Ancestral polymorphisms explain the role of chromosomal inversions in speciation (when a new species is created)

Charles Darwin was among the first to recognize that –– if a species separates into two geographically distinct niches and undergoes a sufficient number of generations –– the two separate groups will become independent species, no longer able to breed with one another. This is called speciation, and (more than a century later) we now know that chromosomal inversions (as well as different numbers of chromosomes) are major causes of this inability of two species to interbreed. During meiosis (pairing of chromosomes of the egg with the sperm), chromosomal inversions and different numbers of chromosomes almost always lead to early embryonic death or, in lesser cases, an infertile offspring (often called the “hybrid”).

Chromosomal inversions are structural rearrangements, in which the linear gene order (across varying lengths of some DNA segment) is reversed (i.e. inverted). In crosses between two species that differ by one or more inversions, the resulting hybrids can experience meiotic chromosome-pairing problems and may, therefore, become sterile [For example, a mule is the offspring of a male donkey and a female horse; Donkeys and horses are different species –– having different numbers of chromosomes: the mule has 63 chromosomes, which reflects a mixture of the donkey’s 62 and the the horse’s 64. The different structures and numbers usually prevent chromosomes from pairing up properly to create successful embryos, rendering mules almost always infertile].

Authors [see attached article] reconstructed the evolutionary histories of chromosomal inversions in fruit flies (Drosophila persimilis and Drosophila pseudoobscura) to show that –– contrary to widely accepted ideas –– these inversions already had existed as polymorphisms in the ancestor of both species before their initial split into separate species. These findings will force evolutionary geneticists to reconsider the role of chromosomal inversions during the process of speciation.

These data raise the possibility that –– the higher genetic divergence of sequences, spanning across these chromosomal inversions, and an association with “hybrid-incompatibility genes” –– may be the most important factors during long-term segregation of these inversions. In other words, the role of chromosomal inversions during speciation should not be seen as protectors of existing hybrid incompatibilities, but rather as a solid foundation for their formation to occur later.

DwN

PLoS Genet July 2o18; 14: e1007526

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Molecular archaeoparasitology identifies cultural changes in the Medieval Era

Intestinal parasites have afflicted humans throughout history and remain common in parts of the developing world. Prior to today’s improvements in hygiene and medicine, gut parasites during the 18th century were prevalent throughout the world, which makes them an intriguing target for investigation of historical events. Previous molecular studies of historical infections have focused mostly on high-impact diseases (e.g. plague, leprosy, smallpox, malaria & tuberculosis); these studies typically fixated on one, or very few, samples from a site and were targeted largely towards identifying the pathogen being studied. However, such infectious disorders often cause acute disease, interfere with the daily lives of infected persons, and can be difficult to detect in archaeological contexts (if identification relies on analysis of mummified or skeletal remains).

In contrast, enteric worms (helminths) do not have devastating clinical effects; their eggs are readily detectable in a wide variety of archaeological contexts associated with human fecal material. “Helminths” is a collective term encompassing nematodes (roundworms), trematodes (flatworms), and cestodes (tapeworms). There are many examples in each group that infect a range of hosts, including humans. Some roundworms are transmitted via the fecal–oral route, whereas tapeworms enter humans when eating undercooked red meat or freshwater fish. Therefore, the type, and number, of eggs found in a fecal deposit can be used to interpret levels of hygiene and/or dietary habits. Authors previously have found that >95% of pre-18th century latrine and other communal deposit samples contain helminth eggs. The high prevalence of these helminths, their low pathogenicity, and robustness of eggs having ancient DNA that can be studied –– are features that can provide answers to historical and archaeological questions.

In the attached publication, authors integrated parasite studies with ancient DNA-sequencing, studying a large sample-set, dating between Neolithic and Early Modern periods, to explore the usefulness of molecular archaeoparasitology –– as a new approach to study History. Molecular analyses provided unequivocal species-level parasite identification and revealed location-specific epidemiological signatures. Roundworms (Ascaris lumbricoides and Trichuris trichiura) were discovered to be ubiquitous across time and space. By contrast, high numbers of tapeworms (Diphyllobothrium latum and Taenia saginata) were restricted to medieval Lübeck (major port city in northern Germany, which dates back to its being the medieval capital of the Hanseatic League, a powerful trading confederation).

The presence of these tapeworms, and changes in their prevalence at approximately 1300 A.D., indicate substantial alterations in diet or parasite availability. The tapeworm DNA sequences revealed two different groups: one ubiquitous; the other restricted to medieval Lübeck and Bristol (port city straddling the River Avon in southwest England, also having a rich maritime history). The high sequence diversity of this specific tapeworm DNA detected in Lübeck is consistent with its importance as a Hanseatic trading center. This study introduces the research field of molecular archaeoparasitology as an artefact-independent source of historical evidence.

DwN

Proc R Soc B, 2o18; 285: 20180991

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The feasibility of asbestos bioremediation

If the topic in these Superfund Research Program (SRP) monthly summaries falls within “bioremediation,” these GEITP pages believe this is close enough to ‘gene-environment interactions’ to warrant the summary as an important, exciting, and valuable teaching item.

