Earth

What started as a hallway conversation between colleagues is now an "engine for the discovery of new therapeutic targets in cells" thanks to Medicine by Design, says Shana Kelley, a University Professor in the Leslie Dan Faculty of Pharmacy at the University of Toronto.

Kelley's lab was developing a portable, chip-like device that uses tiny magnets to sort large populations of mixed cell types as part of her Medicine by Design team project. She wondered if the device could be coupled with a CRISPR-based gene-editing technology, developed by another Medicine by Design team leader, Jason Moffat, a professor in the Donnelly Centre for Cellular and Biomolecular Research. They reasoned that the two methods together could speed up combing through the human genome for potential drug targets. "We casually agreed to combine our technologies -- and it worked incredibly well," says Kelley.

"This is the advantage of being part of the dynamic research ecosystem of Toronto and Medicine by Design," says Kelley. "I would have never known how to position this technology and link it with CRISPR it if I did not have all these great people around to talk to."

The result of their joint effort, also in collaboration with Stephane Angers, a professor at Pharmacy, and Edward Sargent, University Professor at the Department of Electrical and Computer Engineering, is called MICS, for microfluidic cell sorting, described in a study published today in the journal Nature Biomedical Engineering.

MICS will enable researchers to scour the human genome faster when searching for genes, and their protein products, that can be targeted by drugs.

In one hour, MICS can collect precious rare cells, in which CRISPR revealed promising drug targets, from a large and mixed cell population of The same experiment would take 20-30 hours using the gold standard method of fluorescence-based sorting.

Researchers use CRISPR to switch off in cells each of around 20,000 human genes and see how this affects levels of a disease-related protein which, say, helps cancer spread. This can reveal other gene candidates, and the proteins they encode, that work in the same pathway and which could be targeted with drugs to remove the target protein and halt cancer. The caveat is that genetic screens result in mixed cell populations, with a desired effect present in a vanishingly small proportion of cells which have to be scooped out for further study. Most cell-sorting instruments use laser beams to separate fluorescently labelled cells, but this takes time.

MICS works faster thanks to tiny magnets engineered to bind to the target protein, which leaves the cells sprinkled with magnetic particles. About half the size of a credit card, its surface is streaked with strips of magnetic material that ferry the cells from one end of the device to another. Once at the far end, the cells fall into distinct collection channels based on how many particles they carry as a proxy for the amount of the target protein.

"As many as one billion cells can travel down this highway of magnetic guides at once and we can process that in one hour," says Kelley." It's a huge gamechanger for CRISPR screens."

To test if MICS can reveal new drug targets, the researchers focused on cancer immunotherapy, in which the immune system is engineered to destroy tumour cells. They looked for a way to reduce the levels of the CD47 protein which sends a "don't eat me" signal to the immune system and is often hijacked by cancer cells as a way of escaping immune detection. Others have found that blocking CD47 directly has harmful side effects, prompting the Medicine by Design team to look for the genes that regulate CD47 protein levels.

A genome-wide CRISPR screen revealed a gene called QPCTL which codes for an enzyme that helps camouflage CD47 from the immune system and that could be blocked with an off-the-shelf drug.

"If you can modulate CD47 levels by acting on QPCTL , that could be an interesting way to trick the immune system to clear cancer" says Moffat.

It's early days yet, but Kelley and Moffat are hopeful about QPCTL's therapeutic potential in cancer, perhaps as a way to get macrophages to target tumor cells. They are also launching a multi-lab collaboration PEGASUS project, for Phenotypic Genomic Screening at Scale, which will scale up the technology to interrogate a broad range of therapeutic targets.

On the regenerative medicine front, MICS will help reveal the genes that activate stem cells to turn into specialized cell types, which will make easier harvesting of desired cell types for therapy.

Although Kelley's team initially developed magnetic cell sorting for isolating tumour cells from the blood, its repurposing for drug target discovery could have a wider impact, with MICS already attracting significant interest from the research community and industry.

NASA calculated the rainfall rates in the Atlantic Ocean's newest tropical cyclone, Lorenzo.

NASA has the unique capability of peering under the clouds in storms and measuring the rate in which rain is falling. Global Precipitation Measurement mission or GPM core passed over the region from its orbit in space and measured rainfall rates in the storms.

The Global Precipitation Measurement mission or GPM core satellite passed over the eastern North Atlantic Ocean on Sept. 23 at 7:46 a.m. EDT (1146 UTC) and provided rainfall rates in Tropical Storm Lorenzo. The heaviest rainfall was occurring around the center, falling at a rate of over 36 mm (about 1.4 inch) per hour and at a rate of 25 mm (about 1 inch) per hour around a band of thunderstorms southeast of center. Both the Japan Aerospace Exploration Agency, JAXA and NASA manage GPM.

Forecasters at NOAA's National Hurricane Center or NHC noted at 11 a.m. EDT (1500 UTC), the center of Tropical Storm Lorenzo was located near latitude 11.1 degrees north and longitude 24.1 degrees west. Interests in the Cabo Verde Islands should monitor the progress of this system.

Lorenzo is moving toward the west near 18 mph (30 kph). Maximum sustained winds have increased to near 40 mph (65 kph) with higher gusts. Additional strengthening is forecast, and Lorenzo is expected to become a hurricane by Wednesday. The estimated minimum central pressure is 1006 millibars. A motion toward the west-northwest is expected starting tonight, and this is forecast to continue through the middle of the week. On the forecast track, the center of the tropical storm should pass well to the south of the Cabo Verde Islands today and tonight.

Hurricanes are the most powerful weather event on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

For updated forecasts, visit: http://www.nhc.noaa.gov

Dads are often happier, less stressed and less tired than moms when taking care of kids, and researchers say these differences may come down to how and when childcare activities are split between parents.

