great many situations where paying attention to punishment is an important social signal telling a person what they shouldn’t be doing. (Of course, there are also many situations where social rules and regulations that include punishments if you don’t do them are things where you have good reason for not wanting to do them, but lets start with the experiment to keep things simple.)

The results of the study are very interesting but it included only female subjects. (I think this would have been a more interesting paper with men as the subjects, since it seems pretty obvious that the male gender is less sensitive to punishment-induced inhibition, if you can judge by (say) the number of fights your male siblings get into as compared to their sisters or the overwhelming number of men in prison for violent crimes as compared to women imprisoned for the same.) In any event, there were 41 healthy young female subjects (mean age 27.6). The key part of the experimental treatment was that 21 of the women were given a “balanced amino acid mixture” that contained tryptophan, the precursor to serotonin, while the other 20 women consumed the same amino acid mixture but without tryptophan. Thus, the latter 20 women received a tryptophan-depleting amino acid mixture to consume.

The researchers collected data on the subjects via questionnaires to account for various aspects of personality, such as impulsiveness, venturesomeness, and empathy to control for possible confounders. The very interesting overall result was that serotonin promotes the inhibition of responses to punishing outcomes, at least in females but almost certainly in males. What this means is that when people are in a state of serotonin depletion (induced in the experiment by a tryptophan depleting amino acid drink) they may be less likely to respond to punishment by being inhibited by it. This could obviously lead to resistance to social mechanisms of punishment. Depending on the situation, this could be good (resisting punishment by Hitler’s goons for assisting Jews) or bad (not paying attention when punished for stealing somebody’s bicycle).

We could even think of reducing recidivism by putting parolees on a high tryptophan diet (such as one enriched in whey protein) to keep them sensitive to social punishment for committing crimes. (Here, Durk wanted to emphasize the importance of being able to convert tryptophan to serotonin, which requires the enzymatic conversion of tryptophan to 5-hydroxytryptophan, 5-HTP. See Durk’s comments below for more on this.)

This paper included only female subjects, but other aspects of serotonin psychopharmacology work the same in males in published scientific studies, such as regulation of impulsiveness. The amazing idea conveyed by this paper is that the consumption of tryptophan is a major element in the social fabric with fascinating implications as to social control. Orwell might have been amazed.

A couple of speculations: Libertarians may be people who have a reduced sensitivity to social punishment, considering their resistance to being told what to do by “authorities.” If true, it could be due to a deficiency of dietary tryptophan or, I think rather more likely, a genetic or epigenetic disposition to be less sensitive to these signals (such as a reduced ability to convert tryptophan to 5-HTP on the pathway to making serotonin). Another speculation would be that children who don’t respond to punishment might be more likely to do so if fed a diet enriched in tryptophan, as is found in whey protein for example (Whey protein has been found to be an antidepressant in a study involving mice) (Ahmed, 2011). Bananas are also highly enriched in tryptophan. A 5-HTP-containing supplement could be an option for those who do not respond to increased dietary tryptophan. You have to keep in mind, though, that if your demands are not perceived as reasonable, your kids may not respond to punishment anyway.

The two of us also speculate that children born in and raised during a war, where their fathers are frequently absent, may also be less sensitive to punishment-induced behavioral inhibition due to the possibility that punishment coming from a father (the stronger, more aggressive, probably larger parent) may be more effective than that from a mother. Just a speculation that we have not seen tested. We would be very interested in research looking for epigenetic effects of being born and raised in wartime. One to look for might be methylation of the promoter for the tryptophan-5’-hydroxylase gene.

Finally, I think this paper might have received more attention than it did if the authors had given it a title that made it a little more clear what they had shown in the experiment. For example, the title “Serotonin is Critical for Punishment-Induced Inhibition” says it with a little more pizazz and understandability and emphasizes its importance. Read the original paper title just below to see what I mean.

References

• Robinson, Cools, Sahakian. Tryptophan depletion disinhibits punishment but not reward prediction: implications for resilience. Psychopharmacology. 219:599-605 (2012).

• Ahmed, Eldenshary, Nada, et al. Pharmacological study of the possible antidepressant activity of whey protein isolate in mice. Aust J Basic & Appl Sci. 5(12):2649-59 (2011).