DwN

Siderophores Reduce Asbestos Toxicity in Soil

Researchers have discovered that natural compounds released from bacteria and fungi in soil, known as siderophores, can decrease the toxicity of asbestos fibers. According to the authors, their results support the feasibility of asbestos bioremediation, or using organisms such as bacteria to degrade contaminants at waste sites.

Asbestos fibers are highly toxic and have been linked to serious health conditions –– including mesotheliomas and lung and stomach cancers. This toxicity is mostly attributed to the long shape of asbestos fibers, which makes it harder for cells of the immune system to remove them from the lung.

Immune cells called macrophages generally destroy foreign materials, such as bacteria and particles like asbestos, by either engulfing the particles or producing reactive oxygen species (ROS) to destroy the material. Because asbestos fibers are often too large to be engulfed, macrophages produce excessive ROS, which can lead to inflammation and DNA damage and may eventually lead to tumor development. Previous studies have shown that the presence of iron, which is often on the outer layer of asbestos, can increase ROS production.The broad goal of the research is to determine whether alteration of asbestos particles by plants or fungi may be useful for bioremediation of asbestos-contaminated sites. Another mechanism for ROS formation by long thin needles is that they generate free electrons at the point of the solid needle form; the free electrons simply invade the surrounding cells at the needle point and create ROS formation.

Based on this connection between iron and asbestos toxicity, researchers explored whether natural soil concentrations of siderophores, which have an affinity to bind to iron, can remove iron from asbestos and thus lower its toxicity. Plants, bacteria, and fungi all release siderophores to bind to iron in soil, facilitating iron uptake. The study, supported by the University of Pennsylvania Superfund Research Program (Penn SRP), was led by Jane Willenbring, PhD, currently at the Scripps Institution of Oceanography, University of California, San Diego.

Iron Removal and Toxicity

The researchers measured the release of iron from asbestos fibers in the presence of natural soil concentration levels of a fungal and a bacterial siderophore and compared that with specific organic acids, which are also released by organisms to bind to iron. They treated solutions containing asbestos with siderophores or organic acids, they extracted samples from those solutions at regular intervals for up to 16 days, and they measured the total dissolved iron. They found that both fungal and bacterial siderophores removed iron from asbestos fibers. The organic acids, on the other hand, proved ineffective.

In collaboration with Penn SRP Center project leader Melpo Christofidou-Solomidou, PhD, the researchers then measured the toxicity of the treated asbestos fibers using a new method developed by the research team. They quantified ROS generated by macrophages from mice exposed to asbestos fibers with and without siderophore treatment and observed a decrease in the amount of ROS generated, and thus decrease in the toxicity of asbestos, when fibers were treated with siderophores. They also discovered that the fungal siderophores were more effective than the bacterial siderophores in diminishing ROS levels.

Potential Site Applications

Because of its fiber strength and heat resistance, asbestos has been used in many materials produced for building or home construction –– such as shingles, ceiling and floor tiles, and attic and pipe insulation –– particularly if they were manufactured prior to 1980. In the U.S., nearly a thousand environmental waste dump sites are contaminated with either asbestos-containing materials or naturally-occurring asbestos minerals. The current standard for treatment of asbestos-contaminated sites is to physically remove the asbestos from the site or to cap the site with soil, both of which are expensive strategies.

According to the authors, this study indicates that siderophores in the soil environment can decrease asbestos fiber toxicity and possibly lower health risks. Removal of iron by siderophores could potentially form the basis of a low-cost bioremediation strategy, which should be explored as a viable approach for managing asbestos-contaminated sites.

For more information, contact:

Jane Willenbring, PhD

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Molecular regulation of carcinogenesis

This brief review [see attached] is a very crisp and excellent article, summarizing the fundamental causes of and treatments for the process of carcinogenesis. For what it’s worth, one of the coauthors is my scientific child (FJG), and two of the other coauthors are my scientific grandchildren (ADP, JMP).

An explosion of knowledge on the molecular and cellular mechanisms that mediate carcinogenesis has occurred in recent years. Although cancer has existed for more than 300,000 years in the human species, effective cures for most cancers that target molecular and cellular pathways have not yet been achieved. Myriad cellular targets have been examined for preventing, as well as treating, cancers –– including, but not limited to: transcription factors, kinase-mediated cell-signaling pathways, and (more recently) epigenetic targeting of oncogenes and tumor suppressor genes, and immunomodulation such as chimeric antigen receptor-T cells.

Even as the state of knowledge of cancer mechanisms increases, there is considerable room for improvement in preventing and treating cancers. Understanding how a normal cell is transformed into a cancer cell is quite well understood; however, there is considerable tissue- and cell type-specificity. This has given rise to the field of precision medicine –– as it applies to cancer therapy. Thus, while the development of preventive and treatment regimens has increased, there are certain obstacles that need to be overcome in order to decrease cancer incidence and increase survival rates of cancer patients.

This review summarizes the advances made in cancer biology and how these advances have been used to develop, or in some cases hinder –– preventive and therapeutic strategies for cancer.

