New cosmological constraints on the nature of dark matter

New research has revealed the distribution of dark matter in never before seen detail, down to a scale of 30,000 light-years. The observed distribution fluctuations provide better constraints on the nature of dark matter.

Mysterious dark matter accounts for most of the matter in the Universe. Dark matter is invisible and makes itself know only through its gravitational effects. Dark matter has never been isolated in a laboratory, so researchers must rely on "natural experiments" to study it.

One type of natural experiment is a gravitational lens. Sometimes by random chance, two objects at different distances in the Universe will lie along the same line-of-sight when seen from Earth. When this happens, the spatial curvature caused by the matter around the foreground object acts like a lens, bending the path of light from the background object and making a lensed image. However, it is difficult to achieve the high resolution to detect clumps of dark matter which are less massive than galaxies in natural experiments, so the exact nature of dark matter has been poorly constrained.

A team of Japanese researchers led by Professor Kaiki Taro Inoue at Kindai University used ALMA (Atacama Large Millimeter/submillimeter Array) to study the gravitational lens system known as MG J0414+0534 in the direction of the constellation Taurus. In this system, the foreground object forms not one, but four images of the background object due to the gravitational force of a massive galaxy acting on the light. With the help of the bending effect and their new data analysis method, the team was able to detect fluctuations in the dark matter distribution along the line-of-sight in higher resolution than ever before, down to a scale of 30,000 light-years.

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Stability inspection for West Antarctica shows: marine ice sheet is not destabilized yet, but possibly on a path to tipping

Antarctica's vast ice masses seem far away, yet they store enough water to raise global sea levels by several meters. A team of experts from European research institutes has now provided the first systematic stability inspection of the ice sheet's current state. Their diagnosis: While they found no indication of irreversible, self-reinforcing retreat of the ice sheet in West Antarctica yet, global warming to date could already be enough to trigger the slow but certain loss of ice over the next hundreds to thousands of years.

"With more and more ice being lost in Antarctica over the last years, concerns have been raised whether a tipping point has already been crossed and an irreversible, long-term collapse of the West Antarctic Ice Sheet has already been initiated," explains Ronja Reese from the Potsdam Institute for Climate Impact Research (PIK) and the Northumbria University, Newcastle. "The results of our studies deliver two messages: First, while a number of glaciers in Antarctica are retreating at the moment, we find no indication of irreversible, self-reinforcing retreat yet, which is reassuring. However, our calculations also clearly indicate that an onset of an irreversible retreat of the ice sheet in West Antarctica is possible if the current state of the climate is sustained."

The main driver of ice loss in West Antarctica is relatively warm ocean water that amplifies melting underneath the ice shelves, which are the floating extensions of the grounded ice sheet. Melting of these ice shelves can enhance ice loss as it speeds up the grounded sections of the ice sheet. That is why the Antarctic margin with its grounding lines -- the zone where the grounded and the floating ice are connected -- is a key indicator of ice sheet health. An accelerated retreat of the grounding lines could indicate a forthcoming collapse of large marine regions of West Antarctica's ice sheet -- those parts of the ice sheet that are grounded below sea level.

Evolving over 10,000 years, triggered today: irreversible ice-loss and sea-level rise

Using state-of-the-art ice sheet models, the researchers not only conducted a thorough inspection of signs of irreversible retreat of marine sectors of the Antarctic ice sheet at present, they also ran simulations to investigate how the ice sheet would evolve over the next 10,000 years if current conditions remained unchanged. These hypothetical experiments indicate that even with no additional warming beyond what we have already experienced today, an irreversible collapse of some marine regions of West Antarctica's ice sheet is possible. Because the ice reacts to changes in temperature very slowly, the authors find that collapse occurs in their simulations at the earliest in 300 to 500 years from now, under current climate forcing. A full collapse would take centuries to millennia.

