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Category Archives: Virginia Stem Cells

Surrozen reloads with $50M for final dash to the clinic, shines some light on lead Wnt-modulating candidates – Endpoints News

Posted: June 20, 2020 at 6:49 pm

Two rounds totalling $83 million have propelled Surrozen through preclinical proof-of-concept, culminating in two antibody candidates modulating the Wnt pathway for tissue regeneration. Now, the South San Francisco biotech is topping up $50 million to complete the sprint to the clinic.

One of the two IND candidates targets liver disease while the other will be initially positioned for inflammatory bowel disease. With the cash infusion, Surrozen can also pursue more discovery projects in different tissues and areas.

Our goal is to file IND applications in 2021 and 2022, CEO Craig Parker said in a statement, 5 and 6 years after the company first set out to catch and push a second wave of regenerative medicine.

Christopher Garcia and Roeland Nusse, two Stanford professors, provided some of the scientific legs for the company. Aside from its role in cancer, Wnt a portmanteau integrating Wingless and Int-1 signaling is also key to the control of cell development and regeneration, but the instability means they are hard to manufacture. As Nusse elucidated crucial aspects of Wnt biology, Garcia inspired the idea to activate or enhance response to endogenous Wnts, through either bispecific or antibody-based molecules.

While it has long been known that the Wnt signaling pathway plays a crucial role in the maintenance and self-renewal of stem cells in a variety of tissues, scientists had been unable to overcome the technical challenges inherent in developing a therapeutic based on Wnt signaling, Nusse, the Virginia and Daniel K. Ludwig Professor of Cancer Research and Professor of Developmental Biology, said. I am hopeful that Surrozens approach to modulating the Wnt pathway, with the flexibility to address insufficient endogenous Wnt or insufficient receptors, may someday lead to therapeutics that have the potential to repair damaged tissue.

Claudia Janda, a postdoc at Garcias lab whos since moved on to the Princess Mxima Center for Pediatric Oncology, remains a scientific advisor alongside Princess Mxima director Hans Clevers and Stanfords Calvin Kuo.

Both tech platforms were represented in the lead nominated candidates.

SZN-043 was designed on SWEETS, or Surrozen Wnt signal enhancers engineered for tissue specificity. Through stabilizing the Frizzled receptors that Wnt proteins signal through, the compound was shown to stimulate hepatocyte proliferation in the liver and reduce fibrosis something that should be helpful in conditions like severe acute alcoholic hepatitis or even cirrhosis.

The possibilities are almost endless, with Surrozen spelling out potential applications in NASH and decompensated liver disease.

SZN-1326, meanwhile, was born out of SWAP (Surrozen Wnt signal activating proteins). The molecule binds to Frizzled receptors directly and should stimulate regeneration of intestinal epithelial cells. Researchers also noted anti-inflammatory effects in animal models.

It is still a ways from human data. But old investors are returning to take that leap with Surrozen, including The Column Group, Hartford Healthcare Trust and Horizons Ventures. Euclidian Capital and three other new believers are jumping on board.

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Surrozen reloads with $50M for final dash to the clinic, shines some light on lead Wnt-modulating candidates - Endpoints News

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Focused Ultrasound Opening Brain to Previously Impossible Treatments – University of Virginia

Posted: May 12, 2020 at 7:41 pm

University of Virginia researchers are pioneering the use of focused ultrasound to defy the brains protective barrier so that doctors could, at last, deliver many treatments directly into the brain to battle neurological diseases.

The approach, the researchers hope, could revolutionize treatment for conditions from Alzheimers to epilepsy to brain tumorsand even help repair the devastating damage caused by stroke.

Richard J. Price, who holds joint faculty appointments in UVAsschools of Medicine and Engineering, is using focused soundwaves to overcome the natural blood-brain barrier, which protects the brain from harmful pathogens. His approach aims to breach the barrier only where needed, and only when needed, and then deliver treatments in exquisitely precise fashion.

The blood-brain barrier is one of the greatest, if not the greatest, challenge to drug delivery for the central nervous system, Price said. Evolution gave us this barrier because the central nervous system needs to be protected. The problem is now we want to deliver something to those cells, and evolution has had millions and millions of years to optimize a solution to stop it. So Im attempting to circumvent biology with physics.

Price was the inaugural recipient of the $75,000 Andrew J. Lockhart Memorial Prize from the Focused Ultrasound Foundation. The funding supports his efforts to use focused ultrasound to develop better treatments for cancer.

Focused ultrasound focuses sound waves inside the brain much like a magnifying glass can focus light, letting doctors manipulate tissue without cutting into the skull. Magnetic resonance imaging, or MRI, lets them watch whats happening inside the brain in real time. While Price, a biomedical engineer, is developing his techniques in the lab, doctors are already using the technology to treat conditions such as Parkinsons tremor.

Price marvels at the approachs specificity. With MRI, we can look at the target, whether its a brain tumor or maybe its a part of the brain we want to do gene therapy on, and we can select itwe can actually make a treatment plan and say, We only want to open the [blood-brain] barrier there. The other 95% of the brain, we dont even touch, said Price,the research director at UVAs Focused Ultrasound Center. Then when we apply the focused ultrasound, it opens the barrier there for a few hours. It lets us get the gene therapy across, and then it closes naturally.

Gene therapy introduced via focused ultrasound would essentially reprogram faulty cells.

For brain tumors, Price is exploring the potential of using focused ultrasound to deliver gene therapy via deep-penetrating nanoparticles. The nanoparticles, designed by Prices collaborators at Johns Hopkins University, are specifically engineered to penetrate the tissue extremely well, he said. The problem has been transporting them where theyre needed, often deep inside the brain, and Price said focused ultrasound holds the answer.

His solution is to use the focused soundwaves to open spaces between cells in the tissue. It doesnt help us if you cant get to the neuron thats 50 microns away, he said. So that becomes an engineering transport problem.

In addition to delivering the therapy, focused ultrasound can precondition targeted tissue to enhance the effectiveness of the gene delivery up to five-fold, Price has found. The preconditioning represents a simple and effective strategy to boost the benefits of the nanoparticles, he and his colleagues report in a scientific paper.

For stroke, a condition that is often debilitating when its not deadly, Price aims to help the brain heal itself. He would do this by using focused ultrasound to put homing molecules inside damaged areas to recruit neural stem cells to do repairs. For this, his team has developed an innovative technique called sonoselective transfection that avoids opening the blood-brain barriers in brains that are already compromised.

With stroke, theres a lot of effort to try to salvage as much neural tissue as possible by doing things like gene therapy, he said. In our lab, we thought, well, maybe we can deliver treatment right to the cells that need it, without breaching the blood-brain barrier. And my students basically figured out how to do that.

That notion of helping the body heal itself, of using focused ultrasound to activate an immune response, could be useful in cancer treatments as well. We would love to be able to put something into those [tumor] cells that will then allow them to start recruiting immune cells into the tumor, he said. We have a lot of evidence that we can we can do some interesting things with focused ultrasound with respect to the internal landscape of those tumors.

Price, of UVAs Department of Biomedical Engineering, emphasizes that his work is still early, but he is excited to be creating new techniques that could change how many major diseases are treated in the not-too-distant future.

Weve had good results [with the research] so far. But what I, as an engineer, get excited about are all these tools we have made, he said. You can use these tools for all these different applications. We think there are a lot of really exciting possibilities.

The researchers have described their latest work in new papers in the scientific journals Science Advances and PNAS, the Proceedings of the National Academy of Sciences. A third paper appeared in the journal Small. The research team includes Tor Breza, Colleen T. Curley, Delaney G. Fisher, William J. Garrison, Catherine M. Gorick, Justin Hanes, Kathryn M. Kingsmore, Namho Kim, Alexander L. Klibanov, James W. Mandell, Alexander S. Mathew, Brian P. Mead, G. Wilson Miller, Jennifer Munson, Karina Negron, Benjamin W. Purow, Divya Rao, Natasha D. Sheybani, Ji Song, Jung Soo Suk and E. Andrew Thim.

