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Archive for September 4th, 2019

Genetics isn’t everything: Bacterial Clones Show Surprising Individuality

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Carrie Arnold writes in Quanta:

Massed at the starting line, the crowd of runners all looked identical. But this wasn’t your standard 5K. Instead, researchers wanted to test both speed and navigational ability as competitors wound their way through a maze, choosing the right direction at every intersection. At the end of the course, the postdocs Mehdi Salek and Francesco Carrara would be waiting to identify each of the finishers. The postdocs wouldn’t have any medals or a commemorative T-shirt for the winners, however, because their racers weren’t human. They were Escherichia coli bacteria.

That there could be individual winners at all is a notion that has shaken the foundations of microbiology in recent years. Working in the lab of Roman Stocker at the Swiss Federal Institute of Technology Zurich (ETH Zurich), a team of microbiologists and engineers invented this unique endurance event. The cells at the starting line of Stocker’s microbial marathon were genetically identical, which implied, according to decades of biological dogma, that their resulting physiology and behavior should also be more or less the same, as long as all the cells experienced identical environmental conditions. At the DNA level, every E. coli cell had a roughly equal encoded ability to swim and steer through the course. A pack of cells that started the race at the same time would in theory all finish around the same time.

But that’s not what Salek and Carrara found. Instead, some bacteria raced through the maze substantially more quickly than others, largely because of varying aptitude for moving toward higher concentrations of food, a process called chemotaxis. What appeared to Salek and Carrara as a mass of indistinguishable cells at the beginning was actually a conglomerate of unique individuals.

“Bacteria can be genetically identical but phenotypically different,” Carrara said.

This bacterial individuality — known more technically as phenotypic heterogeneity — upends decades of traditional thinking about microbes. Although scientists knew that, for example, antibiotics didn’t always kill every last microbe in a colony of identical clones, both the cause of these differences and the resulting implications remained shrouded in mystery. Now advances in microscopy and microfluidics (the technology Stocker’s lab used to build the bacterial maze) have begun to lift the veil on an important evolutionary process.

“This has been a relatively overlooked phenomenon,” said Hesper Rego, a microbiologist at the Yale School of Medicine. “The idea that microbial populations could evolve heterogeneity and control it using genetics is a really powerful concept.”

From Populations to Individuals

Ever since the days of Robert Koch and Louis Pasteur in the 1870s, microbiologists have typically studied groups of bacteria rather than individuals. Much of this was out of necessity: The technology didn’t exist to allow scientists to do much more with single cells than peer at them through a microscope. Besides, if the bacteria were all identical, then there seemingly wasn’t a need to study every cell. An individual cell deposited on a plate of nutrient-rich jelly would divide and divide until it formed a visible colony of cells, all clones of the original cell. All the bacteria in this colony could be expected to show the same behaviors, physiology and physical appearance — the same phenotype — when placed in identical environments. By and large, they did.

The development of antibiotics in the 1940s revealed a curious anomaly, however. In many cases, antibiotics didn’t annihilate all the bacteria, even in groups of cells that were fully susceptible to the killing power of antibiotics. The surviving cells were considered “persistent.” They just hunkered down and waited out the chemical barrage of penicillin or similar drugs. Initially, scientists thought that persisters might come from a genetically distinctive subpopulation that grew more slowly even before the antibiotic treatments. But when microbiologists looked for genes that could predict which cells would become persisters, they were disappointed.

“There was no such [distinct persistent] subpopulation,” said Laurence van Melderen, a microbiologist at the Free University of Brussels in Belgium. “In every population, you will find some persisters if you look for them.” For scientists, this posed a major quandary: How could identical bacteria have such radically different behaviors?

By the late 1970s, researchers had identified one possible answer. Scientists at the University of California, Berkeley showed that random chance alone could lead to different behaviors even in genetically identical cells. Bacteria with whiplike flagella can swim in a straight line (known as “running”) or lurch in random directions. Swimming cells spend much of their time tumbling about, actively sampling their environment. But to move toward higher concentrations of nutrients and away from toxins and predators, bacteria must use a direct run. When they can no longer sense a gradient, they return to tumbling.

Berkeley microbiologists studying E. coli found that each cell stopped swimming and started tumbling at a different concentration of various chemical attractants, including aspartate and L-serine. Even after considering random statistical variations and any influence from unlikely spontaneous mutations during the experiment, the researchers couldn’t account for the cells’ marked and persistent individual differences in running and tumbling. That mystery, according to Thierry Emonet, a biophysicist at Yale, was “a big deal.”

The study appeared during the heyday of the idea that a single gene made a single protein, which would subsequently elicit a consistent behavior when all the cells were in the same environment. After a century of experimentation on batches of bacteria, scientists were accustomed to slight collective deviations in “identical” traits, but their data still tended to cluster tightly around a mean. The Berkeley scientists, in contrast, found that sensitivity to the attractants was smeared out over a broad concentration, not a single mean. Their paper challenged the general assumption by showing substantial cell-to-cell variation in swimming behavior among the individual bacteria. No longer could phenotypic heterogeneity be shrugged off as a quirk of the bacterial response to antibiotics.