DwN

Toxicol Sci Oct 2018; 165: 277–283

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Joachim Ronneberg Dies at Age 99

J By Robert D. McFadden

· Oct. 22, 2018

The Norwegian saboteurs skied across the Telemark pine forest in winter whites, phantom apparitions gliding over moonlit snow. They halted at a steep river gorge and gazed down at a humming hydroelectric power plant where Nazi scientists had developed a mysterious, top-secret project.

Lt. Joachim Ronneberg, the 23-year-old resistance fighter in command, and his eight comrades — all carrying cyanide capsules to swallow if captured — had been told by British intelligence only that the plant was distilling something called heavy water, and that it was vital to Hitler’s war effort.

Hours later, in one of the most celebrated commando raids of World War II, Lieutenant Ronneberg and his demolition team sneaked past guards and a barracks full of German troops, stole into the plant, set explosive charges and blew up Hitler’s hopes for a critical ingredient to create the first atomic bomb.

Mr. Ronneberg, the last surviving member of the 1943 raid and one of the most decorated war heroes of a nation renowned for valorous resistance to the 1940-45 German Occupation, died on Sunday in Alesund, Norway, his daughter, Birte Ronneberg, said. He was 99.

Mr. Ronneberg and his saboteurs were showered with international honors after the war for what they had regarded as a suicide mission. It was celebrated in books, documentaries and films, notably Anthony Mann’s 1965 production, “The Heroes of Telemark,” starring Kirk Douglas, in what critics called a fact-flawed version of what had happened.

It was not until the war’s end in 1945 that Mr. Ronneberg learned the significance of the raid. “The first time I heard about atomic bombs and heavy water was after Americans dropped the bomb on Hiroshima and Nagasaki,” he told The New York Times in 2015. Had the raid failed, he concluded, London would have ended up “looking like Hiroshima.”

Historians have long debated how close Hitler came to nuclear weapons. A German writer, Rainer Karlsch, claimed in “Hitler’s Bomb” (2005), that German physicists conducted three nuclear tests in 1944 and 1945. But he gave no proof. A more widely accepted view is that Hitler’s program, which predated the Manhattan Project, faltered in midwar because of scientific errors and Norway’s successful saboteurs.

Ihttps://static01.nyt.com/images/2018/10/23/obituaries/23RONNEBERG5/merlin_63850127_0cc1e0ee-aee7-43a8-b207-7e603c84b711-articleLarge.jpg?quality=75&auto=webp&disable=upscale

A hydroelectric power plant in the Norwegian town of Rjukan, where German scientists tried to produce the “heavy water” necessary for the manufacture of atomic weaponry. The Germans were experimenting with the process as early as 1940, but the project was sabotaged by commandos led by Mr. Ronneberg.

By 1942, the British knew that Germany had chosen heavy water, or deuterium oxide, to moderate atom-splitting chain reactions to produce bomb-grade plutonium. They knew further that the Norsk Hydro plant in Norway, which had been extracting heavy water since 1934 for making fertilizer, had been taken over by Nazi invaders as the world’s best source of the isotope for Berlin’s atomic weapons program.

A 35-man British commando team had been lost on a 1942 mission to sabotage the plant. Britain then enlisted the Norwegian volunteers under Mr. Ronneberg for Operation Gunnerside, endorsed by Prime Minister Winston Churchill. Air attacks were not ordered for fear of heavy casualties to Norwegian workers and a low probability of success because the heavy water had been distilled in a basement fortified against bombs.

After training in Britain, the group parachuted into Norway. A four-member advance team with a radio and supplies went first, in October 1942. Six others followed in February. They rendezvoused at a cabin 40 miles from the target, at Vemork, on the forested plateau called the Telemark, a national park today.

Blizzards stalled them for a week. Finally, they moved out. One man was designated to break off from the team to maintain radio contact with London. Nine others set off with rations for five days, explosives, fuses, Tommy guns, grenades, compasses and a pair of metal shears that Mr. Ronneberg had picked up at a London hardware store. That final item would prove critical.

They skied by night, rested by day and reached the gorge late on the night of Feb. 27, 1943. Steep slopes plunged 1,000 feet to the Mana River. The power plant was perched on a ledge halfway up the far slope. A guarded suspension bridge over the river led to the front entrance. At the back was a railway line and the German troops’ barracks. Guards patrolled the tracks and a wire fence around the back entrance.

There was no easy way in. “There were so many things that were just luck and chance,” Mr. Ronneberg told The Times. “There was no plan. We were just hoping for the best.” They decided to try the back way.

They waited for hours after midnight, watching the changes of night-shift workers and guards. Then, 75 yards upstream, they climbed down into the windswept gorge, clinging to shrubs and branches to break falls. They crossed the river on an ice bridge, then slogged up the far slope, waist-deep in snowdrifts. They saw guards on the suspension bridge, but the rushing river and the plant’s hum masked their own noises.

