Research sheds new light on body parts’ sensitivity to environmental changes

Research by a team of Michigan State University scientists has shed new light on why some body parts are more sensitive to environmental change than others, work that could someday lead to better ways of treating a variety of diseases, including Type-2 diabetes.

MSU assistant zoology professor Alexander Shingleton used fruit flies as a model for his research into why some body parts are more sensitive to environmental changes than others. Fruit flies use the same genes to control this process as humans do. Photo by G.L. Kohuth.

The research, led by assistant zoology professor Alexander Shingleton, is detailed in the recent issue of the Proceedings of the Library of Science Genetics.

In particular, Shingleton is studying the genetics of fruit flies and zeroing in on why some of the insects’ body parts will grow to full size even when suffering from malnutrition, while others will not. He uses fruit flies because they use the same genes to control this process as humans.

“The developmental mechanisms by which these changes in body proportion are regulated are really unknown,” Shingleton said.

Shingleton said that in humans, a person’s brain will grow to near full size despite malnutrition or other environmental, or nongenetic, problems.

If scientists can figure out why some organs or body parts are either overly sensitive or insensitive to environmental factors, then it’s possible that therapies could be developed to deal with any number of maladies.

“If we know how we can control sensitivity to environmental issues such as malnutrition, we can, in principle, manipulate genes that are regulating that sensitivity,” Shingleton said. “Genes can be activated so they can actually restore sensitivity.”

Type-2 diabetes is a good example of the body’s insensitivity to nongenetic issues. The most common form of diabetes, Type-2, occurs when the body becomes insensitive to insulin, which is released in response to blood sugar levels. The body needs insulin to be able to use glucose for energy.

“In diabetes, that response is suppressed,” Shingleton said. “We get desensitization. We know people become insulin resistant, but we’re not quite sure why.”

What Shingleton and colleagues discovered is that even when malnourished, the genitals of a male fruit fly continue to grow to normal size.

“The same developmental mechanism that a fly uses to make its genitals insensitive to changes in nutrition may be the same that we as humans use to modulate the responsiveness of individual body parts to changes in nutrition,” he said. “Our job is to try to understand why some body parts are responsive to changes in nutrition and others aren’t.”

Using the fruit fly for this type of research “gives us enormous information about how we as humans work and how we respond to our environment,” Shingleton said. “This provides information on biomedical issues that arise from things like malnutrition or insulin resistance.”

Shingleton’s research is funded by the National Science Foundation and MSU’s Bio/computational and Evolution in Action Consortium, or BEACON.

______

Future prostate cancer treatments might be guided by math

Prostate cancer forms in the prostate gland, and can sometimes be felt on digital rectal examination. Photo: ADAM             Scientists have designed a first draft of a mathematical model that someday could guide treatment decisions for advanced prostate cancer, in part by helping doctors predict how individual patients will respond to therapy based on the biology of their tumors.

These decisions would apply to treatment of cancer that has already spread beyond the prostate gland or that has recurred after initial treatments, such as surgery or radiation. Patients with this more advanced prostate cancer receive a therapy called androgen ablation, which inhibits production of testosterone – the culprit that allows a tumor to keep growing.

Though the model’s outcomes remain theoretical at this point, the researchers have developed enough of a system to show that their incorporation of some personalized data – details about a patient’s tumor cell characteristics in particular – would give doctors more than they currently have to work with in making decisions about this stage of treatment.

“The model in its current form is proof of the concept that we can capture all of these different outcomes that are observed clinically. But we still need to refine the model with as much individual data as we can obtain,” said Harsh Jain, a postdoctoral fellow in Ohio State University’s Mathematical Biosciences Institute and lead author of the study.

“We envision that this model would be useful for clinicians who could keep feeding the equations with data about how a patient is responding to therapy, which would offer clues about how his cancer cells are mutating. Once you have an idea about that for the short or medium term, the model could predict the optimal therapy for that patient,” Jain said.

The model is described this week in the online early edition of the Proceedings of the National Academy of Sciences. Jain conducted the work with co-authors Steven Clinton, professor, and Arvinder Bhinder, assistant professor-clinical, in Ohio State’s division of medical oncology, and Avner Friedman, a Distinguished University Professor at Ohio State.

