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  • richardmitnick 4:01 pm on December 19, 2014 Permalink | Reply
    Tags: , , , Medicine   

    From: “Knee meniscus fixed using revolutionary stem cell procedure” 

    Cornell Bloc

    Cornell University

    Dec. 19, 2014
    Krishna Ramanujan

    Researchers report on a revolutionary new procedure that uses 3-D printing and the body’s stem cells to regenerate knee meniscus, a tissue lining that acts as a natural cushion between the femur and tibia.

    People with damaged menisci develop arthritis and are forced to limit their activity.

    The procedure, published online Dec. 10 in the journal Science Translational Medicine, has proved successful in sheep at Cornell University six months after surgery, though the researchers will monitor the sheep for a year to ensure the animals do not develop arthritis. Sheep menisci are structurally similar to those of humans, and clinical trials in humans could begin in two to three years.

    “Most middle-aged people who end up with a degenerate meniscus have it trimmed up [surgically], but if you lose more than 20 to 30 percent, then you are very prone to arthritis,” said Lisa Fortier, professor of large animal surgery at Cornell’s College of Veterinary Medicine and a co-author of the paper; she led the meniscus surgeries on sheep. “If everybody who needed it could replace their meniscus they could slow arthritis and maintain their full function,” Fortier added.

    Lise Fortier checks the meniscus of a sheep that she operated on last summer, using a groundbreaking new procedure to regenerate knee meniscus. (Meg Goodale)

    The technique was developed by the paper’s senior author Jeremy Mao, professor of dental medicine at Columbia University Medical Center, and involves taking an MRI of the patient’s (in this case sheep’s) knee. Using a 3-D printer, Mao printed a biodegradable polyester scaffold in the exact shape of a patient’s meniscus. Through multiple lab experiments, Mao’s group discovered that two growth factors, when used in specific concentrations and at critical times, recruited the most stem cells for meniscal repair. The growth factors were then laced into the scaffold, allowing the body’s stem cells build a new meniscus four to six weeks after surgery.

    Currently, a torn meniscus requires replacement with cadaver tissue, which has a low success rate and can lead to disease and rejection, and synthetic menisci have proved ineffective and hard to fit properly in diversely built patients.

    Approximately a million people undergo meniscus surgeries each year in the United States.

    Co-authors include Scott Rodeo, orthopedic surgeon at the Hospital for Special Surgery, an affiliate of Weill Cornell Medical College; and Chang H. Lee, Chuanyong Lu and Cevat Erisken, all at Columbia University Medical Center.

    The study was funded by the National Institutes of Health, the Arthroscopy Association of North America, the American Orthopaedic Society for Sports Medicine and the Harry M. Zweig Foundation.

    See the full article here.

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    Once called “the first American university” by educational historian Frederick Rudolph, Cornell University represents a distinctive mix of eminent scholarship and democratic ideals. Adding practical subjects to the classics and admitting qualified students regardless of nationality, race, social circumstance, gender, or religion was quite a departure when Cornell was founded in 1865.

    Today’s Cornell reflects this heritage of egalitarian excellence. It is home to the nation’s first colleges devoted to hotel administration, industrial and labor relations, and veterinary medicine. Both a private university and the land-grant institution of New York State, Cornell University is the most educationally diverse member of the Ivy League.

    On the Ithaca campus alone nearly 20,000 students representing every state and 120 countries choose from among 4,000 courses in 11 undergraduate, graduate, and professional schools. Many undergraduates participate in a wide range of interdisciplinary programs, play meaningful roles in original research, and study in Cornell programs in Washington, New York City, and the world over.

  • richardmitnick 10:13 am on December 19, 2014 Permalink | Reply
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    From ICL: “New study shows how some E. coli bacteria hijack key proteins to survive longer” 

    Imperial College London
    Imperial College London

    19 December 2014
    Laura Gallagher

    A new study shows how two strains of the intestinal bug E. coli manage to hijack host proteins used to control the body’s immune system.


    The research, carried out by scientists at Imperial College London and published in the journal Nature Communications, shows how E. coli bacteria can block key human enzymes, in a way that has not previously been shown in any other biological context.

    The enzymes, known as kinases, are molecular switches that control processes such as immune responses to infection and cancers in humans. Better understanding how the E. coli bacteria interfere with kinases will provide valuable avenues for investigating new therapies.

    There are many different strains of E. coli. While some are good bacteria, others can cause symptoms ranging from mild diarrhoea and nausea to kidney failure and death. The two strains examined in this study are E. coli O157, which causes food-borne infections, and enteropathogenic E. coli (EPEC), which is a major cause of infantile diarrhoea in low-income countries.

    At present there are no vaccines or effective drugs to combat these infections – in fact antibiotic treatment of E. coli O157 infection can cause the invading bacteria to release more toxins, making the symptoms worse. Patients are treated with fluids and nutrients to enable their immune system to fight the infection.

    One reason why these strains are so dangerous is that they inject bacterial proteins into human cells. These proteins hijack the cell’s signalling network to promote their growth and survival, for example by preventing the host from recognising them as harmful bacteria.

    The new research found that E. coli O157 and EPEC inject a protein called EspJ which inhibits the kinases from signalling.

    “The way in which the EspJ protein blocks the activity of human kinases is completely novel,” says Professor Gad Frankel, from the MRC Centre for Molecular Bacteriology and Infection. “This study will help us better understand how pathogens are able to hijack cells and how they prevent the immune system from fighting the infection.”

    The team reached their conclusions after performing biochemical, mass spectrometry and cell biology assays. This study provides valuable new avenues of investigation: further research will look at whether EspJ-like proteins in other intestinal pathogens, such as Salmonella, behave in similar ways, and also what effect EspJ proteins in E. coli O157 might have on other types of kinases.

