Ant behavior: How to avoid heavy traffic

This is an unusual (i.e. most people would not think of this as an) example of gene-environment interactions. The environmental stimulus is density and space for movement; how the organisms (ants, in this case) respond to this environmental stimulus of course involves genetic and behavioral networks. Many organisms (e.g. herds of migrating wildebeests, swarms of insects and bacteria, flocks of starlings, shoals of fish, crowds of pedestrians) take part in flow-like collective movements. In most cases, all individuals cruise along the same path in a unique direction — which enables incredible coordination among large numbers of individuals.

The task of maintaining smooth and efficient movement becomes more challenging — when individuals travel in opposite directions and are likely to collide. As well as humans driving vehicles on the highway, ants are one of the rare animals in which collective movements are bidirectional. Ants are “central-place foragers”, which entails a succession of individual journeys between their nest and their foraging site. When exploiting large food sources, many species lay chemical trails (environmental signals), along which individuals commute back and forth. Flow of individuals on these trails can reach several hundred ants per minute; yet, ants seem to fare better than humans, when it comes to traffic management. ☹ However, until this study [see attached article], there was a lack of direct experimental evidence, showing that ants at high density do not get “stuck in traffic jams.”

Authors [see attached] designed experiments to investigate whether ants can maintain a steady stream of traffic — when their path to food gets more crowded. This involved manipulating the density of ants, using a combination of different-sized colonies (ranging from 400 to 25,600 Argentine ants) and changing the width of the bridge connecting the ants to their food source. The experiment was repeated 170 times, and data were collected on traffic flow, speed of ant movement, and number of collisions. For pedestrians and vehicular traffic, the flow of movement will slow down — if occupancy levels (density) reach more than 40% — whereas for ants, the flow of traffic showed no signs of declining, even when bridge occupancy reached 80%. The experiments revealed that ants do this by adjusting their behavior to their circumstances: they speed up at intermediate densities, avoid collisions at large densities, and avoid entering overcrowded trails.

This study [see attached article] embraces molecular biology, statistical physics, and telecommunications. It may also have relevance for managing human traffic, particularly as scientists develop autonomous vehicles that might be programmed to work together cooperatively as ants do. Efficient transportation is crucial for urban mobility, cell function, and survival of certain animal groups. From humans driving on the highway, to ants running on a trail, the main challenge — faced by all collective systems — is how to prevent traffic jams in crowded environments. How many years will it take, until car companies design vehicles that are as efficient as ants in traffic under crowded conditions…?? 😉

DwN

eLife 2019; 8: e48945 (2019)

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Bangladesh may become first country to adopt transgenic rice enriched in vitamin A

This topic is tangentially related to gene-environment interactions, i.e. do genetically modified organisms (GMOs) affect the environment, or other plants growing nearby, or expression of other genes in the genome of the GMO? GMOs have been the subject of much debate, often irrational or (especially in the EU) hysterical about “eating food that has been genetically modified.” However, if you think about it, Mother Nature, over many thousands of years of evolution, has inserted hundreds or thousands of pieces of foreign DNA into “natural” plants — due to such processes as horizontal gene transfer [movement of genetic material between unicellular (e.g. bacteria, yeast) and multicellular organisms (e.g. fungi, grasses, flowering plants, sea squirts, even humans) by processes other than transmission of DNA from parent to offspring; HGT has been an important factor during evolution of many organisms].

Ever since “Golden Rice” first made headlines ~20 years ago, it has been a controversial flashpoint in debates over GMO crops. Advocates have praised Golden Rice as an example of their potential benefit to humanity, whereas opponents of transgenic crops have criticized it as a risky and unnecessary approach to improving health in the developing world.

Bangladesh now appears about to become the first country to approve Golden Rice for planting [see 1-page editorial, attached]. This approval appears to show that agricultural biotechnology can be successfully developed by publicly-funded research centers for

the benefit of humankind. Still — environmental activists have not stopped expressing their strong opposition; the first harvest is not expected until at least 2021, and perhaps later. More research will be needed to demonstrate the extent of real-world benefits from Golden Rice (e.g. remedying health, lowering diseases, improving nutritional status of Third-World country citizens).

Golden Rice was first developed in the late 1990s by German plant scientists — to combat vitamin A deficiency, the leading cause of childhood blindness. Low levels of vitamin A (comprising a group of fat-soluble retinoids, including retinol, retinal, and retinyl esters) also contribute to morbidity and mortality from infectious diseases such as measles and other viruses as well as bacterial inflammatory processes. Spinach, sweet potato, and other vegetables supply ample amounts of vitamin A, but in some countries — particularly those where rice is a major part of the diet — vitamin A deficiency is still widespread. In Bangladesh, for example, vitamin A deficiency affects about one-fifth of all children.