Prostate cancer is diagnosed in about 240,000 American men and leads to about 34,000 deaths each year, according to the National Cancer Institute.

The treatment of this cancer in its more advanced stages brings about chemical castration by targeting one of several mechanisms involved in the production of testosterone. In most patients, cancer cells develop castration resistance over time – on average, between 1½ and two years after the start of treatment. However, the overall range of resistance development spans from a few months to more than 10 years.

Jain said that some scientists have proposed that this treatment leads directly to castrate-resistant disease because once testosterone is removed from the body, mutant cancer cells that can survive in a no- or low-testosterone environment are able to take over the tumor.

Currently, continuous treatment to eliminate testosterone is the standard of care. But because clinicians know castration resistance is inevitable, a new approach is under study. A national clinical trial is assessing the benefits and risks of intermittent androgen ablation – keeping patients on the drugs until symptoms improve, and then giving men time off from the medication until the disease begins to progress again.

The math model developed by Ohio State scientists suggests that based on average clinical data currently available, such intermittent therapy could actually accelerate the development of castration resistance.

“In the same way that intermittent use of antibiotics gives a chance for bacteria that are resistant to the drug to take over, you might actually end up with intermittent anti-androgen therapy even more positively selecting for mutating cancer cells,” Jain said.

However, the averages don’t always apply, which is why the scientists are pursuing a system of differential equations to account for individual differences. For example, the “normal” levels of prostate-specific antigen, or PSA, in men’s blood cover a fairly broad range, Jain noted. Yet the PSA test remains the most common screening method for prostate cancer, and is used to gauge the effectiveness of treatments in advanced stages, as well.

“The PSA ranges are massive. It’s a very heterogeneous thing,” Jain said. “When we are talking about cancer, our point is that those variables should be personalized. Everyone’s cancer grows differently.

“There are a lot of questions. If you take an intermittent therapy route, how do you decide the scheduling of treatment? Is it based solely on PSA levels? Shouldn’t there be some incorporation of personal patient characteristics into these treatment decisions? Can you identify a subgroup of patients who are predicted to respond well to this, or are there conditions when one treatment vs. another could actually make things worse?”

Math offers some answers. The model’s foundation is based on existing animal and human data on prostate cancer characteristics. Beyond that, the researchers have selected parameters to plug into the equations that more specifically detail what could be going on in an individual tumor: cancer cell growth rates, cancer cell death rates, the level of activation of PSA in tumor cells, and how quickly one person’s PSA can travel from the prostate to the bloodstream.

The scientists even took into account the competitive power of individual types of cancer cells – for example, some mutated cancer cells aren’t as strong as their normal cancer cell counterparts. In those cases, the math model predicts, the best treatment option would be intermittent therapy because the stronger normal cancer cells would keep mutant cells in check during time off from the medication. With the cancer consistently dominated by cells that rely on the presence of testosterone, the treatment would continue to target those stronger cells that respond to androgen ablation therapy, Jain explained.

“That’s an important question with any therapy – is it making things better or worse in terms of allowing mutated cells to take over?” he said.

Jain and colleagues are now working to boost the model’s power by adding parameters that account for the blood vessel architecture in prostate tumors, a major indicator of how persistent the cancer will be. They also plan to add hundreds of individual patients’ case study data to make its predictions even more authentic.

___________

This research was supported by Ohio State’s Mathematical Biosciences Institute, the National Science Foundation, and a Molecular Carcinogenesis and Chemoprevention Program Grant from Ohio State’s Comprehensive Cancer Center.

New medical, research tool possible by probing cell mechanics

Researchers are making progress in developing a system that measures the mechanical properties of living cells, a technology that could be used to diagnose human disease and better understand biological processes.