Although the researchers knew that this individuality resulted both from how tightly each cell regulated tumbling and from its response to L-serine, quantifying this variation in specific cells was more challenging. In 2002, glowing E. coli changed all of that.

The biophysicist Michael Elowitz, now at the California Institute of Technology, inserted two fluorescent genes — one yellow, one cyan — into specimens of E. coli. The fluorescent genes were under the control of the exact same machinery, so prevailing wisdom held that the bacteria would glow a uniform green, a constant mixture of the yellow and blue.

Yet they didn’t. Elowitz and his colleagues found that the ratio of yellow and cyan fluorescence varied from cell to cell, proving that gene expression varied among cells in the same environment. The team described that variation precisely in a 2002 Science paper. This work, van Melderen says, sparked a renaissance in the study of phenotypic heterogeneity.

Selection of Diversity

Advances in microscopy and microfluidics allowed researchers to build rapidly on Elowitz’s 2002 discovery. Two particular cellular behaviors — chemotaxis, or navigation along a chemical gradient, and the microbial stress response — figured prominently in their experiments. That’s because both of these responses, which are easily measured in a lab, allow cells to respond to a changing environment, according to Jessica Lee, a microbiology fellow at Global Viral who studied bacterial individuality as a postdoc in the lab of Chris Marx at the University of Idaho.

Take chemotaxis. If bacteria are moving toward something they like, they swim more and tumble less. But the point at which they make this switch varies from individual to individual, as Berkeley scientists discovered 40 years ago. Subsequent experiments revealed the . . .

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Written by LeisureGuy

4 September 2019 at 3:21 pm

Posted in Science

Top Interior official who pushed to expand drilling in Alaska to join oil company there

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Seems an obvious quid pro quo. Juliet Eilperin and Steven Mufson report in the Washington Post:

Last summer, Scott Pruitt left his job heading the Environmental Protection Agency and within a few months had started consulting for coal magnate Joseph W. Craft III. Three weeks after leaving the Interior Department, energy counselor Vincent DeVito joined Cox Oil Offshore, which operates in the Gulf of Mexico, as its executive vice president and general counsel. Now, Joe Balash — who oversaw oil and gas drilling on federal lands before resigning from Interior on Friday — is joining a foreign oil company that is expanding operations on Alaska’s North Slope.

Balash, who served as the Interior Department’s assistant secretary for land and minerals management for nearly two years, confirmed in a phone interview Tuesday night that he will begin working for the Papua New Guinea-based Oil Search, which is developing one of Alaska’s largest oil prospects in years. On Wednesday, Oil Search officials said he would become senior vice president for external affairs in the company’s Alaska operations.

The company is drilling on state lands that lie outside — but nearby — two federal reserves where the Trump administration is pushing to increase oil and gas development: the Arctic National Wildlife Refuge and the National Petroleum Reserve-Alaska. During his time at Interior, Balash oversaw the department’s preparations to hold lease sales on the coastal plain of the 19.3 million-acre refuge and to expand drilling on the 22.8 million-acre reserve to the west of the refuge. Both sites are home to large numbers of migratory birds as well as caribou, polar bears and other wildlife.

Balash said that even though in his new role he would oversee employees who would work with the federal government on energy policy, he would abide by the Trump ethics pledge barring appointees from lobbying their former agencies for five years.

“I’ll supervise those who do,” he said, referring to Oil Search staffers with business before the federal government, “but I have a ton of restrictions dealing with the Department of Interior. Most of Oil Search’s properties are state lands. There isn’t really the federal nexus.”

Nonetheless, Sen. Tom Udall (D-N.M.) sent a letter to Interior’s ethics official Wednesday asking that the department provide copies of all ethics filings made by Balash and any notifications of his negotiations for future employment or compensation.

Udall is the ranking Democrat on the Senate Appropriations Subcommittee on the Interior, Environment, and Related Agencies.

“I believe the public has a compelling interest in knowing whether the necessary steps were taken to address this potential conflict of interest,” Udall wrote.

Oil Search, along with its partner Repsol, has been expanding aggressively in Alaska, where it says it has acquired leases with more than 700 million barrels of crude reserves. In May, the company received the go-ahead from the Army Corps of Engineers, and it plans to ramp up production operations this year and over the winter.

Balash noted that Interior “was not even a cooperating agency” in the decision to grant Oil Search the recent permit under the Clean Water Act.

Oil Search staffers working on community outreach, government affairs, and communications in Alaska will report to Balash in his new position, according to a company spokeswoman.