To create Golden Rice, original experiments inserted — into the rice genome — beta-carotene synthesis genes from maize (non-domesticated corn). These GMO plants then paved the way for other researchers to breed the Golden Rice organism into varieties that suit local tastes and geographical growing conditions. Over the past 2 years, regulators in the U.S., Canada, New Zealand, and Australia have approved Golden Rice for consumption. There are no plans to grow Golden Rice in these four countries, but approval in these four Western-World countries will prevent any lawsuits or other legal issues, if Golden Rice somehow accidentally turns up in the food supply of any of these countries [see attached editorial for more].

DwN

Science 22 Nov 2019; 366: p. 934 (1-page editorial)

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Individual differences in aversive-stimulus processing — appears to explain alcohol use disorded (AUD) in mice

Why are some people able to control their alcohol drinking, whereas others feel compelled to drink — despite undesirable health, personal, and/or social consequences? Today’s topic is well suited for GEITP, because gene-environment interactions play a central role in alcohol use disorder (AUD). AUD is defined as “losing control over alcohol drinking to the point of compulsion” (i.e. consuming excessive amounts of alcohol, despite negative consequences of developing numerous diseases). Almost 20% of adults worldwide engage in heavy alcohol drinking episodes during their lifetimes; in the U.S. only about half of these heavy drinkers are able to control this habit, or quit drinking entirely — even when faced with adverse health consequences caused by heavy drinking. Neither individual differences that drive compulsion, nor (central nervous system; CNS) circuitry of compulsive alcohol intake, are well understood.

Authors [see attached article & editorial] demonstrate individual differences in neuronal activity that represent a newly described brain circuit in mice during early alcohol addiction. [Gee whizzikers, just think of that!! … genetics might be involved.] This neuronal activity predicts escalation of alcohol drinking from mild, to compulsive, amounts of consumption. People drink alcohol to excess for a variety of reasons; but, as the mouse model demonstrates [in the attached article], not all heavy drinkers become compulsive drinkers. Compulsive drinkers are able to bypass this aversion (physiological or emotional response to a stimulus indicating that an object, organism, or situation, should be avoided; it is normally accompanied by a desire to withdraw from, or avoid, the unpleasant stimulus).

It seems likely that a genetic predisposition underlies the likelihood of developing addictive alcohol intake; in this study, authors take a major leap forward to show individual differences in compulsion — specifically, the consumption of bitter and unpleasant quinine-adulterated alcohol — at the level of neuronal activity (this would be equivalent to drinking gin-and-tonics daily ☹ ] By measuring neuronal changes in intracellular calcium concentrations (as a proxy for neuronal electrical activity during alcohol drinking), the authors identified clusters of neuronal activity when mice licked tubes of alcohol.

The alcohol drinking–associated neuronal activity was found to be located in a circuit between the medial prefrontal cortex (mPFC) and dorsal peri-aqueductal grey (dPAG) of the brain stem. Multiple lines of evidence from animal models had previously suggested a role of the PFC in compulsive alcohol drinking; the PFC lies in the frontal cortex (just behind the forehead in humans) and is responsible for “executive” functions, i.e. judgment, decision-making, and behavioral mood control. These functions are impaired during drug and alcohol addiction, especially in severe AUD. Hence, authors focused in detail on anatomical studies of calcium tracers, which showed that this mPFC-dPAG circuit responds to unpleasant stimuli in the brain. The PAG, best known for its role in pain, has reciprocal connections with many addiction-relevant brain regions, including the PFC. Recent discoveries have extended the role of the PAG to punishment and aversion signals — both of which are aspects of compulsion and addiction. Thus, it is not surprising that this mPFC-dPAG circuit has a role in alcohol compulsive behavior.These data provide detail on brain-and-behavioral relationships that underlie the individual differences in compulsive alcohol drinking in mice.

DwN

Science 22 Nov 2019; 366: 1008-1012

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Why Fewer Toys Is the Better Option

This is an interesting article from Psychology Today — very appropriate for this time of year, when I’ve seen in past years some parents INUNDATING their children with not one or two “major” toys for Christmas, but rather six or ten. My first thought was GLUTTONY, i.e. “the number and cost of all the toys” are not correlated with “the amount of happiness” in the recipient child…

D

Why Fewer Toys Is the Better Option
When it comes to toys, in terms of development and creativity, less is more.

