In the fight against diseases, one thing is absolutely vital: B-cells. These particular cells, which belong to a class of white blood cells called lymphocytes, are the only cells in the immune system capable of making antibodies. The Y-shaped proteins latch onto foreign structures such as bacteria or viruses, thus marking them as intruders for elimination by phagocytes and other immune cells.

B1 cells are already present in newborns and play an important role in natural immunity

There are two types of B cells. B2 cells, which make up the largest portion of the white blood cells in the body, mainly circulate in the blood and in the lymphoid organs such as the thymus, spleen, lymph nodes, and bone marrow. B1 cells, on the other hand, are mainly present in the peritoneal and pleural cavities, and hence in the areas around the intestinal tract and the lungs. They respond to a wide range of foreign proteins, called antigens, but also to some of the body’s own antigens — and in a different manner than the highly specialized B2 cells.

B1 cells constitute the majority of all B lymphocytes in newborns, but in adults the proportion of B1 cells drops to only a few percent. This is one of the reasons why B1 cells are considered carriers of natural immunity — i.e. the innate immune system — while B2 cells are mainly responsible for adaptive immunity, which emerges, for example, after an infection or a vaccination.

For decades, immunologists have debated the origin of B cells

Until now, it was unclear how the different types of B cells developed. “Some immunologists think B1 and B2 cells emerge from different progenitor cells,” says Dr. Robin Graf, one of the lead authors of the Science article and a member of the Immune Regulation and Cancer research group at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin, which is headed by Prof. Klaus Rajewsky. “Other immunologists believe special autoreactive B-cell receptors trigger the formation of B1 cells.”

The new study, in which also other scientists from Rajewsky’s group who were at the time in Cologne and Boston played a major role, now provides clear evidence for the validity of the second hypothesis. “We replaced the B-cell receptor in mature B2 cells with a B1-typical B-cell receptor, which is found in nature only on B1 cells,” explains Graf.

The manipulated B2 cells assumed the properties of B1 cells

This procedure transformed the B2 cells into B1 cells. “We were able to show that the cells acquired the B1-typical surface markers,” reports Graf. The manipulated B2 lymphocytes also took on the functional properties of B1 lymphocytes. “When we transplanted them into mice, they were homing to those parts of the body where B1 cells are naturally found,” says the MDC researcher.

In addition, the cells began to spontaneously produce antibodies. “That’s also a typical feature of B1 cells,” explains Graf. What’s more, once the B1-typical receptor was expressed on the B2 lymphocytes, the cells started to multiply in great numbers over a period of one to two weeks. This strikingly resembles the natural development of B1 cells at early stages — a process that has barely been studied.

The end to a longstanding debate is in sight

Later in the study, Graf measured the activity of thousands of genes in the manipulated B2 cells. “Here we found that the same genes were active in these cells as in normal B1 cells,” reports the scientist.

Graf expects that the new study will convince immunologists that B1 cells emerge as a consequence of the specificity of their B-cell receptors.

A separate study has also shown for the first time that the treatment works for some autistic adults.

The Blue Room, developed by specialists at Newcastle University working alongside innovative technology firm Third Eye NeuroTech, allows the team to create a personalised 360 degree environment involving the fear which may debilitate the person with autism in real life.

Within this virtual environment, which requires no goggles, the person can comfortably investigate and navigate through various scenarios working with a therapist using iPad controls but remain in full control of the situation.

Funded by the National Institute for Health Research (NIHR), the research findings are published in two papers today in the Journal of Autism and Developmental Disorders and in Autism in Adulthood.

“For many children and their families, anxiety can rule their lives as they try to avoid the situations which can trigger their child’s fears or phobia,” says Professor Jeremy Parr, Institute of Neuroscience, Newcastle University, who led the studies.

“To be able to offer an NHS treatment that works, and see the children do so well, offers hope to families who have very few treatment options for anxiety available to them.”

Autism can affect a child’s learning and development, often resulting in impaired social and communication skills and many also have fears or phobias which can be very distressing but are often overlooked. It is thought these phobias affect around 25% of children with autism. In the trial phobias included travelling on public transport, school classrooms, dogs and balloons.

The Newcastle University experts describe the randomised controlled trial involving 32 children with autism aged 8 — 14 years. Half received treatment in the Blue Room straight away and half acted as a control group, receiving delayed treatment six months later.

Accompanied by a psychologist they underwent four sessions in a week involving a personalised scenario in the Blue Room. Parents were able to watch the treatment via a video link.

