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Category Archives: Protein Folding

Wow your New Year’s Eve guests with a puff pastry appetizer – KARE11.com

GOLDEN VALLEY, Minn. Chef Lindsay Guentzel stopped by KARE 11 Saturday to share a simple and delicious appetizer idea for New Year's Eve celebrations. Her recipe for Holiday Brie En Croute uses puff pastry with an egg wash that helps the pastry bake perfectly, as the protein and fats in the egg give you that perfectly golden brown finish.

Holiday Brie En Croute

1 sheet frozen puff pastry, thawed out8 oz. brie cheese, sliced cup dried cranberries cup walnuts, choppedHoney, drizzledEgg wash

Preheat oven to 400.

Line baking sheet with parchment paper. Lay out rectangular puff pastry.

Using palms, gently spread out dough.

Starting at one end of pastry shell, place brie in a line down the center running the long way (think long like a hot dog bun, not short like a hamburger bun). The slices will overlap.

Spread cranberries and walnuts over brie evenly and drizzle with honey.

Starting at one end, slowly fold the sides of the pastry shell up over the brie by pinching the corners of the dough between your fingers, lifting up and twisting over (the twists add texture and dimension to the top of the pastry). Move a few inches down the pastry shell and repeat folding movements, gently shaping the dough as you go along.

Using a pastry brush, gently brush egg wash over the pastry shell.

Bake for 20 minutes until golden brown.

Serve on platter warm with knife and serving spatula.

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The 10 most compelling product innovations of 2019 – Fast Company

As the 10 most important product innovations of 2019 showfrom plant-based burgers to alternate reality headsetsthe world still has plenty of room for innovation in meatspace. The brightest products of the past year arent just enticing or convenient for users. These products are often using design to question the ritual of consumption as we know it.

[Photo: Motorola]The original Motorola Razr (2004) changed the world of technology forever, turning clunky phones into sleek, fashion-forward objects of desire. The followup, 15 years later, features a folding OLED display. Its a mechanical marvel, and the first flexible screen device that makes any real sense at all, because it turns our too-large smartphones into pocketable devices. The Razr offers an early taste of the bendable, ergonomic electronics to come. [Link]

[Photo: Logitech]Video game controllers are now so advanced that the military uses them to control tanks and drones. But they require fine motor control that can leave people with disabilities behind. The Xbox Adaptive Controller launched last year, with two giant buttons and lots of extra input options to allow users to connect extra buttons as needed. Then, this year, Logitech decided to actually make those extra buttons. Its $99 kit includes mix-and-match hardware thats built less for profitability than the needs of diverse users. [Link]

[Photo: Air Co.]My dad always said there was no problem too great that you couldnt drink yourself out of it. Okay, that isnt true. But carbon-capturing vodka comes pretty close. A company called Air Co. uses recaptured carbon in the place of yeast to produce vodka. Each bottle scrubs the air as effectively as eight trees breathing for a day. And as an added bonus, Air Co.s production footprint needs just 500 to 1,000 square feet compared with the acres of land required by traditional distilling. Then take a sip while wearing this compelling, carbon-negative raincoat, and you wont have to worry about spilling on yourself. [Link]

[Photo: Motorola]First responders are going into some of the most dangerous places on earth, and in these places, your typical iPhone wont do because it relies on an infrastructure of fallible antennas to work. Instead, first responders still rely on long-range walkie-talkies. Anew walkie-talkie from Motorola Solutions, the APX Next, can be used both hands-free and without an operator on the other end of the line, thanks to a novel voice assistant that helps you access private information without direct internet access. Siri may be an overrated way to find sushi. But the APX Next can literally help save lives; as a firefighter or police officer uses two hands to free someone from a pile of rubble, she can use the APX Next to simultaneously call for help. [Link]

[Photo: Analogue]The Nintendo Switch is the best portable gaming system ever madethanks to a perfect size, a massive library of games, the option to seamlessly dock it to a TV, and controllers that put smartphones to shame. And yet, 2019 brought us two compelling handheld video game consoles (both expected to be released in 2020). Each proves that the independent spirit of hardware design is alive and well.