Posted Dec 14, 2017

Syda Productions/Shutterstock

Source: Syda Productions/Shutterstock

Toys seem like an inevitable by-product of parenting. If your home teems with too many must-have fad items, toys, or gizmos that ever caught your child’s fancy, you’re not alone.

Now there is good news for parents who fear their children’s play areas resemble a toy store: A study from the University of Toledo in Ohio suggests “an abundance of toys present reduced quality of toddlers’ play.” Having fewer toys can lead a young child to focus and engage in more creative, imaginative play, according to the study, “The influence of the number of toys in the environment on toddlers’ play” published in the journal Infant Behavior and Development. Fewer toys, it turns out, result in healthier play, and, ultimately, deeper cognitive development.

Researchers observed 36 toddler subjects between the ages of 18 and 30 months in free-play sessions. The toddlers were given either four toys or 16. “There was a significant difference in the quality of toddlers’ play between the two toy conditions,” the study reports. “As measured by sustained play and variety of manners of play, toddlers had a greater quality of play in the Four Toy condition compared to the Sixteen Toy condition.” Essentially, when given a few toys, the toddlers played with them in more varied ways and for longer periods of time.

The study echoes several experts who in recent years have advocated for streamlined, or even toy-free, play areas for young children. In his book Clutterfree with Kids, Joshua Becker describes too many toys as a distraction from development. “Imagine the impact that hundreds of toys in our homes may be having on our kids,” he wrote in response to the new findings.

Alexia Metz, one of the researchers in the Toledo study, notes that all the participants played under both conditions — four and 16 toys — on different days and in random order, so that the difference reflected the change in the environment and controlled to some extent for variability among children. When the children were given 16 toys, Metz and her colleagues were able to confirm the distraction and disadvantage: “The results of the present study suggest that an abundance of toys may create such a distraction. With fewer toys present [referring to the four toy group], participants engaged in longer epochs of play.”

The children with four toys exhibited one-and-a-half times more interactions with the toys, indicating that young children “are more likely to play in more sophisticated, advanced ways with fewer toys present,” according to the study. This increased involvement with a toy has positive implications for many facets of development, including imaginative and pretend play, self-expression, physical skills such as fine motor coordination, and problem-solving.

This isn’t to say that parents should toss their children’s toys or discourage play time. If you are, however, bending over backward or spending more than you would like on gifts for children, particularly very young ones, it may be worth pausing to ask: Does this child really need this item? Will it enrich her playtime — or simply be used for a week or two and then ignored?

No doubt you’ve heard a parent say, “My kids have so many toys, and they don’t play with them.” You have probably said it yourself.

Memories are more precious than presents.

When it comes to making your children happy, consider creating bonding rituals and traditions for children to look back on and cherish instead of automatically heading to the store to buy another toy or gadget. Have a monthly or weekly movie date or game night, a cookie bake-in, or make a ritual of preparing a weekend meal together.

Research backs up the notion that parents should invest in activities over material goods. Cornell University psychologist Thomas Gilovich found that people look back on experiences with more satisfaction than they do on their material purchases. He “discovered that people thinking about impending experiential purchases, such as ski passes or concert tickets, have higher levels of happiness than those who anticipate spending money on things.”

article continues after advertisement

Elect to spend money on events or embark on free activities, such as walking around a park, heading to your local community center, taking a bike ride or doing a craft at home.

References

Dauch, C., Imwalle, M., Ocasio, B., and Metz, A. (2018). The influence of the number of toys in the environment on toddlers’ play. Infant Behavior and Development. https://doi.org/10.1016/j.infbeh.2017.11.005

Kumar, A., Killingsworth, M., & Gilovich, T. (2014). Waiting for merlot: Anticipatory consumption of experiential and material purchases. Psychological Science doi:10.1177/0956797614546556

Newman, Susan. (2014) Little Things Long Remembered: Making Your Children Feel Special Every Day. New York: Iron Gate Press.

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Evolutionary history of “tissue-bending”

This (developmental biology) story is an awesome example of gene-environment interactions. 😊 To start with, animal embryos shape their tissues during development through a variety of mechanisms — one of which involves coordinated constriction of one side of a sheet of embryonic cells, leading to tissue bending. This constriction mechanism during tissue morphogenesis occurs in most animal groups, suggesting evolutionarily that it was inherited from a common ancestor. Authors [see attached article and editorial] describe a remarkable discovery of a new species of colony-forming unicellular eukaryote — which uses collective cell contraction to change its morphology and behavior in response to absence of light. Because the new species belongs to the closest living relatives of animals (i.e. the choanoflagellates), these results cast new light on the evolutionary origin of collective cell contractility.