The researchers work has been supported by the National Institutes of Health, grants R01CA164789, R01CA197111, R01EB020147, R21EB024323 and F31EB023090; National Heart, Lung and Blood Institute-sponsored Basic Cardiovascular Research Training Grant T32 HL007284; the Robert Wagner Fellowship; and American Heart Association Fellowship 18PRE34030022.

To keep up with the latest medical research news from UVA, subscribe to theMaking of Medicineblog.

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First-of-its-Kind Bio-Artificial Pancreas on Track for Type-I Diabetes Cure – Global Trade Magazine

Posted: February 8, 2020 at 4:47 pm

Imagine a world where those living with Type 1 Diabetes, a chronic illness affecting more than 60 million adults globally, no longer had to deal with regular blood glucose monitoring, daily insulin injections or life-threatening nighttime hypoglycemic events, but instead could eat, exercise and sleep worry-free. Thats the kind of future an up-and-coming breakthrough technology is on track to creating.

Beta-O2 Technologies, a privately held biomedical company headquartered in Israel with research and industry affiliates across the U.S., is working to deliver a first-of-its-kind bio-artificial pancreas as a safe, effective and long-term cure for the disease. With preliminary animal trials showing promising results for its second generation breakthrough device, called Bio-artificial Pancreas (Air), the company is planning to begin human clinical trials within the year.

We have strong pre-clinical evidence to prove the safe operation of our device on animals, said Beta-O2 CEO Amir Lichter, noting that the second generation Air is performing well in ongoing animal studies. Its an enormous achievement that is paving the road for human trials.

Measuring approximately 2.5 by 2.5 inches, Air is made of titanium. It has two components: a macrocapsule that contains pancreatic cells and an oxygen tank equipped with an external port, so patients can easily refresh oxygen levels weekly. Once implanted under a patients skin, it becomes a natural source of insulin, sensing blood glucose levels and delivering insulin as required.

While there are a couple of other artificial pancreatic solutions being explored by different industry players, Beta-O2s disruptive technology is the only bio-artificial pancreas to incorporate an active oxygen supply, necessary to keep the pancreas cells in the implanted device functional and viable over the long term. Other solutions are demonstrating limited success because they rely on a patients bloodstream to deliver enough oxygen to keep the transplanted cells viable, which is problematic, Lichter explained.

Pancreas cells (islets) are extremely delicate, he said. We solve the problem by proactively supplying oxygen through an external source, providing a superior solution.

Lichter said the beauty of the Beta-O2 solution which holds 10 global patents for its exclusive immune protection capabilities and oxygen supply mechanisms is that its very generic, meaning it can contain cells from a human donor, cells from the pancreas of a pig, or cells derived in a lab from stem cells. Other advantages are that Beta-O2s bio-artificial pancreas does not require a patient to take intensive immunosuppression therapies after implant due to its protective encapsulation capabilities, and the device can quickly be retrieved from a patient if necessary due to malfunction or other health concerns, he explained.

Beta-O2 is currently collaborating with several U.S.-based pharmaceutical companies and academics, including researchers from Harvard University, MIT, University of Virginia and Cornell University, to further enhance the Air oxygen supply and its ability to measure glucose levels and secrete insulin once implanted. The company is also in negotiations to solidify its collaboration with several stem cell providers as it looks to secure an additional $15 million in investment funds to support its aggressive go-to-market strategy.

The active oxygen supply used by Beta-O2 is currently the best and most advanced technique for maintaining viability and function of large numbers of pancreaticislets (or stem cell-derived islets) in an encapsulation transplantation device, said Clark K. Colton ofthe Department of Chemical Engineering at MIT andBeta-O2 Scientific Advisory Board member.

Calling the Beta-O2 device a next-gen treatment option, Dr. Jos Oberholzer, Professor of Surgery, Biomedical Engineering and Experimental Pathology at the University of Virginia and Beta-O2 Scientific Advisory Board member, explained that after years of insulin injections and closed-loop insulin pumps and glucose sensors, patients will finally have access to a biological device solution to treat the most brittle forms of diabetes. The Beta-O2 device is the only implant that has shown reproducible results in humans with diabetes, with measurable insulin production originating from human islet cells within the device without the need for recipients to take any immunosuppressive drugs.

An earlier safety trial involving four patients in Sweden, supported by New York-based JDRF (Juvenile Diabetes Research Foundation), successfully demonstrated that Beta-O2s device is fully safe for use. No side effects were observed in patients who carried the device for up to 10 months, and the cells remained viable and functional.

Now, current animal trials underway at Beta-O2 are focused on extending the life of functional cells even further, with promising early results showing that rats implanted with Air are maintaining normal glucose levels.

With tangible evidence that we can maintain the viability and functionality of our cells for a long duration in rats, which have an immune system very similar to humans, we are looking forward to moving ahead with our second round of human clinical trials, Lichter said, noting that the company aims to be first to show that implanted biological pancreatic cells can successfully achieve normal blood sugar levels in diabetic patients without the need for immunosuppression therapy.

___________________________________________________________

About Beta-O2 Technologies Ltd. (www.beta-o2.com)

Beta-O2 Technologies Ltd. is a biomedical company developing a proprietary implantable bioreactor, the Air, for the treatment of Type 1 Diabetes. Air is designed to address the main problems of the otherwise successful procedures in which islets of Langerhans (i.e. pancreatic endocrine cells) are transplanted in diabetic patients, such as the need for life-long immunosuppressive pharmacological treatment and limited functionality of the transplanted islets over time due to an insufficient oxygen supply. Beta-O2 investors include SCP Vitalife Partners, Sherpa Ventures, Aurum Ventures, Pitango Venture Capital, Saints Capital, Japanese and Chinese private investors.

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Bent into shape: The rules of tree form – Knowable Magazine

Posted: February 4, 2020 at 2:46 am

Theres a place in West Virginia where trees grow upside-down. Branches sprout from their trunks in the ordinary fashion, but then they do an about-face, curving toward the soil. On a chilly December day, the confused trees bare branches bob and weave in the breeze like slender snakes straining to touch the ground.

Its really kind of mind-boggling, says plant molecular biologist Chris Dardick, waving toward the bizarro plum trees. Theyre completely messed up.

Im visiting an orchard at the Appalachian Fruit Research Station, an outpost of the US Department of Agriculture nestled in the sleepy Shenandoah Valley. Here, at Dardicks workplace, the disoriented plums are but one in an orchard of oddities, their outlines, seasonally stripped of leaves, standing out in stark relief.

There are trees with branches that shoot straight up, standing to attention in disciplined rows, with nary a sideways branch. There are trees with branches that elegantly arch, like woody umbrellas; others with appendages that lazily wander this way and that.

Dwarf trees crouch, sporting ball-like crowns akin to Truffula trees. Compact trees poke from the ground in clumps of scraggly, knee-high sticks. Apple trees with some hidden predicaments grow in a greenhouse nearby: Their roots reach sideways rather than down. The topsy-turvy growth of all of these trees comes from genetic variations that cause the dialing up, dialing down or elimination altogether of the activity of key genes controlling plant architecture.

Understanding these misfits has real-world applications: It could help grow the next generation of orchards that, densely packed with trees, produce more fruit while using less land and labor than today. But Dardick is also trying to answer a fundamental question: How do different trees get their distinctive shapes? From the towering spires of spruce and fir, the massive spreading limbs of an oak to the stately arching canopies of an elm, the skeletal shapes of trees offer signature silhouettes.

Dardicks work and that of other researchers also could help to explain how the shapes of individual trees are far from fixed. Trees, much more than we can, will morph in response to their literal neck of the woods. Limbs in the shade reach toward spots of sunlight. Trees on windswept hills bend trunk and branches into gnarled architectures.

The familiar shape of a regular plum tree (left) is transformed by dialing down the activity of certain plant architecture genes, leading to plums with erect branches that shoot straight up (middle) or plums with branches that cascade downward (right).