“People with autism can find imagining a scene difficult which is why the Blue Room is so well-received. We are providing the feared situation in a controlled way through virtual reality and we are sitting alongside them to help them learn how to manage their fears,” explains Dr Morag Maskey, researcher from the Institute of Neuroscience, Newcastle University.

“It is incredibly rewarding to see the effect it can have for some, overcoming a situation which just a week previously would have been so distressing.”

After receiving the treatment and with the support of their parents, the children were then introduced to the scenario in the real world.

Two weeks after treatment, the research shows that four of the first 16 (25%) had responded to treatment and were able to cope with a specific phobia. This effect remained with a total of six showing improvement after six months (38%), however, one reported a worsening of their phobia. Meanwhile, in the control group, five untreated participants had become worse in the six months.

The control group went on to be treated in the Blue Room after this time. Results showed that overall 40% of children treated showed improvement at 2 weeks, and 45% at 6 months.

This improvement is comparable with other treatments and the team intend to further examine why some don’t respond.

The Blue Room for adults with autism

For the first time, the Blue Room treatment was offered to autistic adults. In a separate publication in Autism in Adulthood by the same team, the VR treatment was shown to work in five out of eight autistic adults.

Aged 18- 57, the adults received four 20 minute sessions in the Blue Room with a personalised computer generated scene. Six months after the sessions, five of the eight participants still had real life day-to-day improvements in relation to their phobia.

Dr Rajesh Nadkarni, Executive Medical Director at Northumberland, Tyne and Wear NHS Foundation Trust, said: “We are proud to be a partner of the Newcastle Blue Room Treatment which is helping people with autism to manage their anxiety. Northumberland, Tyne and Wear NHS Foundation Trust has a strong track record in providing nationally recognised autism services, and we welcome this new research demonstrating the positive effects of this highly innovative treatment.”

Eddie Nelson is Director of Third Eye NeuroTech, the immersive reality technology company based in County Durham which provides the Blue Room facility. He says: “It is rare as a business that we get the chance to help young people and their families in such a dramatic and tangible way. But what we see with the Blue Room is very anxious young people and adults coming in, yet within four of these specialised sessions they come out having combatted their fears.”

Specific phobias which were addressed in the Blue Room treatment included: Dogs, Wasps/bees, lifts, fear of the dark, flying, dolls, balloons, public transport, school, walking into rooms.

Alongside the NHS Service, the Newcastle University team are continuing further research into the effectiveness and lasting effect of the Blue Room.

The finding, published in the journal Nature, will allow scientists to explore for the first time how the complex functions and could have implications for the production of a variety of bioproducts, including plastic alternatives and biofuels.

“This work will lead to a better understanding of how photosynthesis occurs, which could allow us to improve the efficiency of photosynthesis in plants and other green organisms — potentially boosting the amount of food, and thus biomass, they produce,” said lead researcher Karen Davies, a biophysicist at Berkeley Lab. “This is particularly important if you want to produce renewable bioproducts that are cost-effective alternatives to current petroleum-based products.”

Discovered decades ago, the protein complex targeted by the researchers, called NADH dehydrogenase-like complex (NDH), is known to help regulate the phase of photosynthesis where the energy of sunlight is captured and stored in two types of cellular energy molecules, which are later utilized to power the conversion of carbon dioxide into sugar. Past investigations revealed that NDH reshuffles the energized electrons moving among other protein complexes in the chloroplast in a way that ensures the correct ratio of each energy molecule is produced. Furthermore, NDH of cyanobacteria performs several additional roles including increasing the amount of carbon dioxide (CO₂) available for sugar production by linking CO₂ uptake with electron transfer.

In order for scientists to truly comprehend how NDH executes these important functions, they needed a molecular blueprint indicating the location and connectivity of all the atoms in the complex. This is something that even highly powerful transmission electron microscopy (TEM) technology simply could not provide until very recently.

“Research on this enzyme has been difficult and experimental results confounding for the last 20 years or so because we have lacked complete information about the enzyme’s structure,” said Davies. “Knowing the structure is important for generating and testing out hypotheses of how the enzyme functions. The resolution we obtained for our structure of NDH has only really been achievable since the commercialization of the direct electron counting camera, developed in collaboration with Berkeley Lab.”

Prior to this invention, explained Davies, a staff scientist in Berkeley Lab’s Molecular Biophysics and Integrative Bioimaging Division (MBIB), determining the structure of a single molecule could take several years because cryo-TEM imaging relied on film, meaning that each exposure had to be developed and scanned before it could be analyzed. The main limitation, however, was that most images turned out blurry. When you directed a beam of electrons at a molecule, the charged, high-energy particles excited the atoms in the molecule, often making them move at the moment of exposure. This meant that researchers needed to take and process hundreds, if not thousands, of film images in order to get an accurate glimpse of an entire molecule.