In a pond on the island of Curaçao, authors found an intriguing creature composed of ~100 cells — with whip-like appendages (flagellae) that together formed a small sheet; the sheet was bent inward, with the flagellae pointing toward the interior of a cup-shaped colony. However, occasionally the sheet would invert its curvature rapidly, and — within 30 seconds — all the flagellae would be facing outward along the radius of the inverted colony [shown in Fig. 1 of article and in diagram on p. 301 of editorial].

This dramatic and quick change in tissue morphology is similar to developmental morphogenesis in complex multicellular animals (including human embryos), in which epithelial sheets fold and invaginate to form multilayered structures. Authors concluded that this organism is a new species of choanoflagellate and named it Choanoeca flexa. Authors managed to keep their C. flexa alive in the laboratory — by growing it in the presence of the bacteria on which it fed in the pond where it was discovered. What happened next is an example of scientific curiosity, clever thinking, and elucidation of mechanism…!!

Authors found that “the inversion behavior” is triggered by switching off the light. Analysis of the C. flexa genome revealed a gene encoding the protein rhodopsin phosphodiesterase, which both “senses” light, and “passes the information on” to other cellular processes by modifying cyclic nucleotides commonly used in intracellular signaling. This gene was a good candidate to explain the observed light-dependent behavior, but how does one prove this premise? Authors knew that photodetection via rhodopsin requires a cofactor — the chromophore retinal, but C. flexa does not have the genes necessary to produce retinal. Therefore, it must be taking up retinal from food, the bacteria. Authors fed their choanoflagellates with bacteria that can, or cannot, produce retinal, and they found that only C. flexa colonies feeding on retinal-producing bacterial strains can “invert” in response to the environmental signal, “darkness”. Moreover, addition of synthetic retinal alone — was also able to trigger the inversion.

Lastly, what does “inversion” of this multicellular colony accomplish for C. flexa? Authors showed that — when the cell colony has its flagellae facing inward — it can consume the bacteria better by capturing them from the surrounding medium. When the creature “inverts”, however, its flagellae are oriented in a way that’s more useful for mobility of the colony (probably to escape a large predator casting a shadow over the colony). Therefore, the sheet inversion appears to mediate a trade-off between feeding and swimming to avoid a predator. This really amazing story might be helpful in reconstructing hypothesized animal ancestors that existed before the evolution of specialized sensory and contractile cells. 😊

DwN

Science 18 Oct 2019; 366: 326-334 & editorial pp 300-301

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Global scale atlas of eaethworm genomes

These GEITP pages recently discussed the evolutionary history and divergence of plant genomes, it seems reasonable to note the evolutionary history and divergence of earthworm genomes. The importance of earthworms has long been recognized for their effects on terrestrial systems — as diverse as tropical rainforests and our backyards. Because of burrowing activities, earthworms are appreciated for stabilizing soil particles into aggregates, increasing soil porosity, and elevating rates at which water infiltrates the soil during rainfall; these animals also reduce erosion of surface soils from hillslopes and accelerate movement of gases into, and out of, the soil.

Earthworms speed up decomposition of organic matter — by ingesting >30 times their own weight in soil per day, they can rapidly mix large amounts of leaf litter into underlying soil layers, increasing the release of plant nutrients. The presence of earthworms obviously enhances plant growth, because of all the processing they do, to the soil. Our ecological understanding of global biodiversity patterns (e.g. latitudinal diversity gradients) is largely based on the distribution of above-ground taxa — yet many soil organisms have shown global diversity patterns that differ from above-ground organisms.

Provisioning of ecosystem functions by earthworms is likely dependent on the abundance, biomass, and ecological group of the earthworm species (see diagram on p 425 of editorial); consequently, understanding global patterns in community metrics for earthworms is critical for predicting how changes in their communities may alter ecosystem functioning. Small-scale field studies have shown that soil properties such as pH and soil carbon influence earthworm diversity. For example, lower pH values constrain the diversity of earthworms by decreasing calcium availability, and soil carbon provides resources that sustain earthworm diversity and population sizes. In addition to many interacting soil properties — a variety of other drivers can shape earthworm diversity, such as climate and habitat cover. However, to date, no framework has integrated a comprehensive set of environmental drivers of earthworm communities to identify the most important drivers on a global scale.