"The thing with sea-level rise from Antarctica is not that changes would happen overnight as an immediate threat to coastal communities. The process of melting would happen over hundreds or thousands of years. However, the cause could be human actions today, as they have the power to trigger and commit a future of 10,000 years to several meters of global sea-level rise. And stronger warming in the future would even speed up this process," Julius Garbe from PIK stresses.

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Dog diversity unveiled by international DNA database

An international consortium of scientists, led by Jeff Kidd, Ph.D. of University of Michigan, Jennifer R. S. Meadows of Uppsala University in Sweden, and Elaine A. Ostrander, Ph.D. of the NIH National Human Genome Research Institute, is using an unprecedentedly large database of canine DNA to take an unbiased look at how our furry friends evolved into the various breeds we know and love.

A new paper, published in the journal Genome Biology, outlines what the Dog10K project discovered after sequencing the genomes of close to 2000 samples from 321 different breed dogs, wild dogs, coyotes, and wolves, and comparing them to one reference sample -- that of a German Shepherd named Mischka.

Analyzing more than 48 million pieces of genetic information, they discovered that each breed dog had around 3 million single nucleotide polymorphism differences. These SNPs or "snips" are what account for most of the genetic variation among people and dogs alike. They also found 26,000 deleted sequences that were present in the German Shepherd but not in the comparison breed and 14,000 that were in the compared breed but missing from Mischka's DNA.

"We did an analysis to see how similar the dogs were to each other, and it ended up that we could divide them into around 25 major groups that pretty much match up with what people would have expected based on breed origin, the dogs' type, size and coloration," said Kidd, a professor of Human Genetics and Computational Medicine and Bioinformatics at the U-M Medical School.

Most of the varying genes, he added, had to do with morphology, confirming that the breed differences were driven by how the dogs look.

Relative to dogs, wolves had around 14 percent more variation. And wild village dogs -- dogs that live amongst people in villages or cities but aren't kept as pets -- exhibited more genetic variation than breed dogs.

The data set, which was processed using the Great Lakes high-performing computing cluster at U-M, also revealed an unusual amount of retrogenes, a new gene that forms when RNA gets turned back into DNA and inserted back into the genome in a different spot. The study found 926 retrogenes, the most famous of which, says Kidd, is a retrogene called FGF4, which results in the short leg phenotype seen in dachshunds and corgis.

"Dogs tend to have an increased amount of retrogenes which have resulted in mutations that were selected for, that perhaps people found cute and bred more of," said Kidd. His lab is attempting to figure out why retrogenes and insertions happen so frequently in dogs.

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Study hints at the existence of the closest black holes to Earth in the Hyades star cluster

A paper published in the journal Monthly Notices of the Royal Astronomical Society hints at the existence of several black holes in the Hyades cluster -- the closest open cluster to our solar system -- which would make them the closest black holes to Earth ever detected. The study results from a collaboration between a group of scientists led by Stefano Torniamenti, from the University of Padua (Italy), with the significant participation of with Mark Gieles, ICREA professor at the Faculty of Physics, the Institute of Cosmos Sciences of the University of Barcelona (ICCUB) and the Institute of Space Studies of Catalonia (IEEC), and Friedrich Anders (ICCUB-IEEC).

Specifically, the finding took place during a research stay of the expert Stefano Torniamenti at the ICCUB, one of the research units that make up the IEEC.

Black holes in the Hyades star cluster?

Since their discovery, black holes have been one of the most mysterious and fascinating phenomena in the Universe and have become the object of study for researchers all over the world. This is particularly true for small black holes because they have been observed during the detection of gravitational waves. Since the detection of the first gravitational waves in 2015, experts have observed many events that correspond to mergers of low-mass black hole pairs.

For the published study, the team of astrophysicists used simulations that track the motion and evolution of all the stars in the Hyades -- located at a distance from the Sun of about 45 parsecs or 150 light-years -- to reproduce their current state.