CREDIT: C. HOLLENDER (LEFT), C. DARDICK (CENTER AND RIGHT)

Work by breeders, biologists and botanists have revealed sizable pockets of knowledge about the hormones, genes and processes that yield the diverse shapes of trees and other plants, between species and within species. It has not been easy: Two of trees most appealing attributes their long lives and large sizes make them intractable research subjects.

But as scientists pursue these questions, commonalities are emerging between vastly different species. The puzzle of shape diversity and adaptability turns out to be tied to the fundamentals of being a plant: grappling with gravity, fighting for sunlight, all while anchored in one place for a lifetime.

Plants are stuck. The best they can do is grow toward something, says Courtney Hollender, a former postdoc of Dardicks who now runs her own lab in the Department of Horticulture at Michigan State University in East Lansing. Thats all theyve got; they cant run, they have to adapt to their environment. And theyve developed brilliant ways to do it.

Scientists have a word for the ability to adapt so readily: plasticity. In plants, this feature is both obvious and astounding. Most animals are born in specific shapes then just grow larger, but plants are modular they grow in various iterations of two building blocks: shoots and roots.

It is the first of these where and when a shoot grows or doesnt grow that governs the basic form a tree takes.

Some aspects are hardwired. Leaves emerge in a pattern that is usually fixed throughout the trees life, with structural arrangements that tend to be shared by members of a given plant family. And shoots emerge where leaves meet the stem. So, for example, plants in the maple family, which have leaves set opposite each other, have branches in the same format. Members of the beech family have leaves, and thus branches, that alternate up the stem.

But the interplay between physiology and external forces also plays a large part. Take your standard-issue plant with a main central stem that grows upward and has few side branches. Most plants, from basil to birch, start out this way, a growth habit that probably evolved because it enables them to quickly reach the light more rapidly than the competition. Called apical dominance (the tip of the plant is the apex), this is largely under the purview of the plant hormone indole acetic acid, also known as auxin. Made in the tip, auxin diffuses downward and blocks the growth of side branches.

This is why pinching the tips off of basil or geranium makes them bushy you are removing the source of that bossy auxin, freeing buds on the stems sides from the prohibition and allowing them to grow. (Though auxin is mighty, its not the only player here. Other plant hormones, along with light intensity and access to nutrients, also wield power.)

Another related and less-understood phenomenon occurs in some tree species. Called apical control, it also is imposed by the tip of a tree and probably also by auxin. But rather than operating at the scale of a branch, it commandeers the whole dang tree.

Think of a pine. At the top, theres a pointy tip, then upper branches that tend to reach skyward. Moving down, the branches become more horizontal, growing out more than up. But unlike a basil plant, a pine tree does not become bushy when you lop off the top. Instead, a new bud near the top grows upward, becoming the new leader. Or an existing branch reorients to grow up and become the new dominant tip.

These two principles are always in the back of arborists minds as they work. They have to consider, If we cut a branch here, that bud below is going to break and well just get a branch in basically the same spot, Dardick says. All of their rules of what to prune and where are based on these physiological factors that contribute to tree shape.

Physiology also underpins the plastic responses trees have to more extreme situations they may face. A tree on a high mountain peak or windswept coast must contend with exposure to mechanical forces that could topple and kill it. To survive, such trees become short and stocky, their bent, asymmetric crowns reducing drag and presumably protecting a tree from violent gusts. The driver is the winds very touch a response now called thigmomorphogenesis that has been observed for hundreds of years.

How it works is still unclear, but over the past decade researchers have made some headway. Theyre actively studying force-sensing proteins and processes that may be involved. And recent work suggests an important role for hormones such as jasmonate, which accumulates in all kinds of plants in response to damage and mechanical stress. In experiments with a weedy mustard called Arabidopsis, plants became stunted when researchers bent their leaves back and forth twice a day.Mutants that couldnt make jasmonate, though, grew normally.

Sometimes, wind does more than gust against a tree: It blows the whole tree over, and that tree, if still rooted, must reorient the growth of its branches and buds toward the sky. Avalanches, erosion and landslides deal similar fates. And trees in all sorts of circumstances must grow around obstacles, away from competitors and toward the light. To get these jobs done, trees make a special kind of wood called reaction wood.

Trees may become contorted in challenging physical environments, such as this ridge in the Rocky Mountains. The touch of wind and other forces prompt physiological responses by the plant that yield a shorter, stockier stature, gnarled asymmetric shape and the development of specialized wood. This characteristic tree form is called a krummholz (German for crooked wood).

CREDIT: BRYCE BRADFORD / FLICKR

Hardwoods such as maple, beech, oak and poplar form this tough stuff (in this case called tension wood) on the upper side of their stems. Incredibly, it creates a tensile force thatpullsthe stem upward. If you walk around the woods, you can see that most species, if not all species, have this kind of reaction wood response, says Andrew Groover, a research geneticist with the USDA Forest Services Pacific Southwest Research Station in Davis, California.

The hardwood tree first discerns that it is off-kilter using specialized gravity-sensing cells. Where these cells reside in trees the woody stem? the tip of new shoots? was unknown until Groover and colleagues detected them in woody and soft tissues of poplar, a few years back. The cells contain organelles called statoliths that sink down in the cell and indicate to the plant that its leaning one way or the other. This, in turn, causes that influential auxin to mobilize, triggering the growth of tension wood on the top. Cellulose with a peculiar gelatinous layer is thought to act as the muscle that generates the pulling-up force.

In this experiment, young, potted poplar trees were placed sideways to investigate the plantsgravity-sensing machinery. The poplar in this time-lapse movie, taken over two weeks, responded to being tipped on its side by reorienting its growth upward. The plant hormone auxin is key to this response. Mutants that cannot respond appropriately to auxins signaling instructions do not right themselves this way. (This particular poplar also received a dose of a chemical called gibberellic acid that interacts with auxin, so that scientists could learn more about its role.)

CREDIT: ANDREW GROOVER AND SUZANNE GERTTULA, US FOREST SERVICE, PACIFIC SOUTHWEST RESEARCH STATION DAVIS CA

Much of the knowledge about the architecture of plants is rooted in millennia of human efforts to alter crop shapes to make them more suitable for cultivation, and modern science is now revealing the genetic changes that lie behind these creations. The lessons, it turns out, apply broadly across the plant kingdom, to herbaceous and woody species alike.

It is hard to overstate the importance to human history of some of these plant-shape changes, says plant molecular geneticist Jiayang Li, who details some of their genetic underpinnings in the Annual Review of Plant Biology. A classic example is the transformation of the ancestor of corn (maize) into a key staple crop for much of the world. It arose from a species of the Central American grasses called teosintes bushy plants with many branches. Domestication, among other things, abolished that branching, yielding the single-stalked upright corn we plant today.

Similarly, explains Li, who works at the Chinese Academy of Sciences Institute of Genetics and Developmental Biology, the green revolution of the 20th century ushered in compact, dwarf varieties of wheat and rice. By modifying the height and thickness of the stems of these grasses, breeders developed varieties that could carry more grain without toppling over in wind and rain.

Much of Lis own research has focused on architectural variation in rice, although the work turns out to have implications for the architecture of plants in general, from lowly mosses to towering trees. Like other grasses, rice grows shoots called tillers specialized, grain-bearing branches that emerge from the base. In cultivated rice, the angle at which these tillers grow varies widely: Some varieties are squat and wide-spreading, others have shoots that are more upright. Breeders are interested in altering tiller angle because upright plants can be grown more densely, giving farmers more bang for their acreage.

In a key advance, in 2007, a team including Li reported theyd discovered the genetic cause of the spread-out architecture trait. The scientists named the responsible gene TAC1, short for tiller angle control. A functional TAC1 gene increases rices tiller angle, leading to open, widely branching plants. Mutations in TAC1 lead to the opposite: plants with erect shoots that reach up, instead of out.