The new electron counting camera solves this problem by taking digital movies with an extremely high frame rate, so individual frames can be aligned to eliminate blurring caused by beam-induced particle motion.

In the current study, first author Thomas Laughlin, a UC Berkeley graduate student with a joint appointment at MBIB, isolated NDH complexes from membranes of a photosynthetic cyanobacterium provided by the Junko Yano and Vittal Yachandra Lab in MBIB and imaged them using a state-of-the-art cryo-TEM instrument fitted with the latest direct electron detector. Located on the UC Berkeley campus, the cryo-TEM facility is managed by the Bay Area CryoEM consortium, which is partly funded by Berkeley Lab.

The resulting atom density map was then used to build a model of NDH that shows the arrangement of all the protein subunits of NDH and the most likely position of all the atoms in the complex. By examining this model, Davies’ team will be able to formulate and then test hypotheses of how NDH facilitates sugar production by balancing the ratio of the two cellular energy molecules.

“While the structure of NDH alone certainly addresses many questions, I think it has raised several more that we had not even thought to consider before,” said Laughlin.

Among the many Berkeley Lab scientists focused on advancing knowledge of fundamental biochemical and biophysical processes, Davies and her staff also use direct electron camera cryo-EM to investigate how variations in the organization of photosynthetic complexes, caused by changes in growth and light conditions, affect the efficiency of photosynthesis. Her project on electron flow in photosynthesis is supported by a five-year DOE Office of Science Early Career Research Program grant that was awarded in 2018.

The study used images taken by a network of more than 150 CubeSats — small satellites about the size of shoeboxes — which made nearly daily observations of more than 85,000 small North American lakes during the summer of 2017. The images enabled the researchers to see how the lakes changed over time. They found small but significant shoreline changes in individual lakes that added up to hundreds of square kilometers of lake area change across the study region.

“There’s been a lot of research on climate-driven changes in lake area, but it’s mainly focused on long-term changes,” said Sarah Cooley, a Ph.D. student at Brown University and the study’s lead author. “This is the first time that anyone has looked at fine-scale, short-term changes, and we found that there’s much more variability within a season than expected.”

The study area captures a substantial swath of Arctic tundra and boreal forest, a biome that circles the Earth’s northern hemisphere in a band from about 50 to 70 degrees north latitude. The region is home to critical forest and tundra ecosystems as well as the planet’s highest density of lakes, so understanding its hydrology is scientifically important. One reason for that is that boreal lakes are a significant source of natural greenhouse gas emissions. Their sediments contain tons of organic carbon, which washes in from the surrounding landscape. Some of that carbon then decomposes and it emitted into the atmosphere in the form of carbon dioxide and methane greenhouse gases.

This new finding of substantial summer shoreline fluctuation has implications for how scientists calculate these emissions, the researchers say. That’s because shoreline areas where water ebbs and flows from season to season are known hotspots for greenhouse gas production and emission. But estimates of lake emissions generally assume shorelines to be stable within each season. The finding of surprising within-season shoreline fluctuation, the researchers say, suggests that current emissions models from boreal lakes may be underestimated.

“A shoreline that’s fluctuating is going to emit more carbon than a stable shoreline,” Cooley said. “These short-term fluctuations, which no one had ever mapped before, suggest these lakes are potentially emitting more gas than people thought.”

Another finding that surprised the research team was the large overall importance of shoreline fluctuations on the ancient Canadian Shield, a rocky, wet landscape in central Canada where millions of small lakes cover 20 percent of the landscape.

“Previous studies assumed lakes in this area to be relatively stable,” said Laurence C. Smith, a co-author of the study and project leader for NASA’s Arctic-Boreal Vulnerability Experiment, which helped fund the study. “To our surprise, the high-resolution, high-frequency imaging afforded by CubeSats revealed that small shoreline fluctuations in this lake-rich area sum to impressively large numbers.”

In all, the study explored four sub-areas of the North American Arctic and sub-Arctic and found the little-studied Canadian Shield to be most dynamic of all, with about 1.4 percent of its landscape seasonally inundated by small fluctuations in lake levels.

Big data, small satellites

Another takeaway from the study, Cooley says, is that it shows the power of CubeSats to acquire data that larger satellites can’t gather.