In a study led by Penn State, researchers looked at childcare through the lens of a "care context." Going beyond measuring how much time mothers and fathers spend taking care of their children, the researchers also looked at the type of childcare activity, when and where it took place, who was present, and how much care was involved.

Cadhla McDonnell, a doctoral candidate in sociology and demography at Penn State, said the results suggest that while fathers in general are much more involved in their children's lives now than in the past, parenting is still highly gendered.

"There are many types of activities that can be considered childcare, but some are more strenuous or less enjoyable than others," McDonnell said. "A family trip to the playground is going to affect someone differently than changing diapers in the middle of the night, for example. In our study, we tried to capture those variations and see if they're related to the differences we see between mothers' and fathers' moods."

According to the researchers, previous work has shown that mothers tend to be more tired, stressed and unhappy than fathers during caregiving. But sociodemographic characteristics alone could not explain some of these differences. The researchers were curious about whether taking a closer look at how childcare activities were divided between parents could help explain discrepancies between parents' moods.

The researchers used data from the American Time Use Survey collected by the U.S. Census Bureau. Data included information about 4,486 childcare activities, as well as who performed the activity and that person's corresponding mood.

Additionally, the researchers analyzed each activity through the care context, which included five dimensions. The first was "activity type," and included physical (basic needs like eating and sleeping), recreational (like play and sports), educational (helping with homework or meeting with teachers), and managerial (planning doctor visits or transporting children).

The remaining dimensions included when and where the activity took place, who was present during the activity, and how much time the activity took.

The researchers found that fathers' childcare activities were more likely to be recreational and take place on the weekend, while mothers' activities were more likely to involve an infant and fit into the category of "solo parenting," that is, parenting without a partner present.

Also, the researchers found that taking the context of childcare activities into account fully explained differences in mother and father happiness, and partially explained differences in stress. It did not explain differences in tiredness.

McDonnell said the study -- recently published in the Journal of Family Issues -- suggests that moms are generally more tired and stressed than dads, and that they also are doing more childcare activities that tend to produce more stress and less happiness. But it is still not clear why these differences exist.

"Our findings show that some aspects of parenting are more enjoyable than others and that the way childcare is distributed between mothers and fathers right now brings more emotional rewards for dads than for moms," McDonnell said. "But it's impossible to say from our data whether this is the result of personal choices or whether it's a reaction to outside forces like job demands."

Additionally, the researchers found that despite their differences, one thing that remained consistent between mothers and fathers was how meaningful they found childcare.

"Traditionally caregiving has been seen as more central to women's identities than it is to men's, and that would suggest that mothers might find caring for their children more meaningful than fathers do," McDonnell said. "But that's not the case -- mothers and fathers both found caring for children highly meaningful and there is no difference by gender."

McDonnell said that in the future, additional research could focus on how gendered caregiving may have additional impacts on parents' well being.

"We know from other research that parents tend to have lower life satisfaction than non-parents, and this is especially true for women," McDonnell said. "An interesting question could be how that's related to gendered caregiving. Why do mothers seem to take on childcare in contexts that are less emotionally rewarding? For couples, how can they share caregiving in a way that is equally rewarding for both partners? These are all important questions."

The Northern Indian Ocean has generated a new tropical cyclone. NASA provided an infrared look a recently formed Tropical Storm Hikaa, moving through the Arabian Sea.

One of the ways NASA researches tropical cyclones is by using infrared data that provides temperature information. The AIRS instrument aboard NASA's Aqua satellite captured a look at those temperatures in Hikaa and gave insight into the storm's rainfall potential. Cloud top temperatures provide information to forecasters about where the strongest storms are located within a tropical cyclone. Tropical cyclones do not always have uniform strength, and some sides have stronger sides than others. The stronger the storms, the higher they extend into the troposphere, and the colder the cloud temperatures are.

NASA provides data to forecasters around the world so they can incorporate that data into their forecasting.

On Sept. 23 at 4:05 a.m. EDT (0905 UTC) NASA's Aqua satellite analyzed the storm using the Atmospheric Infrared Sounder or AIRS instrument. AIRS found coldest cloud top temperatures as cold as or colder than minus 63 degrees Fahrenheit (minus 53 degrees Celsius) from west to south around Hikaa's center. NASA research has shown that cloud top temperatures that cold indicate strong storms that have the capability to create heavy rain.

At 11 a.m. EDT (1500 UTC), The Joint Typhoon Warning Center said the center of Tropical Hikaa was located near latitude 20.2 degrees north and longitude 65.5 degrees east. It is located about 265 miles east of Masirah Island, Oman. The tropical storm was moving toward the west. Maximum sustained winds are near 60 knots (69 mph/111 kph) with higher gusts.

Hikaa will strengthen slightly before making landfall in Oman after a day or so.

The AIRS instrument is one of six instruments flying onboard NASA's Aqua satellite, launched on May 4, 2002.

Hurricanes are the most powerful weather event on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

Over millions of years, Earth's summits and valleys have moved and shifted, resulting in the dramatic landscapes of peaks and shadows we know today. Mountains often form when pressure under Earth's surface pushes upward, yet many factors impact their ultimate height, including the erosion of the areas between mountains, known as channels.

Scientists have long assumed that as land is pushed faster upward to form a mountain, its height increases in a continuous and predictable way. But new research shows that these predictions may stop working for the steepest mountains and therefore limit their height - and this may hold true for ranges on the entire planet.