Creeping down the railway tracks unseen, they hid behind storage sheds near the perimeter fence. Five remained concealed there, ready to fire on the barracks or the guards, but they were not seen. When a sentry left the fence to make rounds, Mr. Ronneberg and three others dashed to the gate, cut a padlock with the shears, and darted into the compound.

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Kirk Douglas, left, and Richard Harris in “The Heroes of Telemark,” a 1965 movie based on the commando raid. Mr. Ronneberg called the film factually flawed. “They took a true story and spun their own idea around it,” he was quoted as saying. “It should never have been allowed.”

They split into two teams. All doors were locked, but Mr. Ronneberg and Fredrik Kayser found a small duct for cables and pipes. Mr. Ronneberg and Mr. Kayser squeezed in, dragging rucksacks of explosives behind them. The duct led to a cavernous hall.

They recognized it as the heavy-water production center: a latticework of iron pipes, rubber tubes, electrical wires and 18 stainless steel cylinders, each 50 inches tall and 10 inches in diameter — the heavy-water containers. There was no guard, only a workman at a desk. They dropped down, and Mr. Kayser put a gun to the man’s chest, urging him to be silent.

Mr. Ronneberg unpacked the rucksacks and began attaching explosives to the storage cylinders and water-distillation apparatus. They were joined by the other two demolition men, who had broken a window to get in. They set fuses on 30-second timers, ignited them with matches and fled.

As they raced past the barracks, they heard the muffled crump of the explosion. Soon sirens began to wail at the plant. But the saboteurs were out of sight by the time Germans scrambled from the barracks and workers scattered in chaos. A hunt by 2,800 soldiers spread over the countryside. But by sunrise, the saboteurs were well away, beginning a 280-mile trek across forests and mountains to neutral Sweden.

The raid — with no shots fired, and no saboteurs wounded — had destroyed the cylinders, sending 1,100 pounds of heavy water down a drain, along with the plant’s capacity to make more. It took the Germans four months to rebuild, and more time to restore full production. But in November, the Vemork operation was crippled again by Allied bombers.

Hitler ordered the project moved to Germany, but a Norwegian ferry carrying the equipment and the remaining stocks of heavy water was sunk on route by resistance saboteurs in early 1944. That ended Nazi Germany’s struggle for Norwegian heavy water and all of the regime’s realistic hopes for an atomic bomb.

Mr. Ronneberg led other raids, attacking German supply lines and destroying a railway bridge with plastic explosives. He received Norway’s highest decoration for military gallantry, the War Cross with Sword, from King Haakon VII; the Distinguished Service Order from Britain; the Legion of Honor and Croix de Guerre from France; and the American Medal of Freedom With Silver Palm. (The latter was established by President Harry S. Truman to honor civilians who aided the war effort; it was replaced in 1963 by the Presidential Medal of Freedom.)

Joachim Holmboe Ronneberg was born in Alesund, on Aug. 30, 1919, one of two sons of Alf and Anna Krag Sandberg Ronneberg. Joachim and his brother, Erling, who also became a wartime resistance fighter, attended schools in Alesund, on Norway’s western coast. At 21 he escaped to England. He was a good skier and enlisted in the Kompani Linge, the Norwegian-exile Special Forces.

https://static01.nyt.com/images/2018/10/23/obituaries/23RONNEBERG2/merlin_145669686_f2fcaf0b-15c8-4dd6-b957-917b7436c2bb-articleLarge.jpg?quality=75&auto=webp&disable=upscale

Mr. Ronneberg with the Norwegian defense minister Anne-Grete Strom-Erichsen and Gen. Harald Sunde at a wreath-laying ceremony in London in 2013 in honor of Mr. Ronneberg’s World War II unit of commandos.

Mr. Ronneberg joined the NRK public broadcasting network in Norway in 1948. He became a journalist and program director and retired in 1988.

He married Liv Foldal, a crafts teacher, in 1949, and had three children: Jostein, Asa and Birte. Aside from his daughter Birte, there was no immediate information on his survivors.

Mr. Ronneberg lectured widely for years about Norway’s history and his wartime experiences. While “The Heroes of Telemark” was filmed on location in Norway, he often scoffed at the liberties taken with the facts. “They took a true story and spun their own idea around it,” he told The Daily Telegraph of London in 2010. “It should never have been allowed.”

Interest in the exploits of Mr. Ronneberg and the nine other Norwegians involved in thwarting the Nazi nuclear project surged in Norway in 2015 when NRK, the state broadcaster, ran “The Heavy Water War,” a six-episode mini-series that became a national sensation. A statue of Mr. Ronneberg in front of City Hall in Alesund, where he lived for most of his life, was put up later that year to observe his 95th birthday.

Mr. Ronneberg applauded the television series for introducing younger Norwegians to wartime history that they knew little about, but he expressed annoyance that it had altered the names of the directors of Norsk Hydro, the company that ran the plant that he blew up; they had collaborated with the Nazis.

He told The Times that it was “quite incredible” that their real identities had been concealed and that painful memories of collaboration with the Nazis by Norway’s wartime leader Vidkun Quisling still hampered a clear and full historical reckoning.