    The research was carried out by a team of scientists at Imperial College London, working in collaboration Albert-Ludwigs-Universität Freiburg, in Germany.

    See the full article here.

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    Imperial College London is a science-based university with an international reputation for excellence in teaching and research. Consistently rated amongst the world’s best universities, Imperial is committed to developing the next generation of researchers, scientists and academics through collaboration across disciplines. Located in the heart of London, Imperial is a multidisciplinary space for education, research, translation and commercialisation, harnessing science and innovation to tackle global challenges.

  • richardmitnick 12:56 pm on December 16, 2014 Permalink | Reply
    Tags: , , Medicine, RPI   

    From RPI: “Researchers Develop ‘Radio-genetics’ – New Method Triggers Gene Expression With Radio Waves or Magnetic Field” 

    Rensselaer Polytechnic Institute

    Rensselaer Polytechnic Institute

    Rensselaer Polytechnic Institute Researchers Partner in Research Described in Nature Medicine

    December 15, 2014
    Mary L. Martialay
    Phone: (518) 276-2146
    E-mail: martim12@rpi.edu

    It’s the most basic of ways to find out what something does, whether it’s an unmarked circuit breaker or an unidentified gene — flip its switch and see what happens. New remote-control technology may offer biologists a powerful way to do this with cells and genes. A team at Rensselaer Polytechnic Institute and Rockefeller University is developing a system that would make it possible to remotely control biological targets in living animals — rapidly, without wires, implants, or drugs.

    In a technical report published today in the journal Nature Medicine, the team describes successfully using electromagnetic waves to turn on insulin production to lower blood sugar in diabetic mice. Their system couples a natural iron storage particle, ferritin, to activate an ion channel called TRPV1 such that when the metal particle is exposed to a radio wave or magnetic field, it opens the channel, leading to the activation of an insulin-producing gene. Together, the two proteins act as a nano-machine that can be used to trigger gene expression in cells.

    Researchers experimented with different configurations for their remote control system, and they found the best relies on an iron nanoparticle (blue), which is tethered by a protein (green) to an ion channel (red). Above, all three appear within cell membranes.

    “The use of a radiofrequency-driven magnetic field is a big advance in remote gene expression because it is non-invasive and easily adaptable,” said Jonathan S. Dordick, the Howard P. Isermann Professor of Chemical and Biological Engineering and vice president for research at Rensselaer Polytechnic Institute. “You don’t have to insert anything — no wires, no light systems — the genes are introduced through gene therapy. You could have a wearable device that provides a magnetic field to certain parts of the body and it might be used therapeutically for many diseases, including neurodegenerative diseases. It’s limitless at this point.”

    Dordick, Ravi Kane, the P.K. Lashmet Professor and head of Chemical and Biological Engineering, within the Rensselaer Center for Biotechnology and Interdisciplinary Studies, and doctoral student Jeremy Sauer collaborated with Rockefeller colleagues Jeffrey Friedman, Rensselaer Class of 1977, and Sarah Stanley on the project.

    Other techniques exist for remotely controlling the activity of cells or the expression of genes in living animals. But these have limitations. Systems that use light as an on/off signal require permanent implants or are only effective close to the skin, and those that rely on drugs can be slow to switch on and off.

    The new system, dubbed radiogenetics, uses a signal, in this case low-frequency radio waves or a magnetic field, to activate ferritin particles. They, in turn, prompt the opening of TRPV1, which is situated in the membrane surrounding the cell. Calcium ions then travel through the channel, switching on a synthetic piece of DNA the scientists developed to turn on the production of a downstream gene, which in this study was the insulin gene.

    In an earlier study, the researchers used only radio waves as the “on” signal, but in the current study, they also tested out a related signal – a magnetic field – that could also activate insulin production. They found it had a similar effect as the radio waves.

    “The method allows one to wirelessly control the expression of genes in a living animal and could potentially be used for conditions like hemophilia to control the production of a missing protein. Two key attributes are that the system is genetically encoded and can activate cells remotely and quickly,” says Friedman, co-senior author on the project and the Marilyn M. Simpson Professor and head of the Laboratory of Molecular Genetics at Rockefeller. “We are now exploring whether the method can also be used to control neural activity as a means for noninvasively modulating the activity of neural circuits.”

    See the full article here.

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  • richardmitnick 5:49 pm on December 15, 2014 Permalink | Reply
    Tags: , Medicine,   

    From MIT: “Sophisticated medicine” 

    MIT News

    December 15, 2014
    Leda Zimmerman | MIT Spectrum

    Sangeeta Bhatia’s research defies tradition, drawing on biological and medical sciences, and multiple engineering disciplines.

    Sangeeta Bhatia’s research draws on biological and medical sciences, and engineering. Photo illustration: Len Rubenstein

    “I’m mostly driven by how to fix things,” states Sangeeta Bhatia. “I’m always thinking about how to solve problems by repurposing tools.” Although not a mechanic, Bhatia, the John J. and Dorothy Wilson Professor of Health Sciences and Technology (HST), Electrical Engineering and Computer Science (EECS), and Institute for Medical Engineering and Science (IMES), does run a repair shop of sorts. As director of the Laboratory for Multiscale Regenerative Technologies, she tackles some of medicine’s most intractable problems, developing sophisticated devices and methods for diagnosing and treating human disease.

    Bhatia’s research defies traditional academic categories, drawing simultaneously on biological and medical sciences, and multiple engineering disciplines. She has generated dozens of patents, several business spinouts, and earned a host of major scientific honors, including the 2014 Lemelson-MIT Prize, a $500,000 award recognizing an outstanding American midcareer inventor, and the David and Lucile Packard Fellowship, given to the nation’s most promising young professors in science and engineering.