That same year, Lis team and a group in Japan both reported another major achievement: finding a long-sought gene behind a curious trait in some rice varieties that gives plant branches a scruffy, lounging look. The trait, known as lazy, had intrigued plant breeders and geneticists since the 1930s, when researchers described its extreme manifestation in corn: The lazy plants grow along the ground, following the unevenness of the surface.

In ordinary rice (left), the hormone auxin helps to tell the plant which direction is up. Auxin transport within the plant goes awry when a gene called LAZY malfunctions, leading to confused plants with sprawling branches (right).

CREDIT: B. WANG ET AL / AR PLANT BIOLOGY 2018

The cause, it turns out, was errors in a gene that normally makes branches shoot straight up. Li and his colleagues surveyed some 30,000 mutant rice plants to pin down that gene, now called LAZY (names of genes, confusingly, often refer to what happens when a gene is mutated and doesnt work, rather than when it is functioning properly). And they provided convincing evidence for an idea batted around for decades that lazy plants have muddled perceptions of gravity and that auxin is centrally involved.

A common test for whether a plants gravity-perception machinery is working is to lay the plant on its side. If it knows up from down, it wont continue to grow sideways, but will start to grow up again, akin to the reaction-wood response of a toppled trees branches. An important step in this reorienting involves auxin pooling on the bottom side of the shoot. But in lazy mutants, proteins that help ferry auxin around the plant are malfunctioning, so instead of shoots growing in the correct direction, theyre prone to casually sprawl about.

Scientists now know that LAZY genes come in multiple versions. Some appear to operate in plant roots, telling them which way is down, probably using similar, auxin-related signals. If those genes are absent or inactive, confused roots grow upward. And though the genes were first found in monocots, a branch of the plant kingdom including rice and corn, researchers now know that LAZY genes exist in numerous plants, including the plums growing in the fruit research station in West Virginia.

A lazy mutant of corn (left) compared with normal corn (right). Such corn mutants were described nearly 100 years ago, but it took 21st century molecular biology to nail down the growth habitscause: genetic malfunctions that meddle with responses to gravity.

CREDIT: T.P. HOWARD III ET AL / PLOS ONE 2014

As our boots crunch along the uneven ground, Dardick points at an errant orchard cat watching our tree tour from a distance. One row of trees stands so upright that a fencepost at the end of it is enough to block the row from view. These regimented trees are pillar peaches, and they are favorites of landscapers (one reason: its easy to get around them with a lawnmower). They also were key to uncovering genes like LAZY and TAC1 at the Shenandoah Valley station.

By comparing ordinary peaches to pillar peaches, and drawing on decades of work by former lead scientist Ralph Scorza, a team of station scientists and others in the US and Germany discovered the cause of the pillar trait: mutations in the peach version of TAC1.

Many of the strange plant architectures under investigation existed as naturally occurring varieties that were developed by breeders for ornamental gardens or orchards; only recently have the genes underlying these forms been identified. Its now known that the upright growth habit of the pillar peach (center), available commercially under the nameCrimson Rocket,results from mutations in a gene that helps plants branch outward.

CREDIT: C. DARDICK

The team also found that LAZY was at work in many of their misfits. Just as with the corn plants described nearly 100 years ago, mutations in LAZY made plums grow topsy-turvy, their branches seeking the soil. Apple trees with LAZY mutations have similarly disoriented roots. And when multiple copies of LAZY genes malfunction in the weed Arabidopsis, its roots grow up, its shoots down.

In the last decade, researchers have found that TAC1 influences branch angle in plums, poplar trees, the grass Miscanthus and Arabidopsis, and it appears to affect leaf angle in corn. But LAZY genes have even deeper roots. Theyre found in all manner of plants, including the evolutionarily older Loblolly pine and even more ancient mosses.

This finding suggests a very old role for LAZY: It may have allowed plants to grow up, literally, when they first colonized land. Plants got their start in water. There, rootless and leafless, they were buoyed, unconcerned with gravity. The transition to land spurred the development of proper roots and stems, and plants then had to figure out up from down. LAZY seems to have allowed plants to orient their above-ground growth away from gravity and up toward the sun.

Scientists think that TAC1 evolved somewhat later, providing a counterpoint to LAZY ensuring that branches dont only grow straight up, but also reach out. Together, these genes laid critical groundwork for the diversity of plant forms we see today, all seeking sustenance in their own ways.

Once you start to grow up as a vascular plant, you need to maximize your resources, you need to capture as much sun as possible, says Hollender, who has been working on yet another gene, called WEEP, that when nonfunctional lends plants a weeping, waterfall-like structure seen here and there in trees of ornamental gardens. (But its probably not responsible for the shape of weeping willow trees.) Modifying your shoot angles is an important adaptive trait for plants that allows them to capture light. Its essential for them to survive.

This kind of research has broad economic implications. Fruit and nut trees bring $25 billion annually in the US alone and there are hefty costs associated with pruning, bending and tying branches; spraying hormones; and the manual labor of picking fruit from an unruly cacophony of limbs. Understanding the genetic controls behind tree architecture could help scientists breed trees that make the whole fruit-farming enterprise more efficient and environmentally friendly.

Orchard systems are not the most sustainable in the world, Dardick says. The idea is, if we can modify tree architecture, if we could reduce their size and limit the amount of area they take up, then we could plant them at higher density and potentially increase their sustainability.

And there may be odder outcomes than friendlier outdoor orchards: In collaboration with NASA, the USDA team is investigating genetic tweaks that might even help bring fruit to space. On that December day, Dardick takes me to a greenhouse tucked in a corner of the lab. In it are plum and apple trees whose shape is so transformed that they look more like the love children of shrubs and vines. This strange growth habit is a side-effect of efforts to breed plants that flower and make fruit sooner and then do so continuously, rather than flowering after growing for several years, and then only in the spring.

The genetic tweaks that sent the trees developmental program into overdrive have also transformed their architecture. In the greenhouse, these precocious trees sprawl, draping lazily along wire trellises, happily flowering and heavy with fruit. Theyre growing almost like tomatoes, Dardick says. So were broaching the concept of, can we bring an orchard indoors?

The strange, vine-like growth of this plum results when a gene controlling the timing of flower development malfunctions. Such unusually shapedtrees may facilitate indoororchards that produce fruit many months of the year.

CREDIT: C. SRINIVASAN

Those ambitions aside, Dardick has his hands full trying to answer numerous basic-science questions about how trees do what they do. Researchers still dont know how different tree species set the angles of their branches going wide like an oak, or arching like an elm. They dont know how trees alter those angles during the course of mature growth, as branches sprout from branches sprouted from branches, until some of them finally point down. Trees are both kindred and foreign to us, their various forms so familiar, but their architectural rules still in so many ways opaque.

I find myself looking at trees all the time now in a new way; they fill space so beautifully and efficiently, Dardick says. They are the biggest organism we have thats visible, thats in our face all the time. But theres so much we dont know.

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Bent into shape: The rules of tree form - Knowable Magazine

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Q&A: Cancer Death Rates Are Falling Nationally. Here’s What’s Happening at UVA – University of Virginia

Posted: January 11, 2020 at 5:51 am

This week, the American Cancer Society released some very welcome news: the cancer death rate in the U.S. dropped by 2.2% from 2016 to 2017, the largest single-year drop ever recorded.

The drop, which the report attributes to plummeting smoking rates as well as new screening and treatment methods, continues a decades-long trend, as cancer death rates have fallen by nearly 30% since 1991 about 2.9 million fewer deaths.

Dr. Thomas Loughran, director of the University of Virginia Cancer Center, said UVA is in step with this national trend.

The UVA Cancer Center is one of 71 National Cancer Institute-designated treatment centers nationwide and ranked among the nations top 50 cancer centers over each of the past four years (No. 26 last year). The center serves approximately 4 million people in Virginia and West Virginia.

We spoke with Loughran about what he is seeing at UVA and beyond, new treatments and research helping to eradicate cancer, and where he sees cancer treatment in five years.

Q. Why have cancer death rates dropped so significantly?

A. As reports of this latest drop have said, a large part of the decline can be attributed to declining rates of lung cancer. The importance of preventing cancer particularly behavioral interventions like stopping smoking has become more prominent, and there have been remarkable declines in smoking across the United States.

