In the digestive system, there’s a delicate balance of bacterial populations. When this balance is disrupted, bad bacteria can take over the colon, causing it to swell, resulting in colitis. Certain diseases, including inflammatory bowel disease and Crohn’s disease, involve chronic colitis and currently require immunosuppressants to treat them. These drugs are expensive and non-specific, sometimes giving rise to antibiotic-resistant bacteria.

An alternative strategy is to deliver beneficial bacteria, or probiotics, to help restore balance. But to reach the colon, a treatment must first pass through stomach acid, withstand being cleared out by the intestine, then fight for space alongside the numerous invading bacteria. Pairing probiotics with a drug delivery system could make this strategy feasible, though most current approaches simply protect the probiotics from digestion without affecting the microbes responsible for the condition. So, Zhenzhong Zhang, Junjie Liu, Jinjin Shi and colleagues wanted to combine probiotics with specialized microgel spheres that could not only protect the good bacteria, but also actively help clear out the bad.

To create their system, the researchers combined sodium alginate, tungsten and calcium-containing nanoparticles into small, spherical microgels, then coated them with beneficial, probiotic bacteria. The gels protected the bacteria as they made their way through the stomach and increased their retention time in the colon. Once there, calprotectin proteins — highly expressed during colitis — bound to the calcium and disassembled the gels, allowing the tungsten to escape. By displacing molybdenum in a key enzyme substrate of the bad bacterium Enterobacteriaceae, tungsten inhibited the microbe’s growth while leaving the probiotics unaffected. In experiments using a colitis mouse model, the system allowed probiotics to proliferate in the intestine without any side effects. Additionally, mice with the microgel spheres did not exhibit many of the hallmarks of colitis, such as shortened colons or damaged intestinal barriers, showing that the delivery system could be a viable treatment strategy. Though the researchers also want to prove its utility in more advanced preclinical models, they say that this work provides a new perspective into treatments using colonizing probiotics.

The authors acknowledge funding from the National Natural Science Foundation of China, the Outstanding Youth Foundation of Henan Province and the China Postdoctoral Science Foundation.

Research by Lancaster University’s School of Engineering and the UK Centre for Ecology and Hydrology combined a tidal range power generation model with its cost model to demonstrate the viability of tidal power.

Professor George Aggidis, Head of Energy Engineering at Lancaster University, said: “The obvious question for the UK, with one of the best tidal resources globally, is why haven’t we already got a tidal barrage scheme?”

The research published in Energy demonstrates the benefits of tidal energy, which does not suffer from unpredictable intermittency as power is generated both day and night.

The creation of a tidal barrage could operate for 120 years or more to meet future demand and storage problems.

Professor Aggidis said: “There is an urgent need to kick-start the selection and development of schemes around Britain. Tidal range generation is predictable renewable energy driven by the gravitational pull of the moon and sun. The environmental and economic benefits are huge as barrages can protect coastal areas from flooding and sea level rise. With two-way generation and pumping, the full range of existing tides can be maintained within impoundments to protect and support low-lying intertidal areas such as saltmarshes and mudflats.

Our studies show that with modern technology and operating procedures, estuarine barrages are the only practical way to protect these vital habitats. Coastal lagoons have also been proposed for several locations around Britain’s coast. Schemes will provide jobs in construction and manufacturing for generations to come as well as opportunities for transport, communication, conservation, and recreation. In the long-term they will provide reliable power with reduced costs.”

The UK has the second highest tidal range in the world and offers the UK a level of independence from global prices and in the long-term cheap clean power.

Currently the Tidal Range projects under commercial consideration offer an achievable 10 GW installed capacity, delivering over 20TWh/y, about 5% of UK energy use. Based on the UK relevant resource availability there is the potential to further increase this installed capacity over 4 to 5 times with other tidal range project sites around the UK.

Such developments are essential to assist the UK to reduce its carbon emissions by replacing fossil fuel power stations. The current UK total generating capacity is around 42.8 GW that includes fossil fuels (19.2GW 44.9%), renewables (16.5GW, 38.5%), and low carbon (7.1GW — 16.6%). The La Rance Tidal Range plant in France today generates the cheapest electricity in the EDF fleet — cheaper than nuclear.

Working with partners, ORNL engineers are placing low-powered sensors in the reflective raised pavement markers that are already used to help drivers identify lanes. According to a paper in IEEE Sensors by ORNL researcher Ali Ekti with lead author Sachin Sharma of WMU, microchips inside the markers transmit information to passing cars about the road shape. They are effective even when vehicle cameras or remote laser sensing called LiDAR are unreliable because of fog, snow, glare or other obstructions.

“We are working to make autonomous driving features accurate and safe in more remote areas,” Ekti said. “And we are doing it by converting a dummy piece of infrastructure into something with many more uses.”