“There is a lot of talk about ‘never again,’ but this is impossible if we don’t remember what happened back then,” Mr. Ronneberg said.

During preparations in England for the raid, the saboteurs had been promised a place in history by the mastermind of the operation, Leif Tronstad. “But none of the men were there for history,” Neal Bascomb said in perhaps the most definitive book on the raid, “The Winter Fortress: The Epic Mission to Sabotage Hitler’s Atomic Bomb” (2016).

“If you went to the heart of the question, none of them were there for heavy water, or for London,” Mr. Bascomb wrote. “They had seen their country invaded by the Germans, their friends killed and humiliated, their families starved, their rights curtailed. They were there for Norway, for the freedom of its lands and people from Nazi rule.”

https://www.nytimes.com/2018/10/22/obituaries/joachim-ronneberg-dead.html?utm_source=pocket&utm_medium=email&utm_campaign=pockethitsoachim Ronneberg, Leader of Raid That Thwarted a Nazi Atomic Bomb, Dies at 99

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Fake News Comes to Academia

Not one, but two, of GEITP’s faithful readers contributed this article [from the Wall Street Journal, online Tues evening Oct 2nd, out in print Wed Oct 3rd] –– suggesting to me that I share this with all GEITP email recipients. So, I am doing what I’ve been asked to do. These GEITP pages have described several previousr examples of scientists using fake names, submitting ridiculous manuscripts to the various “predatory online open-access” journals (of which there are now more than 15,000, and the publishers of which are earning hundreds of thousands of dollars each year in ‘page charges’), and having the papers “fake-reviewed” and published within a few days.

This topic [below] is humorous, sad, absurd, and shocking –– but worth pondering. Does such “Soft Science” (as what is described herein), qualify as “Science”? Or should it be relegated simply to some category of “social media issues”?

DwN

Fake News Comes to Academia
How three scholars duped academic journals to publish hoax papers on ‘grievance studies’

482 Comments

By Jillian Kay Melchior

Oct. 2, 2018 6:55 p.m. ET

Fake News Comes to Academia

The existence of a monthly journal focused on “feminist geography” is a sign of something gone awry in academia. The journal in question—Gender, Place & Culture—published a paper online in May whose author claimed to have spent a year observing canine sexual misconduct in Portland, Oregon, parks.

The author admits that “my own anthropocentric frame” makes it difficult to judge animal consent. Still, the paper claims dog parks are “petri dishes for canine ‘rape culture’ ” and issues “a call for awareness into the different ways dogs are treated on the basis of their gender and queering behaviors, and the chronic and perennial rape emergency dog parks pose to female dogs.”

The paper was ridiculous enough to pique my interest—and rouse my skepticism, which grew in July with a report in Campus Reform by Toni Airaksinen. Author Helen Wilson had claimed to have a doctorate in feminist studies, but “none of the institutions that offers such a degree could confirm that she had graduated from their program,” Ms. Airaksinen wrote. In August Gender, Place & Culture issued an “expression of concern” admitting it couldn’t verify Ms. Wilson’s identity, though it kept the paper on its website.

All of this prompted me to ask my own questions. My email to “Helen Wilson” was answered by James Lindsay, a math doctorate and one of the real co-authors of the dog-park study. Gender, Place & Culture had been duped, he admitted. So had half a dozen other prominent journals that accepted fake papers by Mr. Lindsay and his collaborators—Peter Boghossian, an assistant professor of philosophy at Portland State University, and Helen Pluckrose, a London-based scholar of English literature and history and editor of AreoMagazine.com.

The three academics call themselves “left-leaning liberals.” Yet they’re dismayed by what they describe as a “grievance studies” takeover of academia, especially its encroachment into the sciences. “I think that certain aspects of knowledge production in the United States have been corrupted,” Mr. Boghossian says. Anyone who questions research on identity, privilege and oppression risks accusations of bigotry.

Beginning in August 2017, the trio wrote 20 hoax papers, submitting them to peer-reviewed journals under a variety of pseudonyms, as well as the name of their friend Richard Baldwin, a professor emeritus at Florida’s Gulf Coast State College. Mr. Baldwin confirms he gave them permission use his name. Journals accepted seven hoax papers. Four have been published.

This isn’t the first time scholars have used a hoax paper to make a point. In 1996 Duke University Press’s journal Social Text published a hoax submission by Alan Sokal, a mathematical physicist at New York University. Mr. Sokal, who faced no punishment for the hoax, told me he was “not oblivious to the ethical issues involved in my rather unorthodox experiment,” adding that “professional communities operate largely on trust; deception undercuts that trust.”

But he also said he was criticizing an academic subculture “that typically ignores (or disdains) reasoned criticism from the outside.” He concluded: “How can one show that the emperor has no clothes? Satire is by far the best weapon; and the blow that can’t be brushed off is the one that’s self-inflicted.” Messrs. Lindsay and Boghossian were already known for a hoax paper titled “The Conceptual Penis as a Social Construct,” which they published in the journal Cogent Social Sciences last year under the names Jamie Lindsay and Peter Boyle.