"People have argued for a long time that as channels get steeper and steeper, the erosion rate keeps increasing," said George Hilley, a professor of geological sciences at Stanford University's School of Earth, Energy & Environmental Sciences (Stanford Earth) and lead author of a study published in Nature Geoscience Sept. 16. "We find that the theory works really well until a certain point and then it breaks down empirically - it seems as though something else kicks in that we don't completely understand."

The researchers analyzed samples from a broad range of mountain landscapes across the tropics, including Venezuela, Brazil, Guatemala, Costa Rica and Taiwan, controlling for rock type and climate conditions to assess parallel comparisons. They found that after mountains reach a certain elevation, channels between mountains suddenly become extremely sensitive to subtle changes in their inclines, thereby limiting the height of the mountains above. They added data from hundreds of mountain ranges worldwide and found they followed a similar pattern: the height, or relief, of the landscape is capped after crossing a threshold driven by channel steepness.

"Areas of land above channels are likely being controlled by how quickly a river can cut down - this is the framework by which we understand how the height of mountains varies as a function of climate and the collision of continents," Hilley said. "The anomaly we observed is kind of a mystery and is not necessarily what conventional theory might predict."

Research impacts

By bringing evidence of this mysterious factor influencing mountain height, the research could impact other work, such as studies on the relationship between mountain erosion rates and climate - important elements for understanding ancient climate and forecasting future patterns.

"Our work adds an interesting depth to some of these studies, because the way in which Earth's topography changes as climates become more or less erosive may also change as the threshold is approached," Hilley said.

The work also has implications for the geophysical links of mountain formation, which scientists are interested in exploring to understand the hidden activity of tectonic movements below our feet.

"People like me have always hoped that you could actually use the topography in order to say something about how quickly faults might be slipping," Hilley said. "What our results say is that you can still do that in landscapes that are moderately steep, but it might become increasingly difficult as landscapes become steeper."

Global patterns

The scientists took a fundamentally different approach to the research by searching the globe for conditions that reveal changes in mountain height rather than focusing on just one location. That search led them to focus on ranges in the tropics, but the conclusions were consistent across all regions of the globe and may also be applied to understand ancient topography.

"The Himalayas are being uplifted pretty rapidly and they expose pretty hard rocks, and indeed, when you measure them out, they are pretty close to this threshold," he said. "You might be able to take this threshold with just the modern configuration of the landscape and actually place some upper bound on what the topography of the ancient Himalayas looked like."

Hilley said the results of the study were surprising, as well as the fact that they remained consistent when compared with global data.

"In retrospect it makes sense when you look at it from the overall context of what our planet actually looks like," Hilley said. "It really speaks to the fact that there might be lots of fertile ground to explore why this might happen. It also points to the fact that there might be something about the way in which rivers incise that we just don't understand yet."

Queensland University of Technology (QUT) researchers have applied artificial intelligence (AI) deep learning techniques to develop a more accurate and detailed method for analysing images of the back of the eye to help clinicians better detect and track eye diseases, such as glaucoma and aged-related macular degeneration.

Their findings have been published in Nature Scientific Reports.

Study lead author QUT Senior Research Fellow Dr David Alonso-Caneiro, from the Faculty of Health, School of Optometry and Vision Science, said the team had explored a range of state-of-the-art deep learning techniques to analyse Optical Coherence Tomography (OCT) images.

OCT is a common instrument used by optometrists and ophthalmologists. It takes cross-sectional images of the eye which show different tissue layers. These images are high-resolution - about 4 microns; much less than, for example, a human hair, which is about 100 microns thick.

Dr Alonso-Caneiro said using OCT scanning to map and monitor the thickness of the tissue layers in the eye can help clinicians to detect eye diseases.

"In our study we looked for a new method of analysing the images and extracting two main tissue layers at the back of the eye, the retina and choroid, with special interest in the choroid," he said.

"The choroid is the area between the retina and the sclera, and it contains the major blood vessels that provide nutrients and oxygen to the eye.

"The standard imaging processing techniques used with OCT define and analyse the retinal tissue layers well, but very few clinical OCT instruments have software that analyses the choroidal tissue.

"So we trained a deep learning network to learn the key features of the images and to accurately and automatically define the boundaries of the choroid and the retina."

The team collected OCT chorio-retinal eye scans from an 18-month longitudinal study of 101 children with good vision and healthy eyes, and used these images to train the program to detect patterns and define the choroid boundaries.

They then compared what they developed with standard image analysis methods and found their program to be reliable and more accurate.

"Being able to analyse OCT images has improved our understanding of eye tissue changes associated with normal eye development, ageing, refractive errors and eye disease," Dr Alonso-Caneiro said.

"Having more reliable information from these images of the choroid, which our program provides, is important clinically and also for advancing our understanding of the eye through research.

"We feel our methods could provide a way to better map and monitor changes in choroid tissue, and potentially diagnose eye diseases earlier."

Dr Alonso-Caneiro said the new program had been shared with eye researchers in Australia and overseas, and it was hoped that makers of commercial OCT instruments may be interested in applying it.

The team also wants to do further research to test the program on images from older populations and people with diagnosed disease.

Scientists studying genetic transcription are gaining new insights into a process that is fundamental to all life. Transcription is the first step in gene expression, the process taking place within all living cells by which the DNA sequence of a gene is copied into RNA, which in turn (most generally speaking) serves as the template for assembling protein molecules, the basic building blocks of life.

Much of what scientists have uncovered about transcription over the past five decades is based on bulk investigative techniques employing large numbers of living cells. Today, advanced imaging techniques allow scientists to probe the inner workings of transcription at the scale of individual genes, and a new more detailed picture of this vital process is emerging.

