Understanding arteriosclerosis: How blood vessels restructure under pressure

 High blood pressure, or hypertension, is a very common condition that can arise from physical activity, stress, or certain disorders. Unfortunately, persistent hypertension can cause long-lasting changes in the structure of vascular smooth muscle cells (the cells making up the walls of blood vessels) through a process called "vascular remodeling." If left unchecked, this restructuring can stiffen arterials walls, which lose their ability to adjust their size appropriately. This, in turn, leads to arteriosclerosis and increases the risk of cerebrovascular disease.

Why and how hypertension triggers vascular remodeling is not entirely clear. Scientists have shown that macrophages, a type of white blood cells that kill foreign bodies, are involved in the transformation. Specifically, the macrophages accumulate within blood vessel walls from outside the vessels and cause chronic inflammation. However, the underlying mechanism that orchestrates this process remains unknown.

Against this backdrop, researchers from Japan and Canada, in a new study, recently investigated a mechanism known as "excitation-transcription (E-T) coupling" in vascular smooth muscle cells. By unveiling the mysteries behind the E-T coupling in these cells through experiments spanning single cells to whole organisms, they successfully linked the E-T coupling mechanism with vascular remodeling. The study, published in the Proceedings of the National Academy of Sciences (PNAS),was led by Junior Associate Professor Yoshiaki Suzuki, Hisao Yamamura and Yuji Imaizumi from Nagoya City University, Japan, and Gerald W. Zamponi and Wayne R. Giles from University of Calgary, Canada.

Various types of cells are known to undergo E-T coupling. In neurons, for example, an excitation in the form of calcium ions (Ca2+) entering the cell through calcium channels activates certain transcription factors and enzymes. These, in turn, trigger the transcription of various genes. Meanwhile, although E-T coupling also occurs in vascular smooth muscle cells after an influx of Ca2+ under high pressure, not much was known about how it happens, what genes are triggered, and the role it plays in our bodies.

The researchers sought to answer these questions by focusing on caveolae, small structures resembling depressions widely present on the cell's membrane. Through detailed experiments in individual cells, cell cultures, and live mice, the team found that a specific protein complex found in caveolae is a key player in E-T coupling in vascular smooth muscle cells.

They proved that this complex, referred to as Cav1.2/CaMKK2/CaMK1a, is formed within caveolae and both CaMKK2 and CaMK1a are directly activated by Ca2+ entering through Cav1.2 when subjected to certain stimuli, such as high pressure. Moreover, they showed that this complex activates a signaling pathway that phosphorylates a transcription factor called CREB, which ultimately leads to an increased transcription of multiple genes.

By taking a detailed look at the genes promoted by E-T coupling and observing their effects when blocked or amplified, the researchers made some important discoveries. Firstly, some of these genes were related to chemotaxis, the phenomenon by which cells movement is triggered and directed by chemical stimuli. This helped explain the accumulation of macrophages in blood vessel walls from outside the vessels.

Additionally, these genes promoted the remodeling of the "medial" layer of arteries, where vascular smooth muscle cells reside and control blood flow through contraction and expansion. "Taken together, our results explain how E-T coupling caused by high pressure in vascular smooth muscle cells can modulate macrophage migration and subsequent inflammation, altering the vascular structure," explains Dr. Suzuki.

The findings of this study have important implications regarding anti-hypertension drugs. For one, they explain why medications like nicardipine, a classic calcium channel blocker, prevents vascular remodeling and the progression of arteriosclerosis. This not only fills an important knowledge gap in medicine but also presents several potential drug targets for treating or preventing vascular remodeling, such as the constituents of the Cav1.2/CaMKK2/CaMK1a complex.

"About 40 million people suffer from hypertension in Japan alone, and are at high risk of stroke, end-stage renal failure, and vascular dementia," says Dr. Suzuki, "Understanding the mechanisms behind arteriosclerosis is, therefore, very important for reducing the incidence, progression, and recurrence of cerebrovascular diseases and extend healthy life expectancy."

Source: ScienceDaily

New miniature heart could help speed heart disease cures

 There's no safe way to get a close-up view of the human heart as it goes about its work: you can't just pop it out, take a look, then slot it back in. Scientists have tried different ways to get around this fundamental problem: they've hooked up cadaver hearts to machines to make them pump again, attached lab-grown heart tissues to springs to watch them expand and contract. Each approach has its flaws: reanimated hearts can only beat for a few hours; springs can't replicate the forces at work on the real muscle. But getting a better understanding of this vital organ is urgent: in America, someone dies of heart disease every 36 seconds, according to the Centers for Disease Control and Prevention.