This artist's conception depicts the use of an atomic force microscope to study the mechanical properties of cells, an innovation that might result in a new way to diagnose disease and study biological processes. Here, three types of cells are studied using the instrument: a rat fibroblast is the long slender cell in the center, an E coli bacterium is at the top right and a human red blood cell is at the lower left. The colored portions show the benefit of the new technique, representing the mechanical properties of the cells, whereas the gray portions represent what was possible using a conventional approach. (Purdue University image/Alexander Cartagena)

The team used an instrument called an atomic force microscope to study three distinctly different types of cells to demonstrate the method’s potentially broad applications, said Arvind Raman, a Purdue University professor of mechanical engineering.

For example, the technique could be used to study how cells adhere to tissues, which is critical for many disease and biological processes; how cells move and change shape; how cancer cells evolve during metastasis; and how cells react to mechanical stimuli needed to stimulate production of vital proteins. The technique could be used to study the mechanical properties of cells under the influence of antibiotics and drugs that suppress cancer to learn more about the mechanisms involved.

Findings have been posted online in the journal Nature Nanotechnology and will appear in the December print issue. The work involves researchers from Purdue and the University of Oxford.

“There’s been a growing realization of the role of mechanics in cell biology and indeed a lot of effort in building models to explain how cells feel, respond and communicate mechanically both in health and disease,” said Sonia Contera, a paper co-author and director of the Oxford Martin Programme on Nanotechnology and an academic fellow at Oxford physics. “With this paper, we provide a tool to start addressing some of these questions quantitatively: This is a big step.”

An atomic force microscope uses a tiny vibrating probe to yield information about materials and surfaces on the scale of nanometers, or billionths of a meter. Because the instrument enables scientists to “see” objects far smaller than possible using light microscopes, it could be ideal for “mapping” the mechanical properties of the tiniest cellular structures.

“The maps identify the mechanical properties of different parts of a cell, whether they are soft or rigid or squishy,” said Raman, who is working with doctoral student Alexander Cartagena and other researchers. “The key point is that now we can do it at high resolution and higher speed than conventional techniques.”

The high-speed capability makes it possible to watch living cells and observe biological processes in real time. Such a technique offers the hope of developing a “mechanobiology-based” assay to complement standard biochemical assays.

“The atomic force microscope is the only tool that allows you to map the mechanical properties – take a photograph, if you will – of the mechanical properties of a live cell,” Raman said.

However, existing techniques for mapping these properties using the atomic force microscope are either too slow or don’t have high enough resolution.

“This innovation overcomes those limitations, mostly through improvements in signal processing,” Raman said. “You don’t need new equipment, so it’s an economical way to bump up pixels per minute and get quantitative information. Most importantly, we applied the technique to three very different kinds of cells: bacteria, human red blood cells and rat fibroblasts. This demonstrates its potential broad utility in medicine and research.”

The technique is nearly five times faster than standard atomic force microscope techniques.

_________

The Nature Nanotechnology paper was written by Raman; Cartagena; Sonia Trigueros, a Senior Research Fellow in the Oxford Martin Programme on Nanotechnology; Oxford doctoral student Amadeus Stevenson; Purdue instructor Monica Susilo; Eric Nauman, an associate professor of mechanical engineering; and Contera.

Scientists develop brand new class of small molecules through innovative chemistry

Inspired by natural products, scientists on the Florida campus of the Scripps Research Institute have created a new class of small molecules with the potential to serve as a rich foundation for drug discovery.

Combining the power of synthetic chemistry with some advanced screening technologies, the new approach could eventually expand by millions the number of provocative synthetic compounds available to explore as potential drug candidates. This approach overcomes substantial molecular limitations associated with state-of-the-art approaches in small molecule synthesis and screening, which often serve as the foundation of current drug discovery efforts.

The study, led by Scripps Research Associate Professor Glenn Micalizio, was published Nov. 20, 2011, in an advanced online edition of the journal Nature Chemistry.

To frame the significance of this advance, Micalizio explains that high-throughput screening is an important component of modern drug discovery. In high-throughput screening, diverse collections of molecules are evaluated en masse for potential function in a biological area of interest. In this process, success is critically dependent on the composition of the molecular collections under evaluation. Modern screening centers maintain a relatively static collection of molecules, the majority of which are commercially available materials that have structures unrelated to natural products — molecules that are appreciated as validated leads for drug development.