Just this week, two new in vivo single-molecule studies of transcription in E. coli were published by scientists at the University of Illinois at Urbana-Champaign, one by Professor Ido Golding and colleagues, unveiling unexpected and up-to-now hidden drivers of cellular individuality; the other by Professor Sangjin Kim and colleagues, demonstrating for the first time that transcription dynamics are affected by molecular-scale long-distance communication between RNA polymerase (RNAP) molecules while they are "reading" a gene sequence one base at a time and assembling the complementary RNA strand.

Taken together, these two studies elucidate new details of the physical processes of gene expression at the level of individual cells and initiate an exciting new direction of inquiry for member scientists of the Center for the Physics of Living Cells (CPLC), a National Science Foundation Physics Frontiers Center in the Department of Physics at the University of Illinois at Urbana-Champaign.

Kim notes, "My dream project is to probe the physical mechanism of this emergent phenomenon--the coupling between DNA supercoiling and RNA polymerase motion. The CPLC is a fantastic place to pursue this and to collaborate with other theoretical and experimental scientists at the intersection of microbiology, biochemistry, and biophysics. I have already connected with wonderful new colleagues who are interested in collaborating on this, including Ido Golding, Nigel Goldenfeld, and Yann Chemla."

Golding and Kim only recently joined the faculty at Illinois Physics, and the two unrelated but complementary experiments were performed at the scientist's respective prior institutions. Golding, who had been a faculty member at Illinois Physics from 2007 to 2009, returned to Illinois Physics in July 2019 from Baylor College of Medicine in Houston, where he held an appointment as a professor of biochemistry and molecular biology. Kim joined the faculty at Illinois Physics in January 2019, following a postdoctoral appointment at Yale University, where she worked in the research group of noted microbiologist Professor Christine Jacobs-Wagner.

Drivers of bacterial individuality

Golding, along with colleagues at Baylor College of Medicine and Shanghai Jiao Tong University in China, have uncovered specific drivers of bacterial individuality, ultimately bringing the process of transcription into greater focus. The researchers used single-cell measurements as well as computational modeling to characterize the phases of gene transcription in terms of their dynamics.

The team's findings were published online in a Nature Microbiology letter on September 16, 2019.

The team observed that a weakly expressed gene exhibits a temporary pulse of transcription activity around the time of gene replication. In other words, transcription responds, directly or indirectly, to the event of gene replication.

"It is too soon to determine definitively what the underlying mechanism is for this coupling of DNA replication and RNA transcription," notes Golding. "But it is clear that this phenomenon is a driver of individuality among cells in a colony, because individual cells in the growing population are unsynchronized in their cell-cycle phase, therefore each will replicate the gene at a different time."

Golding adds, "While we still do not know the reason for this coupling of transcription and gene replication, there are many plausible hypotheses, and theorists have been speculating on this for many years. It's been suggested, for example, that the newly synthesized DNA--the gene--is more susceptible to binding by the cellular machines that drive transcription (RNAP and others)."

Golding's postdoctoral researcher Mengyu Wang, who is co-lead author on this study, followed Golding to Illinois and the CPLC. Wang remembers his initial surprise when repeated experimental runs yielded another transcription correlation. The researchers found that when there are two or more copies of the same gene within the same cell, they can sometimes affect each other, switching transcription on or off in unison.

Wang comments, "Scientists had assumed there is no correlation between different gene copies. We repeated our experiment several times and, within each run, there were a few samples, so we are confident in our result. There exists a correlation between different copies of the same gene, and this correlation depends on the growth conditions. Further investigation is necessary to understand the underlying mechanism at work here."

Golding notes that there is still a lot of ground to cover in our investigations of RNA transcription, to bring the process into greater focus.

"Theoretical models that both interpret and predict the results of
bulk studies represent the intracellular process of transcription as stochastic--it's inherently random and unpredictable at the level of the cell. These models are very useful to our understanding of what's happening both at the level of individual cells and within colonies of cells. But such course-grained pictures run the risk of labelling everything that's unknown as unknowable and random," remarks Golding.

New research initiatives at the Center for the Physics of Living Cells promise to help uncover the specifics of the most fundamental biological processes involved in heredity and the uniqueness of individuals.

"By examining transcription as it takes place at an individual copy of a single gene in the cell, rather than making deductions from the overall number of RNA molecules present in the cell, we were able to observe new details that current theoretical models of the process don't take into account," Golding concludes.

At Illinois, Golding is a member of the CPLC and is an affiliate of the Carl R. Woese Institute for Genomic Biology and of the Department of Microbiology.

This work was supported by the National Institutes of Health, the National Science Foundation, and by grants from private foundations and Chinese national funding agencies. The conclusions presented are those of the researchers and not necessarily those of the funding agencies.

Long-range "communication" among RNA polymerase molecules on a single gene

Kim, along with colleagues at the interdisciplinary Microbial Sciences Institute at Yale University, performed in vitro and in vivo experiments on genes having multiple RNAPs simultaneously transcribing the gene, each at different points of progress along the gene. The team observed long-range interactions that accelerated or impaired neighboring RNAPs' transcription speed, depending on whether the gene was turned on or off in response to environmental conditions.

These findings were published online on September 19, 2019 in the journal Cell.

The team observed that, surprisingly, RNAPs can communicate with each other from distances as far as two thousand bases apart on the DNA. And when there are multiple RNAPs, they translocate faster than a single RNAP.

Kim explains the mechanism underlying this communication.

"This communication is coming from a property of DNA called supercoiling, which dynamically changes during both replication and transcription," she describes.

"DNA is a double helix that supercoils--like a rope that can be twisted--in response to a portion of the double strand being opened so that it can be read," Kim continues. "The twisting is a natural consequence of the function. In transcription, as RNAP translocates along the DNA, DNA becomes twisted, but our study shows that this in turn becomes a mechanism allowing for the long-distance communication between RNAPs."

