Posts Tagged ‘research’


Signals long thought to be “noise” appear to represent a distinct form of brain activity.

By Tanya Lewis

Every few seconds a wave of electrical activity travels through the brain, like a large swell moving through the ocean. Scientists first detected these ultraslow undulations decades ago in functional magnetic resonance imaging (fMRI) scans of people and other animals at rest—but the phenomenon was thought to be either electrical “noise” or the sum of much faster brain signals and was largely ignored.

Now a study that measured these “infraslow” (less than 0.1 hertz) brain waves in mice suggests they are a distinct type of brain activity that depends on an animal’s conscious state. But big questions remain about these waves’ origin and function.

An fMRI scan detects changes in blood flow that are assumed to be linked to neural activity. “When you put someone in a scanner, if you just look at the signal when you don’t ask the subject to do anything, it looks pretty noisy,” says Marcus Raichle, a professor of radiology and neurology at Washington University School of Medicine in St. Louis and senior author of the new study, published in April in Neuron. “All this resting-state activity brought to the forefront: What is this fMRI signal all about?”

To find out what was going on in the brain, Raichle’s team employed a combination of calcium/hemoglobin imaging, which uses fluorescent molecules to detect the activity of neurons at the cellular level, and electrophysiology, which can record signals from cells in different brain layers. They performed both measurements in awake and anesthetized mice; the awake mice were resting in tiny hammocks in a dark room.

The team found that infraslow waves traveled through the cortical layers of the awake rodents’ brains—and changed direction when the animals were anesthetized. The researchers say these waves are distinct from so-called delta waves (between 1 and 4 Hz) and other higher-frequency brain activity.

These superslow waves may be critical to how the brain functions, Raichle says. “Think of, say, waves on the water of Puget Sound. You can have very rough days where you have these big groundswells and then have whitecaps sitting on top of them,” he says. These “swells” make it easier for brain areas to become active—for “whitecaps” to form, in other words.

Other researchers praised the study’s general approach but were skeptical that it shows the infraslow waves are totally distinct from other brain activity. “I would caution against jumping to a conclusion that resting-state fMRI is measuring some other property of the brain that’s got nothing to do with the higher-frequency fluctuations between areas of the cortex,” says Elizabeth Hillman, a professor of biomedical engineering at Columbia University’s Zuckerman Institute, who was not involved in the work. Hillman published a study in 2016 finding that resting-state fMRI signals represent neural activity across a range of frequencies, not just low ones.

More studies are needed to tease apart how these different types of brain signals are related. “These kinds of patterns are very new,” Hillman notes. “We haven’t got much of a clue what they are, and figuring out what they are is really, really difficult.”

https://www.scientificamerican.com/article/superslow-brain-waves-may-play-a-critical-role-in-consciousness1/

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Scientists have revealed a new link between alcohol, heart health and our genes.

The researchers investigated faulty versions of a gene called titin which are carried by one in 100 people or 600,000 people in the UK.

Titin is crucial for maintaining the elasticity of the heart muscle, and faulty versions are linked to a type of heart failure called dilated cardiomyopathy.

Now new research suggests the faulty gene may interact with alcohol to accelerate heart failure in some patients with the gene, even if they only drink moderate amounts of alcohol.

The research was carried out by scientists from Imperial College London, Royal Brompton Hospital, and MRC London Institute of Medical Sciences, and published this week in the latest edition of the Journal of the American College of Cardiology.

The study was supported by the Department of Health and Social Care and the Wellcome Trust through the Health Innovation Challenge Fund.

In the first part of the study, the team analysed 141 patients with a type of heart failure called alcoholic cardiomyopathy (ACM). This condition is triggered by drinking more than 70 units a week (roughly seven bottles of wine) for five years or more. In severe cases the condition can be fatal, or leave patients requiring a heart transplant.

The team found that the faulty titin gene may also play a role in the condition. In the study 13.5 per cent of patients were found to carry the mutation – much higher than the proportion of people who carry them in the general population.

These results suggest this condition is not simply the result of alcohol poisoning, but arises from a genetic predisposition – and that other family members may be at risk too, explained Dr James Ware, study author from the National Heart and Lung Institute at Imperial.

