Jan 6, 2018

Unusual gene evolution in bacteria

A Chilean cicada, which hosts particularly unusual symbiotic bacteria.
University of Montana researchers have made another discovery at the cellular level to help understand the basic processes of all life on our planet -- this time within the unusual bacteria that has lived inside cicada insects since dinosaurs roamed Earth.

During the past 70 million years, the bacteria underwent extreme adaptations to live within the insects' bodies, losing between an estimated 95 to 97 percent of their genes and resulting in some of the smallest genomes known to any organisms. In the process, they lost the ability to live anywhere outside of cicadas.

"Cicada symbiotic complexes are very different from any other known organism," said Matt Campbell, a UM graduate student who studies cicadas in UM biology Associate Professor John McCutcheon's lab, based in the Division of Biological Sciences.

Many insects live in very close associations with beneficial, or "symbiotic," bacteria. These bacterial symbioses are critically important for insects that consume only one type of food that is missing some essential nutrients. Examples include blood-feeding lice as well as insects that feed on plant sap -- aphids, leafhoppers and cicadas.

The UM research has shown that cicadas' symbiotic bacteria produce amino acids and vitamins that their insect hosts require to grow and reproduce. During three field seasons studying a South American cicada, UM postdoctoral researcher Piotr Lukasik found many of the species' single symbiotic bacterium evolved into complexes of several different types of bacterium in the same cicada.

"Through that process, individual bacteria have lost many genes and now depend on each other because every type contains unique, essential genes," Lukasik said. "The different types must all work together to provide the amino acids and vitamins their cicada host requires."

A different species of cicada, located in the eastern U.S., contains dozens of small, rapidly evolving types of bacterium. Individual types typically contain few recognizable genes and are distributed among different cellular compartments within a cicada in a way that is not fully understood.

"Cicadas host symbiotic complexes rather than a single, well-behaved bacteria, which could be a challenge for the species," Lukasik said. "After all, when you need a meal -- whether it is a vitamin required by a cicada or a pizza craved by a hungry student -- it's easier to obtain it from a single source rather than cobbling it together from several different sources."

Read more at Science Daily

Mechanism that converts white fat to brown identified

Obesity definition
An international team of researchers led from Karolinska Institutet have, in experiments on mice, pinpointed a mechanism for the conversion of energy-storing white fat into energy-expending brown fat. The study is published in the Journal of Experimental Medicine.

Obesity is a major global health issue, affecting all age groups. Obesity increases the risk of several serious human diseases, including cardiovascular disease, type 2 diabetes and cancer. Despite this knowledge, effective drugs for the treatment of obesity and related metabolic disease are lacking.

Scientists differentiate between white adipose tissue, which constitutes most human fat and which stores surplus energy, and brown adipose tissue, which generates heat by consuming energy. One possible way of tackling potential obesity, suggest researchers, is to stimulate the conversion of parts of the white fat into brown.

In a new study conducted on obese mice, a research team led by Professor Yihai Cao Karolinska Institutet and their colleagues at the University of Connecticut and Qingdao University stimulated the formation of blood vessels in white adipose tissue by blocking the receptor molecule for a growth factor known as VEGFR1, an effect that was achieved in one group of mice by means of a drug, and on another through genetic modification. The result was an increase in the conversion of white fat to brown, as well as a reduction in obesity and improved sensitivity to insulin.

"Our discoveries can hopefully help us to develop new drugs for the treatment of obesity and diabetes," says Yihai Cao, professor in vascular biology at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

Professor Cao´s research was financed by the European Research Council, the Swedish Research Council, the Swedish Cancer Foundation, the Karolinska Institute Foundation, the Karolinska Institute distinguished professor award, the Torsten Soderberg Foundation, the Maud and Birger Gustavsson Foundation, the NOVO Nordisk Foundation and the Knut and Alice Wallenberg Foundation.

From Science Daily

Jan 5, 2018

Mirror neuron activity predicts people's decision-making in moral dilemmas

Researchers found that the brain's inferior frontal cortex (circled) is more active in people who are more averse to harming others when facing moral dilemmas.
It is wartime. You and your fellow refugees are hiding from enemy soldiers, when a baby begins to cry. You cover her mouth to block the sound. If you remove your hand, her crying will draw the attention of the soldiers, who will kill everyone. If you smother the child, you'll save yourself and the others.

If you were in that situation, which was dramatized in the final episode of the '70s and '80s TV series "M.A.S.H.," what would you do?

The results of a new UCLA study suggest that scientists could make a good guess based on how the brain responds when people watch someone else experience pain. The study found that those responses predict whether people will be inclined to avoid causing harm to others when facing moral dilemmas.

"The findings give us a glimpse into what is the nature of morality," said Dr. Marco Iacoboni, director of the Neuromodulation Lab at UCLA's Ahmanson-Lovelace Brain Mapping Center and the study's senior author. "This is a foundational question to understand ourselves, and to understand how the brain shapes our own nature."

In the study, which was published in Frontiers in Integrative Neuroscience, Iacoboni and colleagues analyzed mirror neurons, brain cells that respond equally when someone performs an action or simply watches someone else perform the same action. Mirror neurons play a vital role in how people learn through mimicry and feel empathy for others.

When you wince while seeing someone experience pain -- a phenomenon called "neural resonance" -- mirror neurons are responsible.

Iacoboni wondered if neural resonance might play a role in how people navigate complicated problems that require both conscious deliberation and consideration of another's feelings.

To find out, researchers showed 19 volunteers two videos: one of a hypodermic needle piercing a hand, and another of a hand being gently touched by a cotton swab. During both, the scientists used a functional MRI machine to measure activity in the volunteers' brains.

Researchers later asked the participants how they would behave in a variety of moral dilemmas, including the scenario involving the crying baby during wartime, the prospect of torturing another person to prevent a bomb from killing several other people and whether to harm research animals in order to cure AIDS.

Participants also responded to scenarios in which causing harm would make the world worse -- inflicting harm on another person in order to avoid two weeks of hard labor, for example -- to gauge their willingness to cause harm for moral reasons and for less-noble motives.

Iacoboni and his colleagues hypothesized that people who had greater neural resonance than the other participants while watching the hand-piercing video would also be less likely to choose to silence the baby in the hypothetical dilemma, and that proved to be true. Indeed, people with stronger activity in the inferior frontal cortex, a part of the brain essential for empathy and imitation, were less willing to cause direct harm, such as silencing the baby.

But the researchers found no correlation between people's brain activity and their willingness to hypothetically harm one person in the interest of the greater good -- such as silencing the baby to save more lives. Those decisions are thought to stem from more cognitive, deliberative processes.

The study confirms that genuine concern for others' pain plays a causal role in moral dilemma judgments, Iacoboni said. In other words, a person's refusal to silence the baby is due to concern for the baby, not just the person's own discomfort in taking that action.

Iacoboni's next project will explore whether a person's decision-making in moral dilemmas can be influenced by decreasing or enhancing activity in the areas of the brain that were targeted in the current study.

"It would be fascinating to see if we can use brain stimulation to change complex moral decisions through impacting the amount of concern people experience for others' pain," Iacoboni said. "It could provide a new method for increasing concern for others' well-being."

The research could point to a way to help people with mental disorders such as schizophrenia that make interpersonal communication difficult, Iacoboni said.

Read more at Science Daily

In scientific first, IU researchers grow hairy skin in a dish

Lee et al. show that hair follicles can be generated from mouse pluripotent stem cells in a 3-D cell culture system. The hair follicles (red) grow radially out of spherical skin organoids and contain follicle-initiating dermal papilla cells (green cells) and hair shafts (cyan).
Researchers at Indiana University School of Medicine have successfully developed a method to grow hairy skin from mouse pluripotent stem cells -- a discovery that could lead to new approaches to model disease and new therapies for the treatment of skin disorders and cancers.

This research, recently published online in the journal Cell Reports, marks the first demonstration that hair follicles can be grown in cultures of stem cells. The study was led by Karl Koehler, PhD, assistant professor of otolaryngology-head and neck surgery at IU School of Medicine, and a postdoctoral fellow in his lab, Jiyoon Lee, PhD.

"The skin is a complex organ that has been difficult to fully recreate and maintain in culture for research purposes," said Dr. Koehler, who explains more in a blog post. "Our study shows how to encourage hair development from lab grown mouse skin, which has been particularly troublesome for researchers to recreate in culture."