The team further found that when the promoter--the portion of a gene that acts like a switch to turn transcription on and off, depending on environmental conditions and cellular needs--was switched off, RNAPs slow down and some become disconnected from the gene.

According to Kim, further study of the collective behavior of RNAPs could shed new light on a variety of molecular processes happening on the DNA, including the evolution of gene mutations.

"It is known that when RNAP stops, it can introduce mutations on the genetic code. This has possible implications for the rise of antibiotic resistance in bacteria. In future work at the CPLC, I want to test this by modulating DNA supercoiling and looking deeper at the mechanics. This line of inquiry provides a great opportunity for collaboration between theory and experiment."

Harnessing light's energy into nanoscale volumes requires novel engineering approaches to overcome a fundamental barrier known as the "diffraction limit." However, University of Illinois researchers have breached this barrier by developing nanoantennas that pack the energy captured from light sources, such as LEDs, into particles with nanometer-scale diameters, making it possible to detect individual biomolecules, catalyze chemical reactions, and generate photons with desirable properties for quantum computing.

The results, which have a broad array of applications that may include better cancer diagnostic tools, were recently published in the Nano Letters, a prestigious peer-reviewed journal published by the American Chemical Society in a paper entitled "Microcavity-Mediated Spectrally Tunable Amplification of Absorption in Plasmonic Nanoantennas," The research was funded by the National Science Foundation.

To create a device capable of overcoming the diffraction limit, graduate student Qinglan Huang and her adviser, Holonyak Lab Director Brian T. Cunningham, a Donald Biggar Willett Professor in Engineering, coupled photonic crystals with a plasmonic nanoantenna, an innovative approach in the field. The photonic crystals serve as light receivers and focus the energy into an electromagnetic field that is hundreds of times greater than that received from the original light source, such as an LED or laser. The nanoantennas, when "tuned" to the same wavelength, absorb the energy from the electromagnetic field and concentrate the energy into a smaller volume that is yet another two orders of magnitude of greater intensity. The energy feedback between the photonic crystal and the nanoantenna, called "resonant hybrid coupling" can be observed by its effects on the reflected and transmitted light spectrum.

"To get cooperative coupling between two things is exciting because it's never been done," said Huang. "It's a general-purpose concept that we have experimentally demonstrated for the first time."

To achieve this, the team carefully controlled the density of the nanoantennas to maximize their energy collection efficiency. They also developed a method that allowed the nanoantennas to be distributed uniformly across the photonic crystal surface and tuned the photonic crystal's optical resonating wavelength to match the absorption wavelength of the nanoantennas.

In addition to changing how researchers can work with light, this new coupling method has the potential to change how and when cancer is diagnosed. One application is to use a gold nanoparticle, not much larger than biomolecules such as DNA, as the nanoantenna. In this case, the feedback provides a way to identify a biomarker unique to a certain type of cancer cell, and the group now linking the resonant hybrid coupling technique to novel biochemistry methods to detect cancer-specific RNA and DNA molecules with single-molecule precision. Cunningham, and other members of the Nanosensor Group will soon publish another paper that focuses specifically on the discovery's applications in regards to cancer diagnostics.

"Nano Letters is a very tough journal to get into," said Cunningham. "But the novel physics in this research and the potential for broad applications are what make this research stand out. The next steps of this research involve delving into the potential applications of this new process.

Almost 50 years since the late Richard Heck discovered the powerful chemical reaction that led to the University of Delaware professor's 2010 Nobel Prize, chemists are still finding new and valuable ways to use the Heck Reaction.

One of them -- Prof. Donald A. Watson -- is part of the Department of Chemistry and Biochemistry where Heck taught during his time on UD's faculty (1971-89). And Watson and his research group have just published new findings that could streamline development and production of small-molecule pharmaceuticals, which comprise the majority of medicines in use today. The active ingredients in these small-molecule drugs are typically delivered by a tablet or capsule and absorbed into the bloodstream.

Their work, published in Angewandte Chemie, shows how the Heck Reaction (which uses palladium as a catalyst to bond carbon molecules) can make it easier and more practical to produce indoline scaffolds -- structures that provide an important platform for new molecules.

Indoline scaffolds are found in many natural products as well as medicines used to treat diseases including cancer, hypertension, migraine headaches and other conditions.

But producing these scaffolds has been challenging, especially when more complexity is required.

Watson and his group saw a new way to deploy the Heck Reaction, using nitrogen, an electron-craving element, to accomplish the assembly in previously unattempted ways and make complex assemblies accessible. With nitrogen as a reagent -- the element that governs the chemical reaction -- new possibilities emerged.

"Everything Heck focused on is based on carbon-based reagents," Watson said. "We are asking, can this be applied to other elements in the periodic table? The answer to that in short is yes. That's what we're finding... We have looked at silicon, boron atoms and, now, nitrogen, which is directly relevant to the fabrication of bioactive compounds."

A bioactive compound is used to provoke a specific biological response in a living organism. The bioactive compounds in medicines, for example, may be used to kill bacteria, lower blood pressure or kill cancer cells.

Watson credits doctoral student Feiyang Xu, the lead author of the article, with finding the path to this conversion process.

"I said, 'wouldn't it be great if we could figure out how to do this?' And Feiyang figured it out," Watson said.

"We've been exploring the parameters of what's allowed," Watson said, "and fleshing out the rules of how these new reactions work. And that's our job as basic scientists, to define and provide tools for other chemists, to find where those tools will and will not work and what you can do with those tools."

Key to the process is forcing nitrogen to do the chemist's bidding in a twist that chemists call "ümpole."