Authors [see attached article and editorial] have developed a global-scale atlas of earthworms. It has been appreciated that earthworms may have greater diversity across the tropics, compared with that in temperate regions. Authors postulated that earthworm diversity might not follow global patterns seen above-ground, but rather may increase with latitude (i.e. heading from the poles toward the equator). Because of the relationship among earthworm communities, habitat cover, and soil properties on local scales — authors found soil properties (e.g. pH and soil organic carbon) to be key environmental drivers of earthworm diversity. Authors compiled a worldwide dataset of sampled earthworm communities from 6,928 sites in 57 countries(!!) as a basis for predicting patterns in earthworm diversity, abundance, and biomass. They found that the richness and abundance of local species typically increased at higher latitudes — displaying patterns opposite to those observed in above-ground organisms. Authors determined that changing climate properties were more influential in shaping earthworm communities than soil properties, or than habitat cover.

DwN

Science 25 Oct 2019; 366: 480-485 & editorial pp 425-426

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One thousand plant transcriptomes and the phylogenomics of green plants

These (gene-environment interactions) GEITP pages have a continued interest in evolution, because that process involves the genomes of all living organisms to “adapt” to changes in the environment in order better to survive (‘survival of the fittest’). Green plants comprise an estimated 450,000–500,000 species; they encompass incredible diversity and evolutionary timescales, and they play important roles in all terrestrial and most aquatic ecosystems.

This ecological diversity arises from developmental, morphological and physiological innovations that have continuously enabled plants to colonize and exploit any novel and emerging habitat. These innovations include: multicellularity and development of the plant cuticle, protected embryos, stomata (for ‘breathing’), vascular tissue, roots, ovules and seeds, and flowers and fruit. Hence, plant evolution ultimately influenced environments globally — and created a cascade of diversity in other lineages throughout the “tree of life.” Plant diversity has also driven innovations in agriculture and aided in the growth of human populations.

Phylogenomic approaches are now widely used to resolve species relationships, as well as the evolution of genomes, gene families (or groups), and gene functions. As part of the One Thousand Plant Transcriptomes Initiative, authors [see attached article] sequenced the transcriptomes (i.e. transcribed RNA from actively expressed genes) of 1,124 species that span the diversity of plants — including green plants (Viridiplantae), glaucophytes (freshwater unicellular algae), and red algae — together with 31 published genomes, to infer species relationships and characterize the relative timing of organism, molecular, and functional diversification across green plants.

Authors evaluated gene history discordance (i.e. inconsistencies) among single-copy genes; discordance is to be expected — in the face of rapid species diversification — owing to incomplete sorting of ancestral variation between events of speciation. Horizontal gene transfer,(i.e. movement of genetic material between unicellular and/or multicellular organisms — other than by the transmission of DNA from parent to offspring) hybridization, gene loss subsequent to gene and genome duplications, and estimation error — all these processes can also contribute to gene-tree discordance. Nevertheless, through rigorous gene- and species-tree analyses, authors carried out robust species-tree estimates (see the fantastic Fig. 2 of attached]. Gene-family expansions and genome duplications are recognized as causes of variation for the evolution of gene function and biological novelties. Authors also inferred the timing of ancient genome-duplications and large gene-family expansions.

This extensive analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported, across multiple species-tree and supermatrix analyses. However, discordance at a few important nodes — highlights the complexity of plant genome evolution (e.g. polyploidy, periods of rapid speciation, and extinction). Incomplete sorting of ancestral variation, polyploidization (i.e. creating more than the two sets of chromosomes, one from each parent), and massive expansions of gene families — punctuate the evolutionary history of green plants. Perhaps the most exciting finding is authors discovered that large expansions of gene families preceded the origins of green plants, land plants, and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of ferns and flowering plants. 😊

DwN

Nature 31 Oct 2019; 574: 679-685

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The microbiome regulates neuronal function and “fear extinction” learning [2] Bonus 2013 article — Parasite makes mice lose fear of cats permanently

These GEITP pages have frequently described the growing appreciation of our intestinal microbiome (bacteria, fungi and viruses) and our increasing appreciation of the brain-gut-microbiome axis. Which species predominate in the microbiota — and what metabolism takes place in the intestine — can have direct impact on health and disease, including our mental behavior. Authors [see attached article & editorial] describe that mice, lacking a particular complex microbiota, exhibit an altered fear-associated behavior, changes in gene expression in cells in the brain, and alterations in the firing patterns and rewiring ability of neurons…!! It is well known that all organisms are constantly updating their responses to environmental cues, throughout their lifetimes; this process of behavioral adaptation is, of course, driven by underlying cellular and molecular changes in the brain.