Dr. Koehler and his team's findings build on their past work creating a technique for growing inner ear cells from stem cells, in which mouse stem cells are cultured in a three-dimensional ball and treated with specific signaling molecules to coax the cells into producing inner ear tissue. The researchers noticed that skin was a byproduct of the inner ear growth process.

"In the developing embryo, the inner ear comes from the same layer of cells as the top layer of the skin, [the epidermis], so it was no surprise that skin and inner ear tissue formed in tandem," Dr. Koehler said. "We were surprised to find that the bottom layer of the skin [the dermis] also develops."

In the current study, Dr. Koehler and his team show how the epidermis and dermis cells form a sphere-like cluster of cells, called a skin "organoid." The cells in skin organoids are organized much like cells in normal skin, but inside-out, meaning the top layer of the skin faces the interior of the organoid.

The team identified culture conditions that allowed skin organoids to proceed through the stages of development much like skin in the embryo.

"After about 20 days, we were amazed to see that skin organoids sprouted hair follicles," Dr. Koehler said. "The roots of the follicles protrude from the skin organoids in all directions."

The researchers confirmed that the timing of development and expression of key proteins closely match skin and hair development in the mouse embryo. To validate their findings, the IU team collaborated with Stefan Heller, PhD, Edward C. and Amy H. Sewall Professor of Otolaryngology-Head and Neck Surgery at Stanford University, whose lab members confirmed that the technique was reproducible with stem cells from other mouse strains.

"In addition to the major epidermal and dermal cell types we also found specialized cell types, such as melanocytes [pigment cells], Merkel cells [touch sensing cells], adipocytes [fat cells], sebaceous gland cells, and hair follicle stem cells in organoids," Dr. Koehler said. "This is fascinating because it shows that if we derive the basic building blocks of skin together in culture, then these diverse cell types will self-assemble on their own."

Dr. Lee, first author on the study, said these findings serve as a blueprint for how to make from scratch the entire skin organ using stem cells.

"My hope is that by improving skin-in-a-dish models we can greatly diminish the sacrifice of experimental animals and ultimately help patients with skin-related issues live a better life," Dr. Lee said.

Dr. Koehler said he cautions that there are several technical hurdles that they have yet to overcome for the skin organoid model to reach its full potential as a drug discovery tool. For instance, the skin organoids are missing immune cells, blood vessels and nerve endings found in normal skin.

"The shape of skin organoids is another problem that needs to be addressed in the future," he said. "Because the organoids are inside-out compared to normal skin, the layers of dead cells and hairs cannot be shed as they are normally, so we need to find a way to flip the structure of skin organoids."

Without these changes, the skin organoids have a shelf life of about a month, which is just long enough to study the complete development of mouse skin and hair.

Koehler and his team are currently using the mouse organoids as a template to derive hairy skin from human pluripotent stem cells. This work has the potential to lead to new skin grafting techniques -- incorporating hair follicles -- and therapies for human diseases, including alopecia, acne and skin cancers.

Read more at Science Daily

Super-silenced DNA study hints at new ways to reprogram cells

Enhanced reprogramming of skin cells (blue) to liver-like cells (red and green) by reducing expression of a repressive protein.
Newly described stretches of super-silenced DNA reveal a fresh approach to reprogram cell identity to use in regenerative medicine studies and one day in the clinic, according to a study in Molecular Cell last week by investigators from the Perelman School of Medicine at the University of Pennsylvania.

"In the past, most labs, including my own, used gene activators to turn on a new program to change the identity in a given cell," said senior author Ken Zaret, PhD, director of the Penn Institute for Regenerative Medicine and a professor of Cell and Developmental Biology. "Our study shows that in some cases we will need to disassemble a cell's gene repression machinery to activate important genes to reprogram a cell's identity."

The team attempted to reprogram skin cells to make new liver cells. Conversions of one cell type to another usually have low efficiencies, and this study identifies one reason why. The long term goal of this preclinical research is to be able to replenish diseased liver tissue with healthy tissue derived from a different tissue, such as skin cells, from the same individual in a process called direct-cell reprogramming

The Zaret lab untangled an extreme form of gene silencing, opening up regions of tightly wound DNA that is difficult for activators to reach to turn on certain genes. They found the regions by characterizing an increase in chemical cross-linking due to DNA being more compacted in the scaffolding of repressed regions of chromosomes

"Think of a piece of fishing line that has been used for a while, with several knots along its length," Zaret said. "The knotted areas are more easily cross-linked regions, reflecting them being super-silenced areas of DNA."

For the body to maintain its 200-plus different cell types, cells must activate genes specific to their type while simultaneously repressing genes of alternative types. Most genes in silenced DNA regions (not available to be "read" and made into a protein) are typically functions not used by the current cell type. Zaret likens it to insurance so cells don't mix up their identity, which could induce problems such as uncontrolled, cancerous cell replications, or so that brain or liver genes are kept from being expressed in skin cells, for example.

The team characterized the proteins that help make the regions "knotted" and found they were more complex than expected. "We found more types of different proteins than we thought we would," Zaret said. To do this, they turned on the activity of once-silenced genes in human skin cells grown in culture to see if the knotted domain would open more easily when each was eliminated. Of the 50 proteins tested, some are also mutated in such neurodegenerative disorders as Lou Gehrig's disease.

Read more at Science Daily

Weighing massive stars in nearby galaxy reveals excess of heavyweights

The star-forming region, 30 Doradus, is one of the largest located close to the Milky Way and is found in the neighboring galaxy, Large Magellanic Cloud. About 2,400 massive stars in the center of 30 Doradus, also known as the Tarantula Nebula, are producing intense radiation and powerful winds as they blow off material.
An international team of astronomers has revealed an 'astonishing' overabundance of massive stars in a neighbouring galaxy.

The discovery, made in the gigantic star-forming region 30 Doradus in the Large Magellanic Cloud galaxy, has 'far-reaching' consequences for our understanding of how stars transformed the pristine Universe into the one we live in today.

The results are published in the journal Science.

Lead author Fabian Schneider, a Hintze Research Fellow in the University of Oxford's Department of Physics, said: 'We were astonished when we realised that 30 Doradus has formed many more massive stars than expected.'

As part of the VLT-FLAMES Tarantula Survey (VFTS), the team used ESO's Very Large Telescope to observe nearly 1,000 massive stars in 30 Doradus, a gigantic stellar nursery also known as the Tarantula nebula. The team used detailed analyses of about 250 stars with masses between 15 and 200 times the mass of our Sun to determine the distribution of massive stars born in 30 Doradus -- the so-called initial mass function (IMF).

Massive stars are particularly important for astronomers because of their enormous influence on their surroundings (known as their 'feedback'). They can explode in spectacular supernovae at the end of their lives, forming some of the most exotic objects in the Universe -- neutron stars and black holes.

Co-author Hugues Sana from the University of Leuven in Belgium said: 'We have not only been surprised by the sheer number of massive stars, but also that their IMF is densely sampled up to 200 solar masses.' Until recently, the existence of stars up to 200 solar masses was highly disputed, and the study shows that a maximum birth mass of stars of 200-300 solar masses appears likely.

In most parts of the Universe studied by astronomers to date, stars become rarer the more massive they are. The IMF predicts that most stellar mass is in low-mass stars and that less than 1% of all stars are born with masses in excess of ten times that of the Sun. Measuring the proportion of massive stars is extremely difficult -- primarily because of their scarcity -- and there are only a handful of places in the local Universe where this can be done.

The team turned to 30 Doradus, the biggest local star-forming region, which hosts some of the most massive stars ever found, and determined the masses of massive stars with unique observational, theoretical and statistical tools. This large sample allowed the scientists to derive the most accurate high-mass segment of the IMF to date, and to show that massive stars are much more abundant than previously thought. Chris Evans from the Science and Technology Facilities Council's UK Astronomy Technology Centre, the principal investigator of VFTS and a co-author of the study, said: 'In fact, our results suggest that most of the stellar mass is actually no longer in low-mass stars, but a significant fraction is in high-mass stars.'

Stars are cosmic engines and have produced most chemical elements heavier than helium, from the oxygen we breathe every day to the iron in our blood. During their lives, massive stars produce copious amounts of ionising radiation and kinetic energy through strong stellar winds. The ionising radiation of massive stars was crucial for the re-brightening of the Universe after the so-called Dark Ages, and their mechanical feedback drives the evolution of galaxies. Philipp Podsiadlowski, a co-author of the study from the University of Oxford, said: 'To quantitatively understand all these feedback mechanisms, and hence the role of massive stars in the Universe, we need to know how many of these behemoths are born.'