Analogue Pocket is a $199 Game Boy reboot, which runs vintage console cartridges but in an industrial design that meshes stark minimalism with a cutting-edge display. Oh, its also an instrument for electronic music. What? [Link]

The Playdate is another enticing bit of gaming hardware, but its more experimental. A surprising crank on the side offers a zany way to play games. And its being released with software partners who are designing new, bite-sized titles for the Playdate and the Playdate alone. Playdate teased a model in which you could buy new seasons of games in packs, and in doing so, Playdate is combining a closed hardware/software ecosystem in a way that only giants such as Apple and Nintendo have ever managed to pull off. [Link]

[Photos: Impossible Foods, Burger King]If 2019 was the year of anything, it was the year of fake meat. Beyond Meat and Impossible both made their mainstream mark. The Impossible Whopperwas such a hit, it gave Burger King its best quarter in four years, cementing nearly a decade of investment in the biology, flavor, and mouthfeel behind a fully engineered burger.Even if faux meats dont outright replace real meat, a little savings in the flexitarian market goes a long way: A pound of beef costs 1,800 gallons of water on top of all sorts of other environmental hazards, which is why experts would like to see beef consumption drop by 50% to save the planet. The Impossible Whopper might not be the best burger youve ever had, but then again, neither is anything else you get at Burger King. [Link]

[Photo: Microsoft]If theres a more complicated industrial design story in 2019 than how Microsoft designed the Hololens 2 augmented reality headset, I havent read it. Its an AR headset that goes on as easily as a baseball cap, making it easy and effortless to hop into the digital world. The combination of materials and hard and soft parts in this design is staggering. And its full of tiny decisions of ergonomics, which work in harmony with technology that requires picometer-level precision (if some parts of the headset come out of the tiniest threshold of alignment, it would literally make you want to vomit). [Link]

[Photo: courtesy Korvaa]The headband is made from lactic acid produced by yeast. The ear padding is a bubbling protein produced by fungus. The leather is mycelium, or the core of a mushroom. And the mesh on your ears is biosynthetic spider silk. Dubbed Korvaa, this is the worlds first microbe-grown pair of headphones. And they are beautiful in their own way. As we reckon with our environmental footprint, projects such as Korvaa are a reminder that there really is another way than simply producing more plastic. [Link]

[Photo: Adidas]The Adidas Loop is a shoethat can be ground down at the end of its life and used to help make new Loop shoes. Whether its the textiles made from plastic, or the business modelwhich may require Adidas to incentivize buybacks of old shoes to make new onesLoop teases an increasingly complicated future for consumer goods (and consumption) in which companies and customers alike are forced to deal with the long-term impacts of products. None of this would matter if Loop shoes were terrible, of course. But they are also a tantalizing garment in their own right, with a shimmery woven plastic thats both beautiful and comfortable. [Link]

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Nanopores can identify the amino acids in proteins, the first step to sequencing – University of Illinois News

CHAMPAIGN, Ill. While DNA sequencing is a useful tool for determining whats going on in a cell or a persons body, it only tells part of the story. Protein sequencing could soon give researchers a wider window into a cells workings. A new study demonstrates that nanopores can be used to identify all 20 amino acids in proteins, a major step toward protein sequencing.

Researchers at the University of Illinois at Urbana-Champaign, Cergy-Pontoise University in France and the University of Freiburg in Germany published the findings in the journal Nature Biotechnology.

Graduate student Kumar Sarthak and physics professor Aleksei Aksimentiev were part of a research team that demonstrated that nanopores could sequence proteins, giving reserachers and clinicians insight into activity within a cell.

Photo by L. Brian Stauffer

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DNA codes for many things that can happen; it tells us what is potentially possible. The actual product that comes out the proteins that do the work in the cell you cant tell from the DNA alone, said Illinois physics professor Aleksei Aksimentiev, a co-leader of the study. Many modifications happen along the way during the process of making protein from DNA. The proteins are spliced, chemically modified, folded, and more.

A DNA molecule is itself a template designed for replication, so making copies for sequencing is relatively easy. For proteins, there is no such natural machinery by which to make copies or to read them. Adding to the difficulty, 20 amino acids make up proteins, as compared with the four bases in DNA, and numerous small modifications can be made to each amino acid during protein production and folding.

