hiccup
good samaritans after all: it’s a truism of social psychology that witnesses are less likely to intervene if other onlookers are present. not true
melanie mcgrath 2019
aeon.co/essays/it-looks-like-human-beings-might-be-good-samaritans-after-all
would i be helped? cross-national cctv footage shows that intervention is the norm in public conflicts
philpot, richard et al. 2019
doi.org/10.1037/amp0000469
beyond economics and ecology: the radical thought of ivan illich
ivan illich, sajay samuel, jerry brown 2013
collects four of illich’s books
war against subsistence
shadow work
energy and equity
the social construction of energy
a shorter working week for everyone: how much paid work is needed for mental health and well-being?
daiga kamerāde et al. 2019
doi.org/10.1016/j.socscimed.2019.06.006
Aside from economic factors, paid employment brings other benefits -- often psychological -- such as self-esteem and social inclusion. Now, researchers at the universities of Cambridge and Salford have set out to define a recommended "dosage" of work for optimal wellbeing.
They examined how changes in working hours were linked to mental health and life satisfaction in over 70,000 UK residents between 2009 and 2018*.
The study, published today in the journal Social Science and Medicine, shows that when people moved from unemployment or stay-at-home parenting into paid work of eight hours or less a week, their risk of mental health problems reduced by an average of 30%.
Yet researchers found no evidence that working any more than eight hours provided further boosts to wellbeing. The full-time standard of 37 to 40 hours was not significantly different to any other working time category when it came to mental health.
As such, they suggest that to get the mental wellbeing benefits of paid work, the most "effective dose" is only around one day a week -- as anything more makes little difference.
"We have effective dosage guides for everything from Vitamin C to hours of sleep in order to help us feel better, but this is the first time the question has been asked of paid work," said study co-author Dr Brendan Burchell, a sociologist from Cambridge University who leads the Employment Dosage research project.
"We know unemployment is often detrimental to people's wellbeing, negatively affecting identity, status, time use, and sense of collective purpose. We now have some idea of just how much paid work is needed to get the psychosocial benefits of employment -- and it's not that much at all."
Supporting the unemployed in a future with limited work is the subject of much policy discussion e.g. universal basic income. However, researchers argue that employment should be retained across adult populations, but working weeks dramatically reduced for work to be redistributed.
"In the next few decades we could see artificial intelligence, big data and robotics replace much of the paid work currently done by humans," said Dr Daiga Kamer?de, study first author from Salford University and Employment Dosage researcher.
"If there is not enough for everybody who wants to work full-time, we will have to rethink current norms. This should include the redistribution of working hours, so everyone can get the mental health benefits of a job, even if that means we all work much shorter weeks."
"Our findings are an important step in thinking what the minimum amount of paid work people might need in a future with little work to go round," she said.
The study used data from the UK Household Longitudinal Study to track the wellbeing of 71,113 individuals between the ages of 16 and 64 as they changed working hours over the nine-year period. People were asked about issues such as anxiety and sleep problems to gauge mental health.
Researchers also found that self-reported life satisfaction in men increased by around 30% with up to eight hours of paid work, although women didn't see a similar jump until working 20 hours.
They note that "the significant difference in mental health and wellbeing is between those with paid work and those with none," and that the working week could be shortened considerably "without a detrimental effect on the workers' mental health and wellbeing."
The team offer creative policy options for moving into a future with limited work, including "five-day weekends," working just a couple of hours a day, or increasing annual holiday from weeks to months -- even having two months off for every month at work.
They also argue that working hour reduction and redistribution could improve work-life balance, increase productivity, and cut down CO2 emissions from commuting. However, they point out that reduction of hours would need to be for everyone, to avoid increasing socioeconomic inequalities.
"The traditional model, in which everyone works around 40 hours a week, was never based on how much work was good for people. Our research suggests that micro-jobs provide the same psychological benefits as full-time jobs," said co-author and Cambridge sociologist Senhu Wang.
"However, the quality of work will always be crucial. Jobs where employees are disrespected or subject to insecure or zero-hours contracts do not provide the same benefits to wellbeing, nor are they likely to in the future."
Dr Burchell added: "If the UK were to plough annual productivity gains into reduced working hours rather than pay rises, the normal working week could be four days within a decade."
abstract •Working 8h a week is sufficient to gain the wellbeing benefits of employment.
•The wellbeing of employees is similar regardless of the length of the working week up to 48.
•There is scope for the working week to be radically reduced.
•Reduced hours of work are preferable to job losses due to artificial intelligence.
There are predictions that in future rapid technological development could result in a significant shortage of paid work. A possible option currently debated by academics, policy makers, trade unions, employers and mass media, is a shorter working week for everyone. In this context, two important research questions that have not been asked so far are: what is the minimum amount of paid employment needed to deliver some or all of the well-being and mental health benefits that employment has been shown to bring? And what is the optimum number of working hours at which the mental health of workers is at its highest? To answer these questions, this study used the UK Household Longitudinal Study (2009–2018) data from individuals aged between 16 and 64. The analytical sample was 156,734 person-wave observations from 84,993 unique persons of whom 71,113 had two or more measurement times. Fixed effects regressions were applied to examine how changes in work hours were linked to changes in mental well-being within each individual over time. This study found that even a small number of working hours (between one and 8 h a week) generates significant mental health and well-being benefits for previously unemployed or economically inactive individuals. The findings suggest there is no single optimum number of working hours at which well-being and mental health are at their highest - for most groups of workers there was little variation in wellbeing between the lowest (1–8 h) through to the highest (44–48 h) category of working hours. These findings provide important and timely empirical evidence for future of work planning, shorter working week policies and have implications for theorising the future models of organising work in society.
retapamulin-assisted ribosome profiling reveals the alternative bacterial proteome
sezen meydan et al. 2019
doi.org/10.1016/j.molcel.2019.02.017
some genes have more than one start site and can specify production of more than one functional protein
Historically, the generally taught scientific premise has been that each gene has one unique start site and is responsible for the creation of only one protein. However, the study, which is published in Molecular Cell, a leading journal on the topic of cellular processes, shows that some genes have more than one start site and can specify production of more than one functional protein.
Their method of identifying gene start sites relies on a common prescription drug called retapamulin, a topical antibiotic. Retapamulin, they showed for the first time, works by causing the ribosome, which reads genetic code, to become stalled at these start sites, inhibiting translation, a key part of the process by which the genetic code in DNA is used to create proteins.
UIC's Alexander Mankin and Nora Vázquez-Laslop led the research, which looked at E. coli cells in response to retapamulin in in vitro and in vivo experiments.
"First, we understood the antibiotic's mechanism and then we applied that knowledge to identify the special 'start' gene signals the cell uses to regulate protein synthesis," said Mankin, the Alexander Neyfahk Professor of Medicinal Chemistry and Pharmacognosy at the UIC College of Pharmacy. "In the past, these start codons were identified by rather difficult processes -- proteins often needed to be isolated and studied to discover where the start sites of their genes are located in the bacterial genome. Now, in a single experiment, we can profile the starts of all the thousands of bacterial genes in a more forward manner."
Mankin and Vázquez-Laslop say using retapamulin to aid in bacterial gene translation profiling opens many new avenues for research.
Using the antibiotic, the researchers from Mankin and Vázquez-Laslop's lab, which included Sezen Meydan, James Marks, Dorota Klepacki and Amira Kefi, were able to identify "cryptic," or alternative start sites within some bacterial genes.
"We saw that many previously hidden proteins were initiated at sites in the middle of the gene and that those proteins were functional and that initiation at alternative start sites is widespread in bacteria," said Vázquez-Laslop, research professor of medicinal chemistry and pharmacognosy at the UIC College of Pharmacy and the Center for Biomolecular Sciences.
The researchers found more than 100 E. coli genes, out of around 4,000, that could initiate protein synthesis at more than one site.
"Proteins initiated at these unknown sites may constitute a previously hidden fraction of the proteome -- the entire set of proteins that can be expressed -- in bacteria and their initiation at these sites may play a role in the life of the cell," said Mankin, who is also director of the Center for Biomolecular Science. "By better understanding the cell and the mechanisms of antibiotic action, we can apply that knowledge to learn more about what makes bacteria become pathogenic."
"We can also apply that knowledge to better understand how to prevent or stop bacteria from causing harm," Vázquez-Laslop said.
abstract
•Retapamulin arrests bacterial ribosomes specifically at translation start sites
•Retapamulin-assisted Ribo-seq reveals known and cryptic translation start sites
•Translation from start sites located within the ORFs may generate functional proteins
•Start-stop sites found within some genes may help to regulate gene expression
The use of alternative translation initiation sites enables production of more than one protein from a single gene, thereby expanding the cellular proteome. Although several such examples have been serendipitously found in bacteria, genome-wide mapping of alternative translation start sites has been unattainable. We found that the antibiotic retapamulin specifically arrests initiating ribosomes at start codons of the genes. Retapamulin-enhanced Ribo-seq analysis (Ribo-RET) not only allowed mapping of conventional initiation sites at the beginning of the genes, but strikingly, it also revealed putative internal start sites in a number of Escherichia coli genes. Experiments demonstrated that the internal start codons can be recognized by the ribosomes and direct translation initiation in vitro and in vivo. Proteins, whose synthesis is initiated at internal in-frame and out-of-frame start sites, can be functionally important and contribute to the “alternative” bacterial proteome. The internal start sites may also play regulatory roles in gene expression.
multi-color single-molecule imaging uncovers extensive heterogeneity in mrna decoding
sanne boersma et al. 2019
doi.org/10.1016/j.cell.2019.05.001
"out-of-frame translation happens surprisingly frequently. In extreme cases, almost half of all the proteins that were built, used a different reading frame or code than the expected code. These surprising findings show that the genetic information stored in our DNA is far more complex than previously thought. Based on the new study, our DNA likely encodes thousands of previously unknown proteins with unknown functions. Sanne Boersma: “Because of our study, we can now ask very important questions: what do all these new proteins do? Do they have important functions in our body or are they waste side-products of translation that can damage our cells?”
The 'reading frame' of genes
The genetic code is translated in groups of 3 letters, each resembling a word, which is translated into a single part of the protein. If a ribosome starts translating the code at the wrong position, a shift in the 3-letter-code can occur. For example, the sentence below should read:
"the man saw his new red car"
However, if a ribosome starts translating this sentence one letter too late, the sentence would read:
"hem ans awh isn ewr edc ar"
In the case of the genetic code, this phenomenon is called 'out-of-frame' translation. Sanne Boersma, researcher at the Hubrecht Institute explains: "As illustrated by the example sentence, out-of-frame translation has a big effect on the protein and usually results in a protein that behaves differently and can damage the cell." Until now, it was unclear how the ribosome knows where to start translating the code, and how often the ribosome gets it wrong.
A new method: SunTag and MoonTag
The researchers developed a new method to visualize the decoding of our genetic information in living cells. They were able to label different protein products in different colors and visualize the production of each type of protein using advanced microscopy. Each protein was labeled using a specific label, or tag, called the SunTag and MoonTag, which they could see through the microscope. By combining the MoonTag and the SunTag, the researchers could now see for the first time how often out-of-frame translation takes place.
A big surprise
The researchers discovered that out-of-frame translation happens surprisingly frequently. In extreme cases, almost half of all the proteins that were built, used a different reading frame or code than the expected code. These surprising findings show that the genetic information stored in our DNA is far more complex than previously thought. Based on the new study, our DNA likely encodes thousands of previously unknown proteins with unknown functions. Sanne Boersma: "Because of our study, we can now ask very important questions: what do all these new proteins do? Do they have important functions in our body or are they waste side-products of translation that can damage our cells?"