Fabian Schneider added: 'Our results have far-reaching consequences for the understanding of our cosmos: there might be 70% more supernovae, a tripling of the chemical yields and towards four times the ionising radiation from massive star populations. Also, the formation rate of black holes might be increased by 180%, directly translating into a corresponding increase of binary black hole mergers that have recently been detected via their gravitational wave signals.'

Read more at Science Daily

Jan 4, 2018

Scientists find surprising evidence of rapid changes in the Arctic

Diminishing sea ice near the Arctic coast leaves more open water near the coast for winds to create waves. The increased wave action reaches down and stirs up sediments on shallow continental shelves, releasing radium and other chemicals that are carried up to the surface and swept away into the open ocean by currents such as the Transpolar Drift. A new study found surprising evidence that climate change is rapidly causing coastal changes in the Arctic that could have significant impacts on Arctic food webs and animal populations.
Scientists have found surprising evidence of rapid climate change in the Arctic: In the middle of the Arctic Ocean near the North Pole, they discovered that the levels of radium-228 have almost doubled over the last decade.

The finding indicates that large-scale changes are happening along the coast -- because the source of the radium is the land and shallow continental shelves surrounding the ocean. These coastal changes, in turn, could also be delivering more nutrients, carbon, and other chemicals into the Arctic Ocean and lead to dramatic impacts on Arctic food webs and animal populations.

The research team, led by Woods Hole Oceanographic Institution (WHOI), suspects that melting sea ice has left more open water near the coast for winds to create waves. The wave action reaches down to the shallow shelves and stirs up sediments, releasing radium that is carried to the surface and away into the open ocean. The same mechanism would likely also mobilize and deliver more nutrients, carbon, and other chemicals into the Arctic Ocean, fueling the growth of plankton at the bottom of the food chain. That, in turn, could have significant impacts on fish and marine mammals and change the Arctic ecosystem.

The study was published Jan. 3, 2018, in the journal Science Advances. The research team included Lauren Kipp, Matthew Charette, and Paul Henderson (WHOI), Willard Moore (University of South Carolina), and Ignatius Rigor (University of Washington).

Scientists have long used radium-228 to track the flow of material from land and sediments into the ocean. It is a naturally occurring isotope produced by the radioactive decay of thorium in sediments. But unlike thorium, it dissolves into water, where scientists can track the sources, amounts, rates, and direction of its flow, said Kipp, who is lead author of the study and a graduate student in the MIT-WHOI Joint Program in Oceanography.

Kipp led efforts to measure radium at 69 locations from the western edge of the Arctic Ocean to the Pole on a two-month voyage aboard the icebreaker Healy in the summer of 2015. The cruise was part of the international GEOTRACES program, which aims to measure chemical tracers in the world's ocean to understand ocean circulation and provide a baseline to assess future chemical changes in the oceans. The U.S. GEOTRACES program and this study are both funded by the National Science Foundation.

To their surprise, the research team found that radium-228 concentrations in the central Arctic Ocean had increased substantially since measurements had last been made in 2007. What was its source and why had it increased?

The team investigated the trajectories of sea ice drifting in the ocean and saw a pattern of ice -- and hence water -- flowing northward from the vast northern coast of Russia toward the middle of the Arctic Ocean, where the radium concentrations had increased. The pattern aligned with the Transpolar Drift, a powerful current flowing in same direction that could transport radium from coastal sources.

They concluded that the excess radium had to have come from sediments in the East Siberian Arctic Shelf off Russia, the largest continental shelf on Earth. It is relatively shallow, with an average depth of 170 feet, but it extends 930 miles off shore and contains a vast reservoir of radium and other chemical compounds.

Something had to have changed along the coast to explain the dramatic surge in radium in the middle of the Arctic Ocean. The scientists theorize that a warming Arctic environment has reduced sea ice cover, allowing for more wave action that stirs up sediments and mobilizes more radium.

But there are other possible contributing factors that are causing changes over the shelf, the scientists say. More wave action can also cause more coastline erosion, adding more terrestrial sediment into the ocean. Warming temperatures can thaw permafrost, liberating more material into the ocean, and increasing river and groundwater runoff can carry more radium, nutrients, carbon, and other material into the Arctic.

"Continued monitoring of shelf inputs to Arctic surface waters is therefore vital to understand how the changing climate will affect the chemistry, biology, and economic resources of the Arctic Ocean," the study's authors wrote.

Read more at Science Daily

How alcohol damages DNA and increases cancer risk

Alcohol bottle and glass
Scientists have shown how alcohol damages DNA in stem cells, helping to explain why drinking increases your risk of cancer, according to research part-funded by Cancer Research UK and published in Nature today (Wednesday).

Much previous research looking at the precise ways in which alcohol causes cancer has been done in cell cultures. But in this study, researchers have used mice to show how alcohol exposure leads to permanent genetic damage.

Scientists at the MRC Laboratory of Molecular Biology, Cambridge, gave diluted alcohol, chemically known as ethanol, to mice. They then used chromosome analysis and DNA sequencing to examine the genetic damage caused by acetaldehyde, a harmful chemical produced when the body processes alcohol.

They found that acetaldehyde can break and damage DNA within blood stem cells leading to rearranged chromosomes and permanently altering the DNA sequences within these cells.

It is important to understand how the DNA blueprint within stem cells is damaged because when healthy stem cells become faulty, they can give rise to cancer.

These new findings therefore help us to understand how drinking alcohol increases the risk of developing 7 types of cancer including common types like breast and bowel.

Professor Ketan Patel, lead author of the study and scientist, part funded by Cancer Research UK, at the MRC Laboratory of Molecular Biology, said: "Some cancers develop due to DNA damage in stem cells. While some damage occurs by chance, our findings suggest that drinking alcohol can increase the risk of this damage."

The study also examined how the body tries to protect itself against damage caused by alcohol. The first line of defence is a family of enzymes called aldehyde dehydrogenases (ALDH). These enzymes break down harmful acetaldehyde into acetate, which our cells can use as a source of energy.

Worldwide, millions of people, particularly those from South East Asia, either lack these enzymes or carry faulty versions of them. So, when they drink, acetaldehyde builds up which causes a flushed complexion, and also leads to them feeling unwell.

In the study, when mice lacking the critical ALDH enzyme -- ALDH2 -- were given alcohol, it resulted in four times as much DNA damage in their cells compared to mice with the fully functioning ALDH2 enzyme.

The second line of defence used by cells is a variety of DNA repair systems which, most of the time, allow them to fix and reverse different types of DNA damage. But they don't always work and some people carry mutations which mean their cells aren't able to carry out these repairs effectively.

Professor Patel added: "Our study highlights that not being able to process alcohol effectively can lead to an even higher risk of alcohol-related DNA damage and therefore certain cancers. But it's important to remember that alcohol clearance and DNA repair systems are not perfect and alcohol can still cause cancer in different ways, even in people whose defence mechanisms are intact."

This research was funded by Cancer Research UK, Wellcome and the Medical Research Council (MRC).

Professor Linda Bauld, Cancer Research UK's expert on cancer prevention, said: "This thought-provoking research highlights the damage alcohol can do to our cells, costing some people more than just a hangover.

Read more at Science Daily

Four-dimensional physics in two dimensions

Illustration of light passing through a two-dimensional waveguide array. Each waveguide is essentially a tube, which behaves like a wire for light, inscribed through high-quality glass using a powerful laser. Many of these waveguides are inscribed closely spaced through a single piece of glass to form the array. Light that flows through the device behaves precisely according to the predictions of the four-dimensional quantum Hall effect.
For the first time, physicists have built a two-dimensional experimental system that allows them to study the physical properties of materials that were theorized to exist only in four-dimensional space. An international team of researchers from Penn State, ETH Zurich in Switzerland, the University of Pittsburgh, and the Holon Institute of Technology in Israel have demonstrated that the behavior of particles of light can be made to match predictions about the four-dimensional version of the "quantum Hall effect" -- a phenomenon that has been at the root of three Nobel Prizes in physics -- in a two-dimensional array of "waveguides."

A paper describing the research appears January 4, 2018 in the journal Nature along with a paper from a separate group from Germany that shows that a similar mechanism can be used to make a gas of ultracold atoms exhibit four-dimensional quantum Hall physics as well.