MORE ABOUT SEROTONIN 
by Sandy with additions suggested to me by Durk Pearson

On converting tryptophan to serotonin: Some people have a reduced ability (due to a lower activity variant or a deficiency of the necessary enzyme) to convert tryptophan to 5-hydroxytryptophan (5-HTP), the first step in the conversion of tryptophan to serotonin. That is why some individuals who use a 5-HTP containing supplement find that it makes them feel better than if they just take a tryptophan supplement.

On dietary change: It is amazing but true that people are very resistant to changes in their diet to the extent of allowing themselves to starve if given food with which they are not familiar. It may be easier to get someone to take a tryptophan or 5-HTP containing supplement than it is to get them to include whey protein or bananas in their diet.

On SSRIs: Selective serotonin reuptake inhibitors, such as fluoxetine (Prozac^®) have been associated with some rare but horrendous massacres by certain students (male but importantly taking an SSRI) at public schools. Most people who take SSRIs find that they feel better and are more able to cope with people they don’t like being with, such as where they work. However, for a certain minority of SSRI users, serotonin can be depleted. SSRIs work by increasing the length of time that serotonin occupies the synapses where its signal is generated, preventing that serotonin from being taken back up, while the serotonin is present in the synapse, into the vesicles where some of it will be destroyed by the enzyme monoamine oxidase or it could be stored for reuse. Hence, there are those who, when taking SSRIs can deplete their store of serotonin and end up behaving as do those with serotonin depletion, insensitive to inhibition by punishment as well as being more prone to impulsive violent actions, a deadly combination in rare cases such as Columbine. (Keep in mind that newspapers publicize all these deadly attacks but not all the immensely larger number of instances when no such deadly attacks took place, giving you an insanely biased idea of how often these school massacres take place and of how dangerous it is for kids to be using SSRIs. (NOTE: We have not studied the literature in detail for how often these adverse effects take place or what sorts of kids may be vulnerable to such adverse effects from SSRIs that can take place in some kids using SSRIs, so don’t take this as a recommendation for or against it. SSRI use is correlated with violent behavior, but correlation is not necessarily evidence of causation though it may be causative. Be particularly cautious in the use of SSRIs by individuals who have agitated depression, who may be particularly sensitive to impulsive acts of violence on SSRIs.

Remembering a Pleasant Experience Protects Mice Against Stress Whereas Experiencing the Pleasant Experience Does Not

Huh? What? You might wonder about the title of this piece. How can it be that remembering a pleasant experience protects mice against “depressive-like stress responses” (Ramirez, 2015) by reactivating neurons that had previously been activated by a positive experience. Yet the pleasant experience itself did NOT provide this stress protection. Here is a paper worth thinking about because if we can use a method similar to what they used in the study to induce remembering a pleasant experience, we might also obtain this “enduring” protection against stress.

Here’s how the experiment was done. A section of the hippocampus that contributes to the generation of cellular representations of experiences by activating neurons is called the dentate gyrus. The dentate gyrus can be genetically tagged with light sensitive molecules while an animal is undergoing an experience. The dentate gyrus can subsequently be reactivated by pulses of light and, the scientists report, exhibit behavior that suggests they are recalling the experience. The physical substrate that is thought to comprise the memory of the experience is called an engram.

The mice with the light tagged dentate gyrus were subject to three possible experiences: a positive one where the male mice were put in a cage with a sexually receptive female, a neutral one where the male mice were put in an empty cage, and a negative one where they were immobilized, thereby being stressed. Following this, all the mice were subsequently exposed to stress for 10 consecutive days. Unsurprisingly, the mice became depressed and lost interest in things they enjoyed previously.

The scientists found that when they reactivated the engram every day for five days (by stimulating the tagged neurons with light), the previously stressed animals had their depressive-like symptoms of passivity and anhedonia REVERSED on day six. Yet exposing the animals to the original pleasant experience did NOT provide this effect.

The reason for this effect was not determined by the scientists that did the experiments. They provided some guesses. For example, the commentary (Dranovsky, 2015) on this study speculated that repeated recall of positive memories might result in resilience to adversity and that nostalgia is a human activity that might serve a stress-reducing purpose.

How might we duplicate these results? It has already been found that memories can be re-experienced during sleep in animals and in humans by playing a sound associated with the original experience itself. Why not just use a short clip of music that has some emotional content to “code” an experience while you undergo it and then the playing of the musical clip might perform a similar function as the light did in the light tagged dentate gyrus of the mice, by inducing a re-experiencing of the original pleasant event. Any human alive must have noticed that certain pieces of music are connected to certain events in a person’s life and induce emotions that connect to those events. Hence, it seems very plausible that this very simple method might do for us what the sophisticated method of light tagging did in the mice.