“Our research strongly suggests alcohol and genetics are interacting – and genetic predisposition and alcohol consumption can act together to lead to heart failure. At the moment this condition is assumed to be simply due to too much alcohol. But this research suggests these patients should also be checked for a genetic cause – by asking about a family history and considering testing for a faulty titin gene, as well as other genes linked to heart failure,” he said.

He added that relatives of patients with ACM should receive assessment and heart scans – and in some cases have genetic tests – to see if they unknowingly carry the faulty gene.

In a second part of the study, the researchers investigated whether alcohol may play a role in another type of heart failure called dilated cardiomyopathy (DCM). This condition causes the heart muscle to become stretched and thin, and has a number of causes including viral infections and certain medications. The condition can also be genetic, and around 12 per cent of cases of DCM are thought to be linked to a faulty titin gene.

In the study the team asked 716 patients with dilated cardiomyopathy how much alcohol they consumed.

None of the patients consumed the high-levels of alcohol needed to cause ACM. But the team found that in patients whose DCM was caused by the faulty titin gene, even moderately increased alcohol intake (defined as drinking above the weekly recommended limit of 14 units), affected the heart’s pumping power.

Compared to DCM patients who didn’t consume excess alcohol (and whose condition wasn’t caused by the faulty titin gene), excess alcohol was linked to reduction in heart output of 30 per cent.

More research is now needed to investigate how alcohol may affect people who carry the faulty titin gene, but do not have heart problems, added Dr Paul Barton, study co-author from the National Heart and Lung Institute at Imperial:

“Alcohol and the heart have a complicated relationship. While moderate levels may have benefits for heart health, too much can cause serious cardiac problems. This research suggests that in people with titin-related heart failure, alcohol may worsen the condition.

“An important wider question is also raised by the study: do mutations in titin predispose people to heart failure when exposed to other things that stress the heart, such as cancer drugs or certain viral infections? This is something we are actively seeking to address.”

The research was supported by the Department of Health and Social Care and Wellcome Trust through the Health Innovation Challenge Fund, the Medical Research Council, the NIHR Cardiovascular Biomedical Research Unit at Royal Brompton & Harefield NHS Foundation Trust and the British Heart Foundation.

Reference: Ware, J. S., Amor-Salamanca, A., Tayal, U., Govind, R., Serrano, I., Salazar-Mendiguchía, J., … Garcia-Pavia, P. (2018). Genetic Etiology for Alcohol-Induced Cardiac Toxicity. Journal of the American College of Cardiology, 71(20), 2293–2302. https://doi.org/10.1016/j.jacc.2018.03.462

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Researching tuberous sclerosis from the left are Adelaide Hebert, M.D.; John Slopis, M.D.; Mary Kay Koenig, M.D.; Joshua Samuels, M.D., M.P.H.; and Hope Northrup, M.D. PHOTO CREDIT Maricruz Kwon, UTHealth

Addressing a critical issue for people with a genetic disorder called tuberous sclerosis complex (TSC), doctors at The University of Texas Health Science Center at Houston (UTHealth) reported that a skin cream containing rapamycin significantly reduced the disfiguring facial tumors affecting more than 90 percent of people with the condition.

Findings of the multicenter, international study involving 179 people with tuberous sclerosis complex appear in the journal JAMA Dermatology.

“People with tuberous sclerosis complex want to look like everyone else,” said Mary Kay Koenig, M.D., the study’s lead author, co-director of the Tuberous Sclerosis Center of Excellence and holder of the Endowed Chair of Mitochondrial Medicine at McGovern Medical School at UTHealth. “And, they can with this treatment.”

Tuberous sclerosis complex affects about 50,000 people in the United States and is characterized by the uncontrolled growth of non-cancerous tumors throughout the body.

While benign tumors in the kidney, brain and other organs pose the greater health risk, the tumors on the face produce a greater impact on a patient’s daily life by making them look different from everyone else, Koenig said.