“This divergence in structure between natural products and commercially available synthetics lies at the heart of our inquiry,” said Micalizio. “Why should we limit discovery of therapeutic leads to compound collections that are influenced by concerns relating to commercial availability and compatibility with an artificial set of constraints associated with the structure of modern screening centers?”

To expand the compounds available for investigation, the scientists embraced an approach to structural diversity that mimics nature’s engine for the discovery of molecules with biological function. This process, termed “oligomerization,” is a modular means of assembling structures (akin to the way that letters are used in a sequence to provide words with meaning) where a small collection of monomeric units can deliver a vast collection of oligomeric products of varying length, structure, and function (like the diversity of words presented in a dictionary).

Coupling this technique with a synthetic design aimed at generating molecules that boast molecular features inspired by the structures of bioactive natural products (specifically, polyketide-derived natural products, which include erythromycin, FK-506, and epothilone), the scientists established a new chemical platform for the discovery of potential therapeutics.

Micalizio points out: “The importance of oligomerization to drive discovery is well appreciated in chemistry and biology, yet a means to realize this process as an entry to small molecule natural product-inspired structures has remained elusive. The crux of the problem is related to challenges associated with the control of shape for each member of a complex oligomer collection — the central molecular feature that defines biological function.”

“It is the stability associated with the shape of these new compounds that lies at the heart of the practical advance,” he continued. “The unique features of this science now make possible the ability to synthesize large collections of diverse natural product-inspired structures that have predictable and stable three-dimensional shapes.”

Micalizio said that the science described represents a first step toward revolutionizing discovery at the interface of chemistry, biology, and medicine by embracing nature’s strategy for molecular discovery. Coupling this type of advance with modern screening technology that can handle the evaluation of large compound collections at low cost (such as work by Scripps Florida Professor Thomas Kodadek, a co-author of the new study), can dramatically enhance the future of pharmaceutically relevant science.

The potential of this vision was highlighted in the new study, in which a 160,000-member compound collection was employed to discover the first non-covalent small molecule ligand to the DNA binding domain of p53 — an important transcription factor that regulates a variety of genes involved in cell cycle control and cell death.

_________

The first author of the study, “A Biomimetic Polyketide-Inspired Approach to Small-Molecule Ligand Discovery,” is Claudio Aquino of Scripps Research. In addition to Micalizio and Kodadek, other authors include Mohosin Sarkar, Michael J. Chalmers, and Kimberly Mendes.

The study was supported by the Fidelity Biosciences Research Initiative, The State of Florida (The Florida Funding Corporation), and the National Institutes of Health.

A corny turn for biofuels from switchgrass

 

Introducing a maize gene into switchgrass substantially boosted the potential of the switchgrass biomass as an advanced biofuel feedstock. (Photo courtesy of USDA/ARS)                                                                                                              Many experts believe that advanced biofuels made from cellulosic biomass are the most promising alternative to petroleum-based liquid fuels for a renewable, clean, green, domestic source of transportation energy.

Nature, however, does not make it easy. Unlike the starch sugars in grains, the complex polysaccharides in the cellulose of plant cell walls are locked within a tough woody material called lignin. For advanced biofuels to be economically competitive, scientists must find inexpensive ways to release these polysaccharides from their bindings and reduce them to fermentable sugars that can be synthesized into fuels.

An important step towards achieving this goal has been taken by researchers with the U.S. Department of Energy (DOE)’s Joint BioEnergy Institute (JBEI), a DOE Bioenergy Research Center led by the Lawrence Berkeley National Laboratory (Berkeley Lab).

A team of JBEI researchers, working with researchers at the U.S. Department of Agriculture’s Agricultural Research Service (ARS), has demonstrated that introducing a maize (corn) gene into switchgrass, a highly touted potential feedstock for advanced biofuels, more than doubles (250 percent) the amount of starch in the plant’s cell walls and makes it much easier to extract polysaccharides and convert them into fermentable sugars. The gene, a variant of the maize gene known as Corngrass1 (Cg1), holds the switchgrass in the juvenile phase of development, preventing it from advancing to the adult phase.