Authors [see attached article] investigated how changes in the gut microbiota affect one specifc adaptation: fear conditioning. First, the authors trained mice to associate a sound with an electric shock — and how strongly that association was formed. The association was seen to develop normally, both in control mice and in microbiota-deficient mice (i.e. those treated with antibiotics to deplete their gut microbiota). Authors then performed an “extinction task”, in which they repeatedly played the tone without an electric shock; this measures the rate at which the animals “updated their behavior” (such an adaptation indicates the fear response has been extinguished). The microbiota-deficient mice were unable to update their response, showing persistent fearful behavior long after control animals had adapted. The same phenomenon was found to occur in mice that had been raised germ-free in sterile isolators (i.e. they had never developed a normal healthy gut microbiome).

Authors then performed nucleus RNA-sequencing in individual cells of the medial prefrontal cortex of the brain; significant changes in gene expression were found in excitatory neurons, glial cells, and other cell-types. Transcranial two-photon imaging showed that deficits in extinction learning — after manipulation of the microbiota in adult mice — were associated with “defective learning-related remodeling” of postsynaptic dendritic spines, and decreased activity in cue-encoding neurons in the medial prefrontal cortex. Furthermore, selective reestablishment of the microbiota revealed a “limited neonatal developmental window” in which microbiota-derived signals can restore normal extinction learning in adulthood.

Lastly, unbiased metabolomics analysis identified four metabolites that were significantly down-regulated in germ-free mice; these same metabolites have been reported to be related to neuropsychiatric disorders in humans and mouse models — strongly suggesting that microbiota-derived chemicals might directly affect brain function and behavior. Together, these data indicate that fear extinction learning requires microbiome-derived signals — both during early postnatal neurodevelopment and in adult mice. These EXCITING BREAKTHROUGH findings have implications for our understanding of how diet, infection, exposure to drugs (especially antibiotics?), and lifestyle can influence brain health and subsequent susceptibility to neuropsychiatric disorders…!! 😊 [See the accompanying article below, from a study six years ago.] 😉

DwN

Nature 24 Oct 2019; 574: 543-548 & editorial pp 488-489

And here is an additional news item (from 6 years ago), pointed out by Elizabeth Kopras, that can now be explained by the 2019 Nature article [above]:

Parasite makes mice lose fear of cats permanently..!!

Behavioral changes persist after Toxoplasma infection is cleared.

· Eliot Barford

18 September 2013 Nature News

cid:image001.jpg@01D597D6.C8C16250

Mice infected with toxoplasmosis lose their instinctive fear for the smell of cats — and the parasite’s effects may be permanent.

A parasite that infects up to one-third of people around the world may have the ability to permanently alter a specific brain function in mice, according to a study published in PLoS ONE today1.

Toxoplasma gondii (a one-celled parasitic eukaryote) is known to remove rodents’ innate fear of cats. The new research shows that even months after infection, when parasites are no longer detectable, the effect remains. This raises the possibility that the microbe causes a permanent structural change in the brain.

The microbe is a single-celled pathogen that infects most types of mammal and bird, causing a disease called toxoplasmosis. But its effects on rodents are unique; most flee cat odor, but infected ones are mildly attracted to it.

This is thought to be an evolutionary adaptation to help the parasite complete its life cycle: Toxoplasma can sexually reproduce only in the cat gut, and for it to get there, the pathogen’s rodent host must be eaten.

In humans, studies have linked Toxoplasma infection with behavioral changes and schizophrenia. One work found an increased risk of traffic accidents in people infected with the parasite2; another found changes in responses to cat odor3. People with schizophrenia are more likely than the general population to have been infected with Toxoplasma, and medications used to treat schizophrenia may work in part by inhibiting the pathogen’s replication.

Schizophrenia is thought to involve excess activity of the neurotransmitter dopamine in the brain. This has bolstered one possible explanation for Toxoplasma’s behavioural effect: the parasite establishes persistent infections by means of microscopic cysts that grow slowly in brain cells. It can increase those cells’ production of dopamine, which could significantly alter their function. Most other suggested mechanisms also rely on the presence of cysts.
Persistent trait

Research on Toxoplasma has mainly used the North American Type II strain. Wendy Ingram, a molecular cell biologist at the University of California, Berkeley, and her colleagues investigated the effects of two other major strains, Type I and Type III, on mouse behavior. They found that within three weeks of infection with either strain, mice lost all fear of cat odor — showing that the behavioral shift is a general trait of Toxoplasma.