Open clusters are loosely bound groups of hundreds of stars that share certain properties such as age and chemical characteristics. The simulation results were compared with the actual positions and velocities of the stars in the Hyades, which are now known precisely from observations made by the European Space Agency's (ESA) Gaia satellite.

"Our simulations can only simultaneously match the mass and size of the Hyades if some black holes are present at the centre of the cluster today (or until recently)," says Stefano Torniamenti, postdoctoral researcher at the University of Padua and first author of the paper.

The observed properties of the Hyades are best reproduced by simulations with two or three black holes at present, although simulations where all the black holes have been ejected (less than 150 million years ago, roughly the last quarter of the cluster's age) can still give a good match, because the evolution of the cluster could not erase the traces of its previous black hole population.

The new results indicate that the Hyades-born black holes are still inside the cluster, or very close to the cluster. This makes them the closest black holes to the Sun, much closer than the previous candidate (namely the black hole Gaia BH1, which is 480 parsecs from the Sun).

In recent years, the breakthrough of the Gaia space telescope has made it possible for the first time to study the position and velocity of open cluster stars in detail and to identify individual stars with confidence.

"This observation helps us understand how the presence of black holes affects the evolution of star clusters and how star clusters in turn contribute to gravitational wave sources," says Mark Gieles, a member of the UB Department of Quantum Physics and Astrophysics and host of the first author in Barcelona. "These results also give us insight into how these mysterious objects are distributed across the galaxy."

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Beaver activity in the Arctic increases emission of methane greenhouse gas

The climate-driven advance of beavers into the Arctic tundra is causing the release of more methane -- a greenhouse gas -- into the atmosphere.

Beavers, as everyone knows, like to make dams. Those dams cause flooding, which inundates vegetation and turns Arctic streams and creeks into a series of ponds. Those beaver ponds and surrounding inundated vegetation can be devoid of oxygen and rich with organic sediment, which releases methane as the material decays.

Methane is also released when organics-rich permafrost thaws as the result of heat carried by the spreading water.

A study linking Arctic beavers to an increase in the release of methane was published in July in Environmental Research Letters.

The lead author is Jason Clark, a former postdoctoral fellow at the University of Alaska Fairbanks Geophysical Institute. Research Professor Ken Tape, also of the Geophysical Institute, was Clark's adviser and is a co-author. Other co-authors include Benjamin Jones, a research assistant professor at the UAF Institute of Northern Engineering; and researchers from the National Park Service and NASA's Jet Propulsion Laboratory.

Tape has done extensive research about the northward migration of beavers and their resultant impact on the Arctic environment.

"What we found is that there are lots of methane hotspots right next to ponds and they start to diminish as you go away from the pond," he said.

The new study is the first to link large numbers of new beaver ponds to methane emissions at the landscape scale. It suggests that beaver engineering in the Arctic will at least initially increase methane release.

"We say 'initially' because that's the data we have," Tape said. "What the longer-term implications are, we don't know."

As a greenhouse gas, methane is 25 times more potent than carbon dioxide at trapping heat in Earth's atmosphere.

It accounts for about 20 percent of global greenhouse gas emissions, according to the U.S. Environmental Protection Agency. The agency says human activities have more than doubled atmospheric methane concentrations in the past two centuries.

The new research focused on 166 square miles of the lower Noatak River basin in Northwest Alaska. Data was obtained by airborne hyperspectral imaging through NASA's Arctic-Boreal Vulnerability Experiment program. That program and the National Science Foundation funded the research.

Hyperspectral cameras image an area in hundreds of wavelengths across the electromagnetic spectrum, including many not visible to the human eye. That differs from other cameras, which typically only image in the primary colors of red, green and blue.

The researchers compared the location of methane hot spots to the locations of 118 beaver ponds and to a number of nearby unaffected stream reaches and lakes. They analyzed the area up to approximately 200 feet from the perimeter of each water body and found a "significantly greater" number of methane hot spots around beaver ponds.