“We show that Cg1 switchgrass biomass is easier for enzymes to break down and also releases more glucose during saccharification,” says Blake Simmons, a chemical engineer who heads JBEI’s Deconstruction Division and was one of the principal investigators for this research. “Cg1 switchgrass contains decreased amounts of lignin and increased levels of glucose and other sugars compared with wild switchgrass, which enhances the plant’s potential as a feedstock for advanced biofuels.”

The results of this research are described in a paper published in the Proceedings of the National Academy of Sciences (PNAS) titled “Overexpression of the maize Corngrass1 microRNA prevents flowering, improves digestibility, and increases starch content of switchgrass.”

Lignocellulosic biomass is the most abundant organic material on earth. Studies have consistently shown that biofuels derived from lignocellulosic biomass could be produced in the United States in a sustainable fashion and could replace today’s gasoline, diesel and jet fuels on a gallon-for-gallon basis. Unlike ethanol made from grains, such fuels could be used in today’s engines and infrastructures and would be carbon-neutral, meaning the use of these fuels would not exacerbate global climate change. Among potential crop feedstocks for advanced biofuels, switchgrass offers a number of advantages. As a perennial grass that is both salt- and drought-tolerant,  switchgrass can flourish on marginal cropland, does not compete with food crops, and requires little fertilization. A key to its use in biofuels is making it more digestible to fermentation microbes.

Overxpression of the Cg1 gene in switchgrass (left) compared to Wild-type of switchgrass of the same age and grown under the same conditions. (Photo courtesy of USDA/ARS)

“The original Cg1 was isolated in maize about 80 years ago. We cloned the gene in 2007 and engineered it into other plants, including switchgrass, so that these plants would replicate what was found in maize,” says George Chuck, lead author of the PNAS paper and a plant molecular geneticist who holds joint appointments at the Plant Gene Expression Center with ARS and the University of California (UC) Berkeley. “The natural function of Cg1 is to hold pants in the juvenile phase of development for a short time to induce more branching. Our Cg1 variant is special because it is always turned on, which means the plants always think they are juveniles.”

Chuck and his colleague Sarah Hake, another co-author of the PNAS paper and director of the Plant Gene Expression Center, proposed that since juvenile biomass is less lignified, it should be easier to break down into fermentable sugars. Also, since juvenile plants don’t make seed, more starch should be available for making biofuels. To test this hypothesis, they collaborated with Simmons and his colleagues at JBEI to determine the impact of introducing the Cg1 gene into switchgrass.

In addition to reducing the lignin and boosting the amount of starch in the switchgrass, the introduction and overexpression of the maize Cg1 gene also prevented the switchgrass from flowering even after more than two years of growth, an unexpected but advantageous result.

“The lack of flowering limits the risk of the genetically modified switchgrass from spreading genes into the wild population,” says Chuck.

The results of this research offer a promising new approach for the improvement of dedicated bioenergy crops, but there are questions to be answered. For example, the Cg1 switchgrass biomass still required a pre-treatment to efficiently liberate fermentable sugars.

“The alteration of the switchgrass does allow us to use less energy in our pre-treatments to achieve high sugar yields as compared to the energy required to convert the wild type plants,” Simmons says. “The results of this research set the stage for an expanded suite of pretreatment and saccharification approaches at JBEI and elsewhere that will be used to generate hydrolysates for characterization and fuel production.”

Another question to be answered pertains to the mechanism by which Cg1 is able to keep switchgrass and other plants in the juvenile phase.

“We know that Cg1 is controlling an entire family of transcription factor genes,” Chuck says, “but we have no idea how these genes function in the context of plant aging. It will probably take a few years to figure this out.”

-Biotechnology Research News

___________

Co-authoring the PNAS paper with Chuck and Simmons were Christian Tobias, Lan Sun, Florian Kraemer, Chenlin Li, Dean Dibble, Rohit Arora, Jennifer Bragg, John Vogel, Seema Singh,  Markus Pauly and Sarah Hake.

This research was supported in part by DOE’s Office of Science and by the USDA-ARS.

A failing sense of smell can be reversed

“A new animal study suggests that with training, smell can improve.” 

