yeast banksters....,

The Scientist | Yeast colonies with mooches, thieves and cheats actually grow faster and larger than colonies without these freeloading individuals, according to a study published 15th September in PLoS Biology, challenging the widely held belief that cheaters bring only bad news to cooperating populations.

Researchers found that when some yeast cheat their neighbors out of glucose, the entire population grows faster. "This is a most surprising result," said Laurence Hurst of the University of Bath in the UK, who coauthored the study. "The theory of cooperation was one of the best worked theories in all of evolution. Everyone assumed that it had to be the case that the world is better off when everyone cooperates."

The results may explain why yeast populations tolerate the presence of cheaters, added Michael Travisano, a biologist at the University of Minnesota, who was not involved in the research -- "because a mixed strategy is to everyone's benefit."

Most yeast secrete invertase, which hydrolyzes sucrose into fructose and glucose, their preferred food. However, some yeast are known to cheat the system. Cheater yeast don't secrete invertase and therefore don't contribute to the glucose production, yet they still eat the glucose that is generated by the rest of the population.

According to the theory of cooperation, which states that organisms are better off when everyone cooperates, yeast populations should be best off when all the yeast produce invertase. This would maximize the availability of glucose, which should enable more yeast growth. But when Hurst and his colleagues grew yeast populations with both producers and non-producers of invertase, this is not what they saw. Instead, the yeast grew the fastest and saw the highest population numbers when a proportion of the population was cheating.

Future Genomics: Don't Edit A Rough Copy When You Can Print A Fresh New One

technologyreview  |  It took Boeke and his team eight years before they were able to publish their first fully artificial yeast chromosome. The project has since accelerated. Last March, the next five synthetic yeast chromosomes were described in a suite of papers in Science, and Boeke says that all 16 chromosomes are now at least 80 percent done. These efforts represent the largest amount of genetic material ever synthesized and then joined together.

It helps that the yeast genome has proved remarkably resilient to the team’s visions and revisions. “Probably the biggest headline here is that you can torture the genome in a multitude of different ways, and the yeast just laughs,” says Boeke.

Boeke and his colleagues aren’t simply replacing the natural yeast genome with a synthetic one (“Just making a copy of it would be a stunt,” says Church). Throughout the organism’s DNA they have also placed molecular openings, like the invisible breaks in a magician’s steel rings. These let them reshuffle the yeast chromosomes “like a deck of cards,” as Cai puts it. The system is known as SCRaMbLE, for “synthetic chromosome recombination and modification by LoxP-mediated evolution.”

The result is high-speed, human-driven evolution: millions of new yeast strains with different properties can be tested in the lab for fitness and function in applications like, eventually, medicine and industry. Mitchell predicts that in time, Sc2.0 will displace all the ordinary yeast in scientific labs.

The ultimate legacy of Boeke’s project could be decided by what genome gets synthesized next. The GP-write group originally imagined that making a synthetic human genome would have the appeal of a “grand challenge.” Some bioethicists disagreed and sharply criticized the plan. Boeke emphasizes that the group will “not do a project aimed at making a human with a synthetic genome.” That means no designer people.

Ethical considerations aside, synthesizing a full human genome—which is over 250 times larger than the yeast genome—is impractical with current methods. The effort to advance the technology also lacks funding. Boeke’s yeast work has been funded by the National Science Foundation and by academic institutions, including partners in China, but the larger GP-write initiative has not attracted major support, other than a $250,000 initial donation from the computer design company Autodesk. Compare that with the Human Genome Project, which enjoyed more than $3 billion in US funding.

the human edge - finding our inner fish

NPR | It took him years of searching in the Canadian Arctic, but in 2004, Neil Shubin found the fossilized remains of what he thinks is one of our most important ancestors.

Turns out, it's a fish.

Shubin says his find, which he named Tiktaalik, represents an important evolutionary step, because it has the structures that will ultimately become parts of our human bodies. Shoulders, elbows, legs, a neck, a wrist — they're all there in Tiktaalik.

"Everything that we have are versions of things that are seen in fish," says Shubin.

Of course, there are things that we have that Tiktaalik doesn't.

"We have a big brain, and portions of that big brain are not seen in Tiktaalik," says Shubin. "But the template, all the way down to the DNA that builds it, is already present in creatures like this."

Inside this fish, Shubin sees us.

"It's like peeling an onion," he says. "Layer after layer after layer is revealed to you. Like in a human body, the first layer is our primate history, the second layer is our mammal history, and on and on and on and on, until you get to the fundamental molecular and cellular machinery that makes our bodies and keeps are cells alive, and so forth."

Our Inner Yeast
In fact, not only are we related to an ancient fish, but many of the parts critical for making yeast are also critical for making us, says Gavin Sherlock, a geneticist at Stanford University.

"About one-third of the yeast genes have a direct equivalent version that still exists in humans," he says.

Sherlock says that not only do many of the same genes still exist in humans and yeast, but they're so similar that you can exchange one for the other.

"There are several hundred examples where you can knock out the yeast gene, put in the human equivalent, and it restores it back to normal," he says.

Think about it, he says: We have a lot in common with yeast. Yeast consume sugars like we do, yeast make hormones like we do, and yeast have sex — not quite like we do, but sex.

Sex isn't just fun and games. Sexual reproduction is critical for stirring the genetic pot, speeding the evolution of endless forms most beautiful, from fruit flies to blue whales to humans.

Now yeast is a single-celled organism. We have trillions and trillions of cells in our bodies — different kinds of cells, all fitting together. How did that happen?

The answer is at the Field Museum in Chicago.

building better bacteria

The Scientist | Researchers from the J. Craig Venter Institute have developed a technique for generating modified strains of bacteria with novel, genetically engineered properties, they report online today (August 20) in Science. The advance could help scientists tweak microorganisms to more efficiently produce biofuels, the researchers say.

"I think it's an important and interesting advance," said James Collins, a bioengineer at Boston University who was not involved in the study. "I suspect this will turn out to be quite important for bioengineering and bioenergy systems."