Such hoaxes are unethical, and The Wall Street Journal doesn’t condone them. The Journal expects op-ed contributors to be truthful about their identities and research, and academic journals also rely on the honesty of their authors.

But the trio defended their actions, saying they viewed the deception not as a prank but as a “hoax of exposure,” or a way to do immersive research that couldn’t be conducted any other way. “We understood ourselves to be going in to study it as it is, to try to participate in it,” Ms. Pluckrose says. “The name for this is ethnography. We’re looking at a particular culture.”

Each paper “combined an effort to better understand the field itself with an attempt to get absurdities and morally fashionable political ideas published as legitimate academic research,” Mr. Lindsay wrote in a project summary. Their elaborate submissions cited and quoted dozens of real papers and studies to bolster the hoax arguments.

One of the trio’s hoax papers, published in April by the journal Fat Studies, claims bodybuilding is “fat-exclusionary” and proposes “a new classification……termed fat bodybuilding, as a fat-inclusive politicized performance.” Editor Esther Rothblum said the paper had gone through peer review, and the author signed a copyright form verifying authorship of the article. “This author put a lot of work into this topic,” she said. “It is an interesting topic, looking at weight and bodybuilding. So I am surprised that, of all things, they’d write this as a hoax. As you can imagine, this is a very serious charge.” She plans to remove the paper from the Fat Studies website.

A hoax paper for the Journal of Poetry Therapy describes monthly feminist spirituality meetings, complete with a “womb room,” and discusses six poems––which Mr. Lindsay generated by algorithm and lightly edited. Founding editor Nicholas Mazza said the article went through blind peer review and revisions before its acceptance in July, but he regrets not doing more to verify the author’s identity. He added that it took years to build credibility and get the Journal of Poetry Therapy listed in major scholarly databases. “You work so hard, and you get something like this,” he said. Still, “I can see how editors like me and journals can be duped.”

Affilia, a peer-reviewed journal of women and social work, formally accepted the trio’s hoax paper, “Our Struggle Is My Struggle: Solidarity Feminism as an Intersectional Reply to Neoliberal and Choice Feminism.” The second portion of the paper is a rewrite of a chapter from “Mein Kampf.” Affilia’s editors declined to comment.

The trio say they’ve proved that higher education’s fixation on identity politics enables “absurd and horrific” scholarship. Their submissions were outlandish—but no more so, they insist, than others written in earnest and published by these journals.

Gender, Place & Culture, for instance, published a 2017 paper that wasn’t a hoax analyzing the “feminist posthumanist politics” of what squirrels eat. This year Hypatia, a journal of feminist philosophy, published an analysis of a one-woman show featuring “the onstage cooking of hot chocolate and the presence of a dead rat.” The performance supposedly offers “a synthaesthetic portrait of poverty and its psychological fallout.”

The trio say the biases in favor of grievance-focused research was so strong that their hoax papers sailed through peer review, acceptance, and publication––despite obvious problems. The data for the dog-park study, Mr. Lindsay says, “was constructed to look outlandish on purpose. So asking us for the data would not have been unreasonable. It would have been appropriate, and we would have been exposed immediately.”

One hoax paper, submitted to Hypatia, proposed a teaching method centered on “experiential reparations.” It suggested that professors rate students’ levels of oppression based on race, gender, class, and other identity categories. Students deemed “privileged” would be kept from commenting in class, interrupted when they did speak, and “invited” to “sit on the floor” or “to wear (light) chains around their shoulders, wrists or ankles for the duration of the course.” Students who complained would be told that this “educational tool” helps them confront “privileged fragility.”

Hypatia’s two unnamed peer reviewers did not object that the proposed teaching method was abusive. “I like this project very much,” one commented. One wondered how to make privileged students “feel genuinely uncomfortable in ways that are humbling and productive,” but not “so uncomfortable (shame) that they resist with renewed vigor.” Hypatia didn’t accept the paper but said it would consider a revised version. In July it formally accepted another hoax paper, “When the Joke Is on You: A Feminist Perspective on How Positionality Influences Satire”—an argument that humor, satire, and hoaxes should only be used in service of social justice, not against it.

Ann Garry, an interim editor of Hypatia, said she was “deeply disappointed” to learn that the papers, which went through double anonymous peer review, may be hoaxes. “Referees put in a great deal of time and effort to write meaningful reviews, and the idea that individuals would submit fraudulent academic material violates many ethical and academic norms,” she said. “It is equally upsetting that the anonymous reviewer comments from that effort were shared with third parties, violating the confidentiality of the peer-review process.” Wiley, Hypatia’s publisher, is investigating in accordance with industrywide ethical guidelines, she said.

After I contacted Gender, Place & Culture about the dog-park hoax paper, I received a statement from Taylor & Francis Group, the journal’s publisher. Tracy Roberts, publishing director for the humanities and social sciences, said that after postpublishing checks raised questions about the author’s identity, the editors launched an investigation several weeks ago. “Helen Wilson” never responded to their queries. “We are now in the process of retracting this article from the scholarly record,” the editorial team said in a statement.