Koenig’s team tested two compositions of facial cream containing rapamycin and a third with no rapamycin. Patients applied the cream at bedtime for six months.

“Eighty percent of patients getting the study drug experienced a significant improvement compared to 25 percent of those getting the mixture with no rapamycin,” she said.

“Angiofibromas on the face can be disfiguring, they can bleed and they can negatively impact quality of life for individuals with TSC,” said Kari Luther Rosbeck, president and CEO of the Tuberous Sclerosis Alliance.

“Previous treatments, including laser surgery, have painful after effects. This pivotal study and publication are a huge step toward understanding the effectiveness of topical rapamycin as a treatment option. Further, it is funded by the TSC Research Program at the Department of Defense. We are so proud of this research,” Rosbeck said.

Rapamycin is typically given to patients undergoing an organ transplant. When administered by mouth, rapamycin suppresses the immune system to make sure the organ is not rejected.

Rapamycin and tuberous sclerosis complex are linked by a protein called mTOR. When it malfunctions, tuberous sclerosis complex occurs. Rapamycin corrects this malfunction.

Rapamycin was initially used successfully to treat brain tumors caused by tuberous sclerosis complex, so researchers decided to try it on TSC-related facial tumors. Building on a 2010 pilot study on the use of rapamycin to treat TSC-related facial tumors, this study confirmed that a cream containing rapamycin shrinks these tumors.

As the drug’s toxicity is a concern when taken by mouth, researchers were careful to check for problems tied to its use on the skin. “It looks like the medication stays on the surface of the skin. We didn’t see any appreciable levels in the bloodstreams of those participating in the study,” Koenig said.

The Topical Rapamycin to Erase Angiofibromas in TSC – Multicenter Evaluation of Novel Therapy or TREATMENT trial involved 10 test sites including one in Australia.

Koenig said additional studies are needed to gauge the long-term impact of the drug, the optimal dosage and whether the facial cream should be a combined with an oral treatment.

Koenig’s coauthors include Adelaide Hebert, M.D.; Joshua Samuels, M.D., M.P.H.; John Slopis, M.D.; Cynthia S. Bell; Joan Roberson, R.N.; Patti Tate; and Hope Northrup, M.D. All are from McGovern Medical School at UTHealth with the exception of Slopis, who is with The University of Texas MD Anderson Cancer Center. Hebert is also on the faculty of the MD Anderson Cancer Center and Northrup on the faculty of The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.

The study was supported in part by the United States Department of Defense grant DOD TSCRP CDMRP W81XWH-11-1-0240 and by the Tuberous Sclerosis Alliance of Australia.

“The face is our window to the world and when you look different from everyone else, it impacts your confidence and your ability to interact with others. This treatment will help those with TSC become more like everyone else,” Koenig said.

https://www.uth.edu/media/story.htm?id=37af25df-14a2-4c5e-b1ee-ac9585946aa0

By Laura Kurtzman

Scientists at UC San Francisco have developed a test to predict a woman’s risk of preterm birth when she is between 15 and 20 weeks pregnant, which may enable doctors to treat them early and thereby prevent severe complications later in the pregnancy.

Preterm birth is the leading cause of death for children under five in the United States, and rates are increasing both in the U.S. and around the world. It is often associated with inflammation and has many potential causes, including an acute infection in the mother, exposure to environmental toxins, or chronic conditions like hypertension and diabetes.

The new test screens for 25 biomarkers of inflammation and immune system activation, as well as for levels of proteins that are important for placenta development. Combined with information on other risk factors, such as the mother’s age and income, the test can predict whether a woman is at risk for preterm birth with more than 80 percent accuracy. In the highest risk pregnancies—preterm births occurring before 32 weeks or in women with preeclampsia, a potentially fatal pregnancy complication marked by high blood pressure in the mother—the test predicted nearly 90 percent of cases.

In the study, published Thursday, May 24, 2018, in the Journal of Perinatology, the researchers built a comprehensive test that would capture both spontaneous preterm births, which occurs when the amniotic sac breaks or contractions begin spontaneously, and “indicated” preterm birth, in which a physician induces labor or performs a cesarean section because the health of the mother or baby is in jeopardy. The researchers also wanted to be able to identify risk for preeclampsia, which is not included in current tests for preterm birth.