This is a very important focus for us at UVA. We serve a large geographical area 90 contiguous counties in Virginia and West Virginia, including rural Appalachia. Southwest Virginia in Appalachia still has high smoking rates, and as a result, high rates of lung cancer. Education, screening and tobacco cessation programs are critically important, especially in those areas.

Q. What advances in treatment have contributed to falling cancer death rates, nationally and at UVA?

A. Screening technology, especially for the more common cancers like lung, colorectal, prostate and breast cancer, has improved. The latest report probably doesnt fully reflect recent implementation of lung cancer screening using a low-dose CT scan, recommended for high risk individuals and especially those with a history of heavy smoking. That has only been around a few years, and its impact will likely show up in future reports.

The second big factor is the development of immunotherapy [cancer treatments that utilize and help the patients immune system]. UVA has invested quite a lot of institutional resources in becoming a state-of-the-art immunotherapy center, and I am proud to say we are a leader in the field.

We have created a Cancer Therapeutics Program to support the development of new therapies. Dr. Craig Slingluff, who leads that program, is a surgical oncologist internationally famous for immunotherapy treatments for melanoma. To strengthen this program, we have recruited a cadre of leading physician scientists from across the country. Dr. Karen Ballen came here to lead our stem cell and bone marrow transplant program. Dr. Lawrence Lum, the scientific director of the transplant program, has developed a novel therapy using antibodies that bind to both T-cells [patient cells that can kill cancer cells] and tumor cells, forming a bridge between the two that helps the T-cells kill the cancer cells. Dr. Trey Lee is a leader in CAR-T cell therapy.

I could keep going; there are so many great people working on this. We also have a new Good Manufacturing Practice lab, supported by a grant from the commonwealth, that will help us grow and modify T-cells as needed and give them to patients under sterile conditions. That just opened and we are very excited about that program.

Q. What other areas of research have shown great promise?

A. Some of our work in nanotechnology is really unique and exciting. [Biomedical engineering professor] Mark Kester directs UVAs nanoSTAR Institute, which is working on delivering cancer therapies by nanotechnology basically, engineering at a very small scale. For example, nanoliposomes a sort of delivery system for cancer therapy are actually smaller than individual cells and can therefore penetrate cancer cells and release treatment from inside those cells.

We are very excited about early phase trials testing this technology on solid tumors, and we also hope to use it to treat patients with acute leukemia over the next few years.

Q. Looking ahead, where do you see the next big gains coming from?

A. Immunotherapy has revolutionized cancer treatment, but why some patients respond well and some dont remains puzzling. I hope that we can begin to discover why some patients are reacting to these newer treatments differently than others. Once we figure out why some patients respond to immunotherapy, we can begin to make improvements that could benefit a larger percentage of patients with these deadly cancers.

CAR T Cell therapy one method of immunotherapy is very effective against leukemia, lymphoma and cancers of the blood, but not yet against solid tumors. Over the next five years, I hope we can determine how to deliver these T-cells to solid tumors such as those found in lung, colorectal and other common cancers again to make this advance more widely applicable to a larger number of patients.

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Q&A: Cancer Death Rates Are Falling Nationally. Here's What's Happening at UVA - University of Virginia

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Brown fat warms your body in cold weather | NOVA – NOVA Next

Posted: December 30, 2019 at 10:52 am

Have you ever wondered why the first cold day of fall feels so much colder than a day the exact same temperature at the end of the winter? Its not just a matter of perspective: Your body really is more prepared for cold conditions at certain times of the yearthanks to a mysterious form of fat.

When you experience cold, your body responds in a few noticeable ways. Your blood vessels constricta process called vasoconstrictiontaking blood away from your extremities and keeping it near your core. And you shiver, meaning certain muscles start shaking to produce heat. But shivering also triggers the release of a hormone called irisin, which jump-starts a lesser-known cold weather response: the activation and buildup of brown fat.

Brown adipose tissue, or brown fat, is different from the white fat we might think of when discussing diet or weight loss. White fat lines our skin and muscles, cushioning our organs and bones. But brown fat appears only in specific areas around the neck, spine, aorta, and kidneys. It builds up in clumps around major blood vessels, warming the blood as it passes through the body. If vasoconstriction is closing the window, brown fat is turning on the heater, says Yossi Rathner, a physiologist at the University of Melbourne.

We dont create enough brown fat to cause noticeable weight gain, but the small deposits are still powerful thanks to their high concentration of energy-creating mitochondria. Instead of burning calories to produce energy to power the body, the mitochondria in brown fat burn calories to produce heat. By acting like little heating stations for blood vessels, these soft clumps of insulation help us deal with the cold more efficiently than shivering, which expends a lot of energy, and vasoconstriction, which puts us at risk of frostbite.

Your body goes from a rickety radiator to a smooth central heating system by the end of the winter, says Francesco S. Celi, a professor of medicine at Virginia Commonwealth University.

But the effect only lasts for as long as we need it. When the temperature warms up, brown fat fades away. If we are not exposed to the cold, the brown fat will atrophy, says Barbara Cannon, a physiologist at Stockholm University. There may be a few stem cells left in the area for later regeneration, but it will nearly disappear, Cannon says.

Even a one-month tropical vacation is enough to deplete ones brown fat reserves, Celi says, creating that extra cold sensation a traveler might feel upon returning to a cold climate.

You could say brown fat is winter's undercover hero, dropping in when we need it most, and disappearing once the job is done. So, the next time a chilly day leaves you shivering, just remember help is on the way.

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Oliver and Elizabeth Hedgepeth column: Human donations are a gift of life – Richmond.com

Posted: November 25, 2019 at 8:42 pm

By Oliver and Elizabeth Hedgepeth

There are special suppliers of life in our great country, from North Carolina to Virginia to Alaska. They are those hospitals that collect the basic raw material for giving life. They work with a network of donor service organizations across the United States. In Virginia, it is Donate Life Virginia. In North Carolina, it is Carolina Donor Services. In Alaska, it is Life Alaska Donor Services.

The raw material that comprises those supply items are you, me, anyone from 3 months old to 75 years old, so far in our experience. Yes, a 3-month-old can die of many causes some accidents, others an incurable disease. But, that 3 month-old can give life and sight and other helpful body parts to others, as can that 75-year-old. The final person to receive such a gift is you, your wife, child, husband, mother, father, a teacher, a prisoner in jail anyone and everyone.

There are more than 50 different parts of a persons body that can be donated to help others live a better life. Those supply items are organs, corneas, tissues, hands and face, blood stem cells, cord blood, bone marrow, blood and platelets. The number of people given this gift of life exceeded 113,000 in 2019.

Real-life experience: We recently attended a Donor Family Tribute in Greenville, N.C. The sponsor of this event was Carolina Donor Services. The building was huge and looked like a country club. We were not sure if we were at the right place, and we even questioned why we should spend our Sunday afternoon there.

This nice-looking building clearly was a place to hold a special event. When we reached the register desk, we discovered our name was not on the list. We debated for three months after the invitation arrived whether we wanted to be around a group of people who lost their loved ones.

There was a meeting and dining area, much as you would expect at a professional conference. There was nice, light music playing in the background, the walls were black and there were quilts hanging all over the front of the room. The quilts had small 12-inch squares on them. It was obvious that the quilt was a remembrance of the ones who had died.

We sat at a table that had many place settings and chairs. We sat quietly for about 30 minutes, as around 200 people entered the room and took their seats. When the room filled, the talking was in whispers, as if we were in church waiting for a service to begin. We thought about quietly getting up and leaving. We did not fit in here.

The 200 people were a mix of races, ages and abilities. A spokesperson on stage invited all the guests to join the buffet line. We all did, and the group ate for about 30 minutes, again like a church social. Then it began.