An aroma might also serve as the associated tag. Scents are processed in an extremely ancient part of the brain.

Nevertheless, neither the commentary or the paper cited here actually noted the potential use of music or scents for this remarkable stress resistance. The authors of the paper (Arzi, 2012), in fact, speculate that “exposure to natural exogenous positive cues may not be able to access similar neural pathways in subjects displaying depression-like symptoms such as passive behavior in challenging situations and anhedonia.” (No references supported this speculation.)

Here we cite a couple of the very many papers showing that exposure to sensory cues, such as music or smells, can (by being administered during an experience and then administered again during sleep), result in enhanced alertness and memory following sleep in humans and in animals.

References

• Ramirez, Liu, MacDonald, et al, Activating positive memory engrams suppresses depression-like behaviour. Nature. 522:335-9 (2015).

• Dranovky and Leonardo. The Power of Positivity. Nature. 522:294-5 (2015).

• Arzi, Shedlesky, Ben-Shaul, et al. Humans can learn new information during sleep. Nat Neurosci. 15(10):1460-5 (2012). In this paper, researchers showed that “sleeping subjects learned novel associations between tones and odors such that they then sniffed in response to tones alone.” The sniffing behavior differed according to the pleasantness of the odor. There was no later awareness of this learning process.

• Also see Payne. Sleep on it!: stabilizizng and transforming memories during sleep. Nat Neurosci. 14(3):272-4 (2011). In this commentary paper (original paper, Diekelmann, 2011), presenting an odor during wakefulness rendered memories that were reactivated during slow wave sleep to be stabilized for the waking event during which the odor was administered. This reactivation was show by fMRI to activate the hippocampus and posterior cortical regions.

• Diekelmann, Büchel, Born, Rasch. Labile or stable: opposing consequences for memory when reactivated during waking and sleep. Nat Neurosci. 14:381-6 (2011).

After a Heart Attack: Promoting Cardiac Repair and Reducing Cardiac Dysfunction

Following a heart attack, a patient is likely to be placed on a number of prescription drugs to help prevent further deterioration (which often takes place, with the eventual development of heart failure) and to help natural healing processes. Still, the number of heart attack patients that eventually develop heart failure is increasing (Wang, 2012) as a result of maladaptive cardiac repair, with the formation of non-contractile scar tissue formation one of the primary problems (Wang, 2012).

It has been reported (Wang, 2012) that “few of the drugs that inhibit scar tissue formation, promote cardiac repair and thereby improve cardiac function after reperfusion have gained clinical acceptance for a routine treatment of MI [myocardial infarction] patients.” Therefore, the researchers here have tested the utility of curcumin, a major constituent of turmeric root and a powerful anti-inflammatory molecule with anti-fibrotic properties (Wang, 2012) in the treatment of Sprague-Dawley rats given experimentally induced heart attacks.

The results showed a number of biochemical changes indicative of improved repair and reduced malfunction: reduced level of malondialdehyde (breakdown product of lipid peroxidation), inhibition of MMPs (matrix metalloproteinases, enzymes that break down proteinaceous tissues, preserved ECM (extracellular matrix) from degradation and attenuated collagen deposition (part of the scar forming process) and fibrosis (scar tissue) in the ischemic/reperfused myocardium. As part of its antifibrotic effects, curcumin significantly down-regulated the expression of TGFbeta1 (transforming growth factor beta one) and phospho-Smad2/3 (mediators of TGFbeta1) and upregulated Smad7 (has opposing effect to Smad2/3). Echocardiography was reported to show a significantly improved left ventricular end-diastolic volume, stroke volume and ejection fraction.

Method: Rats were subject to 45 minutes of ischemia followed by 7, 21, and 42 days of reperfusion respectively. Curcumin was fed to the ischemia-treated rats orally at a dose of 150 mg/kg per day only during reperfusion.

This is a small but convincing study, using a common animal model for a heart attack that includes the blockage of blood flow and its subsequent reinitiation. The very extensive testing and measurements of major players in the events that take place during and after a heart attack shows very well how the curcumin made a very important difference in how the animals’ hearts recovered from the severity of a heart attack. The authors of the study suggest that “[c]urcumin has potential as a treatment for patients who have had a heart attack.”