"Everything has its own inherent activity," said doctoral student Katerina M. Korch, who helped to design experiments, develop a substrate table (that provides the results of all tests done on the compounds studied) and write the manuscript. "Doing the ümpole is forcing it do something it wouldn't do naturally."

Naturally, nitrogen is an electron hog. In this process, the researchers have created elements where nitrogen doesn't have enough electrons, steering it in the direction needed for this process.

"Carbon is easy to do that with," Watson said. "Getting nitrogen to behave this way in these types of reactions is the new thing that we're trying to figure out how to exploit."

As the work proceeds, Watson expects even more benefits.

"This chemistry is going to be very scalable," he said. "And it uses readily available materials."

The Watson team uses UD's nuclear magnetic resonance (NMR) spectroscopy facilities to observe and analyze the molecular structure of the materials.

"There are a million ways you can do things," Watson said. "But some answers wind up better than others. This provides an easier way to prepare things, with more simple starting materials and streamlines how you can access more complex molecules."

Murray Johnston, associate dean of the College of Arts and Sciences and professor of chemistry, said it was gratifying to see Watson and his group continuing to advance Heck's science.

"The groundwork laid by Professor Heck continues to thrive at UD," Johnston said. "In Don Watson and his group, we have a new generation of researchers who are modifying this chemistry in clever ways to make bioactive molecules."

And that could lead to tremendous advances.

"What gets all of us up every day and motivates us to do what we do is this: There are a lot of medical needs in the world," Watson said. "Our group tries to develop tools so medicinal chemists who are developing new medicines have those tools to make the compounds they need to treat disease."

The low FODMAP diet, a diet low in carbohydrates that trigger digestive symptoms like bloating and stomach pain, is a useful treatment in children and adolescents with gastrointestinal problems, new University of Otago research confirms.

The Otago research involved a clinical review of 29 children from Christchurch Public Hospital aged between 4 and 17 who were following the low FODMAP diet under the guidance of specialists.

Complete resolution of gastrointestinal symptoms was observed in 92 per cent of the children with bloating, 87 per cent of those with diarrhoea and 77 per cent of those with abdominal pain.

Lead author of the review, Professor Andrew Day from the University of Otago, Christchurch, explains that while the low FODMAP diet is well established as a safe and effective dietary strategy to alleviate bowel symptoms in adults, there is currently little data examining the benefits and safety of dietary interventions that restrict carbohydrates in children with bowel disorders.

"To our knowledge the present study is the only one to report efficacy and safety data for the low FODMAP diet in children with functional bowel disorders in a real-world setting," Professor Day, a paediatric gastroenterologist, says.

Given the increase in the number of children worldwide suffering from some form of functional bowel disorders, Professor Day says studies are required to determine the efficacy and safety of the diet in children.

"This study showed that more than 50 per cent of children with a bowel disorder who complete the FODMAP restriction and reintroduction process will have complete resolution of symptoms, particularly those with lower GI (gastrointestinal) symptoms."

The results are similar to those previously reported in adults. The diet appears to be more beneficial for participants with symptoms of flatulence, diarrhoea, abdominal pain and distention.

In the study, most participants reported a "substantial improvement" of their symptoms with those with abdominal bloating having the highest rate of improvement, followed by those with abdominal pain.

Fructans were the most common intolerance (67 per cent), followed by lactose (56 per cent), polyols (7 per cent), fructose (7 per cent) and galactose oligosaccharides (7 per cent). Six children (24 per cent) specifically identified that apples (fructose and sorbitol) triggered symptoms.

Professor Day says further studies are needed in children to better understand factors such as the impacts on growth and the gut microbiome and the consequences of long-term dietary restriction.

They've been called the "special forces" of the immune system: invariant natural killer T cells. Although there are relatively few of them in the body, they are more powerful than many other immune cells.

In experiments with mice, UCLA researchers have shown they can harness the power of iNKT cells to attack tumor cells and treat cancer. The new method, described in the journal Cell Stem Cell, suppressed the growth of multiple types of human tumors that had been transplanted into the animals.

"What's really exciting is that we can give this treatment just once and it increases the number of iNKT cells to levels that can fight cancer for the lifetime of the animal," said Lili Yang, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and the study's senior author.

Scientists have hypothesized that iNKT cells could be a useful weapon against cancer because it has been shown that they are capable of targeting many types of cancer at once -- a difference from most immune cells, which recognize and attack only one particular type of cancer cell at a time. But most people have very low quantities of iNKT cells; less than 0.1% of blood cells are iNKT cells in most cases.

Still, Yang and her colleagues knew that previous clinical studies have shown that cancer patients with naturally higher levels of iNKT cells generally live longer than those with lower levels of cells.

"They are very powerful cells but they're naturally present in such small numbers in the human blood that they usually can't make a therapeutic difference," said Yang, who also is a UCLA assistant professor of microbiology, immunology and molecular genetics and a member of the UCLA Jonsson Comprehensive Cancer Center. ¬¬

The researchers' goal was to create a therapy that would permanently boost the body's ability to naturally produce more iNKT cells. They started with hematopoietic stem cells -- cells found in the bone marrow that can duplicate themselves and can become all types of blood and immune cells, including iNKT cells. The researchers genetically engineered the stem cells so that they were programmed to develop into iNKT cells.

They tested the resulting cells, called hematopoietic stem cell-engineered invariant natural killer T cells, or HSC-iNKT cells, on mice with both human bone marrow and human cancers -- either multiple myeloma (a blood cancer) or melanoma (a solid tumor cancer) -- and studied what happened to the mice's immune systems, the cancers and the HSC-iNKT cells after they had integrated into the bone marrow.

They found that the stem cells differentiated normally into iNKT cells and continued to produce iNKT cells for the rest of the animals' lives, which was generally about a year.