The speaker asked if anyone would like to tell about a loved one who donated to help others live. Slowly, people many of whom had never spoken in front of a group walked to the microphone. One woman, smiling and happy with tears of joy running down her face, spoke about finding her 15-year-old son in his room at home, hanged. She described how it took three days for him to die of his suicide.

Then, she happily said his hand was being used by another young boy who had lost his in an accident and how her sons eyes would make another person see for the first time in years.

Another person shared the story of how a 3-month-olds death from an incurable disease helped other life-threatened babies live. The sharing of stories went on for about three hours.

When we gathered to leave, we and those 200 people were all the same. We were friends, like long-lost relatives. There was no age or race or illness separating us. We all treated each other as the same.

People are waiting: When someone you love dies, grief memoirs seem the same. Being around those who also have lost someone and are grieving seems to be a logical connection. The topic of conversation is similar and shared. But the loss is still there for the person so loved. Something changed with this donor tribute.

The 200 or so people with their common loss encountered a gain. Many of them know the person who has received a new hand, or can see, or can talk for the first time in years. Knowing that their loved one is still alive in a small part of someone else, maybe even the heart itself, gives comfort to us who have been left with such grief in the past.

The donor process of giving was not around when our parents died. If it had been, our visits to the gravesites would hold a little more light of happiness, knowing someone was walking around on a farm or in an office with our loved ones heart or arteries or hands.

Donate Life Virginia is a small part of life-giving across all of America. Please, donate in your state when your time comes. We are.

Oliver Hedgepeth is professor of logistics for the American Military University. Elizabeth Hedgepeth is former managing editor of the Petersburg Progress-Index. Contact them at: blh4835@gmail.com

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Dr. Christopher Good | Spinal Surgeon | Virginia Spine

Posted: May 13, 2019 at 3:55 pm

Christopher R. Good, M.D, F.A.C.S.

Spine SurgeonDirector of Scoliosis & Spinal Deformity President of Virginia Spine Institute

Dr. Good has pioneered the use of robotics and navigation in spine surgery, established as a world expert in the field. Most recently, he performed the first and the most advanced robotic spine surgery using Mazor XTM Stealth Edition technology. Through extensive research, his surgical techniques are proven to decrease complications and improve patient safety and recovery time. The wide-reaching impact of his innovation has transformed the lives of patients suffering from complex neck or back conditions.

His passion to become a spine surgeon began at an early age when his father suffered a traumatic spinal injury. This life-changing event inspired Dr. Good to evolve treatment solutions for his patients with complex scoliosis and kyphosis, failed prior surgery, and severe degenerative conditions. Heralded for his compassionate approach, Dr. Good personally connects with patients, working together to create a tailored treatment plan that will achieve their goals for recovery. Learn more about his path to become a spine surgeon.

As the President of Virginia Spine Institute, Dr. Good has also pioneered the use of regenerative stem cell therapy for lumbar disc disease, helping many patients with low back pain to improve their quality of life and avoid surgery; he has performed the most intra-discal injections of stem cells in the region. He is currently studying the outcomes of his patients and uses these outcome studies to improve access to these revolutionary treatments for more people who suffer from back pain.

Through his leadership and vast experience, Dr. Good is reshaping the future of spine surgery and his research has helped develop surgical techniques that are proven to improve patient safety, decrease radiation during surgery and reduce recovery time. Dr. Good is the principal investigator of an FDA trial investigating a revolutionary new cervical disc replacement surgery and he has participated in multiple FDA studies evaluating the safety and efficacy of genetically engineered bone graft to promote fusion.He also participates in multiple scientific advisory boards working to improve patient safety and spinal balance; he routinely presents his findings, both nationally and internationally.

View Dr. Good's Complete CV

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Top 25 Most Haunted Places in Virginia – Colonial Ghosts

Posted: May 13, 2019 at 3:55 pm

Out of the one hundred and seventy supposedly haunted places in Virginia, only twenty five locations satisfied Colonial Ghosts huge scares criteria. Rumors were not enough to earn a spot on the list below!

Why is Virginia known to be one of the nations most haunted states?Well, to begin with, it is among the countrys oldest colonies. The first successful English settlement in America, Jamestown, was established here on May 13, 1607. Its earliest inhabitants, though, are believed to be of Asian descent. These first Virginians arrived some 11,000 years ago. After that, the state became the home of various Native American tribes. They were all united under the powerful Powhatan chiefdom by the time John Smith and his crew of European pioneers reached Virginia.

Virginia has thus had plenty of time to accumulate some spooky stories.Beforethe 1600s, itsoccupants were practitioners of shamanism and believers in the afterlife. Many Native American ceremonies, for instance, sought to make contact with the dead, even bring them back to life. During the colonial era, Virginia continued to be marked with instances of black magic. Several people were tried for dabbling in witchcraft,wrongly convicted, and sentenced to death. Indian burial grounds andold prisonsare thus among the states most paranormally active locations.

Then there are Virginias numerous battlegrounds. Whether fights pitted Americans against Indians, the British, or each other, they all resulted in the same thing:high casualties. The states pivotal location and importance as a hub of commercial and political activities made it the site of several significant Civil War battles. At justoneof its parks, (the Fredericksburg and Spotsylvania National Military Park), four major battles occurred. And you can be sure that there are ofplenty of ghostsroaming the bloodiest ground in North America!

Lets not forget all thegruesome murders,tragic suicides,violent massacres,horrible accidents, andcreepy medical experimentsthat have happened in Virginia. No wonder the state boasts nearlyone hundred and seventysupposedly haunted destinations. So how on earth is a fear enthusiast to know which ones are actuallywortha visit?

There are a lot of rankings out there, but the problem is that few stem fromreputablesources. The so called hauntings of many locations are simply based on urban legend and third party claims. Even stories from locals are not always reliable. People tend to over exaggerate and embellish stories in order to scare listeners.

Finally, someone decided that horror hunters need a directory of locations thats well curated, in-depth,andaccurate. Presented here areVirginias Top 25 Most Haunted Places, as ranked byColonial Ghosts. Know that their recommendations are fortruefear fans only to be included on this list, a site had to have paranormal activities well documented.

Ready for the countdown? Here are the 25 most haunted places in Virginia

25.The Public Hospital, Williamsburg

24.Crawford Road, Yorktown

23.Lightfoot House, Williamsburg

22.Bacons Castle, Surry

21.Edgewood Plantation, Charles City

20.Spotsylvania Court House, Spotsylvania

19.Staunton Train Depot, Staunton

18.Swannanoa Palace, Afton

17.Salubria Manor, Stevensburg

16.Paxton Manor, Leesburg

15.Fort Magruder Hotel, Williamsburg

14.Major Grahams Mansion, Wythe County

13.Boxwood Inn Bed & Breakfast, Newport News

12.Public Gaol, Williamsburg

11.Wythe House, Williamsburg

10.Historic Avenel, Bedford

9.Weems-Botts Museum, Dumfries

8.Ferry Plantation House, Virginia Beach

7.Graffiti House, Brandy Station

6.Cold Harbor Battlefield, Mechanicsville

5.Historic Jordan Springs, Stephenson

4.Henricus Historical Park, Chester

3.The Exchange Hotel Civil War Medical Museum, Gordonsville

2.St. Albans Sanatorium, Radford

1.The Peyton Randolph House, Williamsburg

Click on the links, and you will be taken to individual blog posts fully dedicated to each location. Learn about the sites origins, owners, architecture and of course, its spectral tenants. Paranormal investigations, if conducted there, are also referenced. What you get from each article is a brief history lessonanda horror recap.

The goal of this list is to take away the guesswork the next time you decide to take a scare-cation. If you are interested in one of the sites located in Williamsburg, check out thetoursoffered byColonial Ghosts. Their guides will certainly take you there, as well as to other creepy spots around the historic city.

If you want to learn more about why Virginias so haunted, browse through theResearchorStoriessection ofColonial Ghosts blog. This way, by the time you arrive at your chosen destination, you will be an expert on all things paranormal.

Here is a quick summary of each location, to kick off your hunt for horrors.