"When it was theorized that the quantum Hall effect could be observed in four-dimensional space," said Mikael Rechtsman, assistant professor of physics and an author of the paper, "it was considered to be of purely theoretical interest because the real world consists of only three spatial dimensions; it was more or less a curiosity. But, we have now shown that four-dimensional quantum Hall physics can be emulated using photons -- particles of light -- flowing through an intricately structured piece of glass -- a waveguide array."

When electric charge is sandwiched between two surfaces, the charge behaves effectively like a two-dimensional material. When that material is cooled down to near absolute-zero temperature and subjected to a strong magnetic field, the amount that it can conduct becomes "quantized" -- fixed to a fundamental constant of nature and cannot change. "Quantization is striking because even if the material is 'messy' -- that is, it has a lot of defects -- this 'Hall conductance' remains exceedingly stable," said Rechtsman. "This robustness of electron flow -- the quantum Hall effect -- is universal and can be observed in many different materials under very different conditions."

This quantization of conductance, first described in two-dimensions, cannot be observed in an ordinary three-dimensional material, but in 2000, it was shown theoretically that a similar quantization could be observed in four spatial dimensions. To model this four-dimensional space, the researchers built waveguide arrays. Each waveguide is essentially a tube, which behaves like a wire for light. This "tube" is inscribed through high-quality glass using a powerful laser.

Many of these waveguides are inscribed closely spaced through a single piece of glass to form the array. The researchers used a recently-developed technique to encode "synthetic dimensions" into the positions of the waveguides. In other words, the complex patterns of the waveguide positions act as a manifestation of the higher-dimensional coordinates. By encoding two extra synthetic dimensions into the complex geometric structure of the waveguides, the researchers were able to model the two-dimensional system as having a total of four spatial dimensions. The researchers then measured how light flowed through the device and found that it behaved precisely according to the predictions of the four-dimensional quantum Hall effect.

"Our observations, taken together with the observations using ultracold atoms, provide the first demonstration of higher-dimensional quantum Hall physics," said Rechtsman. "But how can understanding and probing higher-dimensional physics have some relevance to science and technology in our three-dimensional world? There are a number of examples where this is the case. For example, 'quasicrystals' -- metallic alloys that are crystalline but have no repeating units and are used to coat some non-stick pans -- have been shown to have 'hidden dimensions:' their structures can be understood as projections from higher-dimensional space into the real, three-dimensional world. Furthermore, it is possible that higher-dimensional physics could be used as a design principle for novel photonic devices."

Read more at Science Daily

Scientists design bacteria to reflect 'sonar' signals for ultrasound imaging

This image is a transmission electron micrograph (TEM) image of a single commensal bacterium, E. coli Nissle 1917, which has been genetically engineered to express gas-filled protein nanostructures known as gas vesicles. The cell is approximately 2 micrometers in length, and the lighter-colored structures contained inside of it are individual gas vesicles.
In the 1966 science fiction film Fantastic Voyage, a submarine is shrunken down and injected into a scientist's body to repair a blood clot in his brain. While the movie may be still be fiction, researchers at Caltech are making strides in this direction: they have, for the first time, created bacterial cells with the ability to reflect sound waves, reminiscent of how submarines reflect sonar to reveal their locations.

The ultimate goal is to be able to inject therapeutic bacteria into a patient's body -- for example, as probiotics to help treat diseases of the gut or as targeted tumor treatments -- and then use ultrasound machines to hit the engineered bacteria with sound waves to generate images that reveal the locations of the microbes. The pictures would let doctors know if the treatments made it to the right place in the body and were working properly.

"We are engineering the bacterial cells so they can bounce sound waves back to us and let us know their location the way a ship or submarine scatters sonar when another ship is looking for it," says Mikhail Shapiro, assistant professor of chemical engineering, Schlinger Scholar, and Heritage Medical Research Institute Investigator. "We want to be able to ask the bacteria, 'Where are you and how are you doing?' The first step is to learn to visualize and locate the cells, and the next step is to communicate with them."

The results will be published in the January 4 issue of the journal Nature. The lead author is Raymond Bourdeau, a former postdoctoral scholar in Shapiro's lab.

The idea of using bacteria as medicine is not new. Probiotics have been developed to treat conditions of the gut, such as irritable bowel disease, and some early studies have shown that bacteria can be used to target and destroy cancer cells. But visualizing these bacterial cells as well as communicating with them -- both to gather intel on what's happening in the body and give the bacteria instructions about what to do next -- is not yet possible. Imaging techniques that rely on light -- such as taking pictures of cells tagged with a "reporter gene" that codes for green fluorescent protein -- only work in tissue samples removed from the body. This is because light cannot penetrate into deeper tissues like the gut, where the bacterial cells would reside.

Shapiro wants to solve this problem with ultrasound techniques because sound waves can travel deeper into bodies. He says he had a eureka moment about six years ago when he learned about gas-filled protein structures in water-dwelling bacteria that help regulate the organisms' buoyancy. Shapiro hypothesized that these structures, called gas vesicles, could bounce back sound waves in ways that make them distinguishable from other types of cells. Indeed, Shapiro and his colleagues demonstrated that the gas vesicles can be imaged with ultrasound in the guts and other tissues of mice.

The team's next goal was to transfer the genes for making gas vesicles from the water-dwelling bacteria into a different type of bacteria -- Escherichia coli, which is commonly used in microbial therapeutics, such as probiotics.

"We wanted to teach the E. coli bacteria to make the gas vesicles themselves," says Shapiro. "I've been wanting to do this ever since we realized the potential of gas vesicles, but we hit some roadblocks along the way. When we finally got the system to work, we were ecstatic."

One of the challenges the team hit involved the transfer of the genetic machinery for gas vesicles into E. coli. They first tried to transfer gas-vesicle genes isolated from a water-dwelling bacterium called Anabaena flos-aquae, but this didn't work -- the E. coli failed to make the vesicles. They tried again using gas-vesicle genes from a closer relative of E. coli, a bacterium called Bacillus megaterium. This didn't succeed either, because the resulting gas vesicles were too small to efficiently scatter sound waves. Finally, the team tried a mix of genes from both species -- and it worked. The E. coli made gas vesicles on their own.

The gas vesicle genes code for proteins that act like either bricks or cranes in building the final vesicle structure -- some of the proteins are the building blocks of the vesicles while some help in actually assembling the structures. "Essentially, we figured out that we need the bricks from Anabaena flos-aquae and the cranes from Bacillus megaterium in order for the E. coli to be able to make gas vesicles," says Bourdeau.

Subsequent experiments from the team demonstrated that the engineered E. coli could indeed be imaged and located within the guts of mice using ultrasound.

"This is the first acoustic reporter gene for use in ultrasound imaging," says Shapiro. "We hope it will ultimately do for ultrasound what green fluorescent protein has done for light-based imaging techniques, which is to really revolutionize the imaging of cells in ways there were not possible before."

The researchers say the technology should be available soon to scientists who do research in animals, although it will take many more years to develop the method for use in humans.

Read more at Science Daily

Jan 3, 2018

Birds and dinosaurs: High-performance breathing in bones

This is part of a neck vertebra of the dwarf sauropod Europasaurus with deep cavities (asterisk) that presumably housed air sacs.
"The respiratory organs of vertebrates exhibit a tremendous degree of diversity, but the lung-air sac system of birds is truly unique among extant species," says Dr. Markus Lambertz from the Institute for Zoology at the University of Bonn in Germany. Air sacs are bellows-like protrusions of the lung, and their volume changes cause the air flow in the separate gas exchanger. This functional separation is crucial for the exceptional efficiency of this respiratory system, but air sacs can do more: they can invade bones, a process called "pneumatization."

Pneumatized bones are very light, because they are filled with air instead of the more heavy marrow, which was not only important for active flight, but also for the evolution of gigantism in sauropod dinosaurs. Through the presence of the resulting pneumatic cavities, it has long been known that air sac-like structures predate the origin of birds, since they were found both in the gigantic sauropods as well as in carnivorous dinosaurs. However, when and potentially how many times air sacs did evolve was inaccessible until now.

Pneumosteum: a hitherto unknown type of bony tissue as a diagnostic tool

Filippo Bertozzo was pretty surprised when he analyzed the bone structure in the course of his master's thesis at the Steinmann-Institute for Geology, Mineralogy and Paleontology of the University of Bonn: "Bones that are in contact with air sacs exhibit a unique structure composed of very fine and densely packed fibers. After it turned out that this was true both in modern birds and extinct dinosaurs, we proposed to name this special kind of bony tissue "pneumosteum." "

Especially astonishing was the fact that pneumosteum was not only restricted to pneumatized bones, but was also found on the surface of conspicuous cavities present in cervical vertebrae of sauropod dinosaurs. Dr. Lambertz adds: "Such cavities had already previously been hypothesized as potential locations of air sacs, but only our microscopic analysis now provides convincing arguments for this."