“What I’m most excited about from a science perspective is the ability to make use of this new CubeSat imagery,” Cooley said. “We couldn’t have made these observations without the CubeSats, and here we show that it’s possible to extract valuable scientific information from those images.”

Large space agency satellites festooned with sensitive scientific instruments can gather all sorts of information, but simply don’t make enough overhead passes to catch changes that occur over short periods of time. And the satellites that do pass over on a daily basis lack the camera resolution to make fine-scale observations of lake area.

The CubeSats, recently launched by a company called Planet, offered a potential solution. The company operates more than 150 satellites, which orbit the Earth in an arrangement that enables them to image Earth’s entire landmass each day as the planet rotates beneath them. And while the tiny satellites lack sophisticated scientific equipment, they do have high-powered cameras capable of capturing images with 3-meter resolution.

But the CubeSat data present some unique challenges, Cooley says. For example, the location data from CubeSats tend not to be as precise as those from space agency satellites. And the CubeSat images lack filters that make them easier to analyze. NASA or European Space Agency (ESA) satellite data are filtered to eliminate images taken on cloudy days or other low-quality images.

So Cooley had to design her own system to compensate for those issues. For the study, she trained a machine learning algorithm to spot anomalous data patterns and throw them away. For example, instances in which a lake suddenly disappears in a day only to return to view a few days later are most likely due to cloud cover or glitchy observations, not an actual lake disappearance. The algorithm could flag such instances and remove them from the data.

Using that algorithm, Cooley and her colleagues were able to sift through more 25 terabytes of CubeSat data. Cooley says she expects more interesting earth science findings to come from CubeSats in the coming years.

“I see this as a beginning of a new period in remote sensing, in that suddenly all sorts of earth observations that may not have been possible before will become possible with these small, simple satellites,” Cooley said.

The research was funded by the NASA Terrestrial Ecology Program Arctic-Boreal Vulnerability Experiment (ABoVE) (#NNX17AC60A) and a National Science Foundation graduate fellowship to Sarah Cooley. Other coauthors on the paper were Jonathan Ryan, Lincoln Pitcher and Tamlin Pavelsky.

The Rice lab of chemist James Tour made test cells with a coat of red phosphorus on the separator that keeps the anode and cathode electrodes apart. The phosphorus acts as a spy for management systems used to charge and monitor batteries by detecting the formation of dendrites, protrusions of lithium that can cause them to fail.

Lithium metal anodes charge much faster and hold about 10 times more energy by volume than common lithium-ion anodes used in just about every electronic device on the market, including cellphones and electric cars. Anodes are one of two electrodes needed for battery operation.

But charging lithium-infused anodes forms dendrites that, if they reach the cathode, cause a short circuit and possibly a fire or explosion. When a dendrite reaches a red phosphorus-coated separator, the battery’s charging voltage changes. That tells the battery management system to stop charging.

Unlike other proposed dendrite detectors, the Rice strategy doesn’t require a third electrode.

“Manufacturing batteries with a third electrode is very hard,” Tour said. “We propose a static layer that gives a spike in the voltage while the battery is charging. That spike is a signal to shut it down.”

The research appears in Advanced Materials.

The red phosphorus layer had no significant effect on normal performance in experiments on test batteries by the Tour lab.

The researchers built a transparent test cell with an electrolyte (the liquid or gel-like material between the electrodes and around the separator that allows the battery to generate a current) known to accelerate aging of the cathode and encourage dendrite growth. That let them monitor the voltage while they watched dendrites grow.

With an ordinary separator, they saw the dendrites contact and penetrate the separator with no change in voltage, a situation that would lead a normal battery to fail. But with the red phosphorus layer, they observed a sharp drop in voltage when the dendrites contacted the separator.

“As soon as a growing dendrite touches the red phosphorus, it gives a signal in the charging voltage,” Tour said. “When the battery management system senses that, it can say, ‘Stop charging, don’t use.'”

Last year, the lab introduced carbon nanotube films that appear to completely halt dendrite growth from lithium metal anodes.

“By combining the two recent advances, the growth of lithium dendrites can be mitigated, and there is an internal insurance policy that the battery will shut down in the unlikely event that even a single dendrite will start to grow toward the cathode,” Tour said.

“Literally, when you make a new battery, you’re making over a billion of them,” he said. “Might a couple of those fail? It only takes a few fires for people to get really antsy. Our work provides a further guarantee for battery safety. We’re proposing another layer of protection that should be simple to implement.”

Story Source:

Materials provided by Rice University. Original written by Mike Williams. Note: Content may be edited for style and length.