•Development of MoonTag, a fluorescence labeling system to visualize translation
•Combining MoonTag and SunTag enables visualization of translational heterogeneity
•mRNAs from a single gene vary in initiation frequency at different start sites
•Ribosomes take many different “paths” along the 5′ UTR of a single mRNA molecule
mRNA translation is a key step in decoding genetic information. Genetic decoding is surprisingly heterogeneous because multiple distinct polypeptides can be synthesized from a single mRNA sequence. To study translational heterogeneity, we developed the MoonTag, a fluorescence labeling system to visualize translation of single mRNAs. When combined with the orthogonal SunTag system, the MoonTag enables dual readouts of translation, greatly expanding the possibilities to interrogate complex translational heterogeneity. By placing MoonTag and SunTag sequences in different translation reading frames, each driven by distinct translation start sites, start site selection of individual ribosomes can be visualized in real time. We find that start site selection is largely stochastic but that the probability of using a particular start site differs among mRNA molecules and can be dynamically regulated over time. This study provides key insights into translation start site selection heterogeneity and provides a powerful toolbox to visualize complex translation dynamics.
linking scaling laws across eukaryotes
ian a. hatton et al. 2019
doi.org/10.1073/pnas.1900492116
we find these simple mathematical relationships that span all life, points to some fundamental process at the heart of living systems that we don't yet fully understand," explains Hatton.
Turns existing theory on its head
The study also presents evidence that suggests one of ecology's most prominent theories, called the Metabolic Theory of Ecology, needs to be re-examined. This theory has played a major role in ecological thinking, based on the idea that an organism's metabolic rate is the principal limit on many other vital traits, including how quickly it can grow.
"One of our key findings is that limits to the rate at which an organism can grow seems to put the brakes on metabolism, rather than the other way around," says co-author Eric Galbraith, also at ICTA-UAB. "This puts growth in the driver's seat for understanding these large-scale patterns."
Given that growth underlies everything from juvenile development to cancer, and from resource productivity to global carbon cycling, understanding growth more generally could prove very important.
"What is so astounding is that no matter where you look, no matter what kind of living system, everything seems to follow the same growth law," says Hatton. "We can't yet explain it, but we know it has deep implications."
abstract Scaling laws relating body mass to species characteristics are among the most universal quantitative patterns in biology. Within major taxonomic groups, the 4 key ecological variables of metabolism, abundance, growth, and mortality are often well described by power laws with exponents near 3/4 or related to that value, a commonality often attributed to biophysical constraints on metabolism. However, metabolic scaling theories remain widely debated, and the links among the 4 variables have never been formally tested across the full domain of eukaryote life, to which prevailing theory applies. Here we present datasets of unprecedented scope to examine these 4 scaling laws across all eukaryotes and link them to test whether their combinations support theoretical expectations. We find that metabolism and abundance scale with body size in a remarkably reciprocal fashion, with exponents near ±3/4 within groups, as expected from metabolic theory, but with exponents near ±1 across all groups. This reciprocal scaling supports “energetic equivalence” across eukaryotes, which hypothesizes that the partitioning of energy in space across species does not vary significantly with body size. In contrast, growth and mortality rates scale similarly both within and across groups, with exponents of ±1/4. These findings are inconsistent with a metabolic basis for growth and mortality scaling across eukaryotes. We propose that rather than limiting growth, metabolism adjusts to the needs of growth within major groups, and that growth dynamics may offer a viable theoretical basis to biological scaling.
tdp-43 and rna form amyloid-like myo-granules in regenerating muscle
thomas o. vogler et al. 2018
doi.org/10.1038/s41586-018-0665-2
“The researchers believe it could ultimately open new avenues for treating musculoskeletal diseases and also lend new understanding to related neurological disorders like Parkinson’s and Alzheimer’s disease, in which different amyloids play a role.
“Many of these degenerative diseases share a similar scenario in which they have these protein aggregates that accumulate in the cell and gum up the system,” said co-first author Joshua Wheeler, also an M.D./PhD candidate in the Department of Biochemistry. “As these aggregates are beneficial for normal regeneration, our data suggest that the cell is just damaged and trying to repair itself.”
For the study, Vogler and MCDB professor Brad Olwin, who study muscle generation, teamed up with Wheeler and Roy Parker, who study RNA, to investigate a protein called TDP-43.
TDP-43 has long been suspected to be a culprit in disease, having been found in the skeletal muscle of people with inclusion body myopathy and the neurons of people with ALS. But when the researchers closely examined muscle tissue growing in culture in the lab, they discovered clumps of TDP-43 were present not only in diseased tissue but also in healthy tissue.
“That was astounding,” said Olwin. “These amyloid-like aggregates, which we thought were toxic, seemed to be a normal part of muscle formation, appearing at a certain time and then disappearing again once the muscle was formed.”
Subsequent studies in muscle tissue growing in culture showed that when the gene that codes for TDP-43 was knocked out, muscles didn’t grow. When the researchers looked at human tissue biopsied from healthy people whose muscles were regenerating, they found aggregates, or “myo-granules,” of TDP-43. Further RNA-protein mapping analysis showed that the clusters — like shipping trucks traveling throughout the cell — appear to carry instructions for how to build contractile muscle fibers.
Wheeler and Vogler, both competitive runners and long-time friends, came up with the initial idea for the study while on a trail run. Wheeler says the data suggest that when healthy athletes push their muscles hard via things like marathons and ultramarathons, they are probably also forming amyloid-like clusters within their cells.
The key question remains: Why do most people quickly clear these proteins while others do not, with. the granules — like sugar cubes that won’t dissolve — clustering together and causing disease?
“If they normally form and go away, something is making them dissolve,” said Olwin. “Figuring out the mechanisms involved could potentially open a new avenue for treatments.”
The team is also interested in exploring whether a similar process may occur in the brain after injury, kick-starting disease. And subsequent studies will go even further to identify what the protein clusters do.
“This is a great example of how collaboration across disciplines can lead to really important work,” said Parker.”
abstract A dominant histopathological feature in neuromuscular diseases, including amyotrophic lateral sclerosis and inclusion body myopathy, is cytoplasmic aggregation of the RNA-binding protein TDP-43. Although rare mutations in TARDBP—the gene that encodes TDP-43—that lead to protein misfolding often cause protein aggregation, most patients do not have any mutations in TARDBP. Therefore, aggregates of wild-type TDP-43 arise in most patients by an unknown mechanism. Here we show that TDP-43 is an essential protein for normal skeletal muscle formation that unexpectedly forms cytoplasmic, amyloid-like oligomeric assemblies, which we call myo-granules, during regeneration of skeletal muscle in mice and humans. Myo-granules bind to mRNAs that encode sarcomeric proteins and are cleared as myofibres mature. Although myo-granules occur during normal skeletal-muscle regeneration, myo-granules can seed TDP-43 amyloid fibrils in vitro and are increased in a mouse model of inclusion body myopathy. Therefore, increased assembly or decreased clearance of functionally normal myo-granules could be the source of cytoplasmic TDP-43 aggregates that commonly occur in neuromuscular disease.
the science and translation of lactate shuttle theory
george a. brooks 2018
doi.org/10.1016/j.cmet.2018.03.008
network science on belief system dynamics under logic constraints
n. e. friedkin, a. v. proskurnikov, r. tempo, s. e. parsegov 2016
dx.doi.org/10.1126/science.aag2624
adaptive nodes enrich nonlinear cooperative learning beyond traditional adaptation by links
shira sardi et al. 2018
doi.org/10.1038/s41598-018-23471-7
hippocampal gaba enables inhibitory control over unwanted thoughts
taylor w. schmitz et al.
doi.org/10.1038/s41467-017-00956-z
a fluid-to-solid jamming transition underlies vertebrate body axis elongation
alessandro mongera et al. 2018
doi.org/10.1038/s41586-018-0479-2
Cells coordinate by exchanging biochemical signals, but they also hold to and push on each other to build the body structures we need to live, such as the eyes, lungs and heart. And, as it turns out, sculpting the embryo is not far from glass molding or 3D printing. In their new work,”A fluid-to-solid jamming transition underlies vertebrate body axis elongation,” published in the journal Nature, Campàs and colleagues reveal that cell collectives switch from fluid to solid states in a controlled manner to build the vertebrate embryo, in a way similar to how we mold glass into vases or 3D print our favorite items. Or, if you like, we 3D print ourselves, from the inside.
Most objects begin as fluids. From metallic structures to gelatin desserts, their shape is made by pouring the molten original materials into molds, then cooling them to get the solid objects we use. As in a Chihuly glass sculpture, made by carefully melting portions of glass to slowly reshape it into life, cells in certain regions of the embryo are more active and ‘melt’ the tissue into a fluid state that can be restructured. Once done, cells ‘cool down’ to settle the tissue shape, Campàs explained.
“The transition from fluid to solid tissue states that we observed is known in physics as ‘jamming’,” Campàs said. “Jamming transitions are a very general phenomena that happens when particles in disordered systems, such as foams, emulsions or glasses, are forced together or cooled down.”
This discovery was enabled by techniques previously developed by Campàs and his group to measure the forces between cells inside embryos, and also to exert miniscule forces on the cells as they build tissues and organs. Using zebrafish embryos, favored for their optical transparency but developing much like their human counterparts, the researchers placed tiny droplets of a specially engineered ferromagnetic fluid between the cells of the growing tissue. The spherical droplets deform as the cells around them push and pull, allowing researchers to see the forces that cells apply on each other. And, by making these droplets magnetic, they also could exert tiny stresses on surrounding cells to see how the tissue would respond.
“We were able to measure physical quantities that couldn’t be measured before, due to the challenge of inserting miniaturized probes in tiny developing embryos,” said postdoctoral fellow Alessandro Mongera, who is the lead author of the paper.
“Zebrafish, like other vertebrates, start off from a largely shapeless bunch of cells and need to transform the body into an elongated shape, with the head at one end and tail at the other,” Campàs said. The physical reorganization of the cells behind this process had always been something of a mystery. Surprisingly, researchers found that the cell collectives making the tissue were physically like a foam (yes, as in beer froth) that jammed during development to ‘freeze’ the tissue architecture and set its shape.
These observations confirm a remarkable intuition made by Victorian-era Scottish mathematician D’Arcy Thompson 100 years ago in his seminal work “On Growth and Form.”
“He was convinced that some of the physical mechanisms that give shapes to inert materials were also at play to shape living organisms. Remarkably, he compared groups of cells to foams and even the shaping of cells and tissues to glassblowing,” Campàs said. A century ago, there were no instruments that could directly test the ideas Thompson proposed, Campàs added, though Thompson’s work continues to be cited to this day.
The new Nature paper also provides a jumping-off point from which the Campàs Group researchers can begin to address other processes of embryonic development and related fields, such as how tumors physically invade surrounding tissues and how to engineer organs with specific 3D shapes.