Other soft tissues, such as muscles, can leave traces in bone as well. "There are several types of fibers within bone tissue, but the pneumosteum is markedly different from them," explains Prof. Dr. Martin Sander from the Steinmann-Institute in Bonn. This characteristic individuality of the pneumosteum thus makes it an excellent diagnostic tool for recognizing bones that were in contact with air sacs.

Access to the past and potential for future research

Given that pneumosteum was only discovered in the dinosaurian lineage now provides the opportunity to trace the evolutionary origin of air sacs. Especially the fact that pneumosteum is not restricted to pneumatized bones but was also found on bone surfaces opens up access to studying species that might have exhibited air sacs as part of their respiratory system, but lack obviously pneumatized bones.

Fossilization of air sacs is nearly impossible because their delicate structure is composed of only a few layers of cells. Professor Sander thus is convinced that the discovery of pneumosteum will lead to a greatly improved understanding of the evolution of the dinosaurian respiratory system. Dr. Lambertz concludes with: "This project once again highlights the importance of the interdisciplinary collaboration between zoologists and paleontologists for elucidating evolutionary history."

From Science Daily

Scientists explore mysteries behind diversity of DNA composition among species

Rendering of DNA.
To make the iconic, twisted double helix that accounts for the diversity of life, DNA rules specify that G always pairs with C, and A with T.

But, when it's all added up, the amount of G+C vs A+T content among species is not a simple fixed percentage or, standard one-to-one ratio.

For example, within single-celled organisms, the amount of G+C content can vary from 72 percent in a bacteria like Streptomyces coelicolor while the protozoan parasite that causes malaria, Plasmondium falciparum, has as little as 20 percent.

In single-celled eukaryotes, yeast contain 38 percent G+C content, plants like corn have 47 percent, and humans contain about 41 percent.

The big question is, why?

"This has been one of the long-standing problems in genome evolution, and prior attempts to explain it have involved considerable arm waving," said Michael Lynch, who leads a new Center for Mechanisms of Evolution at Arizona State University's Biodesign Institute.

Is there something within the chemical nature of DNA itself that favors one nucleotide over the other, or does the bias of mutation pressure vary, and if so, why would this be different among species?

"In the absence of key observations on the mutation process, there has been a struggle to fathom what the mechanism is," said Lynch.

Michael Lynch's group has now experimentally demonstrated that G+C composition is generally strongly favored, whereas this is often opposed by mutational pressure of various strengths in the opposite direction.

"On average, natural selection or some other factor (possibly associated with recombinational forces) favors G+C content, regardless of the class of DNA, size of a species' genome, or where the species is found on the evolutionary tree of life," said Lynch.

The study was published in the journal Nature Ecology and Evolution.

To err is universal

Driving evolution are DNA mutations, errors in the genome that are introduced and passed along to the next generation, so that over time, providing the fuel for the invention of new adaptations or traits.

To get to the heart of the matter, the scientists wanted a way to quantify the full spectrum of DNA mutations in the lab across a wide swath of species.

This can now be done due in part by new technologies to make DNA sequencing faster and cheaper. It has fueled a golden age of evolutionary experimental biology.

"We started with knowledge of the mutational spectrum that occurs at the genome level in about 40 species examined in my lab," said Lynch. "You can use such information to calculate what the GC composition would be in the absence of selection. And then we can compare this null expectation with the the actual genome content, the difference being due to selection."

In a tour de force experiment that is the largest survey to date, they examined every single DNA mutation across different species, sequencing billions of DNA chemical bases.

"This represented a very substantial work load, effort and cost that was necessary to test different evolutionary models with high statistical power," said Hongan Long, a postdoctoral researcher who led the experiments.

They also took advantage of an analysis of 25 current datasets of mutations and 12 new mutation-accumulation (MA) experiments (many from their own lab), including bacteria and a menagerie of multicellular organisms including yeast, worms, fruit flies, chimpanzees and humans.

During each MA experiment, they performed complete genome sequencing of about 50 different bacterial lines that had been passaged through severe, single-cell bottlenecks for thousands of cell divisions.

"This single-cell passage of each line acts like a filter, eliminating the ability of natural selection to modify the accumulation of all but the most severe and deleterious mutations, giving us an effectively unbiased view of the mutation process," said Long.

With each generation, they carefully measured the mutation rate, or every occurrence of when just a single DNA letter is changed.

This can happen in two ways: a single G or C DNA base pair being converted to the A+T direction; or the opposite can happen, with an A or T base switching in the G+C direction.

After all the number and data crunching, a striking pattern emerged between G+C content and the expectations based on DNA mutations.

"It turns out, they are correlated," said Lynch.. "The G+C composition is always higher than you expect, based on neutrality. That tells us that there is pervasive selection. So mutation drives the overall pattern, but selection for G's and C's over A's and T's boosts the genome content above the neutral mutational expectation.

This seems to be almost universally true."

The end of the beginning

Now that they've shown the G+C composition correlation, it has opened up the door to many more questions, and answers that remain elusive.

"One question is, 'why does the mutation spectrum change so dramatically across species'"? asked Lynch. "Species don't have the same mutation spectrum. There are species whose mutation profiles are more AT rich and others more GC rich. We still don't know the mechanisms behind such divergence in the mutational spectrum."

They may be due to simple differences in chemistry and biophysics.

One general force that may be of relevance is DNA stability, driven by the chemistry of the DNA letters. The forces that keep the DNA ladder intact are called hydrogen bonds. G:C pairs involve three hydrogen bonds, whereas, A:T pairs involve only two.

"The prevailing thought is that more G:C content adds to genome stability," said Lynch.

Another possibility is during reproduction, when the DNA strands intertwine from each parent to make a fertilized egg, mismatches can occur in the base pairing, leading to mistakes that DNA proofreading enzymes have to fix later on. Sometimes, a G can get changed to an A, or a T becomes a C, converting genes during this mismatch repair process.

"That's generally thought to be biased towards Gs and Cs," said Lynch.

Read more at Science Daily

Spider's web inspires removable implant that may control type 1 diabetes

Doctoral students Alan Chiu, left, and Duo An hold a sample of TRAFFIC (Thread-Reinforced Alginate Fiber for Islets enCapsulation). In the background, left to right, are Minglin Ma, Dan Luo, Meredith Silberstein and Dr. James Flanders.
For the more than 1 million Americans who live with type 1 diabetes, daily insulin injections are literally a matter of life and death. And while there is no cure, a Cornell University-led research team has developed a device that could revolutionize management of the disease.

In Type 1 diabetes, insulin-producing pancreatic cell clusters (islets) are destroyed by the body's immune system. The research group, led by assistant professor Minglin Ma from the Department of Biological and Environmental Engineering, has devised an ingenious method for implanting hundreds of thousands of islet cells into a patient. They are protected by a thin hydrogel coating and, more importantly, the coated cells are attached to a polymer thread and can be removed or replaced easily when they have outlived their usefulness.

Transplantation of stem cell-derived, insulin-producing islet cells is an alternative to insulin therapy, but that requires long-term immunosuppressive drug administration. One well-researched approach to avoid the immune system's response is to coat and protect the cells in tiny hydrogel capsules, hundreds of microns in diameter. However, these capsules cannot be taken out of the body easily, since they're not connected to each other, and there are hundreds of thousands of them.

And the ability to remove the transplant is key because of its potential to form tumors.

"When they fail or die, they need to come out," Ma said. "You don't want to put something in the body that you can't take out. With our method, that's not a problem."

Taking inspiration from the way water beads on a spider's web, Ma and his team first attempted to connect the islet cell-containing capsules through a string but realized that it would be better to put the hydrogel layer uniformly around a string instead. That string: an ionized calcium-releasing, nanoporous polymer thread.

This thread -- which the group has dubbed TRAFFIC (Thread-Reinforced Alginate Fiber For Islets enCapsulation) -- was inspired by a spider's web but, according to Ma, is even better because the hydrogel covers the thread uniformly.

"You don't have any gaps between capsules," he said. "With a spider's silk, you still have gaps between the water beads. In our case, gaps would be bad in terms of scar tissue and the like."