Last year, Venter, an author on the paper (and a member of The Scientist's editorial board), reported that he and his collaborators had created a synthetic bacterial genome and cloned it into a yeast cell. However, they were unable to transfer the genome into a cell that would use the genetic code to produce a functioning version of the organism. In the current paper, the researchers present a technique for doing just that.

The Venter team first cloned the genome of the bacterium Mycoplasma mycoides into a yeast cell. They then altered the genome, using the myriad tools available for yeast gene manipulation. In the procedure's trickiest step, they transplanted the yeast-bound bacterial genome into a closely related bacterium, Mycoplasma capricolum, coaxing it to "take this bacterial genome and boot it up" and generate their mutant strain, said Sanjay Vashee, a synthetic biologist at the institute and the corresponding author on the paper.

The hurdle Vashee and his team had to overcome to achieve this feat involved bypassing the bacterial equivalent of an immune system -- essentially a collection of restriction enzymes. These enzymes, thought to have evolved to chew up the genomes of viruses infecting bacterial cells, were preventing the successful transplantation of the modified M. mycoides genome into wild-type M. capricolum. So the group developed two fixes, which together solved the problem: First, they inactivated M. capricolum's restriction enzymes. Then, they chemically modified their mutant M. mycoides genome where these enzymes typically cleave the genomes of intruders.

Decades of research on yeast genetics have yielded the know-how to do extensive genomic manipulations in yeast, but that capability doesn't exist for other microorganisms. "There are so many organisms in nature that we cannot manipulate," said Vashee. "If we can extend this -- and put those genomes into yeast, to manipulate them there -- we've got a new technology that can bring genomics to a wide host of organisms." (Vashee noted that the current study was conducted in a natural Mycoplasma genome -- not the synthetic genome the group assembled last year.)

sources of heritable novelty

How is new genetic material acquired? How much new genetic material can be acquired a gene at a time, or just a few genes - the ones desired? The new technology of DNA-sequencing lets us answer these questions directly.

The minimal heritable genetic change is a single base-pair change in DNA - from A-T to G-C (or from G-C to A-T). The maximal heritable change is the acquisition of an entire set of genes to run an organism (the genome) along with the rest of the organism in a healthy state so that the genome may have something to run. In between are many other ways in which organisms gain and retain heritable novelty. When the complete sequencing of the human genome was announced at the beginning of this millennium, many were quite surprised to learn that some 250 of the more than 30,000 human genes of our bodies have come directly from bacteria. These genes, long sequences of DNA that code for proteins, are as recognizably of bacterial origin as a feather is recognizably from a bird rather than, say, a shark's mouth.

How bacteria passed genes to people no one knows, but a good guess is via viruses. Bacteria are notorious for harboring viruses and moving them to new localities, such as to other bacteria.

The genome of the common yeast Saccharomyces cerevisiae has been fully sequenced, and it gave the scientists who did it a nice surprise. The chose S. cerevisiae-a single-celled fungus-as the representative of the fungus kingdom to sequence because this versatile little cell's life is tied to ours in many ways. This yeast makes dough rise, and therefore most baked goods - bread or cake or brioche - depend on it. It brews beer, therefore all beer with alcohol depends on happy growing conditions for Saccharomyces cerevisiae. It abounds in yougurt and other dairy products. It grows quickly and well under laboratory conditions and has been a favorite object of study in the investigation of fungal sex, fungal viruses, chromosome behaviour, growth, and survival as well as spore formation. Each Saccharomyces cerevisiae yeast cell, as was well known, is "haploid", which means it has only one copy of each of its ten chromosomes. (We human animals are diploid, which means each of us has two copies of each of our twenty-three chromosomes; one set comes from our father, the other comes from our mother). What surprised everyone was that haploid yeast had two copies of nearly all the genes.

The yeast story adds another item to our collection of ways to gain new genetic materials: duplication. Every organism that has been studied has some detectable degree of gene duplications; a part of an older gene, and entire single gene, a set of a few genes, a chromosome's worth, or - as in yeast - nearly every gene in the cell's little body. Just as extra copies of manuscripts or instruction booklets free up the originals to differ from the copies, extra sets of genes have proved to be very useful as yeasts and other organisms have evolved to larger sizes and more complexity. Principles of Evolutionary Novelty - Acquiring Genomes - Dr. Lynn Margulis and Dorion Sagan.

sure, on an individual basis - and I'll prove it

How otherwise could I offer you this guaranteed recipe for rolls easy enough for a child to make - and upon which you and yours are guaranteed to absolutely hurt yourself (in the best possible way of course). These go well with turkey and all the trimmings, or, standalone with jams, jellies, and preserves.

You'll need 3 packets of yeast,
1/3rd cup of lukewarm water
soften/dissolve yeast in the warm water

2/3rds cup of sugar,
1 tablespoon of salt
3 tablespoons of vegetable oil
3 cups of boiling water
mix these together and set them aside to cool

1 tablespoon of sugar
3 room temperature eggs
whisk these together in your largest mixing bowl

12 cups of sifted flour

Pour the dissolved yeast onto the egg and sugar mixture and gently whisk these together. (gotta jump start the yeasty proliferation) When the boiling salty, sugary, oily water is lukewarm, pour it into the jumpstarted egg/yeast/sugar mixture in the bowl and gently integrate it all with your whisk.

To this fragrant, active, yeasty brown egg broth - you will add your twelve cups of sifted flour. Up until the 8th cup or so, it's pretty easy, but from the 8th to the 12th cup, it becomes somewhat drier and more difficult to whisk and integrate additional flour.

Anyway, once you get all that biologically active mass of dough pulled together in your big mixing bowl, you'll probably want to break it up into a couple, possibly three smaller batches for overnight population explosion. (i.e., letting the dough rise, as the yeast devours the sugar and emits mass quantities of CO2 into the mass)

Be sure to cover each of your smaller rising bowls with a wet towel (cheesecloth) (so that as the dough rises overnight, it doesn't dry out on its surface) put the wet towel covered rising bowls in the refrigerator overnight (the cold will only moderate the yeasty population explosion) come late morning, you'll have big swollen. fragrant, yeasty dough balls trying to burst through the moist towels covering each bowl.