Not only does the technology provide more accurate information about the driving environment, but it also shifts some of the processing load from the car’s software onto infrastructure. This saves electric vehicle battery power, extending driving range to promote wider EV adoption. Compared with a leading camera and LiDAR-based autonomous driving technology, the chip-enabled pavement markers can reduce navigational power consumption by up to 90%, the authors reported in a technical paper.

The technology has potential for use with not only tomorrow’s self-driving vehicles, but also today’s common autonomous driving features, such as lane assist.

The effort is part of a larger project led by WMU, which is teaming with research and industry partners to develop related sensor and autonomous driving technologies such as radar retro-reflectors, high-definition mapping, computational offloading and weather sensing. WMU researchers are also using a vehicle driving on a closed course to measure the reduction in vehicle energy use that is enabled by these technologies, said Zachary Asher, assistant professor of mechanical and aerospace engineering and director of the WMU Energy Efficient and Autonomous Vehicles Lab.

ORNL researchers experimented to find the best combination of transceiver, battery and antenna for the sensor package inside standard road markers, as well as those that are designed to withstand snowplows. They then utilized a communications protocol that involves hopping across a particular radio frequency spectrum up to 50 times a second. “It’s hard to detect, works well against interference, is low cost and doesn’t consume a lot of power,” Ekti said. Adjustments to the equipment could ensure its battery would last for the same replacement cycle as the pavement markers, typically a year.

Ekti’s team created algorithms that triangulate among the GPS coordinates of lane markers to reconstruct an image of the drivable area. One algorithm is embedded in a microchip inside the pavement marker, while a decoding algorithm is incorporated into the car’s software.

ORNL researchers field-tested the sensor platform in a variety of weather conditions and in a remote national park in Montana with no wireless access. They found that it transmits more than five times beyond the original 100-meter goal.

“It’s amazing how far it can transmit — over hills, in snow. It’s a big deal,” Asher said. “Every step of the way, we’re surprised at how well this technology is working, and we’re finding some really cool ways it could be integrated.”

The sensors could also signal temporary lane shifts or closures in construction zones when high-definition maps might be out of date. Marker sensors could eventually convey information about temperature, humidity and traffic volume, Ekti said. The project team plans to work with students to build a smaller microchip for the markers as a substitute for more expensive off-the-shelf products.

Asher is planning road demonstrations for stakeholders including the Tennessee and Michigan departments of transportation, the Michigan Office of Future Mobility and the City of Chattanooga. These government agencies decide which technologies are implemented in infrastructure, so their involvement in the development process is critical, Asher said.

Venture capitalists and Silicon Valley have typically regarded self-driving vehicles as a software problem, Asher said. “With the hindsight of 10 years of highly- funded development, we now know that software and cameras alone don’t provide an easy solution,” he said. “Perhaps a more patient approach, using infrastructure-based hardware in coordination with government transportation agencies, is the way to achieve zero-accident vehicles which actually use energy sustainably.”

Part of the ORNL research was conducted at DOE’s National Transportation Research Center. The Vehicle Technologies Office under DOE’s Office of Energy Efficiency and Renewable Energy provided funding. Contributing ORNL researchers include Ross Wang, Jason Richards, Elizabeth Piersall, David Pesin, Ozgur Alaca and Shean Huff.

New research from Whitehead Institute Member Jonathan Weissman; University of California, San Francisco Assistant Professor Alex Pollen; Weissman lab postdoc Richard She; Pollen lab graduate student Tyler Fair; and colleagues uses cutting edge tools developed in the Weissman lab to narrow in on the key differences in how humans and chimps rely on certain genes. Their findings, published in the journal Cell on June 20th, may provide unique clues into how humans and chimps have evolved, including how humans became able to grow comparatively large brains.

Studying function rather than genetic code

Only a handful of genes are fundamentally different between humans and chimps; the rest of the two species’ genes are typically nearly identical. Differences between the species often come down to when and how cells use those nearly identical genes. However, only some of the many differences in gene use between the two species underlie big changes in physical traits. The researchers developed an approach to narrow in on these impactful differences.

Their approach, using stem cells derived from human and chimp skin samples, relies on a tool called CRISPR interference (CRISPRi) that Weissman’s lab developed. CRISPRi uses a modified version of the CRISPR/Cas9 gene editing system to effectively turn off individual genes. The researchers used CRISPRi to turn off each gene one at a time in a group of human stem cells and a group of chimp stem cells. Then they looked to see whether or not the cells multiplied at their normal rate. If the cells stopped multiplying as quickly or stopped altogether, then the gene that had been turned off was considered essential: a gene that the cells need to be active-producing a protein product-in order to thrive. The researchers looked for instances in which a gene was essential in one species but not the other as a way of exploring if and how there were fundamental differences in the basic ways that human and chimp cells function.