    A member of the Koch Institute for Integrative Cancer Research, her unorthodox career got an early start, thanks in part to Bhatia’s self-described passion for “tinkering.” As a child, she could fix the family’s broken answering machine, and was handy with hot glue guns “in a Martha Stewart way.” Her father, recognizing her potential as an engineer, brought her to the lab of an MIT acquaintance who was using focused ultrasound to heat up tumors. Her encounter with technology used against deadly disease proved formative.

    Bhatia was determined to become a biomedical engineer, earning an undergraduate degree in the field. She came to view the human body “as a fascinating machine” whose failures she might address by designing interventions. But it was while she was simultaneously pursuing her doctorate in medical engineering at MIT and her MD at Harvard Medical School that Bhatia’s core research concerns began to crystallize.

    Investigating a potential artificial organ to process the blood of patients suffering liver failure, Bhatia improvised a novel approach. Borrowing microfabrication technology from the semiconductor industry, she arrayed liver cells on a synthetic surface, and to her delight, this hybrid tissue remained alive in the lab for weeks. Scientists had long sought a way to sustain liver cells ex vivo, and Bhatia had delivered a biomedical first.

    With her innovative adaptation of engineering tools for medically useful applications, Bhatia conjured a unique research methodology. And she also found her primary research subject: “I had an ‘aha’ moment, and realized I loved studying the liver.”

    Diseases of the liver, unlike those of other organs, don’t have ready treatments. Severe alcohol abuse, hepatitis, and a host of other liver diseases sicken and kill millions each year. In addition, many aspects of the liver remain a mystery, including its unique tissue architecture and ability to regenerate. “It seemed like an incredible opportunity; anything you provided might have an impact,” says Bhatia.

    Motivated by this opportunity, Bhatia began generating a steady stream of liver-focused bioengineering tools. For instance, she transformed her hybrid microfabricated liver tissue into a platform for screening drugs outside the body. In a current study, Bhatia is using an artificial liver as a testing ground for a drug with the potential to destroy the malaria parasite at different stages of its life cycle.

    She is also closing in on the “naively audacious” goal of building a replaceable liver for patients in need of a liver transplant. Her team has identified chemical compounds that send regeneration signals to liver cells, and she is now successfully growing human livers in mice.

    Bhatia has more recently aimed her biotech arsenal at targets beyond the liver. Exploiting nanoparticles, she is devising an inexpensive urine test for cancer that could prove immensely useful in the developing world. She has also begun attacking two of the deadliest cancers, ovarian and pancreatic, designing nanomaterials that can penetrate tumors with a cargo of RNA to silence spreading cancer genes.

    “As an engineer, I have a hammer, and look for the next nail,” Bhatia says. “But as a physician, I also want to pick problems with the most clinical impact.”

    See the full article here.

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  • richardmitnick 9:44 am on December 12, 2014 Permalink | Reply
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    From NYT: “An Evolutionary Battle Against Bacteria” 

    New York Times

    The New York Times

    DEC. 11, 2014
    Carl Zimmer

    Every disease has a history. Some of that history is written in books, and some is written in our DNA.

    The earliest records of meningitis — an infection of the membranes that line the brain — reach back to 1685. The British physician Thomas Willis described fevered patients, some of whom suffered from “continual raving” and others who suffered from “horrible stiff extensions in the whole body.”

    But meningitis was a threat long before Willis put quill to paper. In a new study, published Thursday in the journal Science, two University of Utah scientists have uncovered a 40-million-year struggle between our ancestors and the bacteria that cause meningitis: As our ancestors evolved new defenses, our enemies evolve counter-defenses. By understanding the history of this struggle, we may be able to fight meningitis more effectively in the future.

    A number of species of bacteria can cause meningitis, but two — Haemophilus influenzae and Neisseria meningitidis — are the top threats. Like all bacteria, these pathogens need iron to grow. But we don’t make it easy for them to find iron inside our bodies.

    Haemophilus influenzae

    Neisseria meningitidis

    To move iron atoms from one cell to another, we seal them inside a kind of molecular lockbox, called transferrin. A cell can load two iron atoms into a single transferrin molecule and deliver it to another cell, which draws the transferrin inside and then opens it.


    Transferrin lets us starve bacteria by making free iron atoms scarce. Simply withholding it from the bacteria “becomes an immune strategy,” said Nels C. Elde, an evolutionary geneticist and an author of the new study.

    A few years ago, Dr. Elde became puzzled by transferrin. Studies by other scientists suggested that it had experienced strong natural selection, changing its molecular structure over generations. But transferrin still does the same job it has been doing for hundreds of millions of years. It ferries iron atoms inside mammals, reptiles, amphibians and even fish.

    To understand what has driven transferrin’s evolution, Dr. Elde teamed with Matthew F. Barber, a postdoctoral researcher in his lab. They carried out an unprecedented study on the evolution of the gene that encodes transferrin, comparing our own version to those in 20 species of apes and monkeys.

    The two scientists confirmed that over the past 40 million years, our transferrin protein had undergone drastic changes. Transferrin is made up of two lobes, each of which grabs an iron atom. By far the most changes had occurred in only one of the lobes. The other one barely evolved.

    This finding gave Dr. Elde a clue as to what was driving the evolution of transferrin: meningitis-causing bacteria.

    Neisseria and Haemophilus can both steal iron from transferrin. They do so with a protein, TbpA, that pries open one of transferrin’s two lobes, exposing the iron atom inside. The lobe under attack is the one that has been evolving swiftly; the unmolested lobe has barely changed.


    As the two Utah scientists were studying these evolutionary changes, researchers at the National Institutes of Health published the molecular details of how TbpA grabs transferrin. When Dr. Barber and Dr. Elde compared their results with the molecular structure, they were shocked. Almost every point at which transferrin made contact with TbpA has evolved, while little has changed beyond them.

    “That was the moment it all snapped together,” said Dr. Elde.