These will stay viable throughout the day into mid-afternoon. A couple of hours before you're ready to bake, melt a stick of butter in a bowl. Punch down a dough ball, roll it out on a floured board, use a juice glass to cut it out into ~3 inch circles.

Have a baking sheet ready.

Dip each circle (roll) into the melted butter and fold it in the middle onto the baking pan. Line these up row after row until the pan is full. Let the divided, conquered, buttered, and beaten rolls sit on that baking sheet to rise for at least 90 minutes (yes, the yeast is still very much alive even after all that abuse)

After that second rising, the baking sheet will be at overflow capacity with monstrous, swollen rolls a good three times larger than they were when you put them on the baking sheet.

Comes now the apocalypse.

Bake the rolls at 350 degrees until they're just a little golden brown 25-35 minutes.

Serve them immediately at the outset of your thanksgiving day feast. Trust me, once you've dropped these heavy, fresh, buttery hard rolls (not like bread at all) on a hungry gathering of friends and family, you will have ruined them for life on any possible alternative. From that point forward, as far as your guests are concerned, your holiday feasts will be all about the rolls. Accept no substitutes....,

the gates of immortality?

The Scientist | I had to wonder, what is aging after all? Is it something positively tangible, something that we could define otherwise than a loss: loss of fitness, loss of potential, loss of viability? There is at least one type of molecular marker that correlates well with aging, at least in yeast: extrachromosomal ribosomal DNA circles (ERCs). These circles, or plasmids, of DNA are excised from the ribosomal DNA (rDNA) locus on the chromosome and replicate at each division cycle. The ERCs, however, are redundant to the chromosomal ribosome genes—unnecessary elements that accumulate in the nucleus of the mother cell as it ages. Although ERCs do not represent the only mechanism of aging in yeast, their accumulation is related to aging: cells in which ERC formation is delayed live longer, whereas cells with increased ERC formation die sooner. It would follow then, that their retention by the mother cell contributes largely to the age asymmetry between mother and bud.

Mortal and immortal lineages
Most buds produced by a mother cell will also become bud-producing mothers themselves. A new mother has the capacity to produce 30 buds before she dies with a large number of extrachromosomal rDNA circles (ERCs) accumulated in her nucleus. When the barrier separating the mother from the bud was experimentally disrupted, it allowed ERCs to enter the bud in large number. As a result, the mother lived longer, while the reproductive life of her daughters was shortened proportionate to the amount of ERCs she received.

ERC retention, then, must rely on some intrinsic asymmetry of the nucleus. For example, the yeast nucleus, which does not disassemble during mitosis, as in mammalian cells, always sends its oldest spindle pole body (SPB) to the bud. The SPB, which organizes the duplicate genomes during mitosis, is embedded in the nuclear envelope, and duplicates at each cycle to form a single new SPB. If we forced the nucleus to send the old SPB to the bud only half of the time, would the ERCs then segregate to the bud the other half of the time? To our surprise, this did not happen; the ERCs remained in the mother cell. The exclusive retention of the ERC plasmids within the nucleus of the mother cell only diminished when we disturbed the septin diffusion barrier that divided the nuclear envelope.8

As a consequence, yeast cells lacking the septin diffusion barrier can pass these molecular markers of aging to their daughters. Without the diffusion barrier the mothers were longer lived, but their daughters behaved as if they were older at birth: in other words, they had the capacity to replicate fewer times. The fact that ERCs remained in the mother’s part of the nucleus indicated that the plasmids had to be linked to something embedded in the nuclear membrane. Since septins only blocked diffusion of molecules in the membrane (they did not, for example, create a webbing across the cytoplasm), none of the molecules freely floating in the nucleoplasm would be affected. We observed that these plasmids were associated with the nuclear envelope, more precisely with the basket of nuclear pores on the inside of the nuclear membrane, and that this association was required for their retention in the mother cell. Taken together, our data suggest the intriguing idea that aging, whatever it is, respects diffusion barriers, and that these boundaries prevent the propagation of aging-related molecules into newborn buds.

It may be that the cell’s solution to its unsolvable problems is simply to age, to compartmentalize the components that bear too much resemblance to self and slough them off.

It is still unclear at this point whether these findings have any parallel in other eukaryotes, but we think they might. Indeed, the process of sperm generation shows intriguing similarities with the budding process in yeast, at least in terms of the maturation of the future sperm’s nuclear envelope. The emergence of the sperm head involves the migration of the nucleus through a perinuclear ring. During this process, the nuclear envelope is combed, leaving behind its nuclear pores, which, in many cases, are then excluded from the sperm nucleus. Thus, it is tempting to speculate that we, too—like yeast—keep our sperm as young as possible each time we prepare to form a newborn.

Over the years, these observations and findings have led me back to Gödel and his ideas of unsolvable problems. Aging seemed the perfect example of a process in which the cell could not detect ambiguous molecules (either overtly damaging, or beneficial) and repair itself.

To my mind, ERCs are emblematic of objects that are ambiguous to the cell. They have the same chemical nature, the same repeating composition as the chromosome, and therefore cannot be targeted for destruction without risking damaging the chromosomes as well. They take on the characteristics of entities that are both self and nonself. Gödel was able to mathematically characterize the unsolvable problems he encountered and describe them with a universal rule. Might ERCs help define the universal properties of the unfixable errors that accumulate with age? What prevented biological systems from being complete?

At its core, the generation and accumulation of ERCs is a problem of symmetry—ERCs are generated by errors in DNA repair. When the DNA repair (or recombination) machinery resolves the Holliday Junction, it has one of two options, excision or repair. But because of the local symmetry at the Holliday Junction, the recombination machinery cannot detect a difference between the incoming strands of DNA, and therefore cannot favor one solution over the other. In order to handle such an unsolvable problem, the cell simply produces both outcomes with equal probability, with the production of ERCs and DNA repair occurring exactly 50 percent of the time.