“One of the hallmarks of cancer is the transition between two different tissue architectures. This transition can in principle be explained as an anomalous switch from a solid-like to a fluid-like tissue state,” Mongera explained. “The present study can help elucidate the mechanisms underlying this switch and highlight some of the potential druggable targets to hinder it.”
abstract Just as in clay moulding or glass blowing, physically sculpting biological structures requires the constituent material to locally flow like a fluid while maintaining overall mechanical integrity like a solid. Disordered soft materials, such as foams, emulsions and colloidal suspensions, switch from fluid-like to solid-like behaviours at a jamming transition1,2,3,7. Similarly, cell collectives have been shown to display glassy dynamics in 2D and 3D8,9 and jamming in cultured epithelial monolayers10,11, behaviours recently predicted theoretically9,10,11 and proposed to influence asthma pathobiology11 and tumour progression12. However, little is known about whether these seemingly universal behaviours occur in vivo13 and, specifically, whether they play any functional part during embryonic morphogenesis. Here, by combining direct in vivo measurements of tissue mechanics with analysis of cellular dynamics, we show that during vertebrate body axis elongation, posterior tissues undergo a jamming transition from a fluid-like behaviour at the extending end, the mesodermal progenitor zone, to a solid-like behaviour in the presomitic mesoderm. We uncover an anteroposterior, N-cadherin-dependent gradient in yield stress that provides increasing mechanical integrity to the presomitic mesoderm, consistent with the tissue transiting from a wetter to a dryer foam-like architecture. Our results show that cell-scale stresses fluctuate rapidly (within about 1 min), enabling cell rearrangements and effectively ‘melting’ the tissue at the growing end. Persistent (more than 0.5 h) stresses at supracellular scales, rather than cell-scale stresses, guide morphogenetic flows in fluid-like tissue regions. Unidirectional axis extension is sustained by the reported rigidification of the presomitic mesoderm, which mechanically supports posterior, fluid-like tissues during remodelling before their maturation. The spatiotemporal control of fluid-like and solid-like tissue states may represent a generic physical mechanism of embryonic morphogenesis.
transcription factors operate across disease loci, with ebna2 implicated in autoimmunity
john b. harley et al. 2018
doi.org/10.1038/s41588-018-0102-3
folk concepts
sarah perry 2017
ribbonfarm.com/2017/11/16/folk-concepts/
The older, illiterate peasants organized the items based on whether they could be useful in a common context: they lumped wood together with hand tools, because hand tools, they said, need wood to be useful. (One informant mentioned that many useful tools could be made from wood, such as door handles.) They lumped a sparrow together with a gun and a dagger, because without the sparrow, you have nothing to hunt or divide. On the other hand, younger, educated subject easily classified objects on the basis of abstract categories (tools, made of glass, weapons, etc.).
The younger people were more willing to organize the world based on abstract categories—”as if” these categories existed. Older people were engaging in “as if” reasoning of a kind (“as if” each skein of yarn was a thing in the world, “as if” one were attempting to use several things at once). But, crucially, the older, illiterate people did not base their answers on “as if” realities on the symbolic, logical, analytic constructs that the younger people took (and most WEIRD people take) as utterly obvious.
unconventional care: offspring abandonment and filial cannibalism can function as forms of parental care
mackenzie e. davenport et al. 2019
doi.org/10.3389/fevo.2019.00113
in some cases, filial cannibalism and offspring abandonment might even be considered forms of parental care. Published in Frontiers in Ecology and Evolution, their mathematical model shows that when overcrowding threatens offspring survival -- which often occurs due to spread of infection or competition for resources -- sacrificing a few so the most can live becomes the ultimate form of tough love.
Putting all your eggs in one basket
To understand the role of overcrowding or 'offspring density' in the survival benefit of filial cannibals, the researchers focused on species that lay eggs.
"Communal egg laying is common in a range of fish, insects, reptiles, and amphibians," says senior author Dr. Hope Klug, Associate Professor at the University of Tennessee, Chattanooga. "This makes it easier to protect, clean, incubate and feed the eggs -- but can also increase disease transmission, and competition for food and oxygen."
Offspring density has been found to affect egg survival, and in some cases abandonment or cannibalism, in many of these species.
"For example, in the beaugregory damselfish, fathers were more likely to eat eggs under low oxygen conditions," notes Klug. "Such cases have led the to the hypothesis that eating or abandoning offspring may be an adaptation to improve overall survival of offspring by reducing their density."
Model parents eat their offspring
Klug and colleagues created a mathematical model to test this hypothesis.
"The model introduced an imaginary individual with a mutation for filial cannibalism or offspring abandonment, into a population of generic egg-laying animals," explains lead author Dr. Mackenzie Davenport, also of the University of Tennessee.
As in the group's previous models, the gene for cannibalism spread throughout the population if it gave parents extra calories.
But for the first time in this model, they found that when offspring mortality increases with egg laying density, both filial cannibalism and offspring abandonment result in increased fitness.
"Under these conditions, the mutants were able to outcompete and replace the generic population," reports Davenport.
This was the case even when cannibal parents were given little or no energy benefit from the extra food -- or when abandoned offspring were assumed to die.
"Our findings suggest that surprisingly, filial cannibalism and offspring abandonment can function as forms of parental care, by increasing total offspring survival."
Live fast, die young, be prepared to abort
"The fitness benefit of offspring abandonment and filial cannibalism also increases as adult death rate increases, particularly for the case of filial cannibalism," adds co-author Prof. Michael Bonsall of the University of Oxford.
In other words: if you've got fewer shots at reproducing, you'll need to be ruthless in protecting your brood. But if offspring mortality is density dependent, why produce so many eggs in the first place?
"It is not always possible for parents to predict the environment that their offspring will end up in," explains Bonsall. "Factors like food availability, oxygen availability, diseases presence and predation, might change in an unpredictable manner. Likewise, in many fish and other animals females deposit their eggs in the nests or territories of males and leave, so cannot predict an optimal laying density given that additional females might subsequently add eggs to the nest."
"It's up to empiricists now to test these models in a variety of species," the authors conclude.
structural and functional features of central nervous system lymphatics
antoine louveau et al. 2015
doi.org/10.1038%2fnature14432
cns lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature
antoine louveau et al. 2018
doi.org/10.1038/s41593-018-0227-9
structure and distribution of an unrecognized interstitium in human tissues
petros c. benias et al. 2018
doi.org/10.1038/s41598-018-23062-6
transcriptomic and morphophysiological evidence for a specialized human cortical gabaergic cell type
eszter boldog et al. 2018
doi.org/10.1038/s41593-018-0205-2
new types of experiments reveal that a neuron functions as multiple independent threshold units
shira sardi et al. 2017
doi.org/10.1038/s41598-017-18363-1
enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease
xianjun dong et al. 2018
doi.org/10.1038/s41593-018-0223-0
the potassium channel subunit kvβ1 serves as a major control point for synaptic facilitation
in ha cho et al. 2020
doi.org/10.1073/pnas.2000790117
A "molecular volume knob" regulating electrical signals in the brain helps with learning and memory, according to a Dartmouth study.
The molecular system controls the width of electrical signals that flow across synapses between neurons.
The finding of the control mechanism, and the identification of the molecule that regulates it, could help researchers in their search for ways to manage neurological disorders, including Alzheimer's disease, Parkinson's disease and epilepsy.
The research, published in Proceedings of the National Academy of Sciences, describes the first study of how the shapes of electrical signals contribute to the functioning of synapses.
"The synapses in our brain are highly dynamic and speak in a range of whispers and shouts," said Michael Hoppa, an assistant professor of biological sciences at Dartmouth and the research lead. "This finding puts us on a straighter path toward being able to cure stubborn neurological disorders."
Synapses are tiny contact points that allow neurons in the brain to communicate at different frequencies. The brain converts electrical inputs from the neurons into chemical neurotransmitters that travel across these synaptic spaces.
The amount of neurotransmitter released changes the numbers and patterns of neurons activated within circuits of the brain. That reshaping of synaptic connection strength is how learning happens and how memories are formed.
Two functions support these processes of memory and learning. One, known as facilitation, is a series of increasingly rapid spikes that amplifies the signals that change a synapse's shape. The other, depression, reduces the signals. Together, these two forms of plasticity keep the brain in balance and prevent neurological disorders such as seizures.
"As we age, its critical to be able to maintain strengthened synapses. We need a good balance of plasticity in our brain, but also stabilization of synaptic connections," said Hoppa.
The research focused on the hippocampus, the center of the brain that is responsible for learning and memory.
In the study, the research team found that the electric spikes are delivered as analog signals whose shape impacts the magnitude of chemical neurotransmitter released across the synapses. This mechanism functions similar to a light dimmer with variable settings. Previous research considered the spikes to be delivered as a digital signal, more akin to a light switch that operates only in the "on" and "off" positions.
"The finding that these electric spikes are analog unlocks our understanding of how the brain works to form memory and learning," said In Ha Cho, a postdoctoral fellow at Dartmouth and first author of the study. "The use of analog signals provides an easier pathway to modulate the strength of brain circuits."
Nobel laureate Eric Kandel conducted work on the connection between learning and the change in shapes of electrical signals in marine sea slugs in 1970. The process was not thought to occur in the more complex synapses found in the mammalian brain at the time.
Beyond discovering that the electrical signals which flow across synapses in the brain's hippocampus are analog, the Dartmouth research also identified the molecule that regulates the electrical signals.
The molecule -- known as Kvβ1 -- was previously shown to regulate potassium currents, but was not known to have any role in the synapse controlling the shape of electrical signals. These findings help explain why loss of Kvβ1 molecules had previously been shown to negatively impact learning, memory and sleep in mice and fruit flies.
The research also reveals the processes that allow the brain to have such high computational power at such low energy. A single, analog electrical impulse can carry multi-bit information, allowing greater control with low frequency signals.
"This helps our understanding of how our brain is able to work at supercomputer levels with much lower rates of electrical impulses and the energy equivalent of a refrigerator light bulb. The more we learn about these levels of control, it helps us learn how our brains are so efficient," said Hoppa.
abstract Analysis of the presynaptic action potential’s (APsyn) role in synaptic facilitation in hippocampal pyramidal neurons has been difficult due to size limitations of axons. We overcame these size barriers by combining high-resolution optical recordings of membrane potential, exocytosis, and Ca2+ in cultured hippocampal neurons. These recordings revealed a critical and selective role for Kv1 channel inactivation in synaptic facilitation of excitatory hippocampal neurons. Presynaptic Kv1 channel inactivation was mediated by the Kvβ1 subunit and had a surprisingly rapid onset that was readily apparent even in brief physiological stimulation paradigms including paired-pulse stimulation. Genetic depletion of Kvβ1 blocked all broadening of the APsyn during high-frequency stimulation and eliminated synaptic facilitation without altering the initial probability of vesicle release. Thus, using all quantitative optical measurements of presynaptic physiology, we reveal a critical role for presynaptic Kv channels in synaptic facilitation at presynaptic terminals of the hippocampus upstream of the exocytic machinery.
spontaneous infra-slow brain activity has unique spatiotemporal dynamics and laminar structure
anish mitra et al. 2018
doi.org/10.1016/j.neuron.2018.03.015
primary cilia signaling shapes the development of interneuronal connectivity
jiami guo et al. 2017
doi.org/10.1016/j.devcel.2017.07.010
Primary cilia signaling regulates interneuronal morphology and synaptic connectivity
Ciliary GPCR signaling is critical for emergence of interneuronal connectivity
Cilia signaling is a non-synaptic mechanism to sculpt interneuronal circuits
Disrupted cilia signaling may underlie circuit malformations in ciliopathies
Appropriate growth and synaptic integration of GABAergic inhibitory interneurons are essential for functional neural circuits in the brain. Here, we demonstrate that disruption of primary cilia function following the selective loss of ciliary GTPase Arl13b in interneurons impairs interneuronal morphology and synaptic connectivity, leading to altered excitatory/inhibitory activity balance. The altered morphology and connectivity of cilia mutant interneurons and the functional deficits are rescued by either chemogenetic activation of ciliary G-protein-coupled receptor (GPCR) signaling or the selective induction of Sstr3, a ciliary GPCR, in Arl13b-deficient cilia. Our results thus define a specific requirement for primary cilia-mediated GPCR signaling in interneuronal connectivity and inhibitory circuit formation.