"One advantage of this approach is that it's a one-time cell therapy that can provide patients with a lifelong supply of iNKT cells," Yang said.

While mice without the engineered stem cell transplants had nearly undetectable levels of iNKT cells, in those that received engineered stem cell transplants, iNKT cells made up as much as 60% of the immune systems' total T cell count. Plus, researchers found they could control those numbers by how they engineered the original hematopoietic stem cells.

Finally, the team found that in both multiple myeloma and melanoma, HSC-iNKT cells effectively suppressed tumor growth.

The study's co-first authors are Yanni Zhu, a UCLA project scientist, and Drake Smith, a UCLA doctoral student.

More work is needed to determine how HSC-iNKT cells might be useful for treating cancer in humans and whether increasing the number of HSC-iNKT cells could cause long-term side effects. But Yang said hematopoetic stem cells collected either from a person with cancer or a compatible donor could be used to engineer HSC-iNKT cells in the lab. The procedure for transplanting stem cells into patients' bone marrow is already well-established as a treatment for many blood cancers.

The biodiversity buzz is alive and well in Fiji, but climate change, noxious weeds and multiple human activities are making possible extinction a counter buzzword.

Just as Australian researchers are finding colourful new bee species, some of them are already showing signs of exposure to environmental changes.

Flinders University PhD candidate James Dorey - whose macrophotography has captured some of Fiji's newest bee species - says the naming of nine new species gives researchers an opportunity to highlight the risks.

"Homalictus terminalis is named so to indicate that, like many Fijian bees, it is nearing its limit and is at risk of climate-related extinction," he says.

"Found only on Mount Batilamu near the city of Nadi, where many tourists launch their holidays, H. terminalis has only been found within 95 metres of the mountain peak."

South Australian university students on the Asutralian Government's New Colombo overseas study program have gone to Fiji in the south-west Pacific for several years, naming nine new species in one of their latest research publications in Zootaxa.

The impressive black Homalictus achrostus, featuring unusual large mandibles, is one of the most interesting endemic bee species on Fiji.

But, like many Fijian bee species, H. achrostus has only ever found on a single mountain top.

"Six individuals were collected on Mount Nadarivatu in the 1970s and two in 2010, but despite frequent searching almost every year since no more have been found," says Flinders University Associate Professor Mike Schwarz, a co-author on the paper.

"A likely driver of this possible extinction is changing climates," Associate Professor Schwarz says.

"The cooler climate of the Fijian highlands could be slowly pushed upwards and off the top of the mountains bringing with it the species that require this climatic refuge.

"With H. achrostus one of the four previously described species of endemic bee in Fiji, this raises real concerns about the extinction of many highland species in Fiji and across all of the tropics."

South Australia Museum senior researcher terrestrial invertebrates, Dr Mark Stevens, says the bee genus Homalictus Cockerell has not been taxonomically reviewed in the Fijian archipelago for 40 years.

"These field trips have allowed us to redescribe four known species and describe nine new ones, bringing the number of endemic Homalictus in Fiji to 13 species," says Dr Stevens, who is collaborating on the study.

"Most of the species diversity (11 species) live 800 metres or more above sea level, which highlights the vulnerability of highland-restricted species to a warming climate."

One of the new species, the eye-catching Homalictus groomi, was named in honour of Flinders biological sciences graduate Dr Scott Groom, who began uncovering this hidden diversity using molecular techniques with Flinders University and the South Australian Museum in 2009.

Previous New Colombo Plan biological sciences field trips have also studied the effects of noxious weeds and human activities on other animals and plants in Fiji.

Increasing nut consumption by just half a serving (14 g or ½ oz) a day is linked to less weight gain and a lower risk of obesity, suggests a large, long term observational study, published in the online journal BMJ Nutrition, Prevention & Health.

Substituting unhealthy foods, such as processed meats, French fries, and crisps (potato chips) with a half a serving of nuts may be a simple strategy to ward off the gradual weight gain that often accompanies the aging process, suggest the researchers.

On average, US adults pile on 1lb or nearly half a kilo every year. Gaining 2.5-10 kilos in weight is linked to a significantly greater risk of heart disease/stroke and diabetes.

Nuts are rich in healthy unsaturated fats, vitamins, minerals and fibre, but they are calorie dense, so often not thought of as good for weight control. But emerging evidence suggests that the quality of what's eaten may be as important as the quantity.

Amid modest increases in average nut consumption in the US over the past two decades, the researchers wanted to find out if these changes might affect weight control.

They analysed information on weight, diet and physical activity in three groups of people: 51,529 male health professionals, aged 40 to 75 when enrolled in the Health Professionals Follow Up Study; 121,700 nurses, aged 35 to 55 when recruited to the Nurses Health Study (NHS); and 116,686 nurses, aged 24 to 44 when enrolled in the Nurses Health Study II (NHS II).

Over more than 20 years of monitoring, participants were asked every 4 years to state their weight, and how often, over the preceding year they had eaten a serving (28 g or 1 oz) of nuts, including peanuts and peanut butter.

Average weekly exercise-- walking, jogging, cycling, swimming, racquet sports and gardening--was assessed every two years by questionnaire. It was measured in metabolic equivalent of task (MET) hours, which express how much energy (calories) is expended per hour of physical activity.

Average annual weight gain across all three groups was 0.32 kg (0.71 lb). Between 1986 and 2010, total nut consumption rose from a quarter to just under half a serving/day in men; and from 0.15 to 0.31 servings/day among the women in the NHS study. Between 1991 and 2011 total daily nut consumption rose from 0.07 to 0.31 servings among women in the NHS II study.