What if structural asymmetries, such as cell polarity, might have actually emerged to counteract the logical problems that symmetric events such as DNA repair generate for the cell? If true, it implies that studying symmetric processes in biology could reveal new insights about aging.

It may be that the cell’s solution to its unsolvable problems is simply to age, to compartmentalize the components that bear too much resemblance to self and slough them off, producing a life that lacks these deformities. Although the yeast cell might not be able to distinguish ERCs from the chromosomes, it found ways to sort them out and confine them to the mother cells. Diffusion barriers could play a central role in this process. It is interesting because they are likely to simply retain in the mother cell anything that is not actively being chosen and pulled into the bud, such as chromosomes or vesicles. Thus, they offer a remarkable solution to the retention of ambiguous objects, that is, objects that the cell cannot distinguish as being right or wrong, objects that therefore remain invisible to cellular machineries.

Last, if aging is a consequence of Gödel’s theorem in biology and of the cell’s incompleteness, then aging is not a program but an inescapable fact. The quest for a cure to the aging “disease” will inevitably fail. But there is a bright side to the fact that the cell is logically incomplete. Would any complete system—one able to detect any damage and repair itself perfectly—have the ability to evolve?

yeast nasty...,

LiveScience | It doesn't take much to get the fungus that causes thrush and other infections in the mood. New research suggests that in addition to chemical signals from its own species, the yeast, called Candida albicans, also gets turned on by the so-called pheromones sent out by other species.

And when turned on, this yeast isn't selective. If cells of the opposite sex aren't around, then it mates with same-sex partners, according to Richard Bennett, one of the study researchers and an assistant professor at Brown University in Rhode Island.

This type of fungus is a natural inhabitant of our bodies, particularly our guts, but, given the opportunity, the yeast can also cause harmful infections, ranging from a superficial thrush infection in the mouth to potentially lethal blood infections among those with weakened immune systems.

C. albicans cells come in two forms: white and opaque, names derived from the appearance of their colonies. Opaque cells are the reproductive ones. They produce a pheromone that prompts other opaque cells to turn on genes associated with mating. In the presence of this pheromone, the opaque cells also put out long projections that search for another cell with which to fuse (the yeast equivalent of sex), according to Bennett.

The white cells do not reproduce, but they also respond to the pheromone, which activates an entirely different set of genes. They become sticky, and start to glom together and to surfaces, such as a catheter, forming what is known as a biofilm. This is a common route to harmful infections.

The researchers synthesized a variety of pheromones produced by this species and a variety of other fungal species, and found that the white and opaque cells were not picky about a trigger for their responses. The normal opaque cell pheromone is a string of 13 amino acids, which are organic compounds.

“In some of the pheromones eight of 13 residues were different,” Bennett said. “That’s why we were so surprised with these pheromones. We didn’t expect them to work because they look so different.”

It is not unusual for one species to respond to pheromones from another, however, it is unusual for that response to lead to productive mating, he said.

C. albicans' lax standards may mean that it could respond to other signals from its environment, including signals directly from the host. The next step, Bennett said, is to figure out how these findings fit in with disease.

The research was published online today (Jan. 24) by the journal Proceedings of the National Academy of Sciences. Fist tap Nana.

Leaven

My favorite line from Proverbs is the one about fear of the Lord as the beginning of wisdom. Does our reptilian brain with its copious reservoir of fear combined with a forebrain coveting order require God to have a sense of security in [a] world fraught with instability? Is the belief in the supernatural the basis for social control? And because of their special connection with God, do some people (Moses, Jesus, Mohammed) and their derivatives come to constitute a ruling class?

My brother asks a series of the most interesting kwestins. I suspect you already know the traditional answers encapsulated in the combined Abrahamic world views? Whether matrilineage, succession, or grace - there is a significant component of that embodied in the "anointed" rulers.

The question this begs for me, is whether there is a significant kernal of truth or implicate order embodied in these long-standing traditions?

Galatians 5:7-10 You were running well; who hindered you from following (the) truth? That enticement does not come from the one who called you. A little yeast leavens the whole batch of dough. I am confident of you in the Lord that you will not take a different view, and that the one who is troubling you will bear the condemnation, whoever he may be.

Matthew 13:33 He proposed another parable to them. "The kingdom of heaven is like a mustard seed that a person took and sowed in a field. It is the smallest of all the seeds, yet when full-grown it is the largest of plants. It becomes a large bush, and the 'birds of the sky come and dwell in its branches.'" He spoke to them another parable. "The kingdom of heaven is like yeast that a woman took and mixed with three measures of wheat flour until the whole batch was leavened."

Luke 13:20-21Then he said, "What is the kingdom of God like? To what can I compare it? It is like a mustard seed that a person took and planted in the garden. When it was fully grown, it became a large bush and 'the birds of the sky dwelt in its branches.'" Again he said, "To what shall I compare the kingdom of God? It is like yeast that a woman took and mixed (in) with three measures of wheat flour until the whole batch of dough was leavened."

Thomas 96. Yeshua [says:] The Sovereignty of the Father is like [a] woman,¹ she has taken a little yeast,¹ she [has hidden] it in dough,¹ she produced large loaves of it. Whoever has ears, let him hear! (¹asyndeta; =Mt 13:33)

97. Yeshua says: The Sovereignty of the [Father] is like a woman who was carrying a jar full of grain. While she was walking [on a] distant road, the handle of the jar broke, the grain streamed out behind her onto the road. She did not know it, she had noticed no accident. When she arrived in her house, she set the jar down— she found it empty. (multiple asyndeta)

98. Yeshua says: The Sovereignty of the Father is like someone who wishes to slay a prominent person. He drew forth his sword in his house,¹ he thrust it into the wall in order to ascertain whether his hand would prevail. Then he slew the prominent person. (¹asyndeton; ‘the sword of one's mouth’: Isa 49:2, Rev/Ap 1:16)

Matthew 16:6-12 In coming to the other side of the sea, the disciples had forgotten to bring bread. Jesus said to them, "Look out, and beware of the leaven of the Pharisees and Sadducees." They concluded among themselves, saying, "It is because we have brought no bread." When Jesus became aware of this he said, "You of little faith, why do you conclude among yourselves that it is because you have no bread? Do you not yet understand, and do you not remember the five loaves for the five thousand, and how many wicker baskets you took up? Or the seven loaves for the four thousand, and how many baskets you took up? How do you not comprehend that I was not speaking to you about bread? Beware of the leaven of the Pharisees and Sadducees." Then they understood that he was not telling them to beware of the leaven of bread, but of the teaching of the Pharisees and Sadducees.