In a new study scientists at NYU Langone Medical Center have shown that the sense of smell can be improved. The new findings, published online November 20, 2011, in Nature Neuroscience, suggest possible ways to reverse the loss of smell due to aging or disease.

Smell is unique among our senses, explains Donald A. Wilson, PhD, professor of child and adolescent psychiatry at NYU Langone Medical Center and senior research scientist at the Emotional Brain Institute at Nathan S. Kline Institute for Psychiatric Research, who led the study. The olfactory bulb, a structure beneath the frontal cortex that receives nerve impulses from the nose, also has direct connections to the amygdala, which controls emotions and physiology, and to higher-order regions like the prefrontal cortex, involved in cognition and planning.

“Unlike information from your eyes and ears that has gone through many connections to reach the frontal cortex, the olfactory system is just two connections away,” says Dr. Wilson. “The result is an immediate pathway from the environment through our nose to our memory.”

Although impairment in the sense of smell is associated with Alzheimer’s disease, Parkinson’s disease, schizophrenia, and even normal aging, exactly why smell weakens remains a mystery, but recent laboratory research led by Dr. Wilson reveals how it may occur. “We located where in the brain loss of smell may happen,” he says. “And we showed that training can improve the sense of smell, and also make it worse.”

Dr. Wilson and Julie Chapuis, PhD, a post-doctoral fellow, placed thirsty rats in boxes with a snout-sized hole in each of three walls and exposed them to brief blasts of odors through the middle hole. There were three smells in all: a mix of 10 chemicals from fruits, oils, cleaning agents, etc.; the same mixture with one chemical replaced by another; and the same mixture minus one of the chemicals. When the rodents identified one smell, they were rewarded with a sip of water by going to the hole in the left side wall, for another smell they received water by going to the right side wall.

Rats could readily distinguish between odors when a chemical had been replaced in one mixture, but when one component had simply been removed, they could not differentiate. The researchers then anesthetized the rats and inserted electrodes into their brains. Within the olfactory bulb, each smell produced a different pattern of electrical activity. But in the piriform (olfactory) cortex, a half-inch-sized area of the rat cerebral cortex, the odors that rats could tell apart produced distinct patterns of activity, while those the rats could not distinguish produced identical patterns.

Drs. Wilson and Chapuis then trained a new group of rats to discriminate between the odors the first animals couldn’t tell apart by rewarding them over and over with sips water for choosing the appropriate hole. “We made them connoisseurs,” says Dr. Wilson. In the rats’ piriform cortex, activity patterns elicited by these similar odors were now different as well.

They trained a third group of animals to ignore the difference between odors the first rats could readily distinguish by giving them water at the same hole after exposure to either odor. This effectively dulled their sense of smell: the rats couldn’t tell one smell from the other, even for a reward. Their loss of discrimination was reflected in the piriform cortex, which now produced similar electrical patterns in response to both odors.

“Our findings suggest that while olfactory impairment may reflect real damage to the sensory system, in some cases it may be a ‘use it or lose it’ phenomenon,” says Dr. Wilson. This opens the door for potential smell training therapies that could help restore smell function in some cases. “Odor training could help fix broken noses,” he says.

UGA scientists invent long-lasting, near infrared-emitting material

Materials that emit visible light after being exposed to sunlight are commonplace and can be found in everything from emergency signage to glow-in-the-dark stickers. But until now, scientists have had little success creating materials that emit light in the near-infrared range, a portion of the spectrum that only can be seen with the aid of night vision devices.

In a paper just published in the early online edition of the journal Nature Materials, however, University of Georgia scientists describe a new material that emits a long-lasting, near-infrared glow after a single minute of exposure to sunlight. Lead author Zhengwei Pan, associate professor of physics and engineering in the Franklin College of Arts and Sciences and the Faculty of Engineering, said the material has the potential to revolutionize medical diagnostics, give the military and law enforcement agencies a “secret” source of illumination and provide the foundation for highly efficient solar cells.

“When you bring the material anywhere outside of a building, one minute of exposure to light can create a 360-hour release of near-infrared light,” Pan said. “It can be activated by indoor fluorescent lighting as well, and it has many possible applications.”