This therapy would involve minimally invasive laparoscopic surgery to implant approximately six feet of hydrogel-coated thread into the patient's peritoneal cavity.

TRAFFIC has received patent protection with the help of Danish pharmaceutical giant Novo Nordisk, which developed injectable insulin more than 90 years ago and is a collaborator on the paper. Other co-authors include professor Dan Luo in the Department of Biological and Environmental Engineering, postdoctoral researcher Wei Song, doctoral students Jason Lu and Yehudah Pardo, fiber science postdoc Dahua Shou, nutritional science professor Ling Qi and postdoc Yewei Ji.

Read more at Science Daily

Tabby's Star: Alien megastructure not the cause of dimming of the 'most mysterious star in the universe'

This illustration depicts an uneven ring of dust orbiting KIC 8462852, also known as Boyajian’s Star or Tabby's Star.
A team of more than 200 researchers, including Penn State Department of Astronomy and Astrophysics Assistant Professor Jason Wright and led by Louisiana State University's Tabetha Boyajian, is one step closer to solving the mystery behind the "most mysterious star in the universe." KIC 8462852, or "Tabby's Star," nicknamed after Boyajian, is otherwise an ordinary star, about 50 percent bigger and 1,000 degrees hotter than the Sun, and about than 1,000 light years away. However, it has been inexplicably dimming and brightening sporadically like no other. Several theories abound to explain the star's unusual light patterns, including that an alien megastructure is orbiting the star.

The mystery of Tabby's Star is so compelling that more than 1,700 people donated over $100,000 through a Kickstarter campaign in support of dedicated ground-based telescope time to observe and gather more data on the star through a network of telescopes around the world. As a result, a body of data collected by Boyajian and colleagues in partnership with the Las Cumbres Observatory is now available in a new paper in The Astrophysical Journal Letters.

"We were hoping that once we finally caught a dip happening in real time we could see if the dips were the same depth at all wavelengths. If they were nearly the same, this would suggest that the cause was something opaque, like an orbiting disk, planet, or star, or even large structures in space" said Wright, who is a co-author of the paper, titled "The First Post-Kepler Brightness Dips of KIC 8462852." Instead, the team found that the star got much dimmer at some wavelengths than at others.

"Dust is most likely the reason why the star's light appears to dim and brighten. The new data shows that different colors of light are being blocked at different intensities. Therefore, whatever is passing between us and the star is not opaque, as would be expected from a planet or alien megastructure," Boyajian said.

The scientists closely observed the star through the Las Cumbres Observatory from March 2016 to December 2017. Beginning in May 2017 there were four distinct episodes when the star's light dipped. Supporters from the crowdfunding campaign nominated and voted to name these episodes. The first two dips were named Elsie and Celeste. The last two were named after ancient lost cities -- Scotland's Scara Brae and Cambodia's Angkor. The authors write that in many ways what is happening with the star is like these lost cities.

"They're ancient; we are watching things that happened more than 1,000 years ago," the authors wrote. "They're almost certainly caused by something ordinary, at least on a cosmic scale. And yet that makes them more interesting, not less. But most of all, they're mysterious."

The method in which this star is being studied -- by gathering and analyzing a flood of data from a single target -- signals a new era of astronomy. Citizen scientists sifting through massive amounts of data from the NASA Kepler mission were the ones to detect the star's unusual behavior in the first place. The main objective of the Kepler mission was to find planets, which it does by detecting the periodic dimming made from a planet moving in front of a star, and hence blocking out a tiny bit of starlight. The online citizen science group Planet Hunters was established so that volunteers could help to classify light curves from the Kepler mission and to search for such planets.

"If it wasn't for people with an unbiased look on our universe, this unusual star would have been overlooked," Boyajian said. "Again, without the public support for this dedicated observing run, we would not have this large amount of data."

Now there are more answers to be found. "This latest research rules out alien megastructures, but it raises the plausibility of other phenomena being behind the dimming," Wright said. "There are models involving circumstellar material -- like exocomets, which were Boyajian's team's original hypothesis -- which seem to be consistent with the data we have." Wright also points out that "some astronomers favor the idea that nothing is blocking the star -- that it just gets dimmer on its own -- and this also is consistent with this summer's data."

Read more at Science Daily

A Previously Unknown Group of Ancient Native Americans Was Just Revealed

Reconstruction of the Upward Sun River base camp in what is now Alaska.
When scientists recently sequenced the genome of a six-week-old infant girl who lived 11,500 years ago at an Alaskan site now called Upward Sun River (USR), they expected that her DNA would match the genetic profile of other northern Native American people.

Instead, the genome of the infant — named Xach'itee'aanenh T'eede Gaay, meaning "Sunrise Girl-Child" and called USR1 by scientists — matched no other known ancient population.

"It was very surprising to find that USR1 belonged to a Native American population that was actually distinct from the two main Native American branches to which all Native American genomes sequenced to date belong to," J. Víctor Moreno-Mayar of the University of Copenhagen Center for GeoGenetics told Seeker.

"This means that this population was living up there, isolated from other Native American groups, for a considerably long time," he added.

Moreno-Mayar and his colleagues' findings, published in the journal Nature, support what is known as the Beringian Standstill Hypothesis. The theory holds that while all Native American ancestry can be traced back to a single East Asian source population, some descendants of this group migrated to eastern Beringia — what is now Alaska — and lived there for thousands of years.

The new paper further shows that eastern Beringia remained inhabited even after a separate branch of Native Americans had already been established in unglaciated North America.

Sunrise Girl-Child was one such early Alaskan. Her remains were found, along with those of another younger female infant named Yelkaanenh T'eede Gaay, meaning "Dawn Twilight Girl-Child," during a 2015 excavation of USR in Interior Alaska, the central region of Alaska's territory.

Researchers excavate the Upward Sun River infants.
The excavations were enabled by an agreement signed, in part, by the Healy Lake Tribal Council and the Tanana Chiefs Conference, which is the traditional tribal consortium of the 42 villages of Interior Alaska.

Just 200 years before the young girls' short lifetimes, the last glacial period of the Pleistocene Epoch (2.6 million–11,700 years ago) ended. A popular hypothesis known as the Bering Land Bridge Theory, first proposed in 1590 by the Spanish missionary Fray Jose de Acosta, posits that during the Pleistocene, Beringia was a vast super-continent that extended from Siberia to what is now the Yukon territory of Canada. The western and eastern portions of Beringia were joined by the Bering Land Bridge that was dissected at times by several rivers.

Geological evidence suggests that waters receded during the Late Pleistocene, better exposing the land bridge and easing navigation over it. Animals, including humans, could likely just walk over the natural bridge until about 10,500 years ago, when waters of the Bering Strait and the Chukchi Sea covered it.

Sunrise Girl-Child, Dawn Twilight Girl-Child, and their families stayed in Beringia, so the researchers have decided to call the population that these early people represent the Ancient Beringians.

"From archaeological data, we can say that the Ancient Beringians were likely present in Alaska from at least 12,500 to 6,000 years ago," co-lead author Ben Potter, a professor of anthropology at the University of Alaska Fairbanks, told Seeker.

"Interestingly," he added, "the tools associated with this group, including microblades, are very similar and historically related to the widespread microblade-using cultures in Northeast Asia, found in Japan, Korea, northern China and Siberia."

The genetic data shows that the two infants were probably first cousins. The DNA samples of Dawn Twilight Girl-Child were not sufficient for extensive further analysis, however, so the researchers instead focused on Sunrise Girl-Child.

Moreno-Mayar, senior author Eske Willerslev and their team compared Sunrise Girl-Child's genome sequence to a set of both ancient and contemporary genomes. The comparison suggests that the ancestors of Ancient Beringians and those of other Native Americans descended from a single founding population that first split from East Asians around 36,000 years ago, although gene flow with North Eurasians — possibly centered around Lake Baikal in southern Siberia — continued until about 25,000 years ago.

Cove at Lake Baikal in the mountainous Russian region of southern Siberia.
The founding population then split into two groups approximately 20,000 years ago, the genetic evidence suggests. According to the researchers, these groups were the newly identified Ancient Beringians and the ancestors of all other Native Americans. There are two possible explanations for where this split occurred, and how the separation affected subsequent migrations.

The first possible scenario is that Ancient Beringians and the ancestors of other Native Americans diverged somewhere in Asia 20,000 years ago. Both populations then could have moved along different routes, or at different times, through Beringia.