Many amino acids are very similar, Aksimentiev said. For example, if you look at leucine and isoleucine, they have the same atoms, the same molecular weight, and the only difference is that the atoms are connected in a slightly different order.

Nanopores, small protein channels embedded in a membrane, are a popular tool for DNA sequencing. Previously, scientists thought that the differences in amino acids were too small to register with nanopore technology. The new study shows otherwise.

The researchers used a membrane channel naturally made by bacteria, called aerolysin, as their nanopore. In both computer modeling and experimental work, they chopped up proteins and used a chemical carrier to drive the amino acids into the nanopore. The carrier molecule also kept the amino acids inside the pore long enough for it to register a measurable difference in the electrical signature of each amino acid even leucine and isoleucine, the near-identical twins.

This work builds confidence and reassures the nanopore community that protein sequencing is indeed possible, said Abdelghani Oukhaled, a professor of biophysics at Cergy-Pontoise whose team carried out much of the experimental work.

The researchers found they could further differentiate modified forms of amino acids by using a more sensitive measurement apparatus or by treating the protein with a chemical to improve differentiation. The measurements are precise enough to potentially identify hundreds of modifications, Aksimentiev said, and even more may be recognized by tweaking the pore.

This is a proof-of-concept study showing that we can identify the different amino acids, he said. The current method for protein characterization is mass spectrometry, but that does not determine the sequence; it compares a sample to whats already in the database. Its ability to characterize new variations or mutations is limited. With nanopores, we finally could look at those modifications which have not yet been studied.

The aerolysin nanopore could be integrated into standard nanopore setups, Aksimentiev said, making it accessible to other scientists. The researchers are now exploring approaches to read the amino acids in sequential order as they are cut from the protein. They also are considering other applications for the system.

One potential application would be to combine this with immunoassays to fish out proteins of interest and then sequence them. Sequencing them will tell us whether theyre modified or not, and that could lead to a clinical diagnostic tool, Aksimentiev said.

This work shows that theres really no limit to how precisely we can characterize biological molecules, he said. Very likely, one day we will be able to tell the molecular makeup of the cell what we are made of, down to the level of individual atoms.

The National Institutes of Health and the National Science Foundation supported this work. Computer modeling was done on the Blue Waters supercomputer at the National Center for Supercomputing Applications at the U. of I.

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The Art of Origami is Now A Key Tool That Helps Doctors Save Lives – Nature World News

Dec 23, 2019 05:03 AM EST

Origami's new role in the field of science and technology has definitely taken a turn for the better in the recent decade. Better known as origami engineering, the practice is used to reduce structures or maximize space and function.

Origami engineering has made great strides in the medical field in particular. The same principles used in origami, when applied to medical devices, allows implants to be folded to minuscule sizes and then unfolded to its actual size. The reverse is also applicable, where like toothpaste tubes, can be fully de-compressed.

Folding techniques could transform flat objects with wrinkles to increase resilience, shock-absorbance, strength, or rigidity. Origami provides a unique insight into how single pieces could sustainably be packaged without cutting, welding, or riveting, allowing for cheaper manufacturing costs and easier assembly.

The utility of origami engineering has captured the attention of people such as Rebecca Taylor, assistant professor at Carnegie Mellon University's Department of Mechanical Engineering. Taylor specializes in microfabrication and biomechanics, a study that has helped her fabricate microscale sensors to reliably assess cardiomyocytes derived from stem cells. A natural inclination to similar practice, Dr. Taylor has developed an origami-based DNA synthetic cardiac contractile protein, which allowed her to observe merging mechanics in multiprotein, acto-myosinc contractile systems.

As a professor, Taylor expands on the utilization of DNA origami in medicine. This technique (also referred to by Dr. Taylor as "bottom-up manufacturing"), allows improvement in nanomanufacturing and nanomechanics of multiprotein systems, paving the way for heart stents that could unfold in a very precise location.

The problem, however, is on how to deploy these structures in a 100% fault-free way. To illustrate this, a common problem that impedes the creation of pop-up tents that could self-assemble at the press of the button is when the folds of the tent get stuck during the folding process on occasion.