“There are multifactorial causes of preterm birth, and that’s why we felt like we needed to build a model that took into account multiple biological pathways,” said first author Laura Jelliffe-Pawlowski, PhD, director of Precision Health and Discovery with the UCSF California Preterm Birth Initiative and associate professor of epidemiology and biostatistics at UCSF. “The model works especially well for early preterm births and preeclampsia, which suggests that we’re effectively capturing severe types of preterm birth.”

The researchers developed the screen using blood samples taken from 400 women as part of routine prenatal care during the second trimester, comparing women who went on to give birth before 32 weeks, between 32 and 36 weeks, and after 38 weeks (full-term). The researchers first tested the samples for more than 60 different immune and growth factors, ultimately narrowing the test down to 25 factors that together could help predict risk for preterm birth. When other data, including whether or not the mother was over 34 years old or if she qualified as low income (indicated by Medicaid eligibility), improved the accuracy of the test by an additional 6 percent.

Researchers said the test could help prevent some cases of preterm birth. Based on a woman’s probability of preterm birth derived by the test, she could discuss with her clinician how best to follow-up and try to lower her risk. Some cases of preterm birth, including those caused by preeclampsia, can be prevented or delayed by taking aspirin, but treatment is most helpful if started before 16 weeks. Physicians could also evaluate high-risk women for underlying infections that may have gone undetected but could be treated. For others, close monitoring by their doctor could help flag early signs of labor like cervical shortening that can be staved off with progesterone treatment.

“We hope that this test could lead to more education and counseling of women about their level of risk so that they know about preterm birth and know what preeclampsia or early signs of labor look like,” said Jelliffe-Pawlowski. “If we can get women to the hospital as soon as possible, even if they’ve gone into labor, we can use medications to stave off contractions. This might give her some additional days before she delivers, which can be really important for the baby.”

A test for preterm birth is currently available, but it is expensive and only screens for spontaneous preterm birth, not for signs that could lead to indicated preterm births or for preeclampsia. Jelliffe-Pawlowski said that the new screen would likely be a fraction of the cost, making it more accessible to women who need it the most.

“One of the reasons we’re most excited about this test is that we see some potential for it addressing preterm birth in those most at risk, including low-income women, women of color, and women living in low-income countries,” she said. “We want to make sure that we’re developing something that has the potential to help all women, including those most in need.”

Other authors on the study were Larry Rand, Scott Oltman, and Mary Norton of UCSF; Bruce Bedell, Jeffrey Murray, and Kelli Ryckman of the University of Iowa; Rebecca Baer of UC San Diego; and Gary Shaw and David Stevenson of Stanford University.

https://www.ucsf.edu/news/2018/05/410456/risk-preterm-birth-reliably-predicted-new-test?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+ucsf_press_releases+%28UCSF+Press+Releases%29


Researchers at the University of Minnesota use a customized 3D printer to print electronics on a real hand. Image: McAlpine group, University of Minnesota

Soldiers are commonly thrust into situations where the danger is the unknown: Where is the enemy, how many are there, what weaponry is being used? The military already uses a mix of technology to help answer those questions quickly, and another may be on its way. Researchers at the University of Minnesota have developed a low-cost 3D printer that prints sensors and electronics directly on skin. The development could allow soldiers to directly print temporary, disposable sensors on their hands to detect such things as chemical or biological agents in the field.

The technology also could be used in medicine. The Minnesota researchers successfully used bioink with the device to print cells directly on the wounds of a mouse. Researchers believe it could eventually provide new methods of faster and more efficient treatment, or direct printing of grafts for skin wounds or conditions.

“The concept was to go beyond smart materials, to integrate them directly on to skin,” says Michael McAlpine, professor of mechanical engineering whose research group focuses on 3D printing functional materials and devices. “It is a biological merger with electronics. We wanted to push the limits of what a 3D printer can do.”

McAlpine calls it a very simple idea, “One of those ideas so simple, it turns out no one has done it.”