Authoriteh's Restive About What You Peasants Get Up To With Synthetic Biology

FT  |  Paul Dabrowa does not know if it is illegal to genetically modify beer at home in a way that makes it glow. The process involves taking DNA information from jellyfish and applying it to yeast cells, then using traditional fermenting methods to turn it into alcohol. But he is worried that it could be against the law given that it involves manipulating genetic material. “This stuff can be dangerous in the wrong hands, so I did that in an accredited lab,” he says, adding that he himself has only got as far as making yeast cells glow in a Petri dish. For the most part Dabrowa, a 41-year old Melbourne-based Australian who styles himself as a bit of an expert on most things, prefers to conduct his biohacking experiments in his kitchen. He does this mostly to find cures for his own health issues. Other times just for fun.

In recent years the community of hobbyists and amateurs Dabrowa considers his kin has been energised by the falling cost and growing accessibility to gene-editing tools such as Crispr. This has led to an explosion of unchecked experimentation in self-constructed labs or community facilities focused on biological self-improvement.

Despite a lack of formal microbiological training, Dabrowa has successfully used faecal transplants and machine learning to genetically modify his own gut bacteria to lose weight without having to change his daily regime. The positive results he’s seen on himself have encouraged him to try to commercialise the process with the help of an angel investor. He hopes one day to collect as many as 3,000 faecal samples from donors and share the findings publicly.

Much of his knowledge — including the complex bits related to gene-editing — was gleaned straight from the internet or through sheer strength of will by directly lobbying those who have the answers he seeks. “Whenever I was bored, I went on YouTube and watched physics and biology lectures from MIT [Massachusetts Institute of Technology],” he explains. “I tried the experiments at home, then realised I needed help and reached out to professors at MIT and Harvard. They were more than happy to do so.”

At the more radical end of the community are experimentalists such as Josiah Zayner, a former Nasa bioscientist, who became infamous online after performing gene therapy on himself in front of a live audience. Zayner’s start-up, The Odin — to which Crispr pioneer and professor of genetics at Harvard Medical School George Church is an adviser — has stubbornly resisted attempts to regulate its capacity to sell gene-editing kits online in the idealistic belief that everyone should be able to manage their own DNA.

These garage scientists might seem like a quirky new subculture but their rogue mindset is starting to generate consternation among those who specialise in managing biological threats in governments and international bodies.

In 2018 the states that are signatories to the 1972 Biological Weapons Convention (BWC) identified gene editing, gene synthesis, gene drives and metabolic pathway engineering as research that qualifies as “dual use”, meaning it is as easy to deploy for harmful purposes as it is for good.
 

The Fungus Among Us...,

scientificamerican |  We are likely to think of fungi, if we think of them at all, as minor nuisances: mold on cheese, mildew on shoes shoved to the back of the closet, mushrooms springing up in the garden after hard rains. We notice them, and then we scrape them off or dust them away, never perceiving that we are engaging with the fragile fringes of a web that knits the planet together. Fungi constitute their own biological kingdom of about six million diverse species, ranging from common companions such as baking yeast to wild exotics. They differ from the other kingdoms in complex ways. Unlike animals, they have cell walls, not membranes; unlike plants, they cannot make their own food; unlike bacteria, they hold their DNA within a nucleus and pack cells with organelles—features that make them, at the cellular level, weirdly similar to us. Fungi break rocks, nourish plants, seed clouds, cloak our skin and pack our guts, a mostly hidden and unrecorded world living alongside us and within us.

That mutual coexistence is now tipping out of balance. Fungi are surging beyond the climate zones they long lived in, adapting to environments that would once have been inimical, learning new behaviors that let them leap between species in novel ways. While executing those maneuvers, they are becoming more successful pathogens, threatening human health in ways—and numbers—they could not achieve before.

Surveillance that identifies serious fungal infections is patchy, and so any number is probably an undercount. But one widely shared estimate proposes that there are possibly 300 million people infected with fungal diseases worldwide and 1.6 million deaths every year—more than malaria, as many as tuberculosis. Just in the U.S., the CDC estimates that more than 75,000 people are hospitalized annually for a fungal infection, and another 8.9 million people seek an outpatient visit, costing about $7.2 billion a year.

For physicians and epidemiologists, this is surprising and unnerving. Long-standing medical doctrine holds that we are protected from fungi not just by layered immune defenses but because we are mammals, with core temperatures higher than fungi prefer. The cooler outer surfaces of our bodies are at risk of minor assaults—think of athlete's foot, yeast infections, ringworm—but in people with healthy immune systems, invasive infections have been rare.

That may have left us overconfident. “We have an enormous blind spot,” says Arturo Casadevall, a physician and molecular microbiologist at the Johns Hopkins Bloomberg School of Public Health. “Walk into the street and ask people what are they afraid of, and they'll tell you they're afraid of bacteria, they're afraid of viruses, but they don't fear dying of fungi.”

Ironically, it is our successes that made us vulnerable. Fungi exploit damaged immune systems, but before the mid-20th century people with impaired immunity didn't live very long. Since then, medicine has gotten very good at keeping such people alive, even though their immune systems are compromised by illness or cancer treatment or age. It has also developed an array of therapies that deliberately suppress immunity, to keep transplant recipients healthy and treat autoimmune disorders such as lupus and rheumatoid arthritis. So vast numbers of people are living now who are especially vulnerable to fungi. (It was a fungal infection, Pneumocystis carinii pneumonia, that alerted doctors to the first known cases of HIV 40 years ago this June.)