"We have these datasets that largely overlap, in space and mostly in time," Tape said. "It's kind of a simple design relying on a new tool."

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Engineers design more powerful RNA vaccines

RNA vaccines against Covid-19 have proven effective at reducing the severity of disease. However, a team of researchers at MIT is working on making them even better. By tweaking the design of the vaccines, the researchers showed that they could generate Covid-19 RNA vaccines that produce a stronger immune response, at a lower dose, in mice.

Adjuvants are molecules commonly used to increase the immune response to vaccines, but they haven't yet been used in RNA vaccines. In this study, the MIT researchers engineered both the nanoparticles used to deliver the Covid-19 antigen, and the antigen itself, to boost the immune response, without the need for a separate adjuvant.

If further developed for use in humans, this type of RNA vaccine could help to reduce costs, reduce the dosage needed, and potentially lead to longer-lasting immunity. The researchers' tests also showed that when delivered intranasally, the vaccine induced a strong immune response when compared to the response elicited by traditional, intramuscular vaccination.

"With intranasal vaccination, you might be able to kill Covid at the mucus membrane, before it gets into your body," says Daniel Anderson, a professor in MIT's Department of Chemical Engineering, a member of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and the senior author of the study. "Intranasal vaccines may also be easier to administer to many people, since they don't require an injection."

The researchers believe that the effectiveness of other types of RNA vaccines that are now in development, including vaccines for cancer, could be improved by incorporating similar immune-stimulating properties.

Former MIT postdoc Bowen Li, who is now an assistant professor at the University of Toronto; graduate student Allen Jiang; and former MIT postdoc Idris Raji, who was a research fellow at Boston Children's Hospital, are the lead authors of the new study, which appears today in Nature Biomedical Engineering. The research team also includes Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, and several other MIT researchers.

Boosting immunity

RNA vaccines consist of a strand of RNA that encodes a viral or bacterial protein, also called an antigen. In the case of Covid-19 vaccines, this RNA codes for a segment of the virus's spike protein. That RNA strand is packaged in a lipid nanoparticle carrier, which protects the RNA from being broken down in the body and helps it get into cells.

Once delivered into cells, the RNA is translated into proteins that the immune system can detect, generating antibodies and T cells that will recognize the protein if the person later becomes infected with the SARS-CoV-2 virus.

The original Covid-19 RNA vaccines developed by Moderna and Pfizer/BioNTech provoked strong immune responses, but the MIT team wanted to see if they could make them more effective by engineering them to have immune stimulatory properties.

In this study, the researchers employed two different strategies to boost the immune response. For the first, they focused on a protein called C3d, which is part of an arm of the immune response known as the complement system. This set of proteins helps the body fight off infection, and C3d's role is to bind to antigens and amplify the antibody response to those antigens. For many years, scientists have been evaluating the use of C3d as a molecular adjuvant for vaccines made from proteins, such as the DPT vaccine.

"With the promise of mRNA technologies being realized with the Covid vaccines, we thought that this would be a fantastic opportunity to see if C3d might also be able to play a role as an adjuvant in mRNA vaccine systems," Jiang says.

To that end, the researchers engineered the mRNA to encode the C3d protein fused to the antigen, so that both components are produced as one protein by cells that receive the vaccine.

In the second phase of their strategy, the researchers modified the lipid nanoparticles used to deliver the RNA vaccine, so that in addition to helping with RNA delivery, the lipids also intrinsically stimulate a stronger immune response.

To identify lipids that would work best, the researchers created a library of 480 lipid nanoparticles with different types of chemistries. All of these are "ionizable" lipids, which become positively charged when they enter acidic environments. The original Covid RNA vaccines also included some ionizable lipids because they help the nanoparticles to self-assemble with RNA and they help target cells to take up the vaccine.

"We understood that nanoparticles themselves could be immunostimulatory, but we weren't quite sure what the chemistry was that was needed to optimize that response. So instead of trying to make the perfect one, we made a library and evaluated them, and through that we identified some chemistries that seemed to improve their response," Anderson says.