Turmeric root contains other constituents, including curcuminoids with even more powerful antioxidant, antiinflammatory, and immunostimulatory effects than curcumin (Chakravarty, 2009). The authors (Chakravarty, 2009) explain that “[p]urification of curcumin eliminates several substances present in the whole extract of turmeric ...” including the antioxidant protein beta-turmerin, turmerone, ar-turmerone, zingiberene, complex arabinogalactan, sesquiterpenes, pinenes, eugenol, limonene, and other substances. “The present study intends to recommend use of turmeric [ethanolic turmeric extract] over curcumin whenever possible.” We, too, recommend the use of turmeric root. Incidentally, the Chakravarty et al paper also notes that it is an age-old custom in India to have oral intake of 5-10 grams of turmeric rhizome with molasses in the morning on an empty stomach. Durk calculated that the dose of curcumin given to the rats was 5 to 10 times the amount found in the traditional Indian turmeric supplemental dose. Because curcumin is more readily absorbed from turmeric root powder than it is as pure curcumin, the differences in the dose is not as great as it appears.

References

• Wang, Wang, Tootie, et al. Curcumin promotes cardiac repair and ameliorates cardiac dysfunction following myocardial infarction. Br J Pharmacol. 167:1550-62 (2012).

• Chakravarty, Chatterjee, Yasmin, Mazumder. Comparison of efficacy of turmeric and commercial curcumin in imunological functions and gene regulation. Int J Pharmacol. 5(6):333-45 (2009).

Using Sleep to Brainwash: Reactivating Memories During Sleep of New Ways to Think About Race Learned While Awake Can Modify “Bad Attitudes,” Scientists Learn (Hu, 2015)

Using the same method of memory reactivation as described in an article above—in this case, memories of messages about race intended to “correct” bad attitudes associated with a sound that could then be used as a cue for memory reactivation during sleep, has produced true brainwashing in sleeping subjects who have no way to defend themselves against it (other than avoiding the “training” that provides the corrective messages in the first place).

As the commentary article (Hu, 2015) explains, the study shows how “... such unwanted attitudes may be persistently changed by a social counter-bias training when the fresh memories of this training are systemically reactivated during sleep after training.” “Only when this sound [the memory reactivation cue] was re-presented during slow wave sleep did the posttraining reduction in implicit social bias survive and was even evident 1 week later.” Whew! Only lasted a week, but you can be sure these do-gooders are looking for more lasting changes. Can you imagine the quiet dormitory with the sleeping students and in the background you hear this sound and, inside the minds of the hapless students, changes are taking place, messages from their “teachers” or authorities who know what is best for them are being subtly snuck into their minds so that when they wake up they have a new, “better” social attitude. Does this sound like Huxley’s “Brave New World” or The Prisoner’s Village? Indeed, the commentary brings up Huxley and his “Brave New World” after it has already occurred to us, mentioning the need for “ethical considerations.” Do you trust the folks who hold your kids prisoners in the public “education” system to share your own idea of appropriate ethical considerations? Getting CONSENT into as many of the things they can do to your kids in public schools is an urgent necessity.

The study was funded by Northwestern University and by National Science Foundation and National Institute of Health grants. However, the most revealing “Acknowledgement” might be that the final scientist on the list of those who did the work and who is, therefore, likely to be the scientist whose laboratory did the work, was said to have been an adviser to Sheepdog Sciences, a company developing educational technologies. Hence, this study is likely (we surmise) to represent the sort of approach to be taken in public education by a company trying to attract interest in its services. (You are the sheep—if you are lucky, you will be regularly sheared ... until you are deemed to be too old to be productive for the state, whence you become mutton.)

Rather than doing a study of learning that involved (say) science, the interest was in modifying racial attitudes. Beware, therefore, those of you who have children in the public education system. Your kids’ attitudes toward race and other politically charged issues that are none of their business seem to be on their minds for “educating” your kids while your kids sleep and you may not be told about this or your consent sought.

References

• Hu, Antony, Creery, et al. Cognitive neuroscience. Unlearning implicit social biases during sleep. Science. 348:1013 (2015).

• Feld and Born. Exploiting sleep to modify bad attitudes. Science. 348:971-2 (2015).