    Dr. Barber and Dr. Elde were able to reconstruct the history of transferrin. Each time its shape changed, it became harder for the bacteria to grab it and steal its iron.

    The scientists wondered if the bacteria had evolved in response to these changes. To find out, they got strains of Haemophilus influenzae and Neisseria meningitis from patients. They looked at the bacteria’s TbpA genes to see where they had evolved new structures.

    It turns out they changed where they made contact with transferrin. “It’s basically a mirror image,” said Dr. Elde.

    He and Dr. Barber argue that our ancestors and meningitis-causing bacteria have been locked in an arms race for 40 million years. Each time we make it harder for the bacteria to steal our iron, the bacteria change their structure to get a better grip on our transferrin.

    The race isn’t over. A new variant of transferrin has evolved in humans, and it is found in 6 to 25 percent of people, depending on their ethnic group. The Utah scientists found that Haemophilus influenzae bacteria can’t steal iron from the new variant. “It’s basically invisible,” Dr. Elde said.

    Harmit S. Malik, an evolutionary geneticist at the Fred Hutchinson Cancer Research Center who was not involved in the research, said that until he saw it, he doubted there were enough clues left in living primates to reconstruct the evolutionary arms race.

    But Dr. Barber and Dr. Elde proved him wrong. “It’s an extremely crisp result,” Dr. Malik said, adding, “Frankly, I didn’t think this could be done.”

    Despite all the defenses our ancestors evolved against these bacteria, they still pose a major threat to humanity. Haemophilus influenzae alone has been estimated to kill 371,000 people a year. Some researchers have investigated treating such infections by giving patients extra transferrin to starve bacteria.

    Dr. Malik suggested that this treatment would be even more effective if scientists used the evolutionary history of transferrin as a guide for designing transferrin that the bacteria can’t attack.

    “I suspect it could be a very, very important therapeutic,” he said. If he is right, our monkeylike ancestors could have a hand in saving the lives of our descendants.

    See the full article here.

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  • richardmitnick 7:45 pm on December 11, 2014 Permalink | Reply
    Tags: , , Medicine,   

    From Scientific American via Cornell University: “Are Algae Blooms Linked to Lou Gehrig’s Disease?” 

    Scientific American

    Scientific American

    Cornell Bloc

    December 11, 2014
    Lindsey Konkel and Environmental Health News

    Medical researchers are now uncovering clues that appear to link some cases of ALS to people’s proximity to lakes and coastal waters.

    For 28 years, Bill Gilmore lived in a New Hampshire beach town, where he surfed and kayaked. “I’ve been in water my whole life,” he said. “Before the ocean, it was lakes. I’ve been a water rat since I was four.”

    Now Gilmore can no longer swim, fish or surf, let alone button a shirt or lift a fork to his mouth. Earlier this year, he was diagnosed with Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.

    In New England, medical researchers are now uncovering clues that appear to link some cases of the lethal neurological disease to people’s proximity to lakes and coastal waters.

    About five years ago, doctors at a New Hampshire hospital noticed a pattern in their ALS patients—many of them, like Gilmore, lived near water. Since then, researchers at Dartmouth-Hitchcock Medical Center have identified several ALS hot spots in lake and coastal communities in New England, and they suspect that toxic blooms of blue-green algae—which are becoming more common worldwide—may play a role.

    Now scientists are investigating whether breathing a neurotoxin produced by the algae may raise the risk of the disease. They have a long way to go, however: While the toxin does seem to kill nerve cells, no research, even in animals, has confirmed the link to ALS.

    No known cause

    As with all ALS patients, no one knows what caused Bill Gilmore’s disease. He was a big, strong guy—a carpenter by profession. One morning in 2011, his arms felt weak. “I couldn’t pick up my tools. I thought I had injured myself,” said Gilmore, 59, who lived half his life in Hampton and now lives in Rochester, N.H.

    Three years and many doctors’ appointments later, Gilmore received the news in June that the progressive weakening in his limbs was caused by ALS.

    Neither Hampton nor Rochester is considered a hot spot for ALS. Gilmore is one of roughly 5,600 people in the United States diagnosed each year with the disease. The average patient lives two to five years from the time of diagnosis.

    There is no cure, and for the majority of patients, no known cause. For 90 to 95 percent of people with ALS, there’s no known genetic mutation. Researchers assume that some unknown interaction between genes and the environment is responsible.

    In recent years, some of this research has focused on blue-green algae, also known as cyanobacteria.


    “There’s a growing awareness of the importance of gene/environment interactions with neurodegenerative diseases. There is more interest in examining environmental exposures, including exposures to cyanobacteria, as possible risk factors for sporadic ALS,” said Paul Alan Cox, director of the nonprofit Institute of Ethnomedicine in Wyoming, which focuses on treatments for ALS and other neurodegenerative diseases.

    Cyanobacteria—some of the oldest organisms on the planet—can occur wherever there is moisture. Blooms are fed largely by nutrients in agricultural and urban runoff.

    Some cyanobacteria produce toxic compounds that can sicken people. In August, hundreds of thousands of people in Toledo, Ohio, were left without tap water for days when toxins from an algal bloom in Lake Erie were found in the water supply.

    While the cyanobacteria toxin that prompted the Toledo water crisis can cause diarrhea, intestinal pain and liver problems, other toxins produced by the blue-green algae can harm the nervous systems of humans and wildlife.

    Scientists have long suspected that a cyanobacteria toxin could play a role in some forms of ALS. After World War II, U.S. military doctors in Guam found that many indigenous Chamorro suffered from a rapidly progressing neurological disease with symptoms similar to both ALS and dementia. Years later, scientists found the neurotoxin BMAA in the brains of Chamorro people who died from the disease. Cyanobacteria that grow on the roots and seeds of cycad trees produce the toxin.