Toward intranasal vaccines

The researchers tested their new vaccine, which included both RNA-encoded C3d and a top-performing ionizable lipid identified from their library screen, in mice. They found that mice injected with this vaccine produced 10 times more antibodies than mice given unadjuvanted Covid RNA vaccines. The new vaccine also provoked a stronger response among T cells, which play important roles in combating the SARS-CoV-2 virus.

"For the first time, we've demonstrated a synergistic boost in immune responses by engineering both the RNA and its delivery vehicles," Li says. "This prompted us to investigate the feasibility of administering this new RNA vaccine platform intranasally, considering the challenges presented by the mucociliary blanket barrier in the upper airways."

When the researchers delivered the vaccine intranasally, they observed a similarly strong immune response in the mice. If developed for use in people, an intranasal vaccine could potentially offer enhanced protection against infection because it would generate an immune response within the mucosal tissues that line the nasal passages and lungs.

Because self-adjuvanting vaccines elicit a stronger response at a lower dose, this approach could also help to reduce the cost of vaccine doses, which might allow them to reach more people, especially in developing nations, the researchers say.

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Ravenous black hole consumes three Earths'-worth of star every time it passes

A star like our own Sun in a nearby galaxy is gradually being eaten away by a small but ravenous black hole, losing the equivalent mass of three Earths every time it passes close.

The discovery by University of Leicester astronomers is reported today (7 September) in Nature Astronomy and provides a 'missing link' in our knowledge of black holes disrupting orbiting stars. It suggests a whole menagerie of stars in the process of being consumed that still lie undiscovered.

The team was supported by the UK Space Agency and the UK Science and technology Facilities Council (STFC).

The astronomers were alerted to the star by a bright X-ray flash that seemed to come from the centre of the nearby galaxy 2MASX J02301709+2836050, around 500 million light-years away from the Milky Way. Named Swift J0230, it was spotted the moment it happened for the first time using a new tool developed by the scientists for the Neil Gehrels Swift Observatory. They rapidly scheduled further Swift observations of it, finding that instead of decaying away as expected, it would shine brightly for 7-10 days and then abruptly switch off, repeating this process roughly every 25 days.

Similar behaviour has been observed in what are termed quasi-periodic eruptions and periodic nuclear transients, where a star has material ripped away by a black hole as its orbit takes it close by, but they differ in how often they erupt, and in whether it is in X-rays or optical light that the explosion is predominant. The regularity of Swift J0230's emissions fell between the two, suggesting that it forms the 'missing link' between the two types of outburst.

Using the models proposed for these two classes of event as a guide, the scientists concluded that the Swift J0230 outburst represents a star of a similar size to our own sun in an elliptical orbit around a low-mass black hole at the centre of its galaxy. As the star's orbit takes it close to the intense gravitational pull of the black hole, material equivalent to the mass of three Earths is wrenched from the atmosphere of the star and heated up as it falls into the black hole. The intense heat, around 2 million degrees Celsius, releases a huge amount of X-rays which were first picked up by the Swift satellite.

Lead author Dr Phil Evans of the University of Leicester School of Physics and Astronomy said: "This is the first time we've seen a star like our Sun being repeatedly shredded and consumed by a low mass black hole. So-called 'repeated, partial tidal disruption' events are themselves quite a new discovery and seem to fall into two types: those that outburst every few hours, and those that outburst every year or so. This new system falls right into the gap between these, and when you run the numbers, you find the types of objects involved fall nicely into place too."

Dr Rob Eyles-Ferris, who works with Dr Evans on the Swift satellite, recently completed his PhD at Leicester, which included the study of stars being disrupted by black holes. He explains: "In most of the systems we've seen in the past the star is completely destroyed. Swift J0230 is an exciting addition to the class of partially-disrupted stars as it shows us that the two classes of these objects already found are really connected, with our new system giving us the missing link."