The material can be fabricated into nanoparticles that bind to cancer cells, for example, and doctors could visualize the location of small metastases that otherwise might go undetected. For military and law enforcement use, the material can be fashioned into ceramic discs that serve as a source of illumination that only those wearing night vision goggles can see. Similarly, the material can be turned into a powder and mixed into a paint whose luminescence is only visible to a select few.

The starting point for Pan’s material is the trivalent chromium ion, a well-known emitter of near-infrared light. When exposed to light, its electrons at ground state quickly move to a higher energy state. As the electrons return to the ground state, energy is released as near-infrared light. The period of light emission is generally short, typically on the order of a few milliseconds.

The innovation in Pan’s material, which uses matrix of zinc and gallogermanate to host the trivalent chromium ions, is that its chemical structure creates a labyrinth of “traps” that capture excitation energy and store it for an extended period. As the stored energy is thermally released back to the chromium ions at room temperature, the compound persistently emits near-infrared light over period of up to two weeks.

In a process that Pan likens to perfecting a recipe, he and postdoctoral researcher Feng Liu and doctoral student Yi-Ying Lu spent three years developing the material. Initial versions emitted light for minutes, but through modifications to the chemical ingredients and the preparation—just the right amounts of sintering temperature and time—they were able to increase the afterglow from minutes to days and, ultimately, weeks.

“Even now, we don’t think we’ve found the best compound,” Pan said. “We will continuously tune the parameters so that we may find a much better one.”

The researchers spent an additional year testing the material—indoors and out, as well as on sunny days, cloudy days and rainy days—to prove its versatility. They placed it in freshwater, saltwater and even a corrosive bleach solution for three months and found no decrease in performance.

In addition to exploring biomedical applications, Pan’s team aims to use it to collect, store and convert solar energy. “This material has an extraordinary ability to capture and store energy,” Pan said, “so this means that it is a good candidate for making solar cells significantly more efficient.”

How the brain senses nutrient balance

There is no doubt that eating a balanced diet is essential for maintaining a healthy body weight as well as appropriate arousal and energy balance, but the details about how the nutrients we consume are detected and processed in the brain remain elusive. Now, a research study discovers intriguing new information about how dietary nutrients influence brain cells that are key regulators of energy balance in the body.

The study, published by Cell Press in the November 17 issue of the journal Neuron, suggests a cellular mechanism that may allow brain cells to translate different diets into different patterns of activity.

“The nutritional composition of meals, such as the protein:carbohydrate (sugar) ratio has long been recognized to affect levels of arousal and attention,” explains senior study author, Dr. Denis Burdakov, from the University of Cambridge. “However, while certain specialized neurons are known to sense individual nutrients, such as the sugar glucose, it remains unclear how typical dietary combinations of nutrients affect energy balance-regulating brain circuits.”

Dr. Burdakov and colleagues studied how physiological mixtures of nutrients influenced “orexin/hypocretin” neurons, which are known to be critical regulators of wakefulness and energy balance in the body. Previous research had demonstrated that orexin/hypocretin neurons are inhibited by glucose. Surprisingly, the current study revealed that physiologically relevant mixtures of amino acids, the nutrients derived from proteins (such as egg white), stimulated and activated the orexin/hypocretin neurons.

The researchers went on to show that when orexin/hypocretin neurons were simultaneously exposed to amino acids and sugars, the amino acids served to suppress the inhibitory influence of glucose.

Taken together, these results support a new and more complex nutrient-specific model for dietary regulation of orexin/hypocretin neurons. “We found that activity in the orexin/hypocretin system is regulated by macronutrient balance rather than simply by the caloric content of the diet, suggesting that the brain contains not only energy-sensing cells, but also cells that can measure dietary balance,” concludes Dr Burdakov.

“Our data support the idea that the orexin/hypocretin neurons are under a ‘push-pull’ control by sugars and proteins. Interestingly, although behavioral effects are beyond the scope of our study, this cellular model is consistent with reports that when compared with sugar-rich meals, protein-rich meals are more effective at promoting wakefulness and arousal.”

_______