    Cox, a researcher in Guam in the 1990s, hypothesized that BMAA worked its way up the food chain from the cycad seeds to bats to the Chamorro who hunted them. But Cox and his colleagues also found BMAA in the brains of Canadian Alzheimer’s patients who had never dined on Guam’s fruit bats. In patients who had died from other causes, they found no traces of it. The source of the BMAA in the Canadians remains unknown.

    Some researchers have suggested that fish and shellfish from waters contaminated with cyanobacteria blooms may be one way that people ingest BMAA. In southern France, researchers suspect ALS cases may be linked to consumption of mussels and oysters. Lobsters, collected off the Florida coast near blooms, also have been found with high levels of BMAA.

    Scientists around the world are investigating how the neurotoxin gets into the body and whether it contributes to disease.

    “We don’t really know what exposure routes are most important,” Cox said.

    New England’s ALS hot spots

    In New Hampshire, Dartmouth neurologist Elijah Stommel noticed that several ALS patients came from the small town of Enfield in the central part of the state. When he mapped their addresses, he saw that nine of them lived near Lake Mascoma.

    Around the lake, the incidence of sporadic ALS—cases for which genetics are not a likely cause—is approximately 10 to 25 times the expected rate for a town of that size.

    “We had no idea why there appeared to be a cluster around the lake,” Stommel said.

    Based on the link between ALS and the neurotoxin in other parts of the world, Stommel and his colleagues hypothesize that the lake’s cyanobacteria blooms could be a factor.

    Across northern New England, the researchers have continued to identify ALS hot spots—a large one in Vermont near Lake Champlain and a smattering of smaller ones among coastal communities in New Hampshire and Maine.

    Earlier this year, the researchers reported that poorer lake water quality increased the odds of living in a hot spot. Most strikingly, they discovered that living within 18 miles of a lake with high levels of dissolved nitrogen—a pollutant from fertilizer and sewage that feeds algae and cyanobacteria blooms—raised the odds of belonging to an ALS hot spot by 167 percent.

    The findings, they wrote, “support the hypothesis that sporadic ALS can be triggered by environmental lake quality and lake conditions that promote harmful algal blooms and increases in cyanobacteria.”

    How people in New England communities could be ingesting the neurotoxin remains largely a mystery. While fish in the lakes do contain it, not everyone in the Dartmouth studies eats fish.

    “We’ve sent questionnaires to patients and there’s really no common thread in terms of diet or activities,” Stommel said. “The one common thing that everybody does is breathe.”

    In other words, it’s possible that a boat, jet ski or even the wind could stir up tiny particles of cyanobacteria in the air, where people then breathe it in.

    Testing the air for a neurotoxin

    Last August, at Lake Attitash, Jim Haney, a University of New Hampshire biologist, waded knee-deep into swirling green water. Cyanobacteria were blooming at the small lake in the northeastern corner of Massachusetts. Haney had rigged up three vacuum-like devices with pipes, plastic funnels and paper to suck up and filter air near the lake’s surface.

    He took the filter papers back to his laboratory and measured the cyanobacteria cells, BMAA and other toxins stuck to them.

    “We want to know what level lake residents may be exposed to through airborne particles,” said Haney, who is sampling the air at Massachusetts and New Hampshire lakes in collaboration with the Dartmouth team.

    Stommel said,“it’s very compelling to look at the filter paper and see it just coated with cyanobacteria.”

    At this point, Haney and graduate students are trying to understand under what conditions the toxins might be coming out of the lake and whether the airborne particles are an important route of exposure.

    Preliminary findings suggest that BMAA and other cyanobacteria cells are being aerolized. “There is potentially a large quantity of cyanobacteria that could be inhaled,” Haney said. He noted, however, that the measurements were taken about eight inches above the water’s surface, making it likely that concentrations would be much lower farther away.

    While the toxins are likely to be most abundant in the air around lakes, they exist all over the planet, even in deserts.

    In 2009, BMAA was even detected in the sands of Qatar. Crusts containing cyanobacteria may lie dormant in the soil for most of the year, but get kicked up during spring rainstorms. Cox and colleagues hypothesized that breathing in toxins from dust might be a trigger for a doubling of ALS incidence in military personnel after Operation Desert Storm.

    Near Haney’s workstation at Lake Attitash, a child splashed in the shallow water off a dock. Haney scooped up a cupful of water. He peered at the tiny green particles in the cup that reflect the sunlight, making the mixture resemble a murky pea soup.

    “We’ve developed this view of nature as idyllic, which is wonderful, but not everything in nature is benign,” he said. “Rattlesnakes are natural and you wouldn’t get too close to one of those.”

    “Proximity does not equal causality”

    The hypothesis that exposure to BMAA may trigger the disease in some people remains controversial.

    Researchers have evidence that people living close to lakes with blooms may be at increased risk for ALS. They’ve even found BMAA in the diseased brain tissue of people who have died of neurodegenerative diseases. Nevertheless, “proximity does not equal causality,” said Deborah Mash, a neuroscientist at the University of Miami in Florida.

    The big, unanswered question is whether the toxin can actually cause the disease. So far, there’s little evidence to show how it could induce the type of brain changes seen in people with ALS.

    Tests of human cells have found that BMAA kills the motor neurons—nerve cells that control muscles—implicated in ALS. Primates fed high levels of BMAA in the 1980s showed signs of neurological and muscular weakness. But the toxin did not kill their motor neurons.

    “What is lacking at this point is a clear animal model that demonstrates that BMAA exposure results in ALS-like neuropathy,” Cox said.

    So what is a possible mechanism for how the toxin may lead to the disease? The body may mistake BMAA for the amino acid L-serine, a naturally occurring component of proteins. When the toxin is mistakenly inserted into proteins, they become “misfolded,” meaning they no longer function properly and can damage cells.