Increasing consumption of any type of nut was associated with less long term weight gain and a lower risk of becoming obese (BMI of 30 or more kg/m²), overall.

Increasing nut consumption by half a serving a day was associated with a lower risk of putting on 2 or more kilos over any 4 year period. And a daily half serving increase in walnut consumption was associated with a 15% lower risk of obesity.

Substituting processed meats, refined grains, or desserts, including chocolates, pastries, pies and donuts, for half a serving of nuts was associated with staving off weight gain of between 0.41 and 0.70 kg in any 4 year period.

Within any 4 year period, upping daily nut consumption from none to at least half a serving was associated with staving off 0.74 kg in weight, a lower risk of moderate weight gain, and a 16% lower risk of obesity, compared with not eating any nuts.

And a consistently higher nut intake of at least half a serving a day was associated with a 23% lower risk of putting on 5 or more kilos and of becoming obese over the same timeframe.

No such associations were observed for increases in peanut butter intake.

The findings held true after taking account of changes in diet and lifestyle, such as exercise and alcohol intake.

This is an observational study, and as such, can't establish cause. And the data relied on personal report, which may have affected accuracy, while only white, relatively affluent health professionals were included, so the findings may not be more widely applicable.

But the findings echo those of previous observational studies, note the researchers, who attempt to explain the associations they found.

Chewing nuts takes some effort, leaving less energy for eating other things, they suggest, while the high fibre content of nuts can delay stomach emptying so making a person feel sated and full for longer.

Nut fibre also binds well to fats in the gut, meaning that more calories are excreted. And there is some evidence that the high unsaturated fat content of nuts increases resting energy expenditure, which may also help to stave off weight gain.

Snacking on a handful of nuts rather than biscuits or crisps may help to ward off the weight gain that often accompanies aging and is a relatively manageable way of helping to curb the onset of obesity, they suggest.

And a nut habit is likely to be good for the planet, they add. "In addition to the impact on human health, using environmentally friendly plant-based protein, such as nuts and seeds to replace animal sources of protein may contribute to the promotion of a global sustainable food system," they write.

What The Study Did: Whether insulin treatment was used less frequently and discontinued more often among older adults (ages 75 to 79) in poor health compared with those in good health was the focus of this observational study that included more than 21,000 adults with type 2 diabetes.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Jonathan Z. Weiner, M.D., M.P.H., of Kaiser Permanente of Northern California in Oakland, is the corresponding author.

(doi:10.1001/jamainternmed.2019.3759)

Editor's Note: The article contains conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Boulder, Colo., USA: The Sahara Desert is vast, generously dusty, and surprisingly shy about its age. New research looking into what appears to be dust that the Sahara blew over to the Canary Islands is providing the first direct evidence from dry land that the age of the Sahara matches that found in deep-sea sediments: at least 4.6 million years old.

"People have been trying to figure it out for several decades," said Daniel Muhs, a geologist with the U.S. Geological Survey in Denver, Colorado. "More recent studies said it was the beginning of the Pleistocene (about 2.6 million years ago). Then others say a few thousand years ago." Added to this is a model suggesting the Sahara Desert first appeared as far back as seven million years ago.

There is also other evidence that the desert has taken breaks and had wetter, greener periods interspersed with arid times. It's this sensitivity to climate -- and the Sahara's role in global climate -- that makes the region so interesting to researchers.

The new work by Muhs and his colleagues in the Canary Islands focused on thick layers of fine reddish-brown soil found among layers of volcanic rocks and dune sands on Fuerteventura and Gran Canaria islands. The islands are off the west coast of North Africa, at the mouth of a spigot that seasonally pours windblown dust off of the Sahara and across the Atlantic Ocean. Muhs is presenting the results tomorrow at the annual meeting of the Geological Society of America in Phoenix, Arizona.

Muhs's and his colleagues' mission was to find, identify, and date any layers of ancient African dust in what are called paleosols, or buried, ancient soils. In one coastal location studied, they found layers of dunes made from local shells of sea animals; in another, there were layers of lava from the volcanoes that built the islands. Both of these geologic archives contained paleosols made of very fine-grained minerals rich in quartz and mica--minerals that do not reflect the local geology of the islands. They do, however, reflect the minerals found on the nearby African mainland.

Luckily for the geologists, the lava flows that sandwich the windblown fine-grained quartz and mica layers made it possible to nail down approximate ages of the Saharan dust. This is because volcanic rocks contain minerals with what are essentially isotopic clocks that start ticking when the minerals in the lava cool and solidify. And since the layers of lava, paleosols, and other local soils are stacked chronologically with the youngest on top, the lava flows provide some boundaries of when the Sahara was dry enough to launch massive dusty storms out over the Atlantic.

In all, the researchers report eight paleosols that record African dust piling up in the Canaries between about 4.8 and 2.8 million years ago, 3.0 to 2.9 million years ago, and at about 400,000 years ago. The oldest paleosols agree with the deep-sea cores, which put the earliest Sahara dust to the Atlantic at about 4.6 million years ago.

That's not to say the Sahara is 4.6-million-years-old. That's only as old as Muhs and his colleagues could determine based on the paleosols and lavas they found.

"We could take it further back in time if we can find the paleosols," Muhs said.

Muhs's presentation is entitled The Antiquity of the Sahara Desert: New Evidence From the Mineralogy and Geochemistry of Pliocene Paleosols on the Canary Islands, Spain (Paper No. 76-1; https://gsa.confex.com/gsa/2019AM/webprogram/Paper335207.html). It is scheduled for Monday, 23 Sept., at 8:05 am in Room 221AB, North Building of the Phoenix Convention Center. It is part of a session titled T2. Geomorphology and Climate Change in Hot Deserts.