The Logic of Increasing Freedom By Appealing to the Scientifically PROVEN Human Desire to “Punish” Bad Actors

1. Increasing Freedom Takes Money

2. It is Difficult to Get People to Donate Money for Public Goods.

3. What If There Were an Easier Way to Get Money from Willing Supporters of Projects to Increase Freedom Because People WANT to Donate Money to Punish a Bad Guy DESPITE That Punishment Being a PUBLIC GOOD?

Raising More Money to Fight for FREEDOM Scientific Data Points the Way to Raising Money By 
Allowing People to “Punish” Bad Actors

How would you like to be able to take action against specific wrongdoers in government and not only would you not have to badger people into contributing money, people would flock to get their money into your hands PROVIDED they had reason to believe that you could deliver the results you promise. Sound unlikely? This is for real. Please read on.

As you know, nearly any action you bring against government is going to be a public good, which means that it is like pulling teeth to find adequate amounts of money to fund your project. (Why would people contribute when they will receive the same benefits whether they do or not?) We will describe to you here the results of scientific research that demonstrates robustly in study after study that PEOPLE WILL VOLUNTARILY PAY TO PUNISH WRONGDOERS EVEN WHEN IT MEANS THAT IT IS AT THEIR EXPENSE AND THEY KNOW IT. It is important to keep in mind that this will work ONLY if you target for punishment a specific wrongdoer who has angered people for his wrongdoing such as Governor Sandoval in the state of Nevada (who lied over and over about not raising taxes), not if you go after, say, an agency where there isn’t any SPECIFIC individual where the anger is focused. Recalling Sandoval, for example, would terminate his political career (a term limit with real teeth).

We are very enthusiastic about the potential for a part of human nature to be used to our advantage, to attract angry people who want to punish a certain politician. The program could have a name such as “PAY TO PUNISH.” This punishment behavior is called “altruism” in the scientific studies in which punishment experiments are reported. That is, the people who put in money are doing it despite the fact that they cannot privatize benefits that results from the use of their money for this purpose. People are apparently hard-wired for this. We’d love to see freedom-oriented institutions that are active in political campaigns (e.g., that support or oppose candidates for political office or who file suits against specific politicians for wrongdoing) take advantage of it.

We describe here two scientific papers published in Science and Nature, arguably the two most highly respected peer reviewed science journals, that have demonstrated the reality of people willingly paying to punish a certain bad guy. There is much more in the scientific literature. We cite a few more at the end of this article.

Hauert, Traulsen, Brandt, Nowak, Sigmund. Via Freedom to Coercion: The Emergence of Costly Punishment. Science .316:1905-7 (2007). Here the authors say, “Many experiments on so-called public goods games have shown that in the absence of such institutions [institutions that impose sanctions on defectors], individuals are willing to punish defectors, even at a cost to themselves.” “... this paves the way for the emergence and establishment of cooperative behavior based on the punishment of defectors. Paradoxically, the freedom to withdraw from the common enterprise leads to enforcement of social norms. Joint enterprises that are compulsory rather than voluntary are less likely to lead to cooperation.”

Fehr, Gachter. Altruistic punishment in humans. Nature. 415:137-40 (2002). Here, the authors say, “If those who free ride on the cooperation of others are punished, cooperation may pay. ... who will bear the cost of punishing the free riders. Everybody in the group will be better off if free riding is deterred, but nobody has an incentive to punish the free riders. Thus, the punishment of free riders constitutes a second-order public good.” The authors carried out experiments, games designed to elicit from human participants what they would willingly contribute to punish free riders (non-cooperators). “The punishment of non-cooperators substantially increased the amount that subjects invested in the public good.” “The average investment of 94.2% of the subjects was higher in the punishment condition.” Remember, these experiments allowed the participants to pay and receive actual money, so the outcome was not without some significance. Yet, in the final period of the punishment condition, 38.9% of the subjects contributed their whole endowment and 77.8% contributed 15 MUs [money units] or more,” whereas in the final period of the no punishment condition 58.9% of the subjects contributed nothing and 75.6% contributed 5 MUs or less.” They further reported that when a subject was actually punished (for not cooperating), there was an increase in the amount of investment subsequently made by those funding the punishment.

We could go on—there is much more published research—but perhaps this will have intrigued you as it did us to think how this human desire to punish specific bad guys can be used to promote freedom. See the end of this article for citations to other studies of “altruistic punishment.”