human sperm uses asymmetric and anisotropic flagellar controls to regulate swimming symmetry and cell steering
hermes gadêlha et al. 2020
doi.org/10.1126/sciadv.aba5168
dynamics of cortical dendritic membrane potential and spikes in freely behaving rats
jason j. moore et al. 2017
doi.org/10.1126/science.aaj1497
mast cell-derived histamine regulates liver ketogenesis via oleoylethanolamide signaling
alessandra misto et al. 2018
doi.org/10.1016/j.cmet.2018.09.014
“Without mast cells, histamine or OEA, we could not survive a marathon or a day-long hike without snacks, or any long period of time without food,” said Piomelli. “What’s fascinating to me is that a cell that was supposed to be the ‘bad guy’ in allergies, is the same one that allows us to survive prolonged lack of food or major physical effort.”
abstract •Fasting stimulates extra-hepatic mast cells to release histamine
•Histamine travels through the hepatic portal system and activates liver H1 receptors
•H1-receptor activation triggers OEA biosynthesis in liver
•Histamine-dependent OEA signaling enhances fasting-induced ketogenesis
The conversion of lipolysis-derived fatty acids into ketone bodies (ketogenesis) is a crucial metabolic adaptation to prolonged periods of food scarcity. The process occurs primarily in liver mitochondria and is initiated by fatty-acid-mediated stimulation of the ligand-operated transcription factor, peroxisome proliferator-activated receptor-α (PPAR-α). Here, we present evidence that mast cells contribute to the control of fasting-induced ketogenesis via a paracrine mechanism that involves secretion of histamine into the hepatic portal circulation, stimulation of liver H1 receptors, and local biosynthesis of the high-affinity PPAR-α agonist, oleoylethanolamide (OEA). Genetic or pharmacological interventions that disable any one of these events, including mast cell elimination, deletion of histamine- or OEA-synthesizing enzymes, and H1 blockade, blunt ketogenesis without affecting lipolysis. The results reveal an unexpected role for mast cells in the regulation of systemic fatty-acid homeostasis, and suggest that OEA may act in concert with lipolysis-derived fatty acids to activate liver PPAR-α and promote ketogenesis.
the ghost in the machine
arthur koestler 1967 0-14-019192-5
the sleepwalkers: a history of man’s changing vision of the universe
arthur koestler 1959 0-14-019246-8
an account of changing scientific paradigms
darkness at noon
the act of creation
did the death of communism take koestler and other literary figures with it?
anne applebaum 2010
huffingtonpost.com/2010/01/26/did-the-death-of-communis_n_435939.html
on the concept of history
walter benjamin 1940
sfu.ca/~andrewf/CONCEPT2.html
Concepts like “belief” and “faith” do not figure very often anymore in contemporary Western politics—and even when they do (as perhaps they did in the 2008 American presidential election) they are almost always a preface to disillusion. In the 1930s and 1940s, by contrast, belief and faith mattered a great deal, and true Communists and fellow travelers did not become disillusioned. They simply altered their analysis of the current situation, put their trust in the ultimate wisdom of the Party, and progressed onward toward the construction of utopia.
koestler: the literary and political odyssey of a twentieth-century skeptic
michael scammell 2010 to read next
n6-methyladenosine of chromosome-associated regulatory rna regulates chromatin state and transcription
jun liu et al. 2020
doi.org/10.1126/science.aay6018
Rather than directions going one-way from DNA to RNA to proteins, the latest study shows that RNA itself modulates how DNA is transcribed — using a chemical process that is increasingly apparent to be vital to biology. The discovery has significant implications for our understanding of human disease and drug design.
“It appears to be a fundamental pathway we didn’t know about. Anytime that happens, it holds promise to open up completely new directions of research and inquiry,” said Prof. Chuan He.
The human body is among the most complex pieces of machinery to exist. Every time you so much as scratch your nose, you’re using more intricate engineering than any rocket ship or supercomputer ever designed. It’s taken us centuries to deconstruct how this works, and each time someone discovers a new mechanism, a few more mysteries of human health make sense — and new treatments become available.
For example, in 2011, He opened a new avenue of research with his discovery of a particular process called reversible RNA methylation, which plays a critical role in how genes are expressed.
The picture many of us remember learning in school is an orderly progression: DNA is transcribed into RNA, which then makes proteins that carry out the actual work of living cells. But it turns out there are a lot of wrinkles.
He’s team found that the molecules called messenger RNA, previously known as simple couriers that carry instructions from DNA to proteins, were actually making their own impacts on protein production. This is done by a reversible chemical reaction called methylation; He’s key breakthrough was showing that this methylation was reversible. It wasn’t a one-time, one-way transaction; it could be erased and reversed.
“That discovery launched us into a modern era of RNA modification research, which has really exploded in the last few years,” said He. “This is how so much of gene expression is critically affected. It impacts a wide range of biological processes — learning and memory, circadian rhythms, even something so fundamental as how a cell differentiates itself into, say, a blood cell versus a neuron.”
He’s team also identified and characterized a number of “reader” proteins that recognize methylated mRNA and impact target mRNA stability and translation.
But as He’s lab worked with mice to understand the mechanisms, they began to see that messenger RNA methylation could not fully explain everything they observed.
This was mirrored in other experiments. “The data coming out of the community was saying there’s something else out there, something extremely important that we’re missing — that critically impacts many early development events, as well as human diseases such as cancer,” he said.
He’s team discovered that a group of RNAs called chromosome-associated regulatory RNAs, or carRNAs, was using the same methylation process, but these RNAs do not code proteins and are not directly involved in protein translation. Instead, they controlled how DNA itself was stored and transcribed.
“This has major implications in basic biology,” He said. “It directly affects gene transcriptions, and not just a few of them. It could induce global chromatin change and affects transcription of 6,000 genes in the cell line we studied.”
He sees major implications in biology, especially in human health — everything from identifying the genetic basis of disease to better treating patients.
“There are several biotech companies actively developing small molecule inhibitors of RNA methylation, but right now, even if we successfully develop therapies, we don’t have a full mechanical picture for what’s going on,” he said. “This provides an enormous opportunity to help guide disease indication for testing inhibitors and suggest new opportunities for pharmaceuticals.”
Their breakthrough is only the beginning, He said. “I believe this represents a conceptual change,” he said. “Barriers like these are hard to crack, but once you do, everything flows from there.”
abstract N6-methyladenosine (m6A) regulates stability and translation of messenger RNA (mRNA) in various biological processes. Here, we showed that knockout of the m6A writer Mettl3 or a nuclear reader Ythdc1 in mouse embryonic stem cells increases chromatin accessibility and activates transcription in an m6A-dependent manner. We found that METTL3 deposits m6A modifications on chromosome-associated regulatory RNAs (carRNAs), including promoter-associated RNAs, enhancer RNAs and repeats RNAs. YTHDC1 facilitates decay of a subset of these m6A-modified RNAs, especially LINE1 elements, through the NEXT-mediated nuclear degradation. Reducing m6A methylation by METTL3 depletion or site-specific m6A demethylation of selected carRNAs elevates the levels of carRNAs and promotes open chromatin state and downstream transcription. Collectively, our results revealed that m6A on carRNAs can globally tune chromatin state and transcription.
i-motif dna structures are formed in the nuclei of human cells
mahdi zeraati et al. 2018
doi.org/10.1038/s41557-018-0046-3
hydrophobic catalysis and a potential biological role of dna unstacking induced by environment effects
bobo feng et al. 2019
doi.org/10.1073/pnas.1909122116
DNA is constructed of two strands, consisting of sugar molecules and phosphate groups. Between these two strands are nitrogen bases, the compounds which make up organisms' genes, with hydrogen bonds between them. Until now, it was commonly thought that those hydrogen bonds were what held the two strands together.
But now, researchers from Chalmers University of Technology show that the secret to DNA's helical structure may be that the molecules have a hydrophobic interior, in an environment consisting mainly of water. The environment is therefore hydrophilic, while the DNA molecules' nitrogen bases are hydrophobic, pushing away the surrounding water. When hydrophobic units are in a hydrophilic environment, they group together, to minimise their exposure to the water.
The role of the hydrogen bonds, which were previously seen as crucial to holding DNA helixes together, appear to be more to do with sorting the base pairs, so that they link together in the correct sequence.
The discovery is crucial for understanding DNA's relationship with its environment.
"Cells want to protect their DNA, and not expose it to hydrophobic environments, which can sometimes contain harmful molecules," says Bobo Feng, one of the researchers behind the study. "But at the same time, the cells' DNA needs to open up in order to be used."
"We believe that the cell keeps its DNA in a water solution most of the time, but as soon as a cell wants to do something with its DNA, like read, copy or repair it, it exposes the DNA to a hydrophobic environment."
Reproduction, for example, involves the base pairs dissolving from one another and opening up. Enzymes then copy both sides of the helix to create new DNA. When it comes to repairing damaged DNA, the damaged areas are subjected to a hydrophobic environment, to be replaced. A catalytic protein creates the hydrophobic environment. This type of protein is central to all DNA repairs, meaning it could be the key to fighting many serious sicknesses.
Understanding these proteins could yield many new insights into how we could, for example, fight resistant bacteria, or potentially even cure cancer. Bacteria use a protein called RecA to repair their DNA, and the researchers believe their results could provide new insight into how this process works -- potentially offering methods for stopping it and thereby killing the bacteria.
In human cells, the protein Rad51 repairs DNA and fixes mutated DNA sequences, which otherwise could lead to cancer.
"To understand cancer, we need to understand how DNA repairs. To understand that, we first need to understand DNA itself," says Bobo Feng. "So far, we have not, because we believed that hydrogen bonds were what held it together. Now, we have shown that instead it is the hydrophobic forces which lie behind it. We have also shown that DNA behaves totally differently in a hydrophobic environment. This could help us to understand DNA, and how it repairs. Nobody has previously placed DNA in a hydrophobic environment like this and studied how it behaves, so it's not surprising that nobody has discovered this until now."
More information on the methods the researchers used to show how DNA binds together:
The researchers studied how DNA behaves in an environment which is more hydrophobic than normal, a method they were the first to experiment with.
They used the hydrophobic solution polyethylene glycol, and step-by-step changed the DNA's surroundings from the naturally hydrophilic environment to a hydrophobic one. They aimed to discover if there is a limit where DNA starts to lose its structure, when the DNA does not have a reason to bind, because the environment is no longer hydrophilic. The researchers observed that when the solution reached the borderline between hydrophilic and hydrophobic, the DNA molecules' characteristic spiral form started to unravel.
Upon closer inspection, they observed that when the base pairs split from one another (due to external influence, or simply from random movements), holes are formed in the structure, allowing water to leak in. Because DNA wants to keep its interior dry, it presses together, with the base pairs coming together again to squeeze out the water. In a hydrophobic environment, this water is missing, so the holes stay in place.
abstract The main stabilizer of the DNA double helix is not the base-pair hydrogen bonds but coin-pile stacking of base pairs, whose hydrophobic cohesion, requiring abundant water, indirectly makes the DNA interior dry so that hydrogen bonds can exert full recognition power. We report that certain semihydrophobic agents depress the stacking energy (measurable in single-molecule experiments), leading to transiently occurring holes in the base-pair stack (monitorable via binding of threading intercalators). Similar structures observed in DNA complexes with RecA and Rad51, and previous observations of spontaneous strand exchange catalyzed in semihydrophobic model systems, make us propose that some hydrophobic protein residues may have roles in catalyzing homologous recombination. We speculate that hydrophobic catalysis is a general phenomenon in DNA enzymes.