By looking for differences in how cells function with particular genes disabled, rather than looking at differences in the DNA sequence or expression of genes, the approach ignores differences that do not appear to impact cells. If a difference in gene use between species has a large, measurable effect at the level of the cell, this likely reflects a meaningful difference between the species at a larger physical scale, and so the genes identified in this way are likely to be relevant to the distinguishing features that have emerged over human and chimp evolution.

“The problem with looking at expression changes or changes in DNA sequences is that there are many of them and their functional importance is unclear,” says Weissman, who is also a professor of biology at the Massachusetts Institute of Technology and an Investigator with the Howard Hughes Medical Institute. “This approach looks at changes in how genes interact to perform key biological processes, and what we see by doing that is that, even on the short timescale of human evolution, there has been fundamental rewiring of cells.”

After the CRISPRi experiments were completed, She compiled a list of the genes that appeared to be essential in one species but not the other. Then he looked for patterns. Many of the 75 genes identified by the experiments clustered together in the same pathways, meaning the clusters were involved in the same biological processes. This is what the researchers hoped to see. Individual small changes in gene use may not have much of an effect, but when those changes accumulate in the same biological pathway or process, collectively they can cause a substantive change in the species. When the researchers’ approach identified genes that cluster in the same processes, this suggested to them that their approach had worked and that the genes were likely involved in human and chimp evolution.

“Isolating the genetic changes that made us human has been compared to searching for needles in a haystack because there are millions of genetic differences, and most are likely to have negligible effects on traits,” Pollen says. “However, we know that there are lots of small effect mutations that in aggregate may account for many species differences. This new approach allows us to study these aggregate effects, enabling us to weigh the impact of the haystack on cellular functions.”

Researchers think bigger brains may rely on genes regulating how quickly cells divide

One cluster on the list stood out to the researchers: a group of genes essential to chimps, but not to humans, that help to control the cell cycle, which regulates when and how cells decide to divide. Cell cycle regulation has long been hypothesized to play a role in the evolution of humans’ large brains. The hypothesis goes like this: Neural progenitors are the cells that will become neurons and other brain cells. Before becoming mature brain cells, neural progenitors divide multiple times to make more of themselves. The more divisions that the neural progenitors undergo, the more cells the brain will ultimately contain — and so, the bigger it will be. Researchers think that something changed during human evolution to allow neural progenitors to spend less time in a non-dividing phase of the cell cycle and transition more quickly towards division. This simple difference would lead to additional divisions, each of which could essentially double the final number of brain cells.

Consistent with the popular hypothesis that human neural progenitors may undergo more divisions, resulting in a larger brain, the researchers found that several genes that help cells to transition more quickly through the cell cycle are essential in chimp neural progenitor cells but not in human cells. When chimp neural progenitor cells lose these genes, they linger in a non-dividing phase, but when human cells lose them, they keep cycling and dividing. These findings suggest that human neural progenitors may be better able to withstand stresses — such as the loss of cell cycle genes — that would limit the number of divisions the cells undergo, enabling humans to produce enough cells to build a larger brain.

“This hypothesis has been around for a long time, and I think our study is among the first to show that there is in fact a species difference in how the cell cycle is regulated in neural progenitors,” She says. “We had no idea going in which genes our approach would highlight, and it was really exciting when we saw that one of our strongest findings matched and expanded on this existing hypothesis.”

More subjects lead to more robust results

Research comparing chimps to humans often uses samples from only one or two individuals from each species, but this study used samples from six humans and six chimps. By making sure that the patterns they observed were consistent across multiple individuals of each species, the researchers could avoid mistaking the naturally occurring genetic variation between individuals as representative of the whole species. This allowed them to be confident that the differences they identified were truly differences between species.

The researchers also compared their findings for chimps and humans to orangutans, which split from the other species earlier in our shared evolutionary history. This allowed them to figure out where on the evolutionary tree a change in gene use most likely occurred. If a gene is essential in both chimps and orangutans, then it was likely essential in the shared ancestor of all three species; it’s more likely for a particular difference to have evolved once, in a common ancestor, than to have evolved independently multiple times. If the same gene is no longer essential in humans, then its role most likely shifted after humans split from chimps. Using this system, the researchers showed that the changes in cell cycle regulation occurred during human evolution, consistent with the proposal that they contributed to the expansion of the brain in humans.

The researchers hope that their work not only improves our understanding of human and chimp evolution, but also demonstrates the strength of the CRISPRi approach for studying human evolution and other areas of human biology. Researchers in the Weissman and Pollen labs are now using the approach to better understand human diseases — looking for the subtle differences in gene use that may underlie important traits such as whether someone is at risk of developing a disease, or how they will respond to a medication. The researchers anticipate that their approach will enable them to sort through many small genetic differences between people to narrow in on impactful ones underlying traits in health and disease, just as the approach enabled them to narrow in on the evolutionary changes that helped make us human.