Understandably, this raises some concern among those who are keen to use self-folding nanomachines in medicine.

So this is where origami comes in.

According to University of Chicago scientists, the limits of self-folding structures could be intrinsic in that so-called "sticking points" seem to be unavoidable.

Previously thought possible to engineer around, the researchers observed the capacity of foldable structures by creating mathematical models. During the experiment, the team had designed structures capable of self-folding, such as paper origami and nanobots, and creating creases in them beforehand. The result was that when more pre-creases were added to the folds, the more branches in the next folding process could form and the more likely the self-folding mechanism is to get stuck.

Origami engineering is a relatively new innovation. Its application is vast and can be of use to not only technology but to medicine as well. The development of the field itself, then, needs to pick up at a faster pace in order to cater to the intelligent design of foldable structures and materials. But while there are creases in the field that needs to be smoothed out, the greater promise of origami engineering has brought about several research papers in its wake.

RELATED ARTICLE: Swallowed a Battery? Ingestible Origami Robot Made from Pig Gut Can Remove It,Stop Stomach Bleeding

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Holiday cookies from around the world | Features – yoursun.com

Cookies are as much a part of Christmas as candles and caroling. They are the gift that everyone loves, the holiday snack supreme. In many respects, they are the reason for the season.

And it is not just in America, by any means. In other parts of the world, too.

So this year, I decided to make holiday cookies from around the globe. To be honest, most of them come from Europe, because many of the best cookies come from there.

Ill start with New Mexico's state cookie,Biscochitos.They are typically served for big occasions and especially for the holidays. The crispy shortbread cookies are infused with anise and orange, and topped with a sprinkling of cinnamon sugar. In the version included here, I used shortening instead of lard.

Next we have Joulutorttu, Finnish Christmas pinwheels with a dollop of prune jam in the middle of each one. If you don't like the idea of prune jam, use raspberry jam. This recipe uses whipped cream and the dough is folded over on itself like puff pastry.

The French shortbread cookie recipe is the one chef Jacques Pepin makes every Christmas. You could think of them as a version of sabls, the traditional French shortbread cookie from Sabl-sur-Sarthe that are often made with almonds.

Austria's Vienna Tarts are flaky crescents rolled up around a bit of apricot jam, topped with chopped walnuts and powdered sugar.

Vanilla Kipferl also come from Austria. These tasty little treats are deceptive; they are easy to make, but they pack an enormous amount of flavor. In fact, my two taste testers said it was their favorite of all the cookies.

There are two reasons for the cookies being so addictive. One is that most of their bulk comes from toasted, ground almonds. And the other is the vanilla. Not only is there vanilla in the dough, but the cookies, once baked, are rolled in a mixture of superfine sugar and blended whole vanilla bean. They are sophisticated and delightful.

According to the King Arthur Flour Cookie Companion cookbook, Mailanderli are Switzerlands favorite holiday cookie. One taste is all it takes to understand why. These crisp and buttery cookies have a subtle flavor of lemon.

And finally, Chocolate-Glazed Lebkuchen is a cookie bar treat from Germany made with a spiced honey cake. With its cinnamon, cardamom, cloves, nutmeg and ginger, plus its candied fruit, it tastes just like the holidays.

And the chocolate glaze on top? Thats like a special Christmas present to you and your friends.

Yield: About 25 cookies

3 cups all-purpose flour

1 1/2 teaspoons baking powder

1/2 teaspoon salt

1 tablespoon anise seed, crushed

Zest of 1 orange

1 1/4 cups lard or vegetable shortening

3/4 cup plus 1/2 cup granulated sugar, divided

1 large egg

1 teaspoon vanilla extract

1 teaspoon ground cinnamon

1. In a large bowl, sift together flour, baking powder and salt. Whisk in the anise and orange zest.

2. In a separate bowl, combine 3/4 cup of the sugar and the lard or shortening. Using an electric mixer, beat the lard or shortening and sugar until light and fluffy, about 3 minutes. Add the egg and vanilla and beat to combine. Gradually beat in the flour mixture and stop as soon as mixture is combined. Dough should be thick and similar in consistency to pie crust dough. Refrigerate for 30 minutes.