Not all of our vulnerability is the fault of medicine preserving life so successfully. Other human actions have opened more doors between the fungal world and our own. We clear land for crops and settlement and perturb what were stable balances between fungi and their hosts. We carry goods and animals across the world, and fungi hitchhike on them. We drench crops in fungicides and enhance the resistance of organisms residing nearby. We take actions that warm the climate, and fungi adapt, narrowing the gap between their preferred temperature and ours that protected us for so long.

But fungi did not rampage onto our turf from some foreign place. They were always with us, woven through our lives and our environments and even our bodies: every day, every person on the planet inhales at least 1,000 fungal spores. It is not possible to close ourselves off from the fungal kingdom. But scientists are urgently trying to understand the myriad ways in which we dismantled our defenses against the microbes, to figure out better approaches to rebuild them.

 

 

 

synthetic genomics and genome engineering rewriting the blueprint of life

genomebiology |  Biology is now undergoing a rapid transition from the age of deciphering DNA sequence information of the genomes of biological species to the age of synthetic genomes. Scientists hope to gain a thorough mastery of and deeper insights into biological systems by rewriting the genome, the blueprint of life. This transition demands a whole new level of biological understanding, which we currently lack. This knowledge, however, could be obtained through synthetic genomics and genome engineering, albeit on a trial and error basis, by redesigning and building naturally occurring bacterial and eukaryotic genomes whose sequences are known. 

Synthetic genomics arguably began with the report from Khorana’s laboratory in 1970 of the total synthesis of the first gene, encoding an artificial yeast alanine tRNA, from deoxyribonucleotides. Since then, rapid advances in DNA synthesis techniques, especially over the past decade, have made it possible to engineer biochemical pathways, assemble bacterial genomes and even to construct a synthetic organism [1]–[11]. Genome editing approaches for genome-wide scale alteration that are not based on total synthesis of the genome are also being pursued and have proved powerful; for example, in the production of a reduced-size genome version of Escherichia coli[4] and engineering of bacterial genomes to include many different changes simultaneously [8]. 

Progress has also been made in synthetic genomics for eukaryotes. Our group has embarked on the design and total synthesis of a novel eukaryotic genome structure - using the well-known model eukaryote Saccharomyces cerevisiae as the basis for a designer genome, known as ‘Sc2.0’. The availability of a fully synthetic genome will allow direct testing of evolutionary questions that are not otherwise approachable. Sc2.0 could also play an important practical role, since yeasts are the pre-eminent organisms for industrial fermentations, with a wide variety of practical uses, including production of therapeutic proteins, vaccines and small molecules through classical and well-developed industrial fermentation technologies. 

This article reviews the current status of synthetic genomics, starting with a historical perspective that highlights the key milestones in the field (Fig. 1) and then continuing with a particular emphasis on the total synthesis of the first functional designer eukaryotic (yeast) chromosome, synIII, and the Sc2.0 Project. Genome engineering using nuclease-based genome editing tools such as zinc finger nucleases, transcription activator-like effector nucleases and RNA-guided CRISPR-Cas9 is not within the scope of this minireview (Box 1). Recent advances in gene synthesis and assembly methods that have accelerated the genome synthesis efforts are discussed elsewhere [12].

"deep" homology - not quite....,

NYTimes | Edward M. Marcotte is looking for drugs that can kill tumors by stopping blood vessel growth, and he and his colleagues at the University of Texas at Austin recently found some good targets — five human genes that are essential for that growth. Now they’re hunting for drugs that can stop those genes from working. Strangely, though, Dr. Marcotte did not discover the new genes in the human genome, nor in lab mice or even fruit flies. He and his colleagues found the genes in yeast.

“On the face of it, it’s just crazy,” Dr. Marcotte said. After all, these single-cell fungi don’t make blood vessels. They don’t even make blood. In yeast, it turns out, these five genes work together on a completely unrelated task: fixing cell walls.

Crazier still, Dr. Marcotte and his colleagues have discovered hundreds of other genes involved in human disorders by looking at distantly related species. They have found genes associated with deafness in plants, for example, and genes associated with breast cancer in nematode worms. The researchers reported their results recently in The Proceedings of the National Academy of Sciences.

The scientists took advantage of a peculiar feature of our evolutionary history. In our distant, amoeba-like ancestors, clusters of genes were already forming to work together on building cell walls and on other very basic tasks essential to life. Many of those genes still work together in those same clusters, over a billion years later, but on different tasks in different organisms.

Studies like this offer a new twist on Charles Darwin’s original ideas about evolution. Anatomists in the mid-1800s were fascinated by the underlying similarities of traits in different species — the fact that a bat’s wing, for example, has all the same parts as a human hand. Darwin argued that this kind of similarity — known as homology — was just a matter of genealogy. Bats and humans share a common ancestor, and thus they inherited limbs with five digits.

Some 150 years of research have amply confirmed Darwin’s insight. Paleontologists, for example, have brought ambiguous homologies into sharp focus with the discovery of transitional fossils. A case in point is the connection between the blowholes of whales and dolphins and the nostrils of humans. Fossils show how the nostrils of ancestral whales moved from the tip of the snout to the top of the head.

In the 1950s, the study of homology entered a new phase. Scientists began to discover similarities in the structure of proteins. Different species have different forms of hemoglobin, for example. Each form is adapted to a particular way of life, but all descended from one ancestral molecule. Fist tap Nana.

evolving multicellularity

Multicellular Yeast from thescientistllc on Vimeo.

The Scientist | In as little as 100 generations, yeast selected to settle more quickly through a test tube evolved into multicellular, snowflake-like clusters, according to a paper published today (January 16) in Proceedings of the National Academy of Sciences. Over the course of the experiment, the clusters evolved to be larger, produce multicellular progeny, and even show differentiation of the cells within the cluster—all key characteristics of multicellular organisms.