The second possible scenario is that Ancient Beringians and the ancestors of other Native Americans diverged in what is now Alaska 20,000 years ago. The latter group then could have moved south of the ice sheets at a later date.

"Regardless of whether scenario one or two is correct, there was a single population of ancestral Native Americans, and they at least migrated to an area where they were genetically isolated from ancestral East Asians and ancestral North Eurasians," Potter said.

Moreno-Mayar noted, "By 20,000 years ago, most of North America was covered by two vast glaciers, so whenever Native Americans made it to Alaska, they most likely still had to wait until a viable route into mid-latitude America was made available."

As for why people then migrated so much, prior research suggests at least one reason. They appear to have been following the movements of prey animals. These could have included migrating schools of fish and/or terrestrial mammals such as woolly mammoths, steppe bison, and caribou.

Geological and ecological evidence suggests that the northwest American coastal route was ice-free and potentially navigable by 16,000 years ago, while the American interior was ice-free by 15,000–14,000 years ago.

A debate now exists as to precisely when humans first colonized the Americas and if those first routes were over land or water. Moreno-Mayar and his team admit that the genetic evidence cannot yet provide definitive answers to these questions.

Archaeological findings ranging from everything to an ancient fishhook to fossilized excrement provide clues, though. Evidence for human settlements at Triquet Island, Paisley Caves, and the Channel Islands along the western North American coast all date to around 13,000–14,000 years ago.

The sites Quebrada Jaguay, Quebrada Tacahuay, Quebrada Santa Julia, and Monte Verde along the western South American coast date to about 13,000 years ago.

On the eastern coast of North America, the site Page-Ladson in Florida dates to approximately 14,500 years ago. Stone tools and mastodon remains suggest that humans there were hunting big game. Yet another early site is Huaca Prieta, north of Peru, which dates to 15,000–14,500 years ago.

Taken together, the genetic and archaeological evidence then suggests that people first expanded out of Beringia by about 16,000 years ago.

Archaeologist Todd Braje of San Diego State University, who recently co-authored a paper published in Science on Native Americans, told Seeker that "the first Americans likely arrived along the Pacific Coast — not crossing the open Pacific but migrating along the Pacific Rim in boats in a step-wise fashion."

1914 image showing canoes of the Kwakiutl, an indigenous people from the Pacific Northwest Coast.
Michael Waters of Texas A&M University also favors the over water migration theory.

"The only logical way people could have come to Florida by 14,600 years ago is if their ancestors entered the Americas by boat along the Pacific Coast," Waters told Seeker. "They could have traveled by boat to central Mexico, crossed and come along the Gulf Coast. They could have entered the Americas via the Columbia River and then traveled inland to the Mississippi River and followed it down and entered the Gulf Coast, eventually making their way to Florida."

Whether or not the first continental Americans arrived in such a way, or by crossing the Bering Land Bridge, remains a mystery for now.

Even more puzzling is the controversial 130,000-year-old Cerutti Mastodon site in coastal San Diego County, California. Its discovery was announced in an April 2017 paper published in Nature. Lead author Steven Holen of the Center for American Paleolithic Research and his team reported finding "hammerstones and stone anvils" along with "spiral-fractured bone and molar fragments" of a mastodon that they believe was butchered.

"We don’t know how this animal died, " University of Michigan paleontologist Daniel Fisher, a co-author of the paper on the Cerutti Mastodon site, remarked to Seeker. "We don’t know whether humans were part of that death. All that we know is that humans came along some time after the death, and they very strategically set up a process involving the harvesting of marrow from the long bones and the recovery of dense fragments of bone that they could use as raw material for producing tools."

Such an early settlement of the Americas is not at present widely supported by other scientists. If additional evidence is found to support the claims, however, this could mean that anatomically modern humans were not the first members of the genus Homo to arrive in the New World.

Moreno-Mayar and his team did find that Sunrise Girl-Child/USR1's genome contained Neanderthal DNA. All people of Native American heritage also retain Neanderthal DNA.

"Interestingly, we found that USR1 carries a slight excess of Denisovan ancestry compared to some Native American groups," Moreno-Mayar said.

Read more at Seeker

Jan 2, 2018

Supermassive black holes control star formation in large galaxies

Young galaxies blaze with bright new stars forming at a rapid rate, but star formation eventually shuts down as a galaxy evolves. A new study, published January 1, 2018, in Nature, shows that the mass of the black hole in the center of the galaxy determines how soon this "quenching" of star formation occurs.

Every massive galaxy has a central supermassive black hole, more than a million times more massive than the sun, revealing its presence through its gravitational effects on the galaxy's stars and sometimes powering the energetic radiation from an active galactic nucleus (AGN). The energy pouring into a galaxy from an active galactic nucleus is thought to turn off star formation by heating and dispelling the gas that would otherwise condense into stars as it cooled.

This idea has been around for decades, and astrophysicists have found that simulations of galaxy evolution must incorporate feedback from the black hole in order to reproduce the observed properties of galaxies. But observational evidence of a connection between supermassive black holes and star formation has been lacking, until now.

"We've been dialing in the feedback to make the simulations work out, without really knowing how it happens," said Jean Brodie, professor of astronomy and astrophysics at UC Santa Cruz and a coauthor of the paper. "This is the first direct observational evidence where we can see the effect of the black hole on the star formation history of the galaxy."

The new results reveal a continuous interplay between black hole activity and star formation throughout a galaxy's life, affecting every generation of stars formed as the galaxy evolves.

Led by first author Ignacio Martín-Navarro, a postdoctoral researcher at UC Santa Cruz, the study focused on massive galaxies for which the mass of the central black hole had been measured in previous studies by analyzing the motions of stars near the center of the galaxy. To determine the star formation histories of the galaxies, Martín-Navarro analyzed detailed spectra of their light obtained by the Hobby-Eberly Telescope Massive Galaxy Survey.

Spectroscopy enables astronomers to separate and measure the different wavelengths of light from an object. Martín-Navarro used computational techniques to analyze the spectrum of each galaxy and recover its star formation history by finding the best combination of stellar populations to fit the spectroscopic data. "It tells you how much light is coming from stellar populations of different ages," he said.

When he compared the star formation histories of galaxies with black holes of different masses, he found striking differences. These differences only correlated with black hole mass and not with galactic morphology, size, or other properties.

"For galaxies with the same mass of stars but different black hole mass in the center, those galaxies with bigger black holes were quenched earlier and faster than those with smaller black holes. So star formation lasted longer in those galaxies with smaller central black holes," Martín-Navarro said.

Other researchers have looked for correlations between star formation and the luminosity of active galactic nuclei, without success. Martín-Navarro said that may be because the time scales are so different, with star formation occurring over hundreds of millions of years, while outbursts from active galactic nuclei occur over shorter periods of time.

A supermassive black hole is only luminous when it is actively gobbling up matter from its host galaxy's inner regions. Active galactic nuclei are highly variable and their properties depend on the size of the black hole, the rate of accretion of new material falling onto the black hole, and other factors.

"We used black hole mass as a proxy for the energy put into the galaxy by the AGN, because accretion onto more massive black holes leads to more energetic feedback from active galactic nuclei, which would quench star formation faster," Martín-Navarro explained.

The precise nature of the feedback from the black hole that quenches star formation remains uncertain, according to coauthor Aaron Romanowsky, an astronomer at San Jose State University and UC Observatories.

Read more at Science Daily

Social susceptibility: Leader-follower dynamics of influential individuals in a social group

Stegodyphus dumicola Previous Pause Next 3 of 3 Stegodyphus dumicola spiders make fast work of a captured ant.
This is the story of a spider, small but bold.

This particular arachnid, in fact, has helped to debunk the Great Man Theory, a 19th-century notion positing that highly influential individuals use their power -- be it personal charisma, intelligence, wisdom or political skill -- to maximize their impact in shaping the course of history.

How better to test that theory than with Stegodyphus dumicola?

Working with these African social spiders in their native habitats, UC Santa Barbara evolutionary ecologist Jonathan Pruitt created a model for exploring leadership dynamics and social susceptibility -- the tendency of individuals to change their behavior in response to interactions with influential group members. He found that the social susceptibility of the population majority -- and not the influence of key individuals -- is what drives leadership. The results appear in the journal Current Biology.

"We knew from previous studies that in a social group, the rare presence of bold individuals -- who constitute between 1 and 5 percent of a population -- radically changes collective behavior," said Pruitt, an associate professor in UCSB's Department of Ecology, Evolution, and Marine Biology (EEMB). "This new research evaluates whether the rise and fall of societies could be contingent on having just one or a few of these key individuals and whether the profitability of their presence might change based on the environment."