Others have used 3D printers to print electronics and biological cells. But printing on skin presented a few challenges. No matter how hard a person tries to remain still, there always will be some movement during the printing process. “If you put a hand under the printer, it is going to move,” he says.

To adjust for that, the printer the Minnesota team developed uses a machine vision algorithm written by Ph.D. student Zhijie Zhu to track the motion of the hand in real time while printing. Temporary markers are placed on the skin, which then is scanned. The printer tracks the hand using the markers and adjusts in real time to any movement. That allows the printed electronics to maintain a circuit shape. The printed device can be peeled off the skin when it is no longer needed.

The team also needed to develop a special ink that could not only be conductive but print and cure at room temperature. Standard 3D printing inks cure at high temperatures of 212 °F and would burn skin.

In a paper recently published in Advanced Materals, the team identified three criteria for conductive inks: The viscosity of the ink should be tunable while maintaining self-supporting structures; the ink solvent should evaporate quickly so the device becomes functional on the same timescale as the printing process; and the printed electrodes should become highly conductive under ambient conditions.

The solution was an ink using silver flakes to provide conductivity rather than particles more commonly used in other applications. Fibers were found to be too large, and cure at high temperatures. The flakes are aligned by their shear forces during printing, and the addition of ethanol to the mix increases speed of evaporation, allowing the ink to cure quickly at room temperature.

“Printing electronics directly on skin would have been a breakthrough in itself, but when you add all of these other components, this is big,” McAlpine says.

The printer is portable, lightweight and cost less than $400. It consists of a delta robot, monitor cameras for long-distance observation of printing states and tracking cameras mounted for precise localization of the surface. The team added a syringe-type nozzle to squeeze and deliver the ink

Furthering the printer’s versatility, McAlpine’s team worked with staff from the university’s medical school and hospital to print skin cells directly on a skin wound of a mouse. The mouse was anesthetized, but still moved slightly during the procedure, he says. The initial success makes the team optimistic that it could open up a new method of treating skin diseases.

“Think about what the applications could be,” McAlpine says. “A soldier in the field could take the printer out of a pack and print a solar panel. On the cellular side, you could bring a printer to the site of an accident and print cells directly on wounds, speeding the treatment. Eventually, you may be able to print biomedical devices within the body.”

In its paper, the team suggests that devices can be “autonomously fabricated without the need for microfabrication facilities in freeform geometries that are actively adaptive to target surfaces in real time, driven by advances in multifunctional 3D printing technologies.”

Besides the ability to print directly on skin, McAlpine says the work may offer advantages over other skin electronic devices. For example, soft, thin, stretchable patches that stick to the skin have been fitted with off-the-shelf chip-based electronics for monitoring a patient’s health. They stick to skin like a temporary tattoo and send updates wirelessly to a computer.

“The advantage of our approach is that you don’t have to start with electronic wafers made in a clean room,” McAlpine says. “This is a completely new paradigm for printing electronics using 3D printing.”

http://www.asme.org/engineering-topics/articles/bioengineering/researchers-3d-print-skin-breakthrough

By Hilary Hurd Anyaso

Leading theories propose that sleep presents an opportune time for important, new memories to become stabilized. And it’s long been known which brain waves are produced during sleep. But in a new study, researchers set out to better understand the brain mechanisms that secure memory storage.

The team from Northwestern and Princeton universities set out to find more direct and precisely timed evidence for the involvement of one particular sleep wave — known as the “sleep spindle.”

In the study, sleep spindles, described as bursts of brain activity typically lasting around one second, were linked to memory reactivation. The paper, “Sleep spindle refractoriness segregates periods of memory reactivation,” published today in the journal Current Biology.

“The most novel aspect of our study is that we found these spindles occur rhythmically — about every three to six seconds — and this rhythm is related to memory,” said James W. Antony, first author of the study and a postdoctoral fellow in Princeton’s Computational Memory Lab.

Three experiments explored how recent memories are reactivated during sleep. While volunteers took an afternoon nap, sound cues were surreptitiously played. Each was linked to a specific memory. The researchers’ final experiment showed that if cues were presented at opportune times such that spindles could follow them, the linked memories were more likely to be retained. If they were presented when a spindle was unlikely to follow, the linked memories were more likely to be forgotten.