“It’s very cool to demonstrate that [multicellularity] can happen so quickly,” said evolutionary biologist Mansi Srivastava of the Whitehead Institute for Biomedical Research in Massachusetts, who was not involved in the research. “Looking at the fossil record, we learned it took a very long time whenever these different transitions to multicellularity happened. Here they show it can happen very quickly.”

“[The study] was provocative,” agreed biochemist Todd Miller of Stony Brook University in New York, who did not participate in the work. “It’s a different way of attacking the problem [of how multicellularity evolved]—coming from a simple system that doesn’t normally do this and seeing what it takes to make it do it.”

The evolution of multicellular life has long intrigued evolutionary biologists. Cells coming together and cooperating for the good of the group goes against basic Darwinian principles. Yet multicellularity has evolved some two dozen times independently in nature, and has shaped the world as we know it.

But because most transitions to multicellularity happened more than 200 million years ago, many questions remain about how it happened. What were the ecological conditions that drove the transitions? And how did organisms overcome the conflicts of interest that accompany any sort of cooperative effort?

increasing human grasp of GOD...,

wired | At the most basic level, scientists create phylogenetic trees by grouping species according to their degree of relatedness. Lining up the DNA of humans, chimpanzees and fish, for example, makes it readily apparent that humans and chimps are more closely related to each other than they are to fish.

Researchers once used just one gene or a handful to compare organisms. But the last decade has seen an explosion in phylogenetic data, rapidly inflating the data pool for generating these trees. These analyses filled in some of the sparse spots on the tree of life, but considerable disagreement still remains.

For example, it’s not clear whether snails are most closely related to clams and other bivalves or to another mollusk group known as tusk shells, said Rokas. And we have no idea how some of the earliest animals to branch off the tree, such as jellyfish and sponges, are related to each other. Scientists can rattle off examples of conflicting trees published in the same scientific journal within weeks, or even in the same issue.

“That poses a question: Why do you have this lack of agreement?” said Rokas.

Rokas and his graduate student Leonidas Salichos explored that question by evaluating each gene independently and using only the most useful genes — those that carry the greatest amount of information with respect to evolutionary history — to construct their tree.

They started with 23 species of yeast, focusing on 1,070 genes. They first created a phylogenetic tree using the standard method, called concatenation. This involves stringing together all the sequence data from individual species into one mega-gene and then comparing that long sequence among the different species and creating a tree that best explains the differences.

The resulting tree was accurate according to standard statistical analysis. But given that similar methods have produced trees of life that are rife with contradiction, Rokas and Salichos decided to delve deeper. They built a series of phylogenetic trees using data from individual yeast genes and employed an algorithm derived from information theory to find the areas of greatest agreement among the trees. The result, published in Nature in May, was unexpected. Every gene they studied appeared to tell a slightly different story of evolution.

“Just about all the trees from individual genes were in conflict with the tree based on a concatenated data set,” says Hilu. “It’s a bit shocking.”

They concluded that if a number of genes support a specific architecture, it is probably accurate. But if different sets of genes support two different architectures equally, it is much less likely that either structure is accurate. Rokas and Salichos used a statistical method called bootstrap analysis to select the most informative genes.

In essence, “if you take just the strongly supported genes, then you recover the correct tree,” said Donoghue. Fist tap Dale.

cellular cloud computing

Science Daily | Gene regulatory networks in cell nuclei are similar to cloud computing networks, such as Google or Yahoo!, researchers report today in the online journal Molecular Systems Biology. The similarity is that each system keeps working despite the failure of individual components, whether they are master genes or computer processors.

This finding by an international team led by Carnegie Mellon University computational biologist Ziv Bar-Joseph helps explain not only the robustness of cells, but also some seemingly incongruent experimental results that have puzzled biologists.

"Similarities in the sequences of certain master genes allow them to back up each other to a degree we hadn't appreciated," said Bar-Joseph, an assistant professor of computer science and machine learning and a member of Carnegie Mellon's Ray and Stephanie Lane Center for Computational Biology.

Between 5 and 10 percent of the genes in all living species are master genes that produce proteins called transcription factors that turn all other genes on or off. Many diseases are associated with mutations in one or several of these transcription factors. However, as the new study shows, if one of these genes is lost, other "parallel" master genes with similar sequences, called paralogs, often can replace it by turning on the same set of genes.

That would explain the curious results of some experiments in organisms ranging from yeast to humans, in which researchers have recently identified the genes controlled by several master genes. Researchers have been surprised to find that when they remove one master gene at a time, almost none of the genes controlled by that master gene are de-activated.

open thread - do my "smart" frog friends feel the west coast pot getting hot yet?

As population increases, while resources (and the associated wealth) decreases, and more people struggle to simply survive, social "niceties" are bound to diminish. In northern California and southern Oregon, there are more and more "transients"/ homeless people... with no investment in what is clearly falling apart, yet interestingly, with an inflated Californian sense of entitlement.

Overseers in every municipality are being put to the test to maintain civility. City councils are passing severe ordinances which prohibit camping, sitting on sidewalks, curbs or the ground, no loitering, no panhandling etc. The Mount Shasta situation has been exasperated given two years with no snow, so what was once a very inhospitable winter climate just a few years ago, now affords year round camping and hanging outdoors.

The mass shootings are a symptom of "overshoot". You humans have gone over the plateau and are on the down edge of collapse.  Meanwhile, down in So-Cal

At Myra Marquez’s house, she checks the gauge on her 2500 gallon water tank before she touches a faucet. The tank gets filled every Monday.

Rationing 2000 gallons over five or six days is tough.

"It’s hard,” she said.
 
It takes $38 million dollars from the state’s Emergency Drought Relief Program to pay for the town’s drinking water and fill residents’ water tanks. (1700 residents)

Isn't anyone else surprised or annoyed that a household in Central California can't make it on 2500 gallons of H2O each week?

Isn't anyone else incredulous that California is paying $38,000,000 to truck water to just 1700 folks?

That's over $22,000 for each person!
 

Who's organizing that water drive, the Pentagon? That's $88,000 for a family of four. California could drill a $30,000 well for each family and save a bundle.

I hear there are plenty of idle drilling rigs in Texas... But, is there any water left?