Forensic artist Hew Morrison created the likeness using measurements of the woman’s skull and tissue depth data for Caucasian females. Without DNA analysis, Morrison could not be sure of her precise eye and hair colour, but the image offers a strong indication of her appearance shortly before she died.

Hew Morrison said: “It was interesting to see her face developing. Her left eye was slightly lower, about half a centimetre, than her right eye. This would have been quite noticeable in life.”

New “you are what you eat” isotopic analysis of the young woman’s bones and teeth conducted by bioarchaeologists Dr Sam Leggett and Dr Alice Rose, and archaeologist Dr Emma Brownlee, during PhD research at the University of Cambridge also reveals that she moved to England from somewhere near the Alps, perhaps southern Germany, sometime after she turned 7 years old.

Leggett and Rose also found that once the girl had arrived in England, the proportion of protein in her diet decreased by a small but significant amount. This change occurred close to the end of her young life, showing that the period between her migration and burial near Cambridge was tragically short.

Dr Leggett, now at the University of Edinburgh, said: “She was quite a young girl when she moved, likely from part of southern Germany, close to the Alps, to a very flat part of England. She was probably quite unwell and she travelled a long way to somewhere completely unfamiliar — even the food was different. It must have been scary.”

Previous analysis indicated that the young woman had suffered from illness but her cause of death remains unknown. She was buried in a remarkable way — lying on a carved wooden bed wearing the cross, gold pins (also on display) and fine clothing.

Hers is one of only 18 bed burials ever uncovered in the UK. Her ornate cross, combining gold and garnets (third quarter of the 7^th century), is one of only five of its kind ever found in Britain and identifies her as one of England’s earliest converts to Christianity and as a member of the aristocracy if not royalty. The best known example of such a cross was found in the coffin of St Cuthbert.

In 597 AD, the pope dispatched St Augustine to England on a mission to convert the pagan Anglo-Saxon kings, a process which continued for many decades.

Dr Leggett said: “She must have known that she was important and she had to carry that on her shoulders. Her isotopic results match those of two other women who were similarly buried on beds in this period in Cambridgeshire.

“So it seems that she was part of an elite group of women who probably travelled from mainland Europe, most likely Germany, in the 7^th century, but they remain a bit of a mystery. Were they political brides or perhaps brides of Christ? The fact that her diet changed once she arrived in England suggests that her lifestyle may have changed quite significantly.”

Dr Sam Lucy, a specialist in Anglo-Saxon burial from Newnham College, Cambridge, who published the Anglo-Saxon excavations at Trumpington**, said:

“These are intriguing findings, and it is wonderful to see this collaborative research adding to our knowledge of this period. Combining the new isotopic results with Emma Brownlee’s research into European bed burials really does seem to suggest the movement of a small group of young elite women from a mountainous area in continental Europe to the Cambridge region in the third quarter of the seventh century.

“Southern Germany is a distinct possibility owing to the bed burial tradition known there. Given the increasingly certain association between bed burial, such cross-shaped jewellery, and early Anglo-Saxon Christianity, it is possible that their movement related to pan-European networks of elite women who were heavily involved in the early Church.”

Dr Jody Joy, the exhibition’s co-curator, said: “The story of this young woman goes to the very heart of what our exhibition is all about — new research making visible the lives of people at pivotal moments of Cambridgeshire’s history. MAA holds one of Britain’s most important collections of Early Medieval archaeology and the Trumpington bed burial is so important. It looks like it still has much more to teach us.”

In the exhibition, the ‘Trumpington Cross’ will be displayed together with the delicate gold and garnet pins connected by a gold chain, which were found near the teenager’s neck. These pins probably secured a long veil to an outer garment of fine linen. The pins would have caught the light as she moved.The burial bed’s decorativeheadboard will also be exhibited.

* The image and artefacts from the mysterious woman’s burial — discovered in 2012 by the Cambridge Archaeological Unit at Trumpington Meadows on Cambridge’s southern limits — including her famous cross will be unveiled in a major new exhibition at Cambridge’s Museum of Archaeology and Anthropology (MAA). ‘Beneath Our Feet: Archaeology of the Cambridge Region’ will run from 21^st June to 14^th April 2024.

**C. Evans, S. Lucy & R. Patten, Riversides: Neolithic Barrows, a Beaker Grave, Iron Age and Anglo-Saxon Burials and Settlement at Trumpington, Cambridge (2018); and S. Lucy, ‘The Trumpington Cross in context’, Anglo-Saxon England (2016).