We hope to hear about the aggressive freedom fighting organizations taking advantage of this. Here in Nevada, we are sick and tired of politicians like Governor Sandoval getting elected by lying intentionally about what they intend to do after getting elected and then doing whatever they think is in THEIR interest. The political class simply lies whenever it is convenient and no longer seems to feel the slightest sense of restraint in doing so. This suggests to us that the political system is on the verge of collapse as people stop trusting the government and the perception that the government is illegitimate becomes increasingly acceptable to people. Being able to punish wrongdoers will at least restore a sense that people can exert some control over the politicians and allow more time for an extended period of orderly consideration of where we go from here. While many people have a sense of what they don’t like about the current political system, far fewer have any real understanding of what should replace it to result in a better system.

As the lyrics from the Buffalo Springfield’s “For What It’s Worth” shows, nothing much has changed. The sense of what is to replace our present disastrous political system still “ain’t exactly clear,” just as it was way back then (mid 1960’s)

“There’s something happening here
What it is ain’t exactly clear
There’s a man with a gun over there
Telling me I got to beware.

I think it’s time we stop, children, what’s that sound
Everybody look what’s going down.
There’s battle lines being drawn
Nobody’s right if everybody’s wrong...
What a field day for the heat
A thousand people in the street
Singing songs and carrying signs
Mostly say hooray, for our side
It’s time we stop, hey, what’s that sound
Everybody look, what’s going down

— Buffalo Springfield (excerpts from “For What It’s Worth” by Stephen Stills. For complete lyrics, see www.metrolyrics.com

Raising Money By Allowing 
People to Target Specific Issues 
We Never Donate $500 or $1,000, But We Would If …

Our second suggestion is that people might be willing to donate a great deal more than they do if they knew it would be used for a specific purpose, not just a general donation to support unstated activities. We never donate more than $100 for a general donation even to the most favored organizations we donate to that promote freedom. We COULD donate more but would only do so if ... we could specify what the money is to be used for. It is the difference between a public good and a good where some privatization of the benefits in exchange for our donation is possible. Right now, we would be willing to donate $500 for a well designed (in our opinion) constitutional challenge to the Sandoval taxes and another $500 for a recall of Sandoval and his #2, Hutchison. As a general donation or a donation that MIGHT include the subject of a solicitation letter, there isn’t enough certainty regarding what the money would be used for to induce us to spend more of our limited funds.

Other Papers on “Altruistic Punishment”

(Altruistic Punishment is Where the Punisher Pays to 
Punish Despite Not Getting Any More of the Bene
fits Than Those Who Don’t Pay to Punish)

Mussweiller and Ockenfels. Similarity increases altruistic punishment in humans. Proc Natl Acad Sci U S A. 110(48):19318-23 (2013). Here, the researchers show, through the use of public goods games with human participants, that perceived similarity substantially increases altruistic punishment. An example could be two conservative organizations that are very similar but differ in certain respects. Those in one group might be more inclined to punish the group that is similar but not exactly the same as they are. The authors propose that anger could result from seeing the other group as sharing basic norms but the difference in their particular understanding of a shared norm might be seen as a deliberate violation of that shared norm. The anger might lead to an increased inclination to punish. (Doesn’t this remind you of the Muslim Sunni versus Shia wars?)

Baldassarri and Grossman. Centralized sanctioning and legitimate authority promote cooperation in humans. Proc Natl Acad Sci U S A. 108(27):11023-11027 (2011). Here, “sanctioning” stands for punishment as in the U.S. has established “sanctions” against certain countries that involve restrictions on trade, for example. This study shows that such punishment can be used to promote cooperation when it is administered by “legitimate” authority. The problem, not dealt with here, is that centralized organizations such as the U.N. or the United States are no longer perceived as being very “legitimate” by rapidly growing numbers of people, but as more like “might makes right” type organizations. So the cooperation that the authors here find in public goods games are heavily reliant on participant belief in the “legitimacy” of the sanctioning authority and the likelihood that this would be forthcoming from centralized sanctioning and legitimate authority that are empowered by political systems built on lies are, we think, not likely to be forthcoming. On the other hand, reputable voluntary organizations such as Underwriters Laboratories or Consumer Reports that seek out fraud in commerce or government and then make efforts to punish the frauds (by negative publicity for example) might still, if they are effective in their policing efforts, increase cooperation.

Krasnow, Cosmides, Pedersen, and Tooby. What are punishment and reputation for? PLOS One. 7(9):e45662 (Sept. 2012).