Pruitt and his team set up 240 experimental societies across two different precipitation gradients in Africa: one in the Namib Desert heading north to Angola and a second from the Kalahari Desert heading east to Lesotho. Some of these colonies contained particularly bold spiders (putative leaders) and some did not. The researchers then monitored these colonies' behavior and survival for the next six months.

The scientists determined the boldness of individual spiders by exposing them to a directional jet of air. Because S. dumicola cannot see well, they interpret air movement as a predator such as a bird, bat or wasp. Their response? A death-feigning posture wherein they tuck their legs and huddle into a ball. Bold individuals don't hide for long, but shy ones can take 20 minutes to an hour to recover.

"We wanted to see whether the presence of these particularly bold individuals changed how a society behaves collectively, and whether the aggressiveness of a society determined the likelihood of its members surviving or dying together in a sudden extinction event," Pruitt explained. "We found no association between how a society behaved and whether it lived or died at wet sites; nor did bold individuals have a large effect on colony behavior at these sites. However, we found a very tight association between the presence of bold individuals and societal aggressiveness at arid sites, and colonies containing bold individuals were far more likely to survive in these habitats."

The fact that the same rare personality types existed at both dry and wet sites, but varied in their degree of apparent social influence across these habitats, allowed the investigators to decipher, for the first time, whether it is the traits of the leaders or the social context in which they reside that truly drives their influence. As it turned out, the population majority determined whether these key group members could emerge at all, thus debunking the Great Man Theory and its parallel hypotheses regarding "keystone individuals" in a variety of animal societies. Instead, social influence appears to emerge from shy, generic spiders.

"When we took bold individuals from a wet site, where they didn't have any social influence, and put them with shy spiders from an arid site, those shy individuals were willing to follow the bold ones regardless of where they were from," Pruitt noted. "So, it wasn't the unique social influence of bold individuals from arid sites but rather the social susceptibility of the population majority that made an advantageous social order emerge."

To further scrutinize their findings, the scientists substituted bold individuals of another independently evolved species of social spider that occurs in southern Africa. Adding bold Stegodyphus mimosarum to groups of shy spiders in both wet and dry sites reproduced the same result at wet sites: The shy individuals were unresponsive to bold foreigners. However, the shy spiders from dry sites, who were used to food-restricted environments, responded equally to bold spiders of both species. Thus, for arid S. dumicola, anything even coarsely approximating the phenotype of a leader is enough to instigate followership in these populations.

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Diabetes drug 'significantly reverses memory loss' in mice with Alzheimer's

A drug developed for diabetes could be used to treat Alzheimer's after scientists found it "significantly reversed memory loss" in mice through a triple method of action.

The research, published in Brain Research, could bring substantial improvements in the treatment of Alzheimer's disease through the use of a drug originally created to treat type 2 diabetes.

Lead researcher Professor Christian Holscher of Lancaster University in the UK said the novel treatment "holds clear promise of being developed into a new treatment for chronic neurodegenerative disorders such as Alzheimer's disease."

Alzheimer's disease is the most common cause of dementia and the numbers are expected to rise to two million people in the UK by 2051 according to Alzheimer's Society, who part- funded the research.

Dr Doug Brown, Director of Research and Development at Alzheimer's Society, said: ""With no new treatments in nearly 15 years, we need to find new ways of tackling Alzheimer's. It's imperative that we explore whether drugs developed to treat other conditions can benefit people with Alzheimer's and other forms of dementia. This approach to research could make it much quicker to get promising new drugs to the people who need them."

Although the benefits of these 'triple agonist' drugs have so far only been found in mice, other studies with existing diabetes drugs such as liraglutide have shown real promise for people with Alzheimer's, so further development of this work is crucial."

This is the first time that a triple receptor drug has been used which acts in multiple ways to protect the brain from degeneration. It combines GLP-1, GIP and Glucagon which are all growth factors. Problems with growth factor signalling have been shown to be impaired in the brains of Alzheimer's patients.

The study used APP/PS1 mice, which are transgenic mice that express human mutated genes that cause Alzheimer's. Those genes have been found in people who have a form of Alzheimer's that can be inherited. Aged transgenic mice in the advanced stages of neurodegeneration were treated.

In a maze test, learning and memory formation were much improved by the drug which also:-

  • enhanced levels of a brain growth factor which protects nerve cell functioning
  • reduced the amount of amyloid plaques in the brain linked with Alzheimer's
  • reduced both chronic inflammation and oxidative stress
  • slowed down the rate of nerve cell loss

Professor Holscher said: "These very promising outcomes demonstrate the efficacy of these novel multiple receptor drugs that originally were developed to treat type 2 diabetes but have shown consistent neuro- protective effects in several studies."

"Clinical studies with an older version of this drug type already showed very promising results in people with Alzheimer's disease or with mood disorders"

"Here we show that a novel triple receptor drug shows promise as a potential treatment for Alzheimer's but further dose-response tests and direct comparisons with other drugs have to be conducted in order to evaluate if this new drugs is superior to previous ones."

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Speed breeding technique sows seeds of new green revolution

Speed breeding means that it is now possible to grow as many as 6 generations of wheat every year -- a threefold increase on the techniques currently used by breeders and researchers.
Pioneering new technology is set to accelerate the global quest for crop improvement in a development which echoes the Green Revolution of the post war period.

The speed breeding platform developed by teams at the John Innes Centre, University of Queensland and University of Sydney, uses a glasshouse or an artificial environment with enhanced lighting to create intense day-long regimes to speed up the search for better performing crops.

Using the technique, the team has achieved wheat generation from seed to seed in just 8 weeks. These results appear today in Nature Plants.

This means that it is now possible to grow as many as 6 generations of wheat every year -- a threefold increase on the shuttle-breeding techniques currently used by breeders and researchers.

Dr Brande Wulff of the John Innes Centre, Norwich, a lead author on the paper, explains why speed is of the essence:

"Globally, we face a huge challenge in breeding higher yielding and more resilient crops. Being able to cycle through more generations in less time will allow us to more rapidly create and test genetic combinations, looking for the best combinations for different environments."

For many years the improvement rates of several staple crops have stalled, leading to a significant impediment in the quest to feed the growing global population and address the impacts of climate change.

Speed breeding, says Dr Wulff, offers a potential new solution to a global challenge for the 21st century.

"People said you may be able to cycle plants fast, but they will look tiny and insignificant, and only set a few seed. In fact, the new technology creates plants that look better and are healthier than those using standard conditions. One colleague could not believe it when he first saw the results."

The exciting breakthrough has the potential to rank, in terms of impact, alongside the shuttle-breeding techniques introduced after the second world war as part of the green revolution.

Dr Wulff goes on to say: "I would like to think that in 10 years from now you could walk into a field and point to plants whose attributes and traits were developed using this technology."

This technique uses fully controlled growth environments and can also be scaled up to work in a standard glass house. It uses LED lights optimised to aid photosynthesis in intensive regimes of up to 22 hours per day.

LED lights significantly reduce the cost compared to sodium vapour lamps which have long been in widespread use but are ineffective because they generate much heat and emit poor quality light.

The international team also prove that the speed breeding technique can be used for a range of important crops. They have achieved up to 6 generations per year for bread wheat, durum wheat, barley, pea, and chickpea; and four generations for canola (a form of rapeseed). This is a significant increase compared with widely used commercial breeding techniques.

Speed breeding, when employed alongside conventional field-based techniques, can be an important tool to enable advances in understanding the genetics of crops.

"Speed breeding as a platform can be combined with lots of other technologies such as CRISPR gene editing to get to the end result faster," explains Dr Lee Hickey from the University of Queensland.

The study shows that traits such as plant pathogen interactions, plant shape and structure, and flowering time can be studied in detail and repeated using the technology.

The speed breeding technology has been welcomed by wheat breeders who have become early adopters.

Ruth Bryant, Wheat Pathologist at RAGT Seeds Ltd, Essex, UK, said: "Breeders are always looking for ways to speed up the process of getting a variety to market so we are really interested in the concept of speed breeding. We are working closely with Dr Wulff's group at the John Innes Centre to develop this method in a commercial setting."

Dr Allan Rattey, a wheat crop breeder with Australian company Dow AgroSciences, has used the technology to breed wheat with tolerance to pre-harvest sprouting (PHS) a major problem in Australia.

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