25.The Public Hospital, Williamsburg

As the first mentalinstitution in North America, The Public Hospital has seen a lot of misery and pain. In fact, one of its superintendents, Dr. John Minson Galt II, took his own life, so stressful was his job. His spirit is believed to still roam the asylum. Other ghosts seen around the creepy hospital include tortured patients and Civil War soldiers, who took over the building during the Battle of Williamsburg.

24.Crawford Road, Yorktown

If you take your vehicle onto Crawford Road, avoid its old bridge. Scary things have happened when people drive under it. In one instance, a group of friends were attacked by something definitely not of this world. It left handprints all over their cars fogged up windows. An abandoned building by Crawford Road is also occupied by the dead. Visitors report of being watched by red eyes while in the spooky structure.

23.Lightfoot House, Williamsburg

This beautiful, 18th century mansion was originally the home of the wealthy Lightfoot family. Many influential people, including foreign ambassadors and celebrities, thus visited the Lightfoot House during the colonial era. Today, however, it appears that pranksters have replaced the privileged. Employees say that the house has poltergeists that like to mess up beds and cause other mischief.

22.Bacons Castle, Surry

During its long history, Bacons Castle has fallen in the path of rebels, Indians even strange, cosmic fireballs. This historic castle, also known as the Arthur Allen House, has thus fascinated historians and paranormal researchers for years. The castles ghosts are known to move objects around, shove visitors, and clamp noisily down the stairs.

21.Edgewood Plantation, Charles City

Edgewood Plantation, now a bed and breakfast, has a charming veneer thats quite misleading. During the Civil War, it witnessed much violence and bloodshed. Inn guests thus frequently spot dead soldiers roaming its grounds. The B&B even has a room named after its most famous ghost, Lizzie. She is said to have been the fiance of a soldier, who never made it home from the battlefield.

20.Spotsylvania Court House, Spotsylvania

Its not too surprising that Spotsylvania Court House earned a spot on this list. Thats because it lies on what is known as the bloodiest ground in North America, Fredericksburg and Spotsylvania National Military Park. Theres a lot to explore at the park, but its most paranormally active spot is definitely the Bloody Angle. Psychics whove visited this location have always gotten strong readings, while ghost hunters have never failed to collect EVPs there.

19.Staunton Train Depot, Staunton

War, fires, derailed trains the Staunton Train Depot has been a site of both bloody and tragic occurrences. The stations ghosts include Civil War soldiers and victims of train crashes. In 1890, a runaway train tore through the depot, destroying the building completely. Many passengers were significantly wounded, but Myrtle Ruth Knoxs injuries were the worst. She was the only one who died, and her spirit is often seen wandering around the stations tracks.

18.Swannanoa Palace, Afton

This stellar but deteriorating mansion has always been the perfect place to shoot some ghostly footage. It was featured in the paranormal reality television show,The R.I.P. Files, in 2014. The palace is said to be roamed by the wife of the estates original owner, James Henry Dooley. After the property left the hands of the Dooley family, it became a mysterious school called The University of Science and Philosophy. Its founder, the famous artist and mystic Walter Russell, islinked to the Illuminati cult. So besides ghosts, people have also seen strange rituals being conducted at Swannanoa Palace.

17.Salubria Manor, Stevensburg

This stately, Georgian-style house issaid to beCulpepper Countys most haunted location. Thanks to a recent earthquake, the manors ghosts are more active than ever. These spectral tenants include Lady Spotswood (the wife of the manors first owner) and Mrs. Hansbrough, a woman who is said to have hung herself in one of the bedrooms. The mansion also has two cemeteries, where spirits have been seen as well.

16.Paxton Manor, Leesburg

Paxton Manor is the perfect place to spend your next Halloween. Since 2009, the team behind the buildings popularShocktoberevent has transformed it into a comprehensive scareground, which includes a spooky fun house and hair-raising hayride. But real ghosts lurk amongShocktobers costumed actors.Jedidiah Carver, a previous owner who was known for mutilating animals, is one of the houses most feared spirits. You certainly wouldnt want to run into him in the manors infamous Well of Souls!

15.Fort Magruder Hotel, Williamsburg

If youre looking for a unique and scary night in Williamsburg, book a room at Fort Magruder Hotel. The property lies on where the epic and bloody Battle of Williamsburg occurred. Guests report of seeing Civil War soldiers in their rooms and even encountering spirits pretending to be hotel staff. Several paranormal investigations have also been conducted at the hotel, during which an abundance of supernatural evidence (i.e. EVP readings and photographic anomalies) has been captured.

14.Major Graham Mansion, Wythe County

The Major Graham Mansion was built in 1826 by a wealthy businessman. For some reason, he decided to construct his home on bloodstained land. In the 1700s, Joseph Baker was murdered by two of his slaves there. Hisgrisly remainswere kept in a barrel of moonshine. Major Grahams wife, Martha, also died on the property. She was a depressed woman who eventually went insane.Her husband, unable to handle her madness, is said to have shackled her in the basement.Martha is among the various ghosts tourists encounter during the manors popular Halloween event.

13.Boxwood Inn Bed & Breakfast, Newport News

During the Civil War, this charming B&B hosted weary Civil War soldiers, including the famous General John J. Blackjack Pershing.Today, its rooms retain their original colonial charm and are haunted by a friendly ghost known as Nannie. Shes known to help out staff and rouse guests in the early mornings. People have also seen the spirit of an old man at the inn.

12.Public Gaol, Williamsburg

This two-story, brick prison is featured onColonial Ghosts comprehensive tour of Williamsburg. From murderers to pirates, the jails inmates during the colonial times included the citys most vicious individuals. Fifteen henchmen of the infamous corsair Blackbeard were incarcerated there. Conditions at the Gaol were as bad as its occupants (picture freezing cells, terrible food, and widespread typhus.) Visitors have seen shackles move on their own and heard screams coming from cells while touring the prison.

11.Wythe House, Williamsburg

The Wythe House is a beautiful Georgian-style mansion built in the mid-1700s. It was constructed by the nations first law professor, George Wythe. Wythe was well known in the city for his work in legislature and contributing to the Declaration of Independence. Unfortunately, smarts and honest living didnt run in the family. Wythes great nephew, George Wythe Sweeney, opted to steal, gamble, and eventually kill his way to money. He poisoned Wythe with arsenic, in order to inherit the familys wealth faster. Today, Wythes spirit is often heard walking around the house. Another ghost, believed to be of Lady Ann Skipwirth, has frightened visitors as well.

10.Historic Avenel, Bedford

Historic Avenel, also known as Avenel Plantation, has been confirmed by many paranormal experts to be officially haunted. The property was inherited by William A. Burrell, the secretary of President Thomas Jefferson, in 1831. It includes several outbuildings, but the main mansion is definitely the most paranormally active. Evidence captured there include EVPs and spooky photographs of eyes. The house is said to be haunted by a cat, as well as a woman known only as The Lady in White.

9.Weems-Botts Museum, Dumfries

Soak up some historyandget some frights at this haunted museum. The house portion of the Weems-Botts Museum was originally a village poor house, where the sick and homeless sought shelter. It then became the home of two famous colonials, Mason Locke Weems (George Washingtons first biographer) and Benjamin Botts (a lawyer on Aaron Burrs defense team.) Today, its haunted by members of the Merchant family. This includes the epileptic Mamie Merchant, who died because of her disease, and her sister, Violet. Violet is often seen through the houses windows, grieving over her dead sibling.

8.Ferry Plantation House, Virginia Beach

Ferry Farm is named after Norfolk Countys first ferry service. Eleven ghosts are believed to haunt this beautiful colonial plantation. In the house, people have encountered a woman known as The Lady in White, who died after falling down the stairs. On the grounds, visitors have spotted the spirit of Henry the slave. In 1706, the infamous trial-by-dunking of Grace Sherwood (aka The Witch of Pungo) was held near the plantation. Grace was wrongly accused of causing the miscarriage of a local woman. Whenever theres a full moon, people see her sopping spirit emerge from banks of the Lynnhaven River.