3. Preheat oven to 350 degrees. Line baking sheet with parchment paper. In a small bowl, combine the remaining 1/2 cup sugar and cinnamon for topping.

4. On a lightly floured surface, roll out dough to 1/4-inch thickness. Cut out cookies (a 21/2-inch cookie cutter yields a good size). Place cookies on prepared baking sheet and bake until just barely golden and set, about 10 to 12 minutes. Be careful not to overcook. Let cookies cool for 1 minute, then carefully dunk them into the sugar mixture. Place on cookie rack until completely cooled.

Per cookie: 157 calories; 9 g fat; 3g saturated fat; 15 mg cholesterol; 2 g protein; 18 g carbohydrate; 6 g sugar; 1 g fiber; 50 mg sodium; 24 mg calcium

Recipe by somethewiser.com

Yield: Around 45 cookies

2 sticks plus 2 tablespoons butter

1 1/4 cups granulated sugar

3 large eggs, at room temperature

3/4 teaspoon salt

1 tablespoon finely grated lemon zest, or 1/8 teaspoon lemon oil

4 1/3 cups all-purpose flour

1 egg yolk plus 1 teaspoon milk, for brushing

1. In a large mixing bowl, beat the butter until soft and creamy. Beat in the sugar. Add the eggs, one at a time, beating well after each addition; scrape down the sides of the bowl once or twice while adding the eggs. Beat in the salt and the lemon zest.

2. Sift the flour and add it, half at a time, to the butter mixture. Mix only until the flour is well incorporated. Gather the dough into a bowl, flatten it into a disk, and refrigerate it for 2 to 3 hours, or overnight.

3. Preheat the oven to 350 degrees. Lightly grease (or line with parchment paper) 2 or 3 baking sheets.

4. Remove the dough from the refrigerator. If its very hard, allow it to warm a little before trying to roll it out. Its best to work with small pieces, about 1/4 of the dough at a time; refrigerate the rest until youre ready to roll it out. On a lightly floured work surface, or between two pieces of plastic wrap, roll the dough to a 1/8-inch thickness. Cut out different shapes with cookie cutters dipped in flour. Transfer the dough to the prepared baking sheets. Re-roll the scraps to make more cookies.

5. Mix the egg yolk and milk in a bowl. Brush the cookies with the egg wash. If possible, refrigerate the cookies for 10 to 15 minutes before baking.

6. Bake the cookies in the middle of the oven for 10 minutes or until theyre an even, pale golden brown. Remove the cookies from the oven. Transfer the baking sheets to a rack to cool almost completely, then transfer to a rack.

Per cookie: 112 calories; 5 g fat; 3 g saturated fat; 29 mg cholesterol; 2 g protein; 15 g carbohydrate; 6 g sugar; no fiber; 45 mg sodium; 6 mg calcium

Recipe from The King Arthur Flour Cookie Companion

Yield: Around 40 cookies

1 3/4 sticks (14 tablespoons) unsalted butter

1/2 teaspoon salt

7 tablespoons plus 1/4 cup granulated sugar, divided

1 teaspoon vanilla extract

1 3/4 cups all-purpose flour

Scant 2 1/3 cups almond flour (from ground almonds that have preferably been toasted)

1/2 to 1 vanilla bean

1. In a medium-sized bowl, beat together the butter, salt, 7 tablespoons of the sugar and vanilla extract until smooth. Add the flour and almond flour, stirring to make a cohesive dough. Wrap the dough in plastic wrap and refrigerate it for at least 1 hour, or overnight.

2. Preheat the oven to 350 degrees. Lightly grease (or line with parchment) two baking sheets.

3. Break off walnut-sized pieces of the dough, and roll them into short (about 2-inch) logs. Shape the logs into crescents, then gently press them to flatten them slightly. Place the cookies on the prepared sheets.

4. Bake for 8 to 10 minutes, until theyre a light, golden brown. Remove them from the oven and let cool on the pan for 10 minutes.

5. While the cookies are cooling, process the remaining 1/4 cup sugar and vanilla bean in a food processor or blender until the bean is thoroughly ground and the sugar is almost powdery. While the cookies are still warm, gently roll them in the vanilla sugar. Transfer them to a rack to cool completely.