Here, the researchers test the hypotheses that punishment favors the protection of group norms versus that it enhances personal gains from cooperation. Their results provided support for the enhancement of personal gains from cooperation. Subjects directed their cooperative efforts toward those they had punished. Rather than trying to expend their efforts to punish non-cooperators in an attempt to induce changes in their behavior, they focused their cooperative efforts on those they had already punished and who, therefore, still posed a risk to others but (because of being punished) represented a lower risk to themselves. Hence, the conclusion here was that punishment benefited punishers by providing more profitable cooperation with previously punished defectors (non-cooperators).

We mention this study because it is an interesting examination of the possibility that punishment may, under certain circumstances, involve benefits for the punisher, and therefore punishment may not always be, as it is generally claimed to be, “altruistic.”

Author’s Summary of “Why the Niacin Flush May Be 
Surprisingly Beneficial to Your Health 

i.e. It May Reduce the Risk of Alzheimer’s Disease, 
Atherosclerosis, Type II Diabetes, and other 
Inflammatory Diseases

 

“The devil is in the details, 
but so are the angels.”

— Sandy Shaw

by Sandy Shaw and Durk Pearson

Here I provide a sketch of what my heavily documented paper on this subject (available at the www.life-enhancement.com website) discusses in detail. You can get a pretty good idea of the main dots that are connected by all the technical detail by reading this summary. Durk contributed to this summary on the basis of discussions with Sandy on her paper, not having had the time to read her lengthy paper before the publication of this issue of the Durk Pearson & Sandy Shaw Life Extension Newsletter.

1. Niacin is called “immediate-release” for plain powdered or crystalline niacin that causes the most intense flush; “extended-release” or “prolonged release” niacin is released gradually over time (the flush is attenuated).

2. The niacin flush is caused by an acute release of prostaglandin D2. Prostaglandin D2 is made in the body from arachidonic acid, which is produced by a long chain of biochemical reactions from polyunsaturated fatty acids of the omega-6 class, such as linoleic acid, but not from the omega-3 (fish oils) class of polyunsaturated fatty acids (such as eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA).

3. Prostaglandin D2 can be released acutely (in a pulse) or chronically (at an elevated level over an extended period of time). The effects of prostaglandin D2 depend critically on whether it is released acutely or chronically. An acutely released pulse of prostaglandin D2 is generally ANTIINFLAMMATORY whereas chronically high release of prostaglandin D2 is generally PROINFLAMMATORY. Other important factors determining whether it is proinflammatory or antiinflammatory include the inflammatory state of the tissue where it is released and the amount that is released.

4. A chronically high level of prostaglandin D2 signaling has been reported in published papers on Alzheimer’s disease as well as in male pattern baldness, the inflammation resulting from gout, and other chronic inflammatory diseases (atherosclerosis, type 2 diabetes, data on these will be discussed in our next newsletter).

5. Whereas a chronically high level of prostaglandin D2 in Alzheimer’s disease is known to be proinflammatory, causing the death of brain cells, we (and possibly others) hypothesize that the pulsatile release of large quantities of prostaglandin D2 (which has a short biological half life) as occurs during the niacin flush might be protective against the adverse effects of chronically high levels of prostaglandin D2 as reported in Alzheimer’s disease and other inflammatory diseases by acting as a signal that attenuates the chronically high level signaling, perhaps by down-regulating its receptors and/or by reducing its chronic production and release.

6. If the pulsatile release of prostaglandin D2 of fast acting (immediate release) niacin is replaced by the longer, more chronic release of prostaglandin D2 by extended release (or prolonged release) niacin, it is more likely to cause inflammatory liver damage, even in patients whose liver can tolerate immediate release niacin in equally high doses.

7. Immediate release niacin combined with a prostaglandin D2 antagonist such as lanoprost that inhibits the niacin flush will not produce the full antiinflammatory benefits of fast acting high dose niacin.

8. The effects of a drug may be related to its time course as well as its dose. Many signaling molecules are released in a pulsatile or cyclic manner, and produce adverse effects when dosed as a prolonged constant level. Examples include insulin, growth hormone, luteinizing hormone, follicle stimulating hormone, thyroid hormone, testosterone, and many others.

9. A signalling molecule released in a pulse into an environment with a high background level of that signalling molecule is likely to be impaired in its ability to transmit the signal carried by the pulse to the tissue where that molecule is part of background “noise.”