Dr Kim Page from the University of Leicester, who worked on the data analysis for the study, said: "Given that we found Swift J0230 within a few months of enabling our new transient-hunting tool, we expect that there are a lot more objects like this out there, waiting to be uncovered."

Dr Chris Nixon is a theoretical astrophysicist who recently moved from the University of Leicester to the University of Leeds. He led the theoretical interpretation of this event. His research is funded by the UK Science and Technology Facilities Council and the Leverhulme Trust.

They estimate that the black hole is around 10,000 to 100,000 times the mass of our sun, which is quite small for the supermassive black holes usually found at the centre of galaxies. The black hole at the centre of our own galaxy is thought to be 4 million solar masses, while most are in the region of 100 million solar masses.

It is the first discovery to be made using the new transient detector for the Swift satellite, developed by the University of Leicester team and running on their computers. When an extreme event takes place, causing an X-ray burst in a region of the sky where there were previously no X-rays, astronomers call it an astronomical X-ray transient. Despite the extreme events they herald, these events are not easy to find, or at least, not quickly -- and so this new tool was developed to look for new types of transients in real time.

Dr Evans adds: "This type of object was essentially undetectable until we built this new facility, and soon after it found this completely new, never-before-seen event. Swift is nearly 20 years old and it's suddenly finding brand new events that we never knew existed. I think it shows that every single time you find a new way of looking at space, you learn something new and find there's something out there you didn't know about before."

Dr Caroline Harper, Head of Space Science at the UK Space Agency, said:"This is yet another exciting discovery from the world-leading Swift mission -- a low mass black hole taking 'bites' from a Sun-like star whenever it orbits close enough.

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Capturing carbon in savannas: New research examines role of grasses for controlling climate change

In recent years, the escalating impact of global warming has prompted efforts to reverse troubling trends, often by planting trees to capture and remove carbon dioxide from the atmosphere and store it. New research from a team led by Young Zhou, from the Quinney College of Natural Resources and the Ecology Center, shows that, in addition to trees, humble grasses also play an essential role in capturing carbon -- more important than previously thought.

A recent initiative set its sights on capturing carbon in tropical savannas, an ecosystem characterized by shared space of trees and grasses. The project initiated a tree planting effort (afforestation) to capture carbon dioxide from the air, which resulted in stored carbon in two primary places: the woody biomass of the growing trees, and in soils. While the effectiveness of storing carbon in trees has been well-established in research, how carbon storage functions in soils was not well defined, and Zhou and his colleagues set out to determine the role grasses played in this effort.

The team, which included scientists from Yale University, Lawrence Berkeley National Laboratory, University of Cape Town, Texas A&M, Kruger National Park, Harvard University, and University of Oregon, conducted a comprehensive study investigating the contribution of grasses to carbon content in savannas soils and assessed the potential impact of increasing tree cover in tropical savannas on soil carbon storage. The study was published in the journal Nature Geoscience.

Using the case study conducted in Kruger National Park, South Africa, and data synthesized from tropical savannas worldwide, the research team demonstrated that savanna soils enriched with carbon from grasses exhibited comparatively higher concentrations of carbon. Their findings showed that grasses accounted for over half of the soil carbon content across tropical savannas, including soils directly beneath trees. This underscores the significant role that grasses play in the accumulation of carbon within tropical savannas.

Their findings showed both carbon gains and losses, as tree cover increased across tropical savannas. The most significant variation was observed in savannas receiving higher rainfall, where tree planting is more likely to thrive, as well as in areas with clay soils and savanna sites that had substantial contributions of carbon storage from grasses.

"This underscores the nuanced nature of increasing tree cover on the dynamics of carbon in savanna soils," Zhou said. "On average, the increase in soil carbon storage resulting from the expansion of tree cover across tropical savannas is negligible."