Per cookie: 106 calories; 5 g fat; 3 g saturated fat; 11 mg cholesterol; 2 g protein; 9 g carbohydrate; 4 g sugar; no fiber; 30 mg sodium; 2 mg calcium

Recipe from The King Arthur Flour Cookie Companion

Yield: Around 30 cookies

3 cups all-purpose flour

1 teaspoon baking powder

1 1/2 cups heavy cream, whipped

1 cup unsalted butter, softened

1/2 cup plus 2 tablespoons prune jam (recipe follows) or raspberry jam

1 egg

1 tablespoon milk

Powdered sugar for sprinkling

1. In the bowl of a stand mixer fitted with a paddle attachment, combine the flour and baking powder. Mix in the whipped heavy cream, followed by the softened butter.

2. On a lightly floured surface, knead the dough until soft and smooth. Shape into a disc, wrap in plastic and refrigerate for at least 1 hour.

3. Preheat oven to 400 degrees. Line 2 baking sheets with parchment paper, or lightly grease.

4. On a lightly floured surface, roll out the dough until 1/4 inch thick. Fold the dough into thirds by folding one-third toward the center, followed by the other third toward the center (fold like a letter). Roll the dough out again, turn, and fold into thirds again along the other side to form the dough into a square. Roll out a third time to make a square about 1/4-inch thick.

5. Cut the sheet of dough into 3-inch squares. To make the traditional shape, use a sharp knife to make cuts from each quarter about halfway toward the center. Place a teaspoon of jam in the center of the square.

6. Lift every other split corner toward the center over the jam filing and pinch together in the middle to form a pinwheel shape. Place on the prepared baking sheets.

7. In a small bowl, beat together the egg and milk. Brush the top of each Joulutorttu with the beaten egg wash. Bake until golden, 7 to 10 minutes.

8. Allow to cool to room temperature and top with powdered sugar. Store in an airtight container if not serving immediately.

Per cookie: 160 calories; 11 g fat; 7 g saturated fat; 36 mg cholesterol; 2 g protein; 14 g carbohydrate; 2 g sugar; no fiber; 7 mg sodium; 30 mg calcium

Recipe from tarasmulticuturaltable.com

Yield: 1 3/4 cups

10 1/2 ounces pitted prunes

1/4 cup granulated sugar

1. Cover the prunes with water and soak for 2 hours. Drain, rinse, and place in a medium saucepan. Add the sugar, top with just enough water to cover, and place over high heat.

2. Once boiling, reduce heat to a simmer and cook, stirring often, until the prunes have softened and are easily mashed, about 20 minutes. If needed, add a little more water to keep the mixture from burning.

3. Mash the jam to desired consistency, or pure. Refrigerate until ready to use.

Per ( 2 tablespoon) serving: 86 calories; no fat; no saturated fat; no cholesterol; no protein; 23 g carbohydrate; 4 g sugar; no fiber; 1 mg sodium; 15 mg calcium

Recipe from tarasmulticulturaltable.com

Yield: 24 cookies

3/4 cup granulated sugar

1 cup plus 1 tablespoon honey

1 tablespoon water

4 tablespoons (1/2 stick) butter, cut into pieces

3/4 cup chopped unblanched almonds

1/3 cup finely chopped candied or dried pineapple (or any other good candied fruit)

1/3 cup lightly beaten egg (more than 1 large egg)

3 tablespoons fresh orange juice

1/2 teaspoon almond extract

1 2/3 cup sifted all-purpose flour

1 teaspoon baking powder

1/2 teaspoon baking soda

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Early detection of brain degeneration on the horizon with innovative sensor – UNM Newsroom

UNM research builds on findings involving protein aggregation in brain cells and neurodegenerative diseases

Neurodegenerative diseases such as Alzheimers and Parkinsons can be devastating to patients and their families. These diseases are difficult to diagnose before symptoms show, meaning its often already too late to reverse the damage to the central nervous system. Early detection is key for management of symptoms and attempts to stall progression of the disease, but current knowledge is limited when it comes to tools that aid in early detection. That knowledge gap is being addressed through cutting-edge research by a team at The University of New Mexicoled by Professor Eva Chi of the Department of Biomedical Engineering.