Hydrophobic base stacking is a major contributor to DNA double-helix stability. We report the discovery of specific unstacking effects in certain semihydrophobic environments. Water-miscible ethylene glycol ethers are found to modify structure, dynamics, and reactivity of DNA by mechanisms possibly related to a biologically relevant hydrophobic catalysis. Spectroscopic data and optical tweezers experiments show that base-stacking energies are reduced while base-pair hydrogen bonds are strengthened. We propose that a modulated chemical potential of water can promote “longitudinal breathing” and the formation of unstacked holes while base unpairing is suppressed. Flow linear dichroism in 20% diglyme indicates a 20 to 30% decrease in persistence length of DNA, supported by an increased flexibility in single-molecule nanochannel experiments in poly(ethylene glycol). A limited (3 to 6%) hyperchromicity but unaffected circular dichroism is consistent with transient unstacking events while maintaining an overall average B-DNA conformation. Further information about unstacking dynamics is obtained from the binding kinetics of large thread-intercalating ruthenium complexes, indicating that the hydrophobic effect provides a 10 to 100 times increased DNA unstacking frequency and an “open hole” population on the order of 10−2 compared to 10−4 in normal aqueous solution. Spontaneous DNA strand exchange catalyzed by poly(ethylene glycol) makes us propose that hydrophobic residues in the L2 loop of recombination enzymes RecA and Rad51 may assist gene recombination via modulation of water activity near the DNA helix by hydrophobic interactions, in the manner described here. We speculate that such hydrophobic interactions may have catalytic roles also in other biological contexts, such as in polymerases.
clades of huge phages from across earth’s ecosystems
al-shayeb, b. 2020
doi.org/10.1038/s41586-020-2007-4
from the guts of premature infants and pregnant women to a Tibetan hot spring, a South African bioreactor, hospital rooms, oceans, lakes and deep underground.
Altogether they identified 351 different huge phages, all with genomes four or more times larger than the average genomes of viruses that prey on single-celled bacteria.
Among these is the largest bacteriophage discovered to date: Its genome, 735,000 base-pairs long, is nearly 15 times larger than the average phage. This largest known phage genome is much larger than the genomes of many bacteria.
“We are exploring Earth’s microbiomes, and sometimes unexpected things turn up. These viruses of bacteria are a part of biology, of replicating entities, that we know very little about,” said Jill Banfield, a UC Berkeley professor of earth and planetary science and of environmental science, policy and management, and senior author of a paper about the findings appearing Feb 12 in the journal Nature. “These huge phages bridge the gap between non-living bacteriophages, on the one hand, and bacteria and Archaea. There definitely seem to be successful strategies of existence that are hybrids between what we think of as traditional viruses and traditional living organisms.”
Ironically, within the DNA that these huge phages lug around are parts of the CRISPR system that bacteria use to fight viruses. It’s likely that once these phages inject their DNA into bacteria, the viral CRISPR system augments the CRISPR system of the host bacteria, probably mostly to target other viruses.
“It is fascinating how these phages have repurposed this system we thought of as bacterial or archaeal to use for their own benefit against their competition, to fuel warfare between these viruses,” said UC Berkeley graduate student Basem Al-Shayeb. Al-Shayeb and research associate Rohan Sachdeva are co-first authors of the Nature paper.
New Cas protein
One of the huge phages also is able to make a protein analogous to the Cas9 protein that is part of the revolutionary tool CRISPR-Cas9 that Jennifer Doudna of UC Berkeley and her European colleague, Emmanuelle Charpentier, adapted for gene-editing. The team dubbed this tiny protein CasØ, because the Greek letter Ø, or phi, has traditionally been used to denote bacteriophage.
“In these huge phages, there is a lot of potential for finding new tools for genome engineering,” Sachdeva said. “A lot of the genes we found are unknown, they don’t have a putative function and may be a source of new proteins for industrial, medical or agricultural applications.”
Aside from providing new insight into the constant warfare between phages and bacteria, the new findings also have implications for human disease. Viruses, in general, carry genes between cells, including genes that confer resistance to antibiotics. And since phages occur wherever bacteria and Archaea live, including the human gut microbiome, they can carry damaging genes into the bacteria that colonize humans.
“Some diseases are caused indirectly by phages, because phages move around genes involved in pathogenesis and antibiotic resistance,” said Banfield, who is also director of microbial research at the Innovative Genomics Institute (IGI) and a CZ Biohub investigator. “And the larger the genome, the larger the capacity you have to move around those sorts of genes, and the higher the probability that you will be able to deliver undesirable genes to bacteria in human microbiomes.”
Sequencing Earth’s biomes
For more than 15 years, Banfield has been exploring the diversity of bacteria, Archaea — which, she says, are fascinating cousins of bacteria — and phages in different environments around the planet. She does this by sequencing all the DNA in a sample and then piecing the fragments together to assemble draft genomes or, in some cases, fully curated genomes of never-before-seen microbes.
In the process, she has found that many of the new microbes have extremely tiny genomes, seemingly insufficient to sustain independent life. Instead, they appear to depend on other bacteria and archaea to survive.
One year ago, she reported that some of the largest phages, a group she called Lak phages, can be found in our guts and mouths, where they prey on gut and saliva microbiomes.
The new Nature paper came out of a more thorough search for huge phages within all the metagenomic sequences Banfield has accumulated, plus new metagenomes provided by research collaborators around the globe. The metagenomes came from baboons, pigs, Alaskan moose, soil samples, oceans, rivers, lakes and groundwater, and included Bangladeshis who had been drinking arsenic-tainted water.
The team identified 351 phage genomes that were more than 200 kilobases long, four times the average phage genome length of 50 kilobytes (kb). They were able to establish the exact length of 175 phage genomes; the others could be much larger than 200 kb. One of the complete genomes, 735,000 base-pairs long, is now the largest known phage genome.
While most of the genes in these huge phages code for unknown proteins, the researchers were able to identify genes that code for proteins critical to the machinery, called the ribosome, that translates messenger RNA into protein. Such genes are not typically found in viruses, only in bacteria or archaea.
The researchers found many genes for transfer RNAs, which carry amino acids to the ribosome to be incorporated into new proteins; genes for proteins that load and regulate tRNAs; genes for proteins that turn on translation and even pieces of the ribosome itself.
“Typically, what separates life from non-life is to have ribosomes and the ability to do translation; that is one of the major defining features that separate viruses and bacteria, non-life and life,” Sachdeva said. “Some large phages have a lot of this translational machinery, so they are blurring the line a bit.”
Huge phages likely use these genes to redirect the ribosomes to make more copies of their own proteins at the expense of bacterial proteins. Some huge phages also have alternative genetic codes, the nucleic acid triplets that code for a specific amino acid, which could confuse the bacterial ribosome that decodes RNA.
In addition, some of the newly discovered huge phages carry genes for variants of the Cas proteins found in a variety of bacterial CRISPR systems, such as the Cas9, Cas12, CasX and CasY families. CasØ is a variant of the Cas12 family. Some of the huge phages also have CRISPR arrays, which are areas of the bacterial genome where snippets of viral DNA are stored for future reference, allowing bacteria to recognize returning phages and to mobilize their Cas proteins to target and cut them up.
“The high-level conclusion is that phages with large genomes are quite prominent across Earth’s ecosystems, they are not a peculiarity of one ecosystem,” Banfield said. “And phages which have large genomes are related, which means that these are established lineages with a long history of large genome size. Having large genomes is one successful strategy for existence, and a strategy we know very little about.”
abstract Bacteriophages typically have small genomes29 and depend on their bacterial hosts for replication30. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is—to our knowledge—the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR–Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR–Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR–Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth’s ecosystems.
waves
extraordinary boulder transport by storm waves (west of ireland, winter 2013–2014), and criteria for analysing coastal boulder deposits
rónadh cox et al. 2018
doi.org/10.1016/j.earscirev.2017.12.014
laboratory recreation of the draupner wave and the role of breaking in crossing seas
m. l. mcallister et al. 2019
doi.org/10.1017/jfm.2018.886
The Draupner wave was one of the first confirmed observations of a freak wave in the ocean; it was observed on the 1st of January 1995 in the North Sea by measurements made on the Draupner Oil Platform.
Freak waves are unexpectedly large in comparison to surrounding waves. They are difficult to predict, often appearing suddenly without warning, and are commonly attributed as probable causes for maritime catastrophes such as the sinking of large ships.
The team of researchers set out to reproduce the Draupner wave under laboratory conditions to understand how this freak wave was formed in the ocean. They successfully achieved this reconstruction by creating the wave using two smaller wave groups and varying the crossing angle -- the angle at which the two groups travel.
Dr Mark McAllister at the University of Oxford's Department of Engineering Science said: 'The measurement of the Draupner wave in 1995 was a seminal observation initiating many years of research into the physics of freak waves and shifting their standing from mere folklore to a credible real-world phenomenon. By recreating the Draupner wave in the lab we have moved one step closer to understanding the potential mechanisms of this phenomenon.'
It was the crossing angle between the two smaller groups that proved critical to the successful reconstruction. The researchers found it was only possible to reproduce the freak wave when the crossing angle between the two groups was approximately 120 degrees.
When waves are not crossing, wave breaking limits the height that a wave can achieve. However, when waves cross at large angles, wave breaking behaviour changes and no longer limits the height a wave can achieve in the same manner.
Prof Ton van den Bremer at the University of Oxford said: 'Not only does this laboratory observation shed light on how the famous Draupner wave may have occurred, it also highlights the nature and significance of wave breaking in crossing sea conditions. The latter of these two findings has broad implications, illustrating previously unobserved wave breaking behaviour, which differs significantly from current state-of-the-art understanding of ocean wave breaking.'
To the researchers' amazement, the wave they created bore an uncanny resemblance to 'The Great Wave off Kanagawa' -- also known as 'The Great Wave' -- a woodblock print published in the early 1800s by the Japanese artist Katsushika Hokusai. Hokusai's image depicts an enormous wave threatening three fishing boats and towers over Mount Fuji which appears in the background. Hokusai's wave is believed to depict a freak, or 'rogue', wave.
The laboratory-created freak wave also bears strong resemblances with photographs of freak waves in the ocean. The researchers hope that this study will lay the groundwork for being able to predict these potentially catastrophic and hugely damaging waves that occur suddenly in the ocean without warning.
Experiments were carried out in the FloWave Ocean Energy Research facility at the University Of Edinburgh.
Dr Sam Draycott at the University of Edinburgh said: 'The FloWave Ocean Energy Research Facility is a circular combined wave-current basin with wavemakers fitted around the entire circumference. This unique capability enables waves to be generated from any direction, which has allowed us to experimentally recreate the complex directional wave conditions we believe to be associated with the Draupner wave event.'
abstract Freak or rogue waves are so called because of their unexpectedly large size relative to the population of smaller waves in which they occur. The 25.6 m high Draupner wave, observed in a sea state with a significant wave height of 12 m, was one of the first confirmed field measurements of a freak wave. The physical mechanisms that give rise to freak waves such as the Draupner wave are still contentious. Through physical experiments carried out in a circular wave tank, we attempt to recreate the freak wave measured at the Draupner platform and gain an understanding of the directional conditions capable of supporting such a large and steep wave. Herein, we recreate the full scaled crest amplitude and profile of the Draupner wave, including bound set-up. We find that the onset and type of wave breaking play a significant role and differ significantly for crossing and non-crossing waves. Crucially, breaking becomes less crest-amplitude limiting for sufficiently large crossing angles and involves the formation of near-vertical jets. In our experiments, we were only able to reproduce the scaled crest and total wave height of the wave measured at the Draupner platform for conditions where two wave systems cross at a large angle.
loopy lévy flights enhance tracer diffusion in active suspensions
kiyoshi kanazawa et al. 2020
doi.org/10.1038/s41586-020-2086-2
Brownian motion describes the random movement of particles in fluids, however, this revolutionary model only works when a fluid is static, or at equilibrium.