7.Graffiti House, Brandy Station

In 1863, during the Battle of Fleetwood Hill, the Graffiti House was transformed into a field hospital. Troops who stayed there passed the time by signing their names and doodling on the buildings walls. But these soldiers have left more than just art work at this historic train station. When people enter the building, theyre often overwhelmed by a sense of pain and misery. Objects are also known to move on their own at the Graffiti House.

6.Cold Harbor Battlefield, Mechanicsville

The Battle of Cold Harbor is said tohave beenone of the nations bloodiest battles. It lasted for nearly two weeks and resulted in a total of 17,332 casualties. Shots of the battlefieldtaken by Civil War photographers show grisly piles of skeletons and severed limbs. Decades after the battle, people are still capturing unsettling images: apparitions, strange shadows, unexplainable mists. Visitors also report of feeling watched while they tour Cold Harbor Battlefield.

5.Historic Jordan Springs, Stephensen

Historic Jordan Springs is one of Virginias few authenticated paranormal sites. Its history dates back to 1549. The area was first inhabited by the Catawba Indians, who had heard about the healing powers of the White Sulphur Spring and the Calibeate Spring. In 1832, Branch M. Jordan started a successful resort business there. Hotel operations were brought to an abrupt halt thanks to the Civil War. The spirits of soldiers have been seen and photographed around the property. Historic Jordan Springs has even been featured on an episode of SciFisGhost Hunters!

4.Henricus Historical Park, Chester

The city of Henricus was established in September 1611 and was Virginias second settlement. The town prospered and grew until the famous Indian Massacre of 1622, during which some 400 colonists wereslaughtered. Henricus was also the site of a bloody, naval Civil War skirmish which lasted from January 23 to 25, 1865. Restless spirits from both events continue to roam the area. Even when no reenactments are being staged at the park, visitors encounter people dressed in colonial garb and hear canon fires in the distance.

3.The Exchange Hotel Civil War Medical Museum, Gordonsville

The Exchange Hotel Civil War Medical Museum is currently run by Historic Gordonsville, Inc. It acquired the property back in 1971 and has been renovating it ever since. The hotel was built in 1859 and spent its early years as a popular place to stay for weary train passengers. Then, in 1862, it was converted into a Civil War receiving hospital. Over 23,000 sick and wounded soldiers were shuttled in and out of the building. Around 700 could not be saved and were buried there. This explains why there have been nearly 80 recorded unexplainable incidents reported at The Exchange Hotel Civil War Medical Museum. One of the museums ghosts is believed to be of a little boy who worked there during the Civil War. The hospitals depressing environment is said to have driven him to commit suicide.

2.St. Albans Sanatorium, Radford

This insane asylums spooky history began before it was even built. The land on which it stands was where a bloody massacre occurred. In 1755, the colonists of Drapers Meadow were attacked by a group of Shawnee Indians. Those who werent killed were taken as hostages. St. Albans Sanatorium was built in 1892, but first functioned as a boys school, where bullying and homicide were not uncommon. The building became a psychiatric hospital in 1916. From insulin-induced comas to lobotomies, the treatment methods at the sanatorium were often more deadly than conducive. Today, plenty of creepy instruments and old gurneys lie rusting in the hospital.

1.Peyton Randolph House, Williamsburg

The Peyton Randolph House is a two-story, Georgian-style mansion built in 1715 by Sir William Robertson. It passed into the hands of Peyton Randolph, a famous revolutionary leader, in 1754. Behind the houses impeccable design lurks plenty of misery and pain. Peytons wife, Betty, was known to be a very cruel slave master. One of her slaves, Eve, is said to have placed a terrible curse on the house. Perhaps this is why decades later, many people diedat the mansion from freak accidents,murder,evenmysterious illnesses. The house is thus one of the hottest attractions alongColonialGhosts guided tour of Williamsburg. Besides seeing and hearing ghosts, people have been attacked by them as well. A security guard, for instance, was trapped in the houses basement by some angry force.

Thank you for reading our list of the most haunted places in Virginia! Of course, there are many more haunted places in Virginia, but the 25 listed hereare amongthe most haunted.

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Stem Cell Therapy in Dallas, TX | National Stem Cell Centers

Posted: March 5, 2019 at 9:44 pm

The doctors affiliated with National Stem Cell Centers in Dallas, TX specialize in harvesting tissue and having the cells processed at our registered tissue processing lab.

The physicians follow compliant protocols where the tissue is not manipulated and there is no tissue or cell expansion.

We also do not use enzymes as per FDA guidelines.

Stem cell procedures hold great potential for the management of joint pain, arthritis, hair loss, cosmetic and other disorders as well as auto-immune, renal, and neurological disorders.

There are various types of stem cells, particularly as they pertain to potential procedures, including umbilical cord cells, adipose (fat-derived), amniotic cells, placenta, bone marrow, exosomes, and others.

The physician will go over your options during your complimentary consultation.

Dr. Baker is a general surgeon by training and a native of Northeast Texas.

His general surgery training makes him uniquely qualified as an excellent stem cell physician.

After graduating from the University of Arkansas with the highest honors,

Dr. Baker attended the University of Texas Medical School at Houston where he was awarded the prestigious Parents and Alumni Scholarship.

During medical school, Dr. Baker was selected to participate in the competitive summer research program and remained active in research throughout medical school.

Following medical school and research commitments, Dr. Baker moved to Phoenix, Arizona where he began his surgical education. It was in the Scottsdale area that Dr. Baker began to hone his artistic eye for body sculpting. Dr. Baker also garnered broad experience in regenerative medicine around this time as aesthetic improvement and restorative complementary medicine techniques often go hand in hand.

In the six years since Dr. Baker has treated thousands of cosmetic patients and a near equal quantity of functional medicine patients. He strives to remain on the cutting edge through continued education and a meticulous attention to detail for all of his patients with a willingness to think outside the box and look for options that traditional medicine might otherwise not consider.

Dr. Thiele is a General Surgeon with five years of training in general surgery.

He is a Diplomate of the American Board of Management Wound which has helped hone his hair transplant techniques including FUT, graft harvesting, recipient site making, anesthesia, pain management and wound healing.

He has worked as a Physician at the East Texas Medical Center and Mother Francis Hospital in Tyler, and served as a Physician with VOHRA Would Physicians, TeleHealth, Murdock & Applegate Recovery.

He attended medical school at the University of Texas in Galveston and trained at Mercer University in Georgia and Charleston Area Medical Center in W. Virginia.

Dr. Thiele performs the FUT as well as FUE procedures at MAXIM Hair Restoration in Houston and Dallas, Texas.

Dr. Smith is Facial Plastic and Reconstructive Surgeon in Dallas, Texas.

He specializes in all types of aesthetic surgery for the face and performs stem cell procedures.

Dr. Smith received his undergraduate degree from Baylor University. He began his medical education at the University of Texas Southwestern Medical Center in Dallas where he received his MD degree.

Dr. Smith completed his internship in general surgery followed by a residency and specialization in Otolaryngology-Head and Neck Surgery at the University of Texas Southwestern Medical Center in Dallas, including Parkland Hospital System.

Dr. Smith was then chosen for a highly specialized Fellowship in Facial Plastic and Reconstructive Surgery sponsored by the American Academy of Facial Plastic and Reconstructive Surgery at the University of California, Los Angeles. During his fellowship at UCLA, his entire experience focused on cosmetic and reconstructive surgery of the face, head, and neck.

He received his training in stem cell therapy with Dr. David Mayer at National Stem Cell Centers in New York City.

Schedule your complimentary stem cell therapy consultation today with one of our affiliated physicians in Dallas, Texas, by calling (972) 865-8810 or submit the Contact Form on this page.

This location serves Dallas, Fort Worth, Arlington, Euless-Bedford-Hurst, Plano, and surrounding areas.

Phone: (972) 865-8810

Address:8111 LBJ Freeway, Suite 655Dallas, TX 75251

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Stem Cell Therapy in Dallas, TX | National Stem Cell Centers

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