    Cox and colleagues soon will test two drugs in FDA-approved clinical trials. They’re about to enter second-phase testing with L-serine. The idea, explained Sandra Banack, a researcher at the Institute for Ethnomedicine, is that large doses of L-serine may be able to “outcompete” low levels of BMAA in the body, preventing it from becoming incorporated into proteins.

    For ALS patients like Gilmore, the research can’t come soon enough. “If they can figure out a cause, then hopefully they can find a cure,” Gilmore said.

    [We need to remember that cyanobacteria are responsible for the first free oxygen in our atmosphere, without which we would not exist. This, from a 2009 Scientific American article:

    It’s hard to keep oxygen molecules around, despite the fact that it’s the third-most abundant element in the universe, forged in the superhot, superdense core of stars. That’s because oxygen wants to react; it can form compounds with nearly every other element on the periodic table. So how did Earth end up with an atmosphere made up of roughly 21 percent of the stuff?

    The answer is tiny organisms known as cyanobacteria, or blue-green algae. These microbes conduct photosynthesis: using sunshine, water and carbon dioxide to produce carbohydrates and, yes, oxygen. In fact, all the plants on Earth incorporate symbiotic cyanobacteria (known as chloroplasts) to do their photosynthesis for them down to this day.]

    See the full article here.

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    Scientific American, the oldest continuously published magazine in the U.S., has been bringing its readers unique insights about developments in science and technology for more than 160 years.

  • richardmitnick 2:27 pm on December 10, 2014 Permalink | Reply
    Tags: , , Medicine, Microbiome,   

    From NOVA: “New Antibiotic Found in Bacteria from the Vaginal Microbiome” 



    12 Sep 2014
    Tim De Chant

    Researchers announced yesterday that they had discovered a new molecule that could be a promising antibiotic capable of killing Staphylococcus aureus, a bacteria that can cause dangerous skin infections. That’s good news, especially since drug resistance among harmful bacteria is evolving at a rapid pace. But what makes this molecule unique is it’s source—our bodies.

    Scanning electron micrograph of S. aureus; false color added.

    Microbiologists have long suspected that new classes of drugs—antibiotics in particular—could be lurking in our microbiomes, where various bacteria duke it out for dominance of a particular niche.

    Lactobacillus bacteria, which produce the antibiotic lactocillin

    This new molecule, called lactocillin, was discovered in a sweep of a database containing genes culled from our microbiome. Michael Fischbach, a microbiologist at the University of California, San Francisco, and his team then traced the genes responsible for lactocillin back to bacteria living in the vagina.

    Erika Check Hayden, reporting for Nature News:

    “We used to think that drugs were discovered by drug companies and prescribed by a physician and then they get to you,” Fischbach says. “What we’ve found here is that bacteria that live on and inside of humans are doing an end-run around that process; they make drugs right on your body.”

    Fischbach’s team then purified one of these: a thiopeptide made by a bacterium that normally lives in the human vagina. The researchers found that the drug could kill the same types of bacteria as other thiopeptides — for instance, Staphylococcus aureus, which can cause skin infections. The scientists did not actually show that the human vaginal bacteria make the drug on the body, but they did show that when they grew the bacteria, it made the antibiotic.

    Fischbach told Check Hayden that, at the current time, he’s not interested in turning lactocillin into a bonafide drug. Instead, he’s going to continue plumbing the depths of these huge databases of microbiome genes, hoping to find even more intriguing and promising candidates.

    See the full article here.

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    NOVA is the highest rated science series on television and the most watched documentary series on public television. It is also one of television’s most acclaimed series, having won every major television award, most of them many times over.

  • richardmitnick 5:52 pm on December 8, 2014 Permalink | Reply
    Tags: , , Flu Viruses, Medicine,   

    From SLAC: “Study May Help Slow the Spread of Flu” 

    SLAC Lab

    December 8, 2014

    X-rays Show How Flu Antibody Binds to Viruses

    An important study conducted in part at the Department of Energy’s SLAC National Accelerator Laboratory may lead to new, more effective vaccines and medicines by revealing detailed information about how a flu antibody binds to a wide variety of flu viruses.

    A false color image of an influenza virus particle, or “virion.” (Centers for Disease Control/Cynthia Goldsmith)

    The flu virus infects millions of people each year. While for most this results in an unproductive and uncomfortable week or two, the flu also contributes to many deaths in the average flu season. And while vaccines are effective in preventing the flu, they require almost yearly reformulation to keep up with the constantly changing virus.

    A team of researchers from The Scripps Research Institute, Fujita Health University and Osaka University studied both samples of flu virus components and an anti-flu antibody. The antibody, called F045-092, was already known to neutralize the flu by connecting to the region of the flu virus that binds to host cells, so it can no longer bind to its target and cause infection.

    Top: The antibody F045-092 inserts a loop (purple) into the region of the flu virus (blue) that would otherwise bind to host cells to initiate infection. With the antibody connected, the flu virus is unable to bind to its target and cannot cause infection. Bottom: Without the antibody present, the flu virus (blue) binds to a host cell receptor (yellow). (Peter Lee et al.)

    “There are patches of the virus that are more hypervariable than others,” said Peter Lee, a postdoctoral research associate at The Scripps Research Institute and first author of the paper. “But the flu always binds to host cells within the same region, and so that binding site needs to be functionally conserved. That makes it a site of vulnerability.”

    The team used the X-ray beams at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) and Argonne National Laboratory’s Advanced Photon Source (APS), both DOE Office of Science User Facilities, to view the structure of the antibody bound to one subtype of the flu virus called H3N2. They discovered that the antibody inserts a loop into the binding site of the virus, which would otherwise attach to a receptor in a host cell. Additional experimental data showed that F045-092 binds a wide variety of strains and subtypes, including all H3 avian and human viruses from 1963 to 2011 that were tested.