In real-life environments, fluids often contain particles that move by themselves, such as tiny swimming microorganisms. These self-propelled swimmers can cause movement or stirring in the fluid, which drives it away from equilibrium.
Experiments have shown that non-moving ‘passive’ particles can exhibit strange, loopy motions when interacting with ‘active’ fluids containing swimmers. Such movements do not fit with the conventional particle behaviours described by Brownian motion and so far, scientists have struggled to explain how such large-scale chaotic movements result from microscopic interactions between individual particles.
Now researchers from Queen Mary University of London, Tsukuba University, École Polytechnique Fédérale de Lausanne and Imperial College London, have presented a novel theory to explain observed particle movements in these dynamic environments.
They suggest the new model could also help make predictions about real-life behaviours in biological systems, such as the foraging patterns of swimming algae or bacteria.
Dr Adrian Baule, Senior Lecturer in Applied Mathematics at Queen Mary University of London, who managed the project, said: “Brownian motion is widely used to describe diffusion throughout physical, chemical and biological sciences; however it can’t be used to describe the diffusion of particles in more active systems that we often observe in real life.”
By explicitly solving the scattering dynamics between the passive particle and active swimmers in the fluid, the researchers were able to derive an effective model for particle motion in ‘active’ fluids, which accounts for all experimental observations.
Their extensive calculation reveals that the effective particle dynamics follow a so-called ‘Lévy flight’, which is widely used to describe ‘extreme’ movements in complex systems that are very far from typical behaviour, such as in ecological systems or earthquake dynamics.
Dr Kiyoshi Kanazawa from the University of Tsukuba, and first author of the study, said: “So far there has been no explanation how Lévy flights can actually occur based on microscopic interactions that obey physical laws. Our results show that Lévy flights can arise as a consequence of the hydrodynamic interactions between the active swimmers and the passive particle, which is very surprising.”
The team found that the density of active swimmers also affected the duration of the Lévy flight regime, suggesting that swimming microorganisms could exploit the Lévy flights of nutrients to determine the best foraging strategies for different environments.
Dr Baule added: “Our results suggest optimal foraging strategies could depend on the density of particles within their environment. For example, at higher densities active searches by the forager could be a more successful approach, whereas at lower densities it might be advantageous for the forager to simply wait for a nutrient to come close as it is dragged by the other swimmers and explores larger regions of space.
“However, this work not only sheds light on how swimming microorganisms interact with passive particles, like nutrients or degraded plastic, but reveals more generally how randomness arises in an active non-equilibrium environment. This finding could help us to understand the behaviour of other systems that are driven away from equilibrium, which occur not only in physics and biology, but also in financial markets for example.”
abstract Brownian motion is widely used as a model of diffusion in equilibrium media throughout the physical, chemical and biological sciences. However, many real-world systems are intrinsically out of equilibrium owing to energy-dissipating active processes underlying their mechanical and dynamical features31. The diffusion process followed by a passive tracer in prototypical active media, such as suspensions of active colloids or swimming microorganisms32, differs considerably from Brownian motion, as revealed by a greatly enhanced diffusion coefficient3,4,5,6,7,8,9,40 and non-Gaussian statistics of the tracer displacements36,39,40. Although these characteristic features have been extensively observed experimentally, there is so far no comprehensive theory explaining how they emerge from the microscopic dynamics of the system. Here we develop a theoretical framework to model the hydrodynamic interactions between the tracer and the active swimmers, which shows that the tracer follows a non-Markovian coloured Poisson process that accounts for all empirical observations. The theory predicts a long-lived Lévy flight regime41 of the loopy tracer motion with a non-monotonic crossover between two different power-law exponents. The duration of this regime can be tuned by the swimmer density, suggesting that the optimal foraging strategy of swimming microorganisms might depend crucially on their density in order to exploit the Lévy flights of nutrients12. Our framework can be applied to address important theoretical questions, such as the thermodynamics of active systems13, and practical ones, such as the interaction of swimming microorganisms with nutrients and other small particles14 (for example, degraded plastic) and the design of artificial nanoscale machines15.
material-independent mechanochemical effect in the deformation of highly-strain-hardening metals
anirudh udupa et al. 2018
doi.org/10.1103/PhysRevApplied.10.014009
rapidly declining body temperature in a tropical human population
michael gurven et al. 2020
doi.org/10.1126/sciadv.abc6599
Dailey adds, “The ANS isn’t controlled by itself — it’s controlled by the brain and the central nervous system. We think the brain is controlling the regeneration of all these tissues through the ANS. But that brings up a bigger picture. For individuals under severe depression or PTSD, for example, you see degeneration of some of their organs. It could be some sort of stress-related effect through the ANS decreasing the regenerative potential of the organs. Based on our findings, it looks like there could be a direct effect.”
evidence for a direct effect of the autonomic nervous system on intestinal epithelial stem cell proliferation
elizabeth a. davis et al. 2018
doi.org/10.14814/phy2.13745
a direct effect of the autonomic nervous system on somatic stem cell proliferation?
elizabeth a. davis et al. 2018
doi.org/10.1152/ajpregu.00266.2018
exponentially faster cooling in a colloidal system
avinash kumar & john bechhoefer et al. 2020
doi.org/10.1038/s41586-020-2560-x
airpods and the three stages of apple criticism
jonathan kim 2018
medium.com/rethink-reviews/airpods-and-the-three-stages-of-apple-criticism-fed70b84e435
she broke japan’s silence on rape
motoko rich 2017
nytimes.com/2017/12/29/world/asia/japan-rape.html
increased circulation time of plasmodium falciparum underlies persistent asymptomatic infection in the dry season
carolina m. andrade et al. 2020
doi.org/10.1038/s41591-020-1084-0
oviposition strategies of florida culex (melanoconion) mosquitoes
erik m. blosser, nathan d. burkett-cadena 2018
doi.org/10.1093/jme/tjx052
a new statistical method to test equivalence: an application in male and female eastern bluebird song
evangeline m. rose et al. 2018
doi.org/10.1016/j.anbehav.2018.09.004
Awareness of female birdsong is growing worldwide, thanks in part to a breakthrough paper by Karan Odom, Ph.D. ‘16, biological sciences, but it’s still understood as a trait found primarily in tropical birds. Evangeline Rose, a current Ph.D. student in the same lab and first author on a new paper in Animal Behavior, wanted to look at song in a temperate species.
During Rose’s fieldwork, “I was finding that the females were singing, to me, what sounded just like male songs,” she says. “So we started thinking about equality, and equivalence, and how to test for it.” On the advice of her advisor, Kevin Omland, professor of biological sciences, she reached out to Thomas Mathew, professor of statistics, who has expertise in statistical equivalence.
Challenging a paradigm
Working together, the team modified a statistical method used in generic drug testing to meet their needs for ecology and animal behavior studies. The existing test helps determine whether generic and brand name drugs are “statistically equivalent,” meaning they are similar enough to be prescribed safely for the same purpose. The new modification will allow scientists in other fields to test for equivalence. Before, researchers could only report they did not find a significant difference — a very different statement than saying two things are conclusively equivalent.
“We’re really hoping this new method is going to address some issues with what kinds of data get published,” Rose says. “The most important thing about being a good scientist is to be unbiased. And the whole tradition of testing for difference really leads to incredible biases in scientists,” Omland says. He adds, “There’s a whole realm of things in nature that we find interesting and important because of their similarity.”
For example, in addition to similarities in songs between the sexes in birds, researchers could use the new test to ask if two species use the same type of habitat, respond the same way to predators, or consume the same food sources. Answers to those questions could fill long-standing knowledge gaps, or even inform conservation efforts.
“This test is really broadly applicable,” says Rose, “and we’re hoping to introduce it more to the ecology and evolution field.”
A new approach
One advantage of the new method is it accounts for unequal sample sizes. In a medical study, researchers can carefully control the size of treatment and control groups. In other fields, from ecology, to engineering, to agriculture, that’s often not possible. The new test also allows researchers to determine the equivalence of several traits simultaneously, Mathew explains. For example, in this study, the authors found that the male and female birds’ songs were statistically equivalent across five different characteristics, such as duration of each song and the range of pitches the birds produced.
Rather than testing whether two things are exactly equal, the team was looking for a way to determine if two things were “close enough,” given a defined allowable margin of difference. Because of that added layer, “There are additional challenges here,” Mathew says.
“Even though this methodology is out there, it hasn’t been applied — even in statistics — with this kind of data. That’s why I was very excited when they brought this project to me,” Mathew says. Rose adds, “It ended up being a really great partnership to look at these questions that hadn’t been asked before for female song, and we also ended up modifying this test in a really cool, new way.”
Changing science
As research on similarities grows, there is also a growing drive to remove the bias against publishing studies that do not find a significant difference, often termed a “negative result.” This paper “is part of an amazing drumbeat that’s building up in the scientific community,” Omland says. “There’s a broader problem with the scientific method that’s being increasingly acknowledged, and the test we’ve developed can at least play a small role, and I hope a big role, in addressing it.”
Rose, who plans to next investigate the function of female bluebird songs, says she will carry these new techniques with her as she moves through her research career. “I think in the future, I’ll be thinking about how equivalence can change the questions we’re asking, and I’ll always keep in mind that we have extra tools in the toolkit.”
•Although understudied, recent studies suggest that female birdsong is widespread.
•We compared male and female song using a novel statistical equivalence test.
•Both sexes had statistically equivalent songs based on five acoustic measures.
•Our equivalence test will have wide applicability in behaviour, ecology and evolution.
Understanding complex natural systems requires approaches with minimal statistical limitations and biases. Previously, however, the fields of behaviour, ecology and evolution generally have been restricted to evaluating differences between statistical distributions. This framework can be very powerful. Unfortunately, it has also created a bias in these, and many other, fields towards publications focusing only on phenomena for which there are statistically significant differences. However, there is a wide range of questions that would benefit from reversing the existing paradigm and testing, instead, for equivalence. We have adapted the two one-sided test (TOST), also known as equivalence testing, from pharmaceutical science to be applicable to behavioural and ecological studies. We created a repeated measures analysis that allows researchers to statistically examine similarities between distributions. We compared song structure in male and female eastern bluebirds, Sialia sialis, as a case study for this method. We failed to find significant differences between male and female songs via a more traditional test, repeated measures ANOVA. Therefore, no definitive conclusion could be drawn about the similarities or differences in song structure. However, our repeated measures equivalence test showed that, based on five standard measures of song variation, male and female eastern bluebirds sing statistically equivalent songs. Our study highlights the presence of complex female song in a temperate songbird species. Additionally, we provide a new statistical test useful for expanding the statistical toolbox to assess new behavioural and ecological questions, and to help counteract publication bias in our fields.
design and production of a novel microfluidic device for the capture and isolation of circulating tumor cell clusters
sebastian w. shaner et al. 2019
doi.org/10.1063/1.5084736
about 90% of cancer deaths are due to metastases, when tumors spread to other vital organs. How does cancer metastasize? After an exhaustive search of the scientific literature, the researchers realized that it's not individual cells but rather distinct clusters of cancer cells that circulate and metastasize to other organs.
As the group reports in AIP Advances, from AIP Publishing, this caused them to question -- if these cell clusters are the "root causes of cancer," why isn't more research being devoted to gaining a better understanding of circulating cancer cell clusters?