More surprising was the situation four months after infection. The Type I pathogen that the researchers used had been genetically modified to provoke an effective immune response, allowing the mice to overcome the infection. After four months, it was undetectable in the mouse brain, indicating that no more than 200 parasite cells remained. “We actually expected that Type I wouldn’t be able to form cysts, and therefore wouldn’t be able to cause the behavior change,” explains Ingram.

But that was not the case: the mice remained as unperturbed by cat odor as they had been at three weeks. “Long after we lose the ability to see it in the brain, we still see its behavioral effect,” says geneticist Michael Eisen, also at Berkeley.

This suggests that the behavioral change could be due to a specific, hard-wired alteration in brain structure, which is generated before cysts form and cannot be reversed. The finding casts doubt on theories that cysts or dopamine cause the behavioural changes of Toxoplasma infections.
Mind over matter

Joanne Webster, a parasite epidemiologist at Imperial College London who co-discovered the fear-negating effects of Toxoplasma in rats4, highlights the worrying implication that if the behavioral changes of Toxoplasma-caused schizophrenia are fixed, treatments that are intended to target cysts might have no effect. However, she notes that mice are not the best model for Toxoplasma infection in humans, because they experience more severe symptoms and complications. Webster uses rats in her research.

Ingram says that her group is using mice because of the better genetic tools available to help to uncover the mechanism behind behavioral changes. However, she is not yet convinced of the link between Toxoplasma infections and schizophrenia. Her findings may actually weaken that link, because they seem to provide evidence against the dopamine hypothesis.

She notes that Toxoplasma infections are common around the world, but their prevalence varies by region, whereas schizophrenia rates are consistent at around 1% globally. Furthermore, it is possible that the increased rate of Toxoplasma infections among people with schizophrenia is caused by them being more likely to pick up the parasite, rather than by the parasite causing schizophrenia.

Nature doi:10.1038/nature.2013.13777

References

1. Ingram, W. M., Goodrich, L. M., Robey. E. A. & Eisen, M. B. PLoS ONE 8, e75246 (2013).

2. Flegr, J., Havlícek, J., Kodym, P., Malý, M. & Smahel, Z. BMC Infect. Dis. 2, 11 (2002).

3. Flegr, J., Lenochová, P., Hodný, Z. & Vondrová, M. PLoS Neglect. Trop. Dis. 5, e1389 (2011).

4. Berdoy, M., Webster, J. P. & Macdonald, D. W. Proc. R. Soc. B 267, 1591–1594 (2000).

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“Quantum supremacy” using a programmable superconducting processo

This topic is only tangentially related to gene-environment interactions, but, given the incredible amounts of data now available — during this past decade of DNA-sequencing, RNA-sequencing transcriptomics, and comparisons of hundreds of genomes from different species — the bigger and better and faster that “supercomputers” can become, the more of these abundant data can be accurately assessed in less time. “Quantum computers” promise to perform certain tasks much faster than ordinary (classical) computers. In essence, a quantum computer carefully orchestrates quantum effects (superposition, entanglement and interference) to explore a huge computational space, and ultimately converge on a solution, or solutions, to a problem. If the numbers of quantum bits (qubits) and operations reach even modest levels — then carrying out the same task on a state-of-the-art supercomputer becomes intractable on any reasonable timescale — a regimen termed quantum computational supremacy. However, reaching this level requires a robust quantum processor, because each additional imperfect operation incessantly chips away at overall “desired performance” (so-called ‘noise’ in the system).

It has therefore been questioned whether a sufficiently large quantum computer could ever be controlled in practice. But now, authors [see attached article and editorial] report quantum supremacy using a 53-qubit processor. Authors [from Google] chose a task that is related to random-number generation (i.e. sampling the output of a pseudo-random quantum circuit). This task is implemented by a sequence of operational cycles, each of which applies operations, called “gates”, to every qubit in an n-qubit processor. These operations include randomly selected single-qubit gates and prescribed two-qubit gates. The output is then determined by measuring each qubit. The resulting strings of 0’s and 1’s are not uniformly distributed over all 2n possibilities.

Instead, these strings have a preferential circuit-dependent structure — with certain strings being much more likely than others because of quantum entanglement and quantum interference. Repeating the experiment, and sampling a sufficiently large number of these solutions — results in a distribution of likely outcomes. Simulating this probability distribution on a classical computer, even using today’s leading algorithms, becomes exponentially more challenging — as the number of qubits and operational cycles is increased.