This finding aligns with the team's previous research published in Nature, which demonstrated that increasing tree cover due to fire suppression led to increased carbon storage in woody biomass, but did not affect soil carbon storage.

"Our findings challenge the commonly held assumption that afforestation uniformly boosts soil carbon storage," Zhou said. "However, we have yet to pinpoint the precise factors responsible for the substantial variation observed in the soil carbon storage response to increased tree cover across tropical savannas."

In general, forests primarily store their carbon in the woody trunks and aboveground leaves. In contrast, a significant portion of carbon in grassy ecosystems, such as savannas and grasslands, is stored in the soil, primarily within the extensive root systems of the grasses as well as decaying organic matter. In the context of long-term carbon storage, carbon retained in soils proves to be more reliable, particularly for a vulnerable future marked by warming and increased likelihood of drought and wildfires, he said.

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Researchers grow embryonic humanized kidneys inside pigs for 28 days

Guangzhou Institutes of Biomedicine and Health researchers have successfully created chimeric embryos containing a combination of human and pig cells. When transferred into surrogate pig mothers, the developing humanized kidneys had normal structure and tubule formation after 28 days. This is the first time that scientists have been able to grow a solid humanized organ inside another species, though previous studies have used similar methods to generate human tissues such as blood or skeletal muscle in pigs. The work appears September 7 in the journal Cell Stem Cell.

The researchers focused on kidneys because they are one of the first organs to develop, and they're also the most commonly transplanted organ in human medicine.

"Rat organs have been produced in mice, and mouse organs have been produced in rats, but previous attempts to grow human organs in pigs have not succeeded," says senior author Liangxue of the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, and Wuyi University. "Our approach improves the integration of human cells into recipient tissues and allows us to grow human organs in pigs."

Integrating human stem cells into pig embryos has been a challenge because pig cells outcompete human cells and pig and human cells have different physiological needs. "We have been working on mechanisms to overcome the extremely low efficiency in interspecies chimera," says senior author Guangjin Pan of the Guangzhou Institutes of Biomedicine and Health. "We identified a couple of critical factors that enhance the formation of interspecies chimera by facilitating cell competition."

The team's technique depends on three key components:
 

• First, they created a niche within the pig embryo so that the human cells would not have to compete with pig cells by using CRISPR to genetically engineer a single-cell pig embryo so that it was missing two genes that are needed for kidney development.
• Second, the researchers engineered human pluripotent stem cells -- cells that have the potential to develop into any cell type -- to make them more amenable to integration and less likely to self-destruct by temporarily shutting down apoptosis. Then, they converted these cells into "naïve" cells resembling early human embryonic cells by culturing them in a special medium.
• Third, before implanting the developing embryos in surrogate sows, the researchers grew the chimeras in conditions that were optimized to provide unique nutrients and signals to both the human and pig cells, since these cells usually have disparate needs.

Altogether, the researchers transferred 1,820 embryos to 13 surrogate mothers. After either 25 or 28 days, they terminated gestation and extracted the embryos to assess whether the chimeras had successfully produced humanized kidneys.

The researchers collected five chimeric embryos for analysis (two at 25 days and three at 28 days post-implantation) and found that they had structurally normal kidneys for their stage of development and were composed of 50-60% human cells. At 25-28 days, the kidneys were in the mesonephros stage (the second stage of kidney development); they had formed tubules and buds of cells that would eventually become ureters connecting the kidney to the bladder.

The team also investigated whether human cells were contributing to other tissues throughout the embryos, which could have ethical implications, especially if abundant human cells were found in neural or germline tissues and the pigs were brought to term. They showed that human cells were mostly localized to the kidneys, whereas the remainder of the embryo was composed of pig cells.

"We found that if you create a niche in the pig embryo, then the human cells naturally go into these spaces," says senior author Zhen Dai of Guangzhou Institutes of Biomedicine and Health. "We saw only very few human neural cells in the brain and spinal cord and no human cells in the genital ridge, indicating that the human pluripotent stem cells did not differentiate into germ cells." This may be further prevented by knocking out further genes in the human pluripotent stem cells, which can be tested in future studies, the researchers say.