"The reason for such little research activity is the overwhelming difficulty of capturing these extremely rare metastatic cancer cell clusters from a patient's blood sample," said Peter Teriete, one of the authors and a research assistant professor at Sanford Burnham Prebys Medical Discovery Institute. "But we realized that if we're ever going to understand the complex process of cancer metastasis, we'd need to develop a tool to easily find these clusters."
To do this, the researchers first identified the basic requirements essential to collecting useful information from isolated cancer cell clusters. It involves a sample size large enough to likely contain appreciable numbers of cancer cell clusters (about 10 milliliters of whole blood), as well as using whole blood to preserve rare circulating clusters. Whole blood, however, requires channel-coating procedures that reduce nonspecific binding properties to prevent biofouling. And the device channel dimensions must be of a suitable size to accommodate single cells and cancer cell clusters of varying diameters.
"Our device's channel design had to generate microfluidic flow characteristics suitable to facilitate cell capture via antibodies within the coated channels," Teriete explained. "So we introduced microfeatures -- herringbone recesses -- to produce the desired functionality. We also developed a unique alginate hydrogel coating that can be readily decorated with antibodies or other biomolecules. By connecting bioengineering with materials science and basic cancer biology, we were able to develop a device and prove that it performs as desired."
The group's microfluidic device brings a new therapeutic strategy to the fight against cancer metastasis. Capturing viable circulating cancer stem cell clusters directly from cancer patients is a novel approach for the development of new anti-metastatic drug therapies.
"Drug development that specifically targets distant metastases has been greatly restricted due to the lack of adequate tools that can readily access the metastatic cells responsible for cancer's dissemination," said Teriete. "Our microfluidic device will provide cancer researchers with actual human cancer cell clusters, so they can begin to understand the critical mechanisms involved with metastasis and develop highly effective drugs that ultimately can save more cancer patients' lives."
abstract The three main challenges of cancer treatment are metastases, recurrence, and acquired therapy resistance. These challenges have been closely linked to circulating cancer cell clusters. A detailed understanding of their genetic and morphological composition is essential. This will not only improve our knowledge of basic cancer biology but enable the successful development of much needed therapies preventing the three main challenges mentioned above. Extensive research effort is underway to isolate, capture, and analyze circulating tumor cells. However, few if any current efforts specifically target cancer cell clusters, and their much greater ability to initiate new tumors. Growing scientific consensus over the last five years has convincingly established the importance of targeting circulating cancer cell clusters verses individual CTCs to prevent the occurrence of metastatic disease. Based on the increased clinical importance of cancer cell clusters as the main driver of cancer metastasis, new and improved methods are much needed to access these larger multi-celled structures. Microfluidic devices offer a readily accessible platform for a customizable microenvironment for cell isolation and analysis. In this study, we show how a well-known passive micromixer design (staggered herringbone mixer - SHM) can be optimized to induce maximum chaotic advection within antibody-coated channels of dimensions appropriate for the capture of cancer cell clusters. The device’s principle design configuration is called: Single-Walled Staggered Herringbone (SWaSH). The preliminary empirical results of our work show that utilization of extensive simulation and modeling can accelerate the development of a working prototype that allows for target-specific cancer cell cluster isolation.
everything you know about the gospel of paul is likely wrong
david bentley hart 2018
aeon.co/ideas/the-gospels-of-paul-dont-say-what-you-think-they-say
a mind-bending translation of the new testament
david bentley hart’s text recaptures the awkward, multivoiced power of the original
james parker 2018
theatlantic.com/magazine/archive/2018/01/the-new-testament-a-translation-david-bentley-hart/546551/
the human cerebellum has almost 80% of the surface area of the neocortex
martin i. sereno et al. 2020
doi.org/10.1073/pnas.2002896117
spatial and temporal organization of the individual human cerebellum
scott marek et al. 2018
doi.org/10.1016/j.neuron.2018.10.010
•Individual-specific functional brain networks can be elucidated in the cerebellum
•Inter-individual variance in cerebellar functional networks exceeds that of cortex
•The frontoparietal control network is 2-fold overrepresented in the cerebellum
•Cerebellar BOLD signals temporally lag the cortex by hundreds of milliseconds
The cerebellum contains the majority of neurons in the human brain and is unique for its uniform cytoarchitecture, absence of aerobic glycolysis, and role in adaptive plasticity. Despite anatomical and physiological differences between the cerebellum and cerebral cortex, group-average functional connectivity studies have identified networks related to specific functions in both structures. Recently, precision functional mapping of individuals revealed that functional networks in the cerebral cortex exhibit measurable individual specificity. Using the highly sampled Midnight Scan Club (MSC) dataset, we found the cerebellum contains reliable, individual-specific network organization that is significantly more variable than the cerebral cortex. The frontoparietal network, thought to support adaptive control, was the only network overrepresented in the cerebellum compared to the cerebral cortex (2.3-fold). Temporally, all cerebellar resting state signals lagged behind the cerebral cortex (125–380 ms), supporting the hypothesis that the cerebellum engages in a domain-general function in the adaptive control of all cortical processes.
right temporal alpha oscillations as a neural mechanism for inhibiting obvious associations
caroline di bernardi luft et al. 2018
doi.org/10.1073/pnas.1811465115
The researchers found that these brainwaves, or alpha oscillations in the right temporal area of the brain, increase when individuals need to suppress misleading associations in creative tasks.
These obvious associations are present in both convergent thinking and also in divergent thinking (when individuals have to come up with several creative ideas).
Higher levels of alpha brainwaves enable people to come up with ideas which are further away from the obvious or well-known uses.
The researchers show that stimulating the right temporal part of the brain in the alpha frequency increases the capability of inhibiting obvious links in both types of creative thinking.
This was demonstrated by applying an electrical current to the brain through a non-invasive technique called transcranial alternating current brain stimulation (tACS) which causes minimal to no side effects or sensations.
The findings have implications for how we understand creativity and opens up potential ways of affecting the creative process including by using tACS.
Lead researcher Dr Caroline Di Bernardi Luft, from Queen Mary University of London, said: "If we need to generate alternative uses of a glass, first we must inhibit our past experience which leads us to think of a glass as a container. Our study's novelty is to demonstrate that right temporal alpha oscillations is a key neural mechanism for overriding these obvious associations.
"In order to understand the processes underlying the production of novel and adequate ideas, we need to break down its constituent processes, dissecting creativity as much as possible at first, and then analysing them in context, before putting them back together to understand the process as a whole."
The researchers demonstrated the neural mechanism responsible for creativity by monitoring the brain's electrical activity through an electroencephalogram (EEG) which picks up electrical signals through small sensors placed on the head. Using tACS also enabled them to probe the waves' causal role.
The experiments they conducted looked at how the brain tackles a series of creative tasks such as finding words that link to one another. For example, every time we search for concepts associated with a word we start from stronger associations to move progressively towards weaker or more remote ones (e.g. cat > dog > animal > pet > human > people > family).
Previous studies show that some people are more creative than others because they are able to avoid strong associations in order to reach more remote ones and this study demonstrates that the alpha brainwaves are crucially involved in this process.
Goldsmiths, University of London's Professor Joydeep Bhattacharya, a co-author of this study, added: "Two roads diverged in a wood, I took the one less travelled by. And that has made all the difference,' wrote Robert Frost in his famous poem."
"Taking a less travelled route is needed for thinking creatively, and our findings provide some evidence on how this is done in our brain."
abstract “Taking a less-traveled path” is often considered an effective approach to creativity (i.e., creative thinking calls for a break from habitual thinking and associations), yet little is known about its underlying neural mechanism. In a series of four independent experiments involving electrophysiological and brain stimulation methods we provide evidence that this process is mediated by the right temporal alpha oscillations. Alpha oscillations are known to represent a process of active inhibition to suppress irrelevant information, such as inhibiting distractions during visual search. Through monitoring the brain’s electrical activity during different creativity tasks and by stimulating the right temporal brain region at the alpha frequency we show that a similar process of active inhibition is also key to creative thinking.
organized toe maps in extreme foot users
harriet dempsey-jones et al. 2019
doi.org/10.1016/j.celrep.2019.08.027
"For almost all people, each of our fingers is represented by its own little section of the brain, while there's no distinction between brain areas for each of our toes," said the study's lead author, PhD student Daan Wesselink (UCL Institute of Cognitive Neuroscience and University of Oxford).
"But in other non-human primate species, who regularly use their toes for dextrous tasks like climbing, both the toes and fingers are specifically represented in their brains. Here, we've found that in people who use their toes similarly to how other people use their fingers, their toes were represented in their brains in a way never seen before in people."
The two study participants are among three professional foot painters in the UK who paint holding paintbrushes between their toes. They also use their toes regularly for everyday tasks such as dressing themselves, using cutlery and typing. To do what most people would do with their two hands, both artists typically use one foot for highly dextrous tasks while using the other foot to stabilise.
Their distinctive experiences extend beyond behaviour; by not regularly wearing enclosed footwear, the foot painters get more complex touch experiences on their toes. This may also have impacted brain development of these organised toe maps.
For the study, funded by Wellcome and the Royal Society, the foot painters (as well as 21 people born with two hands, who served as a control group) completed a series of tasks testing their sensory perception and motor control of their toes.
The participants then underwent ultra high-resolution fMRI brain scanning of the brain's body area -- the somatosensory cortex. While inside the scanner, a researcher tapped the toes of the study participants, first looking for activity in the foot area of the body map.
In the foot painters, specific sections of the brain's foot area clearly reacted to their toes being touched. Brain maps comprised of individual toes were seen for the artists' dextrous foot, with a similar but less pronounced pattern showing in their stabilising foot. The two-handed controls showed no such maps. Other analyses showed the foot painters' feet were represented in the brain in a 'hand-like' way, but not the control participants' feet.
The researchers also found that the foot painters' toes were additionally represented in the part of their brain that would otherwise have served their missing hands. This corresponds with another study from the same lab finding that the brain's hand area gets used to support body parts being used to compensate for disability, such as the lips, feet or arms of people who were born with only one hand.
Perhaps surprisingly, motor tasks showed the foot painters were not any better than controls at wiggling one toe at a time, but they did have heightened sensory perception for their toes compared to controls.
Peter Longstaff, one of the foot painters who took part in the study, said he was fascinated to learn about how his brain developed differently due to how he has used his feet. Longstaff, who ran his own pig farm for 20 years, turned to foot painting in 2002.
"I've enjoyed helping science by demonstrating how most people's feet are not used to their full potential, and I hope the results will encourage other people to consider unconventional ways to get by without the use of hands," he said.
The researchers say the findings reveal that all people may have an innate capacity for forming these ordered maps of each toe in the brain -- similar to our monkey relatives. Most people's brains don't develop as such, however, probably due to a lack of necessary experience.
"The body maps we have in our brains are not necessarily fixed -- it appears as such because they are very consistent across almost all people, but that's just because most people behave very similarly," said co-lead author Dr Harriet Dempsey-Jones (UCL Institute of Cognitive Neuroscience).