“One particularly remarkable aspect of the study was that we were able to monitor spindles moment by moment while people slept,” said Ken A. Paller, senior author of the study and professor of psychology at Northwestern’s Weinberg College of Arts and Sciences. “Therefore, we could know when the brain was most ready for us to prompt memory reactivation.”
If the researchers reminded people of a recently learned fact, a spindle would likely be evident in the cerebral cortex, and memory for that information would be improved, added Paller, also director of Northwestern’s Cognitive Neuroscience Program.

“In memory research, we know it’s important to segregate experiences while you’re awake so that everything doesn’t just blend together,” said Antony, who worked in Paller’s lab at Northwestern as a doctoral student. “If that happens, you may have difficulty retrieving information because so many things will come to mind at once. We believe the spindle rhythmicity shown here might play a role in segregating successive memory reactivations from each other, preventing overlap that might cause later interference between memories.”

Ultimately, the researchers’ goal is to understand how sleep affects memory under natural conditions and how aging or disease can impact these functions.

“With that goal in mind, we’ve helped elucidate the importance of sleep spindles more generally,” Antony said.

Paller said they are on the trail of the physiology of memory reactivation.

“Future work will be needed to see how spindles fit together with other aspects of the physiology of memory and will involve other types of memory testing and other species,” Paller said.

In addition to Antony and Paller, co-authors are Luis Piloto, Margaret Wang, Paula Pacheco and Kenneth A. Norman, all of Princeton.

https://news.northwestern.edu/stories/2018/may/bursts-of-brain-activity-linked-to-memory-reactivation/


Adipose Connective Tissue Stores Fat in Our Body. Credit: Berkshire Community College Bioscience Image Library

A new technique to study fat stores in the body could aid efforts to find treatments to tackle obesity.

The approach focuses on energy-burning tissues found deep inside the body – called brown fat – that help to keep us warm when temperatures drop.

Experts are aiming to find it this calorie-burning power can be harnessed to stop weight gain, but little is known about how the process works.

Previous studies have mainly relied on a medical imaging technique called PET/CT to watch brown fat in action deep inside the body. But the method is unable to directly measure the chemical factors in the tissue.

Scientists at the University of Edinburgh developed a technique called microdialysis to measure how brown fat generates heat in people.

The approach involves inserting a small tube into an area of brown fat in the body and flushing it with fluid to collect a snapshot of the tissues’ chemical make-up.

The team tested the technique in six healthy volunteers, using PET/CT to guide the tube to the right location.

They discovered that in cold conditions, brown fat uses its own energy stores and other substances to generate heat.

Brown fat was active under warm conditions too, when the body does not need to generate its own heat, an outcome that had not been seen before.

Researchers hope the technique will help them to analyse the specific chemicals involved, so that they can better understand how brown fat works.

Most of the fat in our body is white fat, which is found under the skin and surrounding internal organs. It stores excess energy when we consume more calories than we burn.

Brown fat is mainly found in babies and helps them to stay warm. Levels can decrease with age but adults can still have substantial amounts of it, mainly in the neck and upper back region. People who are lean tend to have more brown fat.

The study, published in Cell Metabolism, was funded by the Medical Research Council and Wellcome.

Lead researcher Dr Roland Stimson, of the British Heart Foundation Centre for Cardiovascular Science at the University of Edinburgh, said: “Understanding how brown fat is activated could reveal potential targets for therapies that boost its energy-burning power, which could help with weight loss.”

This article has been republished from materials provided by the University of Edinburgh. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: Weir, G., Ramage, L. E., Akyol, M., Rhodes, J. K., Kyle, C. J., Fletcher, A. M., … Stimson, R. H. (2018). Substantial Metabolic Activity of Human Brown Adipose Tissue during Warm Conditions and Cold-Induced Lipolysis of Local Triglycerides. Cell Metabolism, 0(0). https://doi.org/10.1016/j.cmet.2018.04.020

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