Now that they have optimized conditions for growing humanized kidneys in human-pig chimeras, the team wants to allow the kidneys to develop for a longer duration. They're also working to generate other human organs in pigs, including the heart and pancreas.

The long-term goal is to optimize this technology for human organ transplantation, but the researchers acknowledge the work will be complex and could take many years. Growing a fully functional humanized organ in a pig would require some additional steps because organs are composed of multiple types of cells and tissues. In this study, the researchers created a niche for only one subset of cells, which meant that the kidneys had pig-derived vascular cells, and this could cause organ rejection if they were used in a transplant scenario.

"Because organs are not composed of just one cell lineage, in order to have an organ where everything comes from the human, we would probably need to engineer the pigs in a much more complex way and that also brings some additional challenges," says senior author Miguel A. Esteban of Guangzhou Institutes of Biomedicine and Health.

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Fiber from crustaceans, insects, mushrooms promotes digestion

Who can forget the stomach-churning moments when "Survivor" contestants forced down crunchy insects, among other unappetizing edibles, for a chance to win $1 million? In daring culinary challenges, the TV show's contestants exhibited gastronomic bravery as viewers watched in discomfort.

Digesting a crunchy critter starts with the audible grinding of its rigid protective covering -- the exoskeleton. Unpalatable as it may sound, the hard cover might be good for the metabolism, according to a new study, in mice, from Washington University School of Medicine in St. Louis.

The researchers, led by Steven Van Dyken, PhD, an assistant professor of pathology & immunology, found in mice that digesting chitin, an abundant dietary fiber in insect exoskeletons and also mushrooms and crustacean shells, engages the immune system. An active immune response was linked to less weight gain, reduced body fat and a resistance to obesity.

"Obesity is an epidemic," Van Dyken said. "What we put into our bodies has a profound effect on our physiology and on how we metabolize food. We're investigating ways to counteract obesity based on what we learn about how the immune system is engaged by diet."

The study is published Sept. 7 in Science.

The immune system is well known for safeguarding the body against various threats, including bacteria, viruses, allergens and even cancer. The researchers found that a particular arm of the immune system also is involved in chitin digestion. Stomach distention after chitin ingestion activates an innate immune response that triggers stomach cells to ramp up production of enzymes, known as chitinases, that break down chitin. Of note, chitin is insoluble -- incapable of being dissolved in liquid -- and thus requires enzymes and harsh acidic conditions to digest.

Do-Hyun Kim, PhD, a postdoctoral research associate and first author on the study, performed the experiments in germ-free mice lacking intestinal bacteria. His results show that chitin activates immune responses in the absence of bacteria.

"We think chitin digestion mainly relies on the host's own chitinases," Van Dyken said. "The stomach cells change their enzymatic output through a process we refer to as adaptation. But it is surprising that this process is happening without microbial input, because bacteria in the gastrointestinal tract are also sources of chitinases that degrade chitin." Van Dyken noted that in mice with intestinal bacteria, dietary chitin altered the bacterial composition in the lower gastrointestinal tract, suggesting that gut bacteria also adapt to chitin-containing food after it leaves the stomach.

The research team found that the greatest impact on obesity in mice occurred when chitin activated the immune system but was not digested. Mice fed a high-fat diet also were given chitin. Some mice lacked the ability to produce chitinases to break down chitin. The mice that ate chitin but couldn't break it down gained the least amount of weight, had the lowest body fat measurements and resisted obesity, compared with mice that didn't eat chitin and with those that did but could break it down.

If the mice could break down chitin, they still benefited metabolically, but they adapted by overproducing chitinases to extract nutrients from chitin.

Van Dyken and his team next plan to follow up on their findings in people, with a goal of determining whether chitin could be added to human diets to help control obesity.

Read more at Science Daily