“Joe is a proud Alaskan and brings significant regulatory and external affairs experience to Oil Search, a company relatively new to operating in the United States,” said Keiran Wulff, Oil Search executive vice president and president for Alaska. “We are excited by the opportunities in Alaska and committed to working with stakeholders in a collaborative manner.”

Danielle Brian, executive director of the Project on Government Oversight, said in an interview that the fact that Balash has been working to make more land available for exploration near Oil Search’s ongoing development raises concerns.

If Balash’s jump to Oil Search “ends up being legal, it’s further confirmation to me that our laws are simply inadequate,” Brian said. “It is hard to have confidence that decisions he was making while he was working for the taxpayers were not impacted by his aspirations or hopes to go work for a company that was materially affected by his work.”

Asked about Balash’s job plans last week, Interior would not comment.

Balash has extensive experience in Alaska state politics. He served as the deputy commissioner for Alaska’s Department of Natural Resources and ran the agency on an acting basis for just over a year, before becoming chief of staff for Sen. Dan Sullivan (R-Alaska). He joined Interior in December 2017.

Earlier, Balash served in the governor’s office as a special assistant on energy and natural resource development. And before that, he worked on the joint legislative budget and audit committee and served as chief of staff to the state Senate president. Balash also attended high school in Fairbanks.

Ethics experts said that regardless of the Alaskan’s job description, his decision to join an oil company raises potential conflict of interest issues, depending in part on the nature of his negotiations with the firm before he left public office.

Under 18 U.S. Code Section 208, a federal official is barred “from participating personally and substantially in a particular Government matter that will affect his own financial interests, as well as the financial interests of” his spouse, children and “a person with whom he is negotiating for or has an arrangement concerning prospective employment.”

“At the point Balash began discussing employment opportunities with Oil Search, he was prohibited from personally and substantially participating in any particular matter that would affect Oil Search’s financial interests,” said Brendan Fischer, federal reform program director at the Campaign Legal Center.

Although Oil Search has not bid on federal leases in Alaska, officials from the firm met with Balash several times while he served as assistant secretary, according to his public calendar. On Jan. 10, 2018, he had a meeting classified as a video call with Wulff and other Oil Search executives, described as a “meet and greet” in his calendar notes. . .

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Not exactly draining the swamp.

Written by LeisureGuy

4 September 2019 at 2:42 pm

It doesn’t matter if it’s sugary or diet: New study links all soda to an early death

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Laura Reiley reports in the Washington Post:

Hold up, diet soda drinkers. Regular consumption of soft drinks — both sugar-sweetened and artificially sweetened — was associated with a greater risk of all causes of death, according to research published this week in JAMA Internal Medicine.

Participants who drank two or more glasses of soft drinks per day had a higher risk of mortality than those who consumed less than one glass per month.

The study, one of the largest of its kind, tracked 451,743 men and women from 10 countries in Europe. It found that consumption of two or more glasses of artificially sweetened soft drinks a day was positively associated with deaths from circulatory diseases. For sugar-sweetened soft drinks, one or more glasses a day were associated with deaths from digestive diseases, including diseases of the liver, appendix, pancreas and intestines.

The researchers recruited people from Britain, Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain and Sweden between 1992 and 2000, surveying them on their food and drink consumption. Participants were excluded if they reported incidents of cancer, heart disease, stroke or diabetes. Mean age was 50.8, and 71.1 percent of participants were women.

Similar results have been shown in several recent studies, but the researchers cautioned that elevated soft-drink consumption may be a marker for an overall unhealthy lifestyle. . .

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Written by LeisureGuy

4 September 2019 at 2:37 pm

More on the keto diet: It doesn’t work

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Written by LeisureGuy

4 September 2019 at 8:22 am

Posted in Food, Health, Low carb, Science

Still thinking about the travel shave kit: Simpson Case with case

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I tend to keep thinking about my decisions once they’re made, which generally leads to on-going revision and refinement. (In programming this is referred to as “iterative development”: build, test, revise, repeat—”Hindsight is your most powerful tool. Use it early and often.” Quote from a Forth programmer.)

So today after a commenter reminded me of the travel cylinder that you can get for the Simpson Case (once known as the Wee Scot 3), I decided to take another look at the travel kit. I don’t leave until tomorrow, so lots of time for changing my mind on various things.

The Case brought forth a reasonable good lather from the Klar Seifen puck, but this morning it wasn’t so luxurious as I wanted. Still, it was perfectly good, and it allowed the RazoRock Mamba to do a good job, though I can tell a blade change is warranted. Still, three passes with a little polish left a smooth face, and I did enjoy Van Yulay’s After Dark again.

But for travel, I’m thinking I’ll stick with the Achilles soap and aftershave, and take the Kent Infinity as the brush, since I think it’s more robust for travel than the Yaqi Target Shot.

Still, there’s time for further reconsideration.

Written by LeisureGuy

4 September 2019 at 8:19 am

Posted in Shaving

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