Authors [see attached article] used a high-fidelity processor capable of running quantum algorithms in an exponentially large computational space; authors created quantum states on 53 qubits, corresponding to a computational state-space of dimension 253 (about 1,016). Measurements from repeated experiments sample the resulting probability distribution, which authors verified as “using classical simulations”. Their “Sycamore processor” required ~200 seconds to sample one instance of a quantum circuit a million times [current benchmarks indicate that the equivalent task for a state-of-the-art classical supercomputer would take ~10,000 years]. Authors claim that “this dramatic increase in speed, compared to all known classical algorithms, is an experimental realization of quantum supremacy for this specific computational task, heralding a much-anticipated computing paradigm.”

HOWEVER, one week later, IBM issued a report contradicting these claims by Google. On 21 Oct 2019, IBM claimed their machine would do this task in only 2.5 days, using a different approach. “This would mean that Google’s machine had achieved an important milestone,” IBM said, but “not quantum supremacy.” Designers of quantum computers “seek a performance edge over classical computers by using strange aspects of quantum mechanics.” ☹

DwN

Nature 24 Oct 2019; 574: 505-510 & editorial pp 487-488

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Dietary salt can promote cognitive impairment by way of tau phosphorylation ??

In keeping with our GEITP gene-environment interactions theme, this topic concerns interactions between “dietary salt” as the environment, and each person’s genome or genetic susceptibility as the genes. Vascular risk factors — including excessive salt consumption — have long been associated with cerebrovascular diseases and cognitive impairment (when someone has problems remembering, learning new things, concentrating, or making decisions that affect his everyday life). A diet rich in salt is an independent risk factor for stroke and dementia.

A high-salt diet (HSD) has been linked to cerebral small vessel disease that underlies vascular cognitive impairment, a condition associated with blood vessel endothelial dysfunction and impaired cerebral blood flow (CBF). In mice, HSD induces cognitive dysfunction by targeting cerebral microvasculature through a gut-initiated adaptive immune response mediated by TH17 lymphocytes; the resulting increases in circulating interleukin-17 (IL17) — lead to inhibition of endothelial nitric oxide synthase (eNOS), and diminished vascular production of nitric oxide (NO), which, in turn, impairs endothelial vasoactivity which can lower CBF by ~25%.

However, it remains unclear how lowered blood flow (hypoperfusion) — resulting from an HSD or other vascular risk factors — might lead to impaired cognition. The prevailing view is that hypoperfusion compromises delivery of O2 (diatomic oxygen) and glucose to energy-demanding brain regions involved in cognition. However, the relatively small decrease in CBF associated with an HSD in mice, and vascular cognitive impairment in humans, does not seem to be sufficient to impair cognitive function; this suggests that

vascular factors — beyond perfusion of blood throughout the brain — are involved.

Excessive phosphorylation of the microtubule-associated protein tau promotes formation of insoluble tau aggregates, which are

thought to mediate neuronal dysfunction and cognitive impairment in Alzheimer disease and other “tau-opathies.” Therefore, authors [see attached article] investigated whether tau accumulation — rather than brain hypoperfusion — contributes to cognitive dysfunction that is induced by an HSD.

First, authors investigated whether an HSD induces phosphorylation of tau. Mice were fed a normal diet or an HSD [4% or 8% sodium chloride (NaCl) — a commonly used model of excessive dietary salt corresponding to an 8–16-fold increase in salt content compared to regular mouse chow]. An HSD (8% NaCl) induced a sustained increase in phosphorylated tau (detected by AT8 antibodies) in several specific regions of the brain. Authors found neither neuronal nor white-matter damage — nor significant changes in astrocytes, microglia/macrophages or pericytes. However, increased phosphorylated tau (detected by antibodies) was observed in the neocortex of mice fed with the 4% HSD.

Thus, dietary salt was found in mice to enhance phosphorylation of tau — followed by cognitive dysfunction; authors subsequently showed these effects are prevented by restoring eNOS production. NO deficiency appears to lower neuronal calpain nitrosylation, resulting in enzyme activation, which, in turn, leads to tau phosphorylation by activating cyclin-dependent kinase. Salt-induced cognitive impairment was not observed in tau-null mice, nor in mice treated with anti-tau antibodies, despite persistent brain hypoperfusion and neurovascular dysfunction. These data therefore identify a causal link between dietary salt, blood vessel endothelial dysfunction, and tau pathology — independent of blood-circulatory insufficiency. Authors suggest that “avoidance of excessive salt intake and maintenance of vascular health may help delay vascular and neurodegenerative pathologies that underlie dementia in the elderly.” More studies on this phenomenon are warranted.

DwN

Nature 31 Oct 2019; 574: 686-690

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