Dr. Eva Chi

In order to understand complex diseases of the brain, one has to understand the complexity of human biology and the brain itself. Of particular importance is proteinsmolecular structures inside a cell that can number into the tens-of-thousandsand their ability to dictate how cells function. Proteins start off with the same basic building blocks, called amino acids. The amino acids organize into a chain, and the unique function of the protein depends on how the amino acids are ordered in the chain. Once the amino acid ordering is complete, the protein chains fold themselves in various ways in order to bind to other molecules to perform certain tasks.

All proteins are made of the same building blocks; the folding of the protein into distinct shapes dictates its unique purpose inside the body. For example, digestive enzyme proteins break down our food into nutrients, and transport proteins such as hemoglobin carry substances throughout our body. Of particular interest to those who study brain degeneration are tau proteins inside neurons (brain cells) that help with cellular and nerve communication in the brain.

Protein folding is an intricate process, and as such, a lot can go wrong inside the cell. Protein folds can fail altogether, or an error in the protein chain could cause a misfold. Some of these misfolds have been linked by research scientists to numerous diseases in humans, especially when the misfolded proteins stick together. The resulting sticky clumps of proteins are called protein aggregates.

Proteins have such important functions in the body, and once they do something else such as aggregate, it can have devasting consequences in the body, creating the potential for systemic and neurodegenerative diseases, says Chi.

Illustration demonstrating how OPEs bond to and illuminate both toxic protein aggregates and proteins with normal folds.

Previous research over the past decade has shown a link between degenerative brain diseases and aggregation of tau proteins inside neurons (tauopathy), as well as plaque-forming clumps of protein fragments called amyloid beta that disrupt the pathways between the cells. Scientists hypothesize that these protein aggregates form in the brain long before symptoms appear, and Chis research is focused on detection of these aggregates using a type of biosensor. Through past research, Chi and her team have developed a highly responsive biosensor called Oligo(p-phenylene ethynylene) electrolytes, or OPEs. OPEs are as a molecular structure created in a lab that can regulate electrical signals between neurons, as well as light up under a microscope when interacting with certain types of proteins.

Aggregates form inside one cell at the start, and as a disease such as Alzheimers progresses into the next stages, the aggregates recruit more healthy proteins inside the cell before spreading to multiple cells in the brain. Since Alzheimers, Parkinsons, and similar diseases are not infectious, is unclear how the aggregation spreads from cell to cell. Mice models can track functionality through cognitive tests, but researchers cannot yet track biochemical changes inside a living human brain. Chi hopes the OPE sensors will also shine some light on this process.

These diseases have a stage based on what the brain looks like, and the disease spreads throughout the brain, but we dont know how it spreads. With other types of problems in the body, there are testsX-rays, MRIsbut there is nothing for aggregates in the brain, and its something the field has been working towards, says Chi. The goal is to discover the next generation of sensors that can detect the protein aggregates that are more relevant to causing these diseases. In the long run, these sensors, if effective, will work along the lines of brain imaging that can detect the size, location, and cell-to-cell spread of the aggregates.

Using mouse models, rat models, and donated human brain tissue in her lab, Chi takes proteins from these models in test tubes and treats them chemically to form aggregates. Her OPE sensors are added, and once the sensors find the aggregates, they bond to them and light up. Chi and her students then look at the results under a powerful microscope to see the features of the proteins and their sensors.

Fundamental interactions between the sensor and the aggregate is the main focus, Chi explains. The sensor can seek out and find these aggregates and could potentially work to repair the damage. This knowledge can be applied for other purposes, such as sensors for antimicrobial applications, or used as therapies.

Chi began this research at UNM in 2013 through a private grant from the Huning family, and her current grant from the National Institutes of Health builds on the knowledge she has gained since starting on this journey. She has published three papers and filed two patent applications for the sensors.Much like the aggregates themselves, understanding diseases of the brain is a tangled web of complexity, but Chis sensors are a huge step forward in the quest for successful treatment and reversal of degenerative diseases, giving hope to the millions of people and their families affected by these devastating illnesses.

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