Now, an interdisciplinary team of engineers, biologists, and geneticists has developed a new way of studying the heart: they've built a miniature replica of a heart chamber from a combination of nanoengineered parts and human heart tissue. There are no springs or external power sources -- like the real thing, it just beats by itself, driven by the live heart tissue grown from stem cells. The device could give researchers a more accurate view of how the organ works, allowing them to track how the heart grows in the embryo, study the impact of disease, and test the potential effectiveness and side effects of new treatments -- all at zero risk to patients and without leaving a lab.

The Boston University-led team behind the gadget -- nicknamed miniPUMP, and officially known as the cardiac miniaturized Precision-enabled Unidirectional Microfluidic Pump -- says the technology could also pave the way for building lab-based versions of other organs, from lungs to kidneys. Their findings have been published in Science Advances.

"We can study disease progression in a way that hasn't been possible before," says Alice White, a BU College of Engineering professor and chair of mechanical engineering. "We chose to work on heart tissue because of its particularly complicated mechanics, but we showed that, when you take nanotechnology and marry it with tissue engineering, there's potential for replicating this for multiple organs."

According to the researchers, the device could eventually speed up the drug development process, making it faster and cheaper. Instead of spending millions -- and possibly decades -- moving a medicinal drug through the development pipeline only to see it fall at the final hurdle when tested in people, researchers could use the miniPUMP at the outset to better predict success or failure.

The project is part of CELL-MET, a multi-institutional National Science Foundation Engineering Research Center in Cellular Metamaterials that's led by BU. The center's goal is to regenerate diseased human heart tissue, building a community of scientists and industry experts to test new drugs and create artificial implantable patches for hearts damaged by heart attacks or disease.

"Heart disease is the number one cause of death in the United States, touching all of us," says White, who was chief scientist at Alcatel-Lucent Bell Labs before joining BU in 2013. "Today, there is no cure for a heart attack. The vision of CELL-MET is to change this."

Personalized Medicine

There's a lot that can go wrong with your heart. When it's firing properly on all four cylinders, the heart's two top and two bottom chambers keep your blood flowing so that oxygen-rich blood circulates and feeds your body. But when disease strikes, the arteries that carry blood away from your heart can narrow or become blocked, valves can leak or malfunction, the heart muscle can thin or thicken, or electrical signals can short, causing too many -- or too few -- beats. Unchecked, heart disease can lead to discomfort -- like breathlessness, fatigue, swelling, and chest pain -- and, for many, death.

"The heart experiences complex forces as it pumps blood through our bodies," says Christopher Chen, BU's William F. Warren Distinguished Professor of Biomedical Engineering. "And while we know that heart muscle changes for the worse in response to abnormal forces -- for example, due to high blood pressure or valve disease -- it has been difficult to mimic and study these disease processes. This is why we wanted to build a miniaturized heart chamber."

Source: ScienceDaily

Astronomers discover micronovae, a new kind of stellar explosion

 A team of astronomers, with the help of the European Southern Observatory's Very Large Telescope (ESO's VLT), have observed a new type of stellar explosion -- a micronova. These outbursts happen on the surface of certain stars, and can each burn through around 3.5 billion Great Pyramids of Giza of stellar material in only a few hours.

"We have discovered and identified for the first time what we are calling a micronova," explains Simone Scaringi, an astronomer at Durham University in the UK who led the study on these explosions published today in Nature. "The phenomenon challenges our understanding of how thermonuclear explosions in stars occur. We thought we knew this, but this discovery proposes a totally new way to achieve them," he adds.

Micronovae are extremely powerful events, but are small on astronomical scales; they are much less energetic than the stellar explosions known as novae, which astronomers have known about for centuries. Both types of explosions occur on white dwarfs, dead stars with a mass about that of our Sun, but as small as Earth.

A white dwarf in a two-star system can steal material, mostly hydrogen, from its companion star if they are close enough together. As this gas falls onto the very hot surface of the white dwarf star, it triggers the hydrogen atoms to fuse into helium explosively. In novae, these thermonuclear explosions occur over the entire stellar surface. "Such detonations make the entire surface of the white dwarf burn and shine brightly for several weeks," explains co-author Nathalie Degenaar, an astronomer at the University of Amsterdam, the Netherlands.