    SSRL at SLAC

    ANL APS interior
    Argonne National Laboratory’s Advanced Photon Source

    This understanding of the antibody’s structural details and binding modes offers new insight for future structure-based drug discovery and novel avenues for designing future vaccines.

    But the only way to achieve those goals is for many groups of scientists to work together, Lee said. “Our lab is very focused on the structure of the virus and antibodies, while there are lots of other labs focused on everything from small protein design to vaccine design,” he said. “Hopefully we can use this structural information and join together as one big team to tackle the flu.”

    SSRL’s Structural Molecular Biology program is supported by the National Institutes of Health and the Office of Biological and Environmental Research of the U.S. Department of Energy.

    See the full article here.

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    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.

  • richardmitnick 1:38 pm on December 8, 2014 Permalink | Reply
    Tags: , Medicine, ,   

    From Sandia: “Turning biological cells to stone improves cancer and stem cell research” 

    Sandia Lab

    December 8, 2014
    Neal Singer, nsinger@sandia.gov, (505) 845-7078

    ‘Zombie’ method also hardens biostructures for mass production

    Changing flesh to stone sounds like the work of a witch in a fairy tale.

    Sandia National Laboratories researchers Bryan Kaehr and Kristin Meyer analyze a silicized surface using optical microscopy and multiphoton fluorescence. (Photo by Randy Montoya)

    But a new technique to transmute living cells into more permanent materials that defy decay and can endure high-powered probes is widening research opportunities for biologists who are developing cancer treatments, tracking stem cell evolution or even trying to understand how spiders vary the quality of the silk they spin.

    The simple, silica-based method also offers materials scientists the ability to “fix” small biological entities like red blood cells into more commercially useful shapes. And, at least in theory, the method can transmute naturally grown objects like livers and spleens from livestock into non-organic “zombie” replicas that function simultaneously at a variety of length-scales, from macro to nano, in more sophisticated ways than the most advanced machinery can produce.

    “Why go to the trouble of making objects if nature will do it for you?” asks lead investigator Bryan Kaehr of the Department of Energy’s (DOE) Sandia National Laboratories.

    The unusual method has been the subject of papers in Proceedings of the National Academy of Sciences, the Journal of the American Chemical Society (JACS), and on Dec. 8, Nature Communications.

    The initial insight came when Kaehr and then-University of New Mexico (UNM) postdoctoral student Jason Townson discovered that the silica slurry they were using had an unexpected property: At a reasonably low pH level, the silica molecules, instead of clotting with each other, bound only to surfaces against which they rested, forming the thinnest of coatings.

    Kaehr wondered if a similar coating on biological cells would strengthen cell structures so they could be examined for longer periods with more powerful tools. So the researchers put cultured tissue cells in a silica solution and let the mix harden overnight. Then they raised the temperature to burn off the biomaterial. What remained, astonishingly, were perfectly replicated cells, like little row houses of glass.

    Chicken feet and skin-cells turned to glass by the Sandia and University of New Mexico silicizing process. (Image courtesy of Sandia National Laboratories)

    But the replicated cells were so sturdy that Kaehr surmised that the slurry must have coated the cells inside as well as out. Breaking a row of cells as one would a tiny pane of glass, the team examined their interiors with an electron microscope. They found they had indeed replicated the nanoscopic organelles of the cell as well as its exterior. They had discovered a way to create a near-perfect silica counterfeit of a biological organism, from its overall shape down to its nanostructures.

    This initial result is already being used by biologists in Finland to create three-dimensional models that preserve the different stages of stem cells as they evolve to their final form, said Sandia fellow and paper co-author Jeff Brinker, who is also a UNM professor.

    Townson, now on the faculty at UNM, uses the method to research the movements of cancer-fighting nanoparticles inserted into chicken cells prior to their conversion to silica. “With optical microscopy, it is difficult to form an image of the interactions of nanoparticles with cells while preserving a three-dimensional context,” he said. Bioreplication, where the sample can be mechanically dissected and investigated with electron microscopes, offers better 3-D resolution at the nanoscale.

    The method also is being used in England’s Oxford University to study the internal biological changes by which spiders create different types of silk, adjusting their mechanisms on the fly (so to speak) to create thicker or stickier strands, said Brinker.

    Red blood cells before being distorted into spiky spheres by the Sandia and University of New Mexico technique for possible commercial use. (Image courtesy of Sandia National Laboratories)

    In the JACS article, Kaehr and colleagues showed they could use the silica technique to make permanent alterations in natural objects. They introduced chemicals that transformed red blood cells from life-saver-like objects to spiky spheres. By introducing the silica slurry to the dish containing the altered red blood cells and letting the mixture harden, Kaehr and colleagues made the change permanent. Burning off the protoplasmic original, the team was left with microparticles that might be useful in rubber composites created by tire companies that routinely insert silica spheres in their tire mix for additional strength. Manufacturers would no longer need an energy-consuming factory to make the inserted material which, by bioreplication, would form cheaply and easily, Kaehr said.

    “Our method has good potential over traditional silica additives, and its raw material — blood — is considered a waste product in the meat industry,” he said.

    In addition to food industry waste products, he said, “there’s a huge amount of harmless bacteria out there we could co-opt to create still other shapes.” Bacteria are harder to harvest, he said, because they are protected by a double sheath against silica invasion, but it could be done.

    In the Nature Communications paper, Kaehr and colleagues took the same technique a step further. They took a liver, submerged it in a silica solution and then heated it anaerobically to come up with a hardened, carbonized, exact duplicate of the liver, from centimeter to nanometer scales.

    “We let nature do the work,” he said, “because we don’t yet know how to build an object accurately across six length scales, from centimeter to nanometers.

    An electron microscope shows the heterogeneity of tissue available in a carbonized spleen. (Image courtesy of Sandia National Laboratories)

    “Think about electrodes in batteries,” he said. “That’s a three-dimensional question. Now in livers and spleens, for example, evolution has already optimized absorption and diffusion in a three-dimensional organization. The liver is a marvelously effective organ with tremendous surface area for absorption and an unparalleled ability to release materials in channels ranging from large arteries to capillaries a few micrometers wide.