Mr. Boghossian doesn’t have tenure and expects the university will fire or otherwise punish him. Ms. Pluckrose predicts she’ll have a hard time getting accepted into a doctoral program. Mr. Lindsay said he expects to become “an academic pariah,” barred from professorships or publications.

Yet Mr. Lindsay says the project is worth it: “For us, the risk of letting biased research continue to influence education, media, policy and culture is far greater than anything that will happen to us for having done this.”

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Evolution of carcinogenesis

For those interested in cancer and, specifically, the history of cancer, you might find this brief fascinating review [attached] of interest. And for any of you who might not look at the South African Journal of Science on a regular basis (like most of us do) –– you might not have noticed that, in 2o16, it was reported [S Afr J Sci 2o16; 112: 1–5.] that an osteosarcoma was found in a 1.7-million-year-old bone from a hominin in South Africa. This finding confirms that cancer has been a disease affecting the human species for thousands of generations, i.e. it’s not simply a disease caused by fossil fuel pollution since the Industrial Revolution. This realization is also supported by a number of other reports suggesting the presence of malignancies –– including multiple myeloma, prostate cancer, and breast cancer in humans between 3,000 and 230 B.C.

The existence of cancer in very early hominins and the Homo sapiens species during the last 300,000 years –– before modernization and introduction of synthetic contaminants into the environment and Western world diets –– could offer clues into the etiology of this disease. Discoveries made in the modern era of scientific investigations have led to a more complete understanding of the mechanisms of carcinogenesis; these are summarized in the attached review in simplified diagrams.

DwN

Toxicol Sci Oct 2o18; 165: 272-276

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Phenotype-Specific Enrichment of Mendelian Disorder Genes near GWAS Regions across 62 Complex Traits

The genetic architecture (defined as the underlying genetic basis of any disease-related or quantitative trait and its variability seen in any population studied) of human traits have traditionally been classified into two major categories: complex traits arising from many low-effect common single-nucleotide variants (SNVs); and rare traits arising from high-effect monogenic SNVs. The underlying distinction between these two categories has historically been based on the presence of high-penetrant, rare, single-gene disruptive mutations causing recognizable clinical syndromes/monogenic diseases (e.g. cystic fibrosis, phenylketonuria) compared to the relative absence of such mutations in complex diseases (such as type-2 diabetes and schizophrenia). Another way to put it: clinical syndromes/monogenic diseases typically can often be diagnosed by a DNA mutation in the coding region (whole-exome sequencing) whereas complex diseases can often be “associated” with SNVs more often in noncoding regions (i.e. best discovered by whole-genome sequencing).

As these GEITP pages have often discussed, “response to a drug” or “response to any environmental agent” should be considered as having a genetic architecture and, in virtually no way different from, any disease-related phenotypic or quantitative trait.

Accumulating evidence now suggests that these two classes of phenotypes might not be so biologically distinct as previously thought, i.e. all traits likely exist as gradients (no surprise there). Thus, multiple exceptions to the ‘‘common disease, common variant’’ hypothesis have been identified for complex traits, and Mendelian disorders have also been found to be affected by multiple or common genetic variants. This suggests that there exists a spectrum of genetic architectures rather than a dichotomous (black vs white) classification.

Authors [see attached article] quantified the overlap of genes identified through large-scale genome-wide association studies (GWAS) for 62 complex traits, and diseases that have been correlated with genes having mutations known to cause 20 broad categories of Mendelian disorders. Authors identified a significant enrichment of genes linked to phenotypically-matched Mendelian disorders in GWAS gene sets; of the total 1,240 comparisons, a higher proportion of phenotypically-matched or related pairs (N = 50 of 92; 54%) than phenotypically unmatched pairs (N = 27 of 1,148; 2%) demonstrated significant overlap –– confirming a phenotype-specific enrichment pattern. Furthermore, they observed elevated GWAS effect-sizes near genes linked to phenotypically-matched Mendelian disorders. Authors also showed examples of GWAS variants (SNVs) localized at the transcription start site (or physically interacting with the promoters of genes linked to phenotypically-matched Mendelian disorders, which would lead to lowered expression ot that gene).

These data are consistent with the hypothesis that –– genes that are disrupted in Mendelian disorders are dysregulated by noncoding SNVs in complex traits. Moreover, the results demonstrate how leveraging findings from related Mendelian disorders, and functional genomic datasets, can prioritize genes that are putatively dysregulated by local and distal (cis and trans) noncoding SNVs.

DwN

Am J Hum Genet 4 Oct 2o18; 103: 535–552

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What genes in genome of the tree shrew allow it to eat very spicy food ???

Recently these GEITP pages discussed the koala genome, including discovery of an “evolutionary bloom, resulting in 31 genes” in the CYP2C subfamily (compared to just four CYP2C genes in human and 15 Cyp2c genes in mouse); it was speculated that one or more of these additional CYP2C enzymes are likely able to metabolize eucalyptus plants which are the main dietary component for the koala, whereas most eucalyptus is too toxic for most animals. There are many other examples of a plant being noxious to almost all animals, while a particular species thrives on that plant. The plant genus Capsicum is an example –– and the topic herein [see attached article].