Who was it that said, "Are humans smarter than yeast?"

Collapse is taking a whole lot longer than I thought it would - which is good - because in the intervening decade, my children have achieved young adulthood and waxed very strong - while I've been afforded an opportunity to carefully observe and study what you do under such self-inflicted, mass, stress conditions.

illinois politricians dumber than yeast...,

illinoispolicy |  Illinois is the only state in the Midwest to have added more people to food-stamp rolls than to employment rolls during the recovery from the Great Recession. Job losses from the Great Recession occurred from January 2008 to January 2010, and since then, states have had five-and-a-half years of recovery.

During the recovery from the Great Recession, the Land of Lincoln, alone in the Midwest, had more people enter the food-stamps program than start jobs. Food-stamps growth in Illinois has outpaced jobs creation by a 5-4 margin.

In every other Midwestern state, jobs growth has dramatically outpaced food-stamps growth during the recovery. In fact, in every other state in the region, jobs growth dwarfs food-stamps growth. But during the recovery, Illinois put more people on food stamps than every other Midwestern state combined.

Manufacturing has borne the brunt of Illinois’ policy failures. From the state’s broken workers’ compensation system, to the highest property taxes in the region, to the lack of a Right-to-Work law while surrounding states enact Right to Work, Illinois has the worst policy environment in the Midwest for manufacturers.

The result for Illinois factory workers? The Land of Lincoln has put 25 people on food stamps for every manufacturing job created during the recession recovery.

are the shambling yeast monkeys REALLY inching up the kardashev scale?

arvix | An experimental investigation of possible anomalous heat production in a special type of reactor tube named E-Cat HT is carried out. The reactor tube is charged with a small amount of hydrogen loaded nickel powder plus some additives. The reaction is primarily initiated by heat from resistor coils inside the reactor tube. Measurement of the produced heat was performed with high-resolution thermal imaging cameras, recording data every second from the hot reactor tube. The measurements of electrical power input were performed with a large bandwidth three-phase power analyzer. Data were collected in two experimental runs lasting 96 and 116 hours, respectively. An anomalous heat production was indicated in both experiments. The 116-hour experiment also included a calibration of the experimental set-up without the active charge present in the E-Cat HT. In this case, no extra heat was generated beyond the expected heat from the electric input. Computed volumetric and gravimetric energy densities were found to be far above those of any known chemical source. Even by the most conservative assumptions as to the errors in the measurements, the result is still one order of magnitude greater than conventional energy sources. Fist tap Dale.

Neuroeconomics - Dopaminergy in the Individual Brain

A couple months ago, I introduced the concept of neuroeconomics in the context of collective psychology. It's time to take that a step further - a la the philosopher Daniel Dennett, channeling the late ATL Gurdjieffian prankster Jan Cox.

Several people have sent me notes about their problems and apparent failures, and have attempted to attribute a psychological basis to them. This is one of the great cutoff points. It is an immediate slap in the intellectual face: to a Revolutionist there is no such thing as "psychological." It is a flawed piece of data. It is as outmoded to a Revolutionist alive today as is the idea of a "capital-g" god. What is called "psychological" is serving, and has served, a purpose with some people. But you must see that any apparent psychological pressures arising from influences apparently "out there" -- your boss, your mother, your mate -- have to enter in through the five senses. Always stop and remind yourself of that even if you can't do anything else. If one or all of your senses were knocked out, you would not be suffering this "psychological pressure." You have to face up to that. Whatever is going on in you is chemical. There are really no such things as drunks; it is people with an alcohol deficiency. Absolutely religious people have a chemical deficiency. The same with people who have phobias, as they are called. It is a chemical imbalance outside the normal bell curve of the populace at their time and place. Jan Cox

From that earlier article I stated that "For decades it has been known that these neurons and the dopamine they release play a critical role in brain mechanisms of reinforcement. Many of the drugs currently abused in our society mimic the actions of dopamine in the brain. This led many researchers to believe that dopamine neurons directly encoded the rewarding value of events in the outside world."

Today's post is one of those hidden in plain sight elaborations on that theme, this time addressing the rewarding value of events in the INSIDE WORLD, the world comprised of the neurons making up your brain. Think about it. That's all I ever ask you to do, and in the process, you will inevitably be led to draw your own validating conclusions. Here's Dennett;

brain cells — I now think — must compete vigorously in a marketplace. For what?

What could a neuron "want"? The energy and raw materials it needs to thrive–just like its unicellular eukaryote ancestors and more distant cousins, the bacteria and archaea. Neurons are robots; they are certainly not conscious in any rich sense–remember, they are eukaryotic cells, akin to yeast cells or fungi. If individual neurons are conscious then so is athlete’s foot. But neurons are, like these mindless but intentional cousins, highly competent agents in a life-or-death struggle, not in the environment between your toes, but in the demanding environment of the brain, where the victories go to those cells that can network more effectively, contribute to more influential trends at the virtual machine levels where large-scale human purposes and urges are discernible.

I now think, then, that the opponent-process dynamics of emotions, and the roles they play in controlling our minds, is underpinned by an "economy" of neurochemistry that harnesses the competitive talents of individual neurons. (Note that the idea is that neurons are still good team players within the larger economy, unlike the more radically selfish cancer cells. Recalling Francois Jacob’s dictum that the dream of every cell is to become two cells, neurons vie to stay active and to be influential, but do not dream of multiplying.)

Intelligent control of an animal’s behavior is still a computational process, but the neurons are "selfish neurons," as Sebastian Seung has said, striving to maximize their intake of the different currencies of reward we have found in the brain. And what do neurons "buy" with their dopamine, their serotonin or oxytocin, etc.? Greater influence in the networks in which they participate.

So simple, elegant, and obvious. Selective governance via the natural tendency of the brain's neuronal circuits to Do What They Do..., what could be easier, more powerful, and more durable than that. The lengths to which some folks will go to furnish elaborate post hoc rationalizations of What It Do - and how that basic fact is exploited by those with the wherewithal to "engineer" values in the outside world - just crack me up.