    “If we transfer the hierarchical structure of a liver to an electrode, rather than having just a passive piece of solid material, we would have greater surface area per volume, greater energy storage, and have a creation that is already optimized to output fluids and small particles to much larger highways like large veins and arteries.”

    The carbonized method also can be used to better examine cancers and other growths without the often tedious and expensive processes normally necessary to “fix,” process and stabilize the organic material for examination to prevent it from falling apart under electron-beam analysis. Carbon, because it conducts electricity instead of absorbing it, is not weakened and destroyed like protoplasm.

    This creative consideration of the possibilities of the natural world in new and dizzying ways is in line with Kaehr’s research sponsor — DOE’s Office of Science, which is interested in “the exploration, discovery and design of biomimetic materials,” he said. Portions of this work were performed at the Center for Intergrated Nanotechnologies, a DOE Office of Science user facility jointly led by Los Alamos and Sandia national laboratories.

    Sandia and UNM have applied for a joint patent on the set of methods.

    See the full article here.

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    Sandia National Laboratories is a multiprogram laboratory operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy’s National Nuclear Security Administration. With main facilities in Albuquerque, N.M., and Livermore, Calif., Sandia has major R&D responsibilities in national security, energy and environmental technologies, and economic competitiveness.

  • richardmitnick 7:05 pm on December 4, 2014 Permalink | Reply
    Tags: Medicine,   

    From Wisconsin: “University spinoff aims to hit the mark precisely with brain-scanning tool” 

    U Wisconsin

    University of Wisconsin

    Aug. 20, 2014
    David Tenenbaum

    As brain surgeons test new procedures and drugs to treat conditions ranging from psychiatric disorders to brain cancer, accuracy is becoming an ever-greater issue.

    In treating the brain, the state of the art today starts with images from a magnetic resonance (MR) scanner, usually made a few days before surgery. Then, in the operating room, multiple cameras track instruments as they are inserted through a hole in the skull, creating images that can be superimposed on the original MR scans.

    Walter Block

    But there is no guarantee that the brain will not shift slightly during the surgery and throw off the best efforts at exact guidance.

    For 20 years, neurosurgeons have discussed a radical way to achieve real-time accuracy in placement: performing surgery with the brain inside an MR machine, says Walter Block, professor of biomedical engineering at the University of Wisconsin-Madison. “When you open the brain for surgery, the tissue can shift slightly, and that will throw off predictions made in advance.”

    To bring the full promise of MR into the operating room, Block has formed a company called InseRT MRI to develop software that allows surgeons to observe the brain in real time on an MR machine during surgery.

    Such a system would have a number of applications, he says. Drugs for brain cancer can be delivered over as long as 54 hours. “It would be valuable to see where the drug is going during the first few hours,” Block says. “Drugs move at different rates through gray and white matter, and this ability to recalibrate the treatment plan, based on actual data on where the drug is moving, would allow you to alter the location of the catheter or the flow rate of the medication.”

    Marvel Medtech in Cross Plains, Wisconsin, is developing a system that would employ InseRT MRI’s guidance to biopsy breast tumors. Photo: Center for Technology Commercialization

    To get that accuracy advantage, Block does not envision forcing surgeons to learn a new operating environment. “Surgeons have operating room tools and work stations that are familiar to them,” he says. “We are creating a set of tools that make the MR space a comfortable place for the surgeon.”

    UW-Madison neurosurgeon Azam Ahmed plans to use the system through test procedures on animal brains and cadavers, Block says. “We are working with Dr. Ahmed to design the workflow so it’s intuitive to him. We are not going to piggyback on top of a large scanner market designed for largely diagnostic purposes, kludging it to make it work for interventional applications.”

    The goal is not to develop software that could be spliced into MR manufacturers’ systems, he says, “since every time they alter their software, we would have to change ours.” Instead, Block is borrowing tactics from the smartphone industry. “People write apps that use various phone resources — GPS, the screen, the orientation system. We look at the MR scanner as a set of resources that we can control. An app writer does not have to go to Samsung or Apple and say, ‘We have this idea.'”

    Block says his software will interact with the MR machine through a software “portal” being developed by another firm.

    “When you open the brain for surgery, the tissue can shift slightly, and that will throw off predictions made in advance.”
    Walter Block

    One obvious market is the pharmaceutical industry. “Any drug trial in the brain will cost hundreds of millions of dollars,” he says, “and we often see trials being repeated after post-mortem analysis raises questions about the accuracy of drug placement.”

    Targeted surgery could also help remove bits of brain tissue to treat severe epilepsy. Marvel Medtech in Cross Plains, Wisconsin, is developing a system that would employ InseRT MRI’s guidance to biopsy breast tumors. The technology also raises the potential for localized psychiatric drug therapy, Block says.

    In the brain, the MR-guidance system is already accurate to less than a millimeter, Block says. While conventional stereotactic systems can approach that accuracy “in the best case,” the error can rise to 1.5 or 2 millimeters — a vast distance in an organ as delicate as the human brain, in which damage to healthy tissue must be minimized.

    Block says InseRT MRI’s competitive advantage resides in his long experience in medical imaging. “Our value is (faster) time to market. We have come up with ways to circumvent the significant hurdles that now limit image-guided therapy, and we believe we can do this faster than anybody else.”

    See the full article here.

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    In achievement and prestige, the University of Wisconsin–Madison has long been recognized as one of America’s great universities. A public, land-grant institution, UW–Madison offers a complete spectrum of liberal arts studies, professional programs and student activities. Spanning 936 acres along the southern shore of Lake Mendota, the campus is located in the city of Madison.

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