Capsicum includes 22 wild species and produces a capsaicinoid called capsaicin, which we all know is VERY spicy hot..!! One of these species, the chili pepper, is a low shrub with capsaicin-containing fruits that are readily accessible to mammals and birds. However, capsaicinoids in these plants repel most animals by evoking a sharp and burning sensation through activation of the nociceptor, transient receptor potential vanilloid type-1 (TRPV1) ion channel. Interestingly, birds are an exception –– due to two specific point mutations in their TRPV1 channel gene that render them insensitive to capsaicin. This environmental adaptation broadens the range of diet in birds and also confers an advantage to the plant, because their seeds can be widely distributed by the birds.

Humans have an acute sensitivity to spicy food, and many find it unbearable; even so, with training, some have learned to enjoy the burning sensation elicited by consuming spicy food –– which might even confer protection against bacterial and fungal infection in the human gut. The tree shrew is a mammal closely related to primates. Authors [see attached paper] found that tree shrews actively feed on chili pepper, when it is provided to them. By whole-genome sequencing (WGS) analysis, authors identified a nucleotide alteration resulting in an amino acid change in the tree shrew TRPV1 gene, and they show that this change renders the TRPV1 channel refractory to capsaicinoid-induced activation.

Moreover, authors discovered that Piper boehmeriaefolium, another spicy plant that overlaps geographically with the ecological niche of the tree shrew, produces Cap2, a capsaicin analog, in abundance. Authors propose that there is a strong selection for the tree shrew TRPV1 gene mutation that might be the result of environmental pressure for positive selection, i.e. part of an evolutionary adaptation mechanism that enables the tree shrew to tolerate pungency –– thus widening the range of its diet for better survival advantage.

PLoS Biol July 2o18; 16: e2004921

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Whole-genome sequencing sheds light on adaptation of koala bears to their diet of eucalyptus leaves

The study reported in the Nature Genetics publication was primarily carried out in order to determine the entire koala genome by whole-genome sequencing (WGS). They found that the haploid genome spanned ~3.42 billion nucleotides, i.e. a diploid genome of ~3.42 gigabase pairs (Gbp). An incredible amount of information was gained by these authors in producing a complete and contiguous marsupial reference genome –– including centromeres.

CYP2C enzyme metabolism and substrate specificity of course could be the project for a future grant proposal. However, constructing 31 CYP2C cDNA expression vectors and inserting each of them into either bacteria or yeast in order to determine enzyme substrate specificity –– is no trivial experiment. However, I hope to see those results completed (by someone) within the next few years. 🙂

From: ((Anonymous))
Sent: Thursday, October 04, 2018 4:19 PM

Dan,

I’m suprised that the journal and the reviewers of this paper did not request proof that one or more of these koala CYP2C enzymes did indeed metabolize camphor or other various eucalyptus oils.
MORE COMMENTS:
We did something like that with 36 sequence variants of POR (P450-oxidoreductase), tested for CYP1A2 and 2C19 activity. Took about a year, but certainly do-able in a small lab –– if you have a plate reader and a colorimetric assay. For anyone interested, the 2008 Pharmacogenet Genom paper is attached. Also, our 2011 review, on the entire topic, in Mol Cell Endocrinol is attached.

MORE COMMENTS:
Along these same lines, just this minute I came across this article [abstract pasted below] –– describing a rapid procedure to measure the functional activity of 1,056 discovered single-nucleotide variants, just within the first 192 amino acids of the BRCA1 protein, measuring efficiency of double-strand DNA breaks. Therefore, ’31 CYP2C variants’, or ’36 POR variants’, would now be ‘small potatoes’ if one considers the latest advances in technology. 🙂

DwN

Am J Hum Genet. 4 Oct 2018; 103: 498-508
A Multiplex Homology-Directed DNA Repair Assay Reveals the Impact of More Than 1,000 BRCA1 Missense Substitution Variants on Protein Function.

Starita LM1, Islam MM2, Banerjee T2, Adamovich AI2, Gullingsrud J3, Fields S4, Shendure J5, Parvin JD6.
Abstract

Loss-of-function pathogenic variants in BRCA1 confer a predisposition to breast and ovarian cancer. Genetic testing for sequence changes in BRCA1 frequently reveals a missense variant for which the impact on cancer risk and on the molecular function of BRCA1 is unknown. Functional BRCA1 is required for the homology-directed repair (HDR) of double-strand DNA breaks, a critical activity for maintaining genome integrity and tumor suppression. Here, we describe a multiplex HDR reporter assay for concurrently measuring the effects of hundreds of variants of BRCA1 for their role in DNA repair. Using this assay, we characterized the effects of 1,056 amino acid substitutions in the first 192 residues of BRCA1. Benchmarking these results against variants with known effects on DNA repair function or on cancer predisposition, we demonstrate accurate discrimination of loss-of-function versus benign missense variants. We anticipate that this assay can be used to functionally characterize BRCA1 missense variants at scale, even before the variants are observed in results from genetic testing.

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