Micronovae are similar explosions that are smaller in scale and faster, lasting just several hours. They occur on some white dwarfs with strong magnetic fields, which funnel material towards the star's magnetic poles. "For the first time, we have now seen that hydrogen fusion can also happen in a localised way. The hydrogen fuel can be contained at the base of the magnetic poles of some white dwarfs, so that fusion only happens at these magnetic poles," says Paul Groot, an astronomer at Radboud University in the Netherlands and co-author of the study.

"This leads to micro-fusion bombs going off, which have about one millionth of the strength of a nova explosion, hence the name micronova," Groot continues. Although 'micro' may imply these events are small, do not be mistaken: just one of these outbursts can burn through about 20,000,000 trillion kg, or about 3.5 billion Great Pyramids of Giza, of material.*

These new micronovae challenge astronomers' understanding of stellar explosions and may be more abundant than previously thought. "It just goes to show how dynamic the Universe is. These events may actually be quite common, but because they are so fast they are difficult to catch in action," Scaringi explains.

The team first came across these mysterious micro-explosions when analysing data from NASA's Transiting Exoplanet Survey Satellite (TESS). "Looking through astronomical data collected by NASA's TESS, we discovered something unusual: a bright flash of optical light lasting for a few hours. Searching further, we found several similar signals," says Degenaar.

The team observed three micronovae with TESS: two were from known white dwarfs, but the third required further observations with the X-shooter instrument on ESO's VLT to confirm its white dwarf status.

"With help from ESO's Very Large Telescope, we found that all these optical flashes were produced by white dwarfs," says Degenaar. "This observation was crucial in interpreting our result and for the discovery of micronovae," Scaringi adds.

The discovery of micronovae adds to the repertoire of known stellar explosions. The team now want to capture more of these elusive events, requiring large scale surveys and quick follow-up measurements. "Rapid response from telescopes such as the VLT or ESO's New Technology Telescope and the suite of available instruments will allow us to unravel in more detail what these mysterious micronovae are," Scaringi concludes.

Source: ScienceDaily

Pacific Northwest wildfires alter air pollution patterns across North America

 Increasingly large and intense wildfires in the Pacific Northwest are altering the seasonal pattern of air pollution and causing a spike in unhealthy pollutants in August, new research finds. The smoke is undermining clean air gains, posing potential risks to the health of millions of people, according to the study.

The research, led by scientists at the National Center for Atmospheric Research (NCAR), found that levels of carbon monoxide -- a gas that indicates the presence of other air pollutants -- have increased sharply as wildfires spread in August. Carbon monoxide levels are normally lower in the summer because of chemical reactions in the atmosphere related to changes in sunlight, and the finding that their levels have jumped indicates the extent of the smoke's impacts.

"Wildfire emissions have increased so substantially that they're changing the annual pattern of air quality across North America," said NCAR scientist Rebecca Buchholz, the lead author. "It's quite clear that there is a new peak of air pollution in August that didn't used to exist."

Although carbon monoxide generally is not a significant health concern outdoors, the gas indicates the presence of more harmful pollutants, including aerosols (airborne particulates) and ground-level ozone that tends to form on hot summer days.

The research team used satellite-based observations of atmospheric chemistry and global inventories of fires to track wildfire emissions during most of the past two decades, as well as computer modeling to analyze the potential impacts of the smoke. They focused on three North American regions: the Pacific Northwest, the central United States, and the Northeast.

Buchholz said the findings were particularly striking because carbon monoxide levels have been otherwise decreasing, both globally and across North America, due to improvements in pollution-control technologies.

The study was published this week in Nature Communications. The research was funded in part by the U.S. National Science Foundation, NCAR's sponsor. The paper was co-authored by researchers from the University of Colorado, Boulder; Columbia University; NASA; Tsinghua University; and Colorado State University.

Increasing impacts on air pollution

Wildfires have been increasing in the Pacific Northwest and other regions of North America, due to a combination of climate change, increased development, and land use policies. The fires are becoming a larger factor in air pollution, especially as emissions from human activities are diminishing because of more efficient combustion processes in motor vehicles and industrial facilities.

To analyze the impacts of fires, Buchholz and her collaborators used data from two instruments on the NASA Terra satellite: MOPITT (Measurements of Pollution in the Troposphere), which has tracked carbon monoxide continually since 2002; and MODIS (Moderate Resolution Imaging Spectrometer), which detects fires and provides information on aerosols. They also studied four inventories of wildfire emissions, which rely on MODIS data.

The scientists focused on the period from 2002, the beginning of a consistent and long-term record of MOPPIT data, to 2018, the last year for which complete observations were available at the time when they began their study.