"Our study demonstrates an extreme example of the brain's natural plasticity, as it can organise itself differently in people with starkly different experiences from the very beginning of their lives," said the study's senior author, Dr Tamar Makin
abstract •We ask if extreme behavior can cause the (re)emergence of somatotopic maps
•We investigated two foot artists, born without arms
•7T fMRI shows individuated maps of up to 5 toes in the artists but not controls
•Activity in artists’ foot and hand areas was more “hand-like” than in controls
Although the fine-grained features of topographic maps in the somatosensory cortex can be shaped by everyday experience, it is unknown whether behavior can support the expression of somatotopic maps where they do not typically occur. Unlike the fingers, represented in all primates, individuated toe maps have only been found in non-human primates. Using 1-mm resolution fMRI, we identify organized toe maps in two individuals born without either upper limb who use their feet to substitute missing hand function and even support their profession as foot artists. We demonstrate that the ordering and structure of the artists’ toe representation mimics typical hand representation. We further reveal “hand-like” features of activity patterns, not only in the foot area but also similarly in the missing hand area. We suggest humans may have an innate capacity for forming additional topographic maps that can be expressed with appropriate experience.
solanum plastisexum, an enigmatic new bush tomato from the australian monsoon tropics exhibiting breeding system fluidity
angela j. mcdonnell et al. 2019
doi.org/10.3897/phytokeys.124.33526
The new species of bush tomato discovered in remote Australia provides a compelling example of the fact that sexuality among Earth's living creatures is far more diverse -- and interesting -- than many people likely realize.
Bucknell University postdoctoral fellow Angela McDonnell and biology professor Chris Martine led the study following an expedition last year to relocate populations of the new plant, which were first noted by Australian botanists during the 1970s.
Herbarium specimens from those few earlier collections are peppered with notes regarding the challenge of identifying the sexual condition of this plant, which appeared at various times to be female, male, or bisexual.
According to Martine, about 85% of the planet's quarter-million flowering plant species have flowers that are bisexual -- with both male and female organs present in every blossom.
"So that's already quite different than what some people might expect; but the remaining 15% or so come in all sorts of forms that push the envelope further, including unisexual flowers and (like we see in a plant like Cannabis) whole plants that are either male or female."
"For the most part, a given plant species will stick to one primary and predictable type of sexual expression," said Martine "but what makes Solanum plastisexum stand out is that it is one of a just a few plants that kind of do it all. It really seems like you never know what you'll get when you come across it."
When DNA studies in Martine's lab offered proof that these plants were not only all the same thing, but a species not yet described, he, McDonnell, Jason Cantley (San Francisco State University), and Peter Jobson (Northern Territory Herbarium in Alice Springs) set out to hunt for populations along the unpaved Buchanan Highway in the remote northwestern region of the Northern Territory.
The botanists were able to collect numerous new specimens and have now published the new species description in the open-access journal PhytoKeys, choosing the name Solanum plastisexum as a nod to the notable variation exhibited by this plant in its sexual condition.
"This name, for us, is not just a reflection of the diversity of sexual forms seen in this species," wrote the authors in the article. "It is also a recognition that this plant is a model for the sort of sexual fluidity that is present across the Plant Kingdom -- where just about any sort of reproductive form one can imagine (within the constraints of plant development) is present."
Also known as the Dungowan bush tomato, Solanum plastisexum is a distant cousin of the cultivated eggplant and is a close relative of two other Australian species recently discovered by Martine and colleagues that were also published in PhytoKeys: Solanum watneyi, named for Mark Watney, the space botanist of the book/film The Martian; and Solanum jobsonii, a species named last year for S. plastisexum co-author Jobson.
The scientists hope that the naming of this latest new species turns a spotlight on the fact that nature is full of examples for the myriad ways in which living things behave sexually.
"In a way, S. plastisexum is not just a model for the diversity of sexual/reproductive form seen among plants -- it is also evidence that attempts to recognize a "normative" sexual condition among the planet's living creatures is problematic."
"When considering the scope of life on Earth," the authors conclude, "The notion of a constant sexual binary consisting of two distinct and disconnected forms is, fundamentally, a fallacy.
abstract A bush tomato that has evaded classification by solanologists for decades has been identified and is described as a new species belonging to the Australian “Solanum dioicum group” of the Ord Victoria Plain biogeographic region in the monsoon tropics of the Northern Territory. Although now recognised to be andromonoecious, S. plastisexum Martine & McDonnell, sp. nov. exhibits multiple reproductive phenotypes, with solitary perfect flowers, a few staminate flowers or with cymes composed of a basal hermaphrodite and an extended rachis of several to many staminate flowers. When in fruit, the distal rachis may abcise and drop. A member of Solanum subgenus Leptostemonum, Solanum plastisexum is allied to the S. eburneum Symon species group. Morphometric analyses presented here reveal that S. plastisexum differs statistically from all of its closest relatives including S. eburneum, S. diversiflorum F. Meull., S. jobsonii Martine, J.Cantley & L.M.Lacey, S. succosum A.R.Bean & Albr. and S. watneyi Martine & Frawley in both reproductive and vegetative characters. We present evidence supporting the recognition of S. plastisexum as a distinctive entity, a description of the species, representative photographs, a map showing the distribution of members of the S. eburneum species group and a key to the andromonoecious Solanum species of the Northern Territory of Australia. This new species is apparently labile in its reproductive expression, lending to its epithet, and is a model for the sort of sexual fluidity that is present throughout the plant kingdom.
cheaper by the dozen
frank gilbreth, ernestine gilbreth carey 1948
genomic adaptations in information processing underpin trophic strategy in a whole-ecosystem nutrient enrichment experiment
jordan g okie et al. 2020
doi.org/10.7554/elife.49816
unusual characteristic of being particularly nutrient-poor and harboring a ‘lost world’ of many below-ground and above-ground aquatic microbes of ancient marine ancestry.
Because of these characteristics, it is an invaluable place for researchers to study and understand how life may have existed on other planets in our solar system.
In a recent study published in the journal eLIFE a team of researchers, including lead author Jordan Okie of Arizona State University’s School of Earth and Space Exploration and senior author Jim Elser of the School of Life Sciences, conducted experiments in the Cuatro Cienegas Basin.
Their goal was to shed light on how fundamental features of an organism’s genome — its size, the way it encodes information, and the density of information — affect its ability to thrive in an extreme environment.
“This area is so poor in nutrients that many of its ecosystems are dominated by microbes and may have similarities to ecosystems from early Earth, as well as to past wetter environments on Mars that may have supported life,” says lead author Okie.
For their experiment, researchers conducted field monitoring, sampling, and routine water chemistry for 32 days in a shallow, nutrient-poor pond called Lagunita in the Cuatro Cienegas Basin.
First, they installed mescocosms (miniature ecosystems) that served as a control group and remained separate from the rest of the pond. They then added a fertilizer solution that was rich in nitrogen and phosphorus to increase microbial growth in the pond.
At the end of the experiment, they examined how the community in the pond changed in response to the additional nutrients, focusing on their ability to process biochemical information within their cells.
J. Craig Venter Institute associate professor Christopher Dupont, who is a senior author on the study, stated, “We hypothesized that microorganisms found in oligotrophic (low nutrient) environments would, out of necessity, rely on low-resource strategies for replication of DNA, transcription of RNA, and translation of protein. Conversely, a copiotrophic (high nutrient) environment favors resource-intensive strategies.”
Ultimately, they found that indeed a nutrient-enriched community became dominated by species that could process biochemical information at a faster rate whereas the original low-nutrient community harbored species with reduced costs of biochemical information processing.
“This study is unique and powerful because it takes ideas from the ecological study of large organisms and applies them to microbial communities in a whole-ecosystem experiment,” says Elser. “By doing so, we were able, perhaps for the first time, to identify and confirm that there are fundamental genome-wide traits associated with systematic microbial responses to ecosystem nutrient status, without regard to the species identity of those microbes.”
What this may suggest for life on other planets is that organisms, no matter where they are, have to have information-processing machinery fine-tuned to the key resources around them. In turn, the supply of these resources will depend on the planetary environment.
“This is very exciting, as it suggests there are rules of life that should be generally applicable to life on Earth and beyond,” says Okie.
abstract Several universal genomic traits affect trade-offs in the capacity, cost, and efficiency of the biochemical information processing that underpins metabolism and reproduction. We analyzed the role of these traits in mediating the responses of a planktonic microbial community to nutrient enrichment in an oligotrophic, phosphorus-deficient pond in Cuatro Ciénegas, Mexico. This is one of the first whole-ecosystem experiments to involve replicated metagenomic assessment. Mean bacterial genome size, GC content, total number of tRNA genes, total number of rRNA genes, and codon usage bias in ribosomal protein sequences were all higher in the fertilized treatment, as predicted on the basis of the assumption that oligotrophy favors lower information-processing costs whereas copiotrophy favors higher processing rates. Contrasting changes in trait variances also suggested differences between traits in mediating assembly under copiotrophic versus oligotrophic conditions. Trade-offs in information-processing traits are apparently sufficiently pronounced to play a role in community assembly because the major components of metabolism—information, energy, and nutrient requirements—are fine-tuned to an organism’s growth and trophic strategy.
the dream of the iron dragon
robert kroese 2018
the dawn of the iron dragon
robert kroese 2018 not yet read
the voyage of the iron dragon
robert kroese 2019 not yet read
the legacy of the iron dragon
robert kroese 2020 not yet read
the strange case of the alchemist’s daughter
theodora goss 2017
european travel for the monstrous gentlewoman
theodora goss 2018
not yet read
…
the witches of karres
james h. schmitz 1966
the wizard of karres
mercedes lackey, eric flint, dave freer 2006
the sorceress of karres
eric flint, dave freer 2010
the shaman of karres
eric flint, dave freer 2020
beneath the rising
premee mohamad 2020
the last human
zack jordan 2020
liquid crystal nightingale
eeleen lee 2020
providence
max barry 2020
eden
tim lebbon 2020
foundryside
robert jackson bennett 2018
shorefall
robert jackson bennett 2020
bridge 108
anne charnock 2020
the vanished birds
simon jimenez 2020
the ten thousand doors of january
alix e. harrow 2019
mainline
deborah teramis christian 1996
splintegrate
deborah teramis christian 2019
veil
eliot peper 2020
elastic: flexible thinking in a time of change
leonard mlodinow 2018
toreadnext
a skeptic’s guide to the mind: what neuroscience can and cannot tell us about ourselves
robert a. burton 2013
a new reality: human evolution for a sustainable future
jonas salk, jonathan salk 2018
always change a losing game: winning strategies for work, home and health
david posen 2018
ask more the power of questions to open doors, uncover solutions, and spark change
frank sesno 2018
genes, brains, and human potential: the science and ideology of intelligence
ken richardson 2017
don’t be such a scientist: talking substance in an age of style
randy olson 2009, 2018
rethink: the surprising history of new ideas
steven poole 2016
deviate: the science of seeing differently
beau lotto 2017
we do things differently: the outsiders rebooting our world
mark stevenson 2018
critical thinking unleashed
elliot cohen 2009
thought and knowledge: an introduction to critical thinking
diane f. halpern 2014
rethink: the surprising history of new ideas
steven poole 2016
parallel thinking
edward de bono 1991
the biological mind: how brain body and environment collaborate to make us who we are
alan jasanoff 2018 to read next
abc the alphabetizaton of the popular mind
ivan illich 1988 to read next
finding meaning in an imperfect world
iddo landau 2017
hypersanity: thinking beyond thinking
neel burton 2019
heaven and hell: the psychology of the emotions
neel burton 2020
the end of animal farming: how scientists, entrepreneurs, and activists are building an animal-free food system
jacy reese 2018
the inflamed mind: a radical new approach to depression
edward bullmore 2018
blindsight
peter watts 2006
the matter of facts: skepticism, persuasion, and evidence in science
gareth leng, rhodri leng 2020
grow the pie: how great companies deliver both purpose and profit
alex edmans 2020 unread
the new testament: a translation
david bentley hart 2018
goldilocks
laura lam 2020
every heart a doorway
seanan mcguire 2016
down among the sticks and bones
seanan mcguire 2017
beneath the sugar sky
seanan mcguire 2018
in an absent dream
seanan mcguire 2019
come tumbling down
seanan mcguire 2020