The results showed an increase in carbon monoxide levels across North America in August, which corresponded with the peak burning season of the Pacific Northwest. The trend was especially pronounced from 2012 to 2018, when the Pacific Northwest fire season became much more active, according to the emissions inventories. Data from the MODIS instrument revealed that aerosols also showed an upward trend in August.

To determine whether the higher pollution levels were caused by the fires, the scientists eliminated other potential emission sources. They found that carbon monoxide levels upwind of the Pacific Northwest, over the Pacific Ocean, were much lower in August -- a sign that the pollution was not blowing in from Asia. They also found that fire season in the central U.S. and the Northeast did not coincide with the August increase in pollution, which meant that local fires in those regions were not responsible. In addition, they studied a pair of fossil fuel emission inventories, which showed that carbon monoxide emissions from human activities did not increase in any of the three study regions from 2012 to 2018.

"Multiple lines of evidence point to the worsening wildfires in the Pacific Northwest as the cause of degraded air quality," Buchholz said. "It's particularly unfortunate that these fires are undermining the gains that society has made in reducing pollution overall."

Risks to human health

The findings have implications for human health because wildfire smoke has been linked to significant respiratory problems, and it may also affect the cardiovascular system and worsen pregnancy outcomes.

Buchholz and her co-authors used an NCAR-based computer model, the Community Atmosphere Model with a chemistry component, to simulate the movement of emissions from the Pacific Northwest fires and their impact on carbon monoxide, ozone, and fine particulate matter. They ran the simulations on the Cheyenne supercomputer at the NCAR-Wyoming Supercomputing Center. The results showed the pollutants could affect more than 130 million people, including about 34 million in the Pacific Northwest, 23 million in the Central U.S., and 72 million in the Northeast.

Although the study did not delve deeply into the health implications of the emissions, the authors looked at respiratory death rates in Colorado for the month of August from 2002 to 2011, compared with the same month in 2012 to 2018. They chose Colorado, located in the central U.S. region of the study, because respiratory death rates in the state were readily obtainable.

They found that Colorado respiratory deaths in August increased significantly during the 2012-2018 period, when fires in the Pacific Northwest -- but not in Colorado -- produced more emissions in August.

"It's clear that more research is needed into the health implications of all this smoke," Buchholz said. "We may already be seeing the consequences of these fires on the health of residents who live hundreds or even thousands of miles downwind."

Source: ScienceDaily

Tumors partially destroyed with sound don't come back

 Noninvasive sound technology developed at the University of Michigan breaks down liver tumors in rats, kills cancer cells and spurs the immune system to prevent further spread -- an advance that could lead to improved cancer outcomes in humans.

By destroying only 50% to 75% of liver tumor volume, the rats' immune systems were able to clear away the rest, with no evidence of recurrence or metastases in more than 80% animals.

"Even if we don't target the entire tumor, we can still cause the tumor to regress and also reduce the risk of future metastasis," said Zhen Xu, professor of biomedical engineering at U-M and corresponding author of the study in Cancers.

Results also showed the treatment stimulated the rats' immune responses, possibly contributing to the eventual regression of the untargeted portion of the tumor and preventing further spread of the cancer.

The treatment, called histotripsy, noninvasively focuses ultrasound waves to mechanically destroy target tissue with millimeter precision. The relatively new technique is currently being used in a human liver cancer trial in the United States and Europe.

In many clinical situations, the entirety of a cancerous tumor cannot be targeted directly in treatments for reasons that include the mass' size, location or stage. To investigate the effects of partially destroying tumors with sound, this latest study targeted only a portion of each mass, leaving behind a viable intact tumor. It also allowed the team, including researchers at Michigan Medicine and the Ann Arbor VA Hospital, to show the approach's effectiveness under less than optimal conditions.

"Histotripsy is a promising option that can overcome the limitations of currently available ablation modalities and provide safe and effective noninvasive liver tumor ablation," said Tejaswi Worlikar, a doctoral student in biomedical engineering. "We hope that our learnings from this study will motivate future preclinical and clinical histotripsy investigations toward the ultimate goal of clinical adoption of histotripsy treatment for liver cancer patients."

Liver cancer ranks among the top 10 causes of cancer related deaths worldwide and in the U.S. Even with multiple treatment options, the prognosis remains poor with five-year survival rates less than 18% in the U.S. The high prevalence of tumor recurrence and metastasis after initial treatment highlights the clinical need for improving outcomes of liver cancer.

Where a typical ultrasound uses sound waves to produce images of the body's interior, U-M engineers have pioneered the use of those waves for treatment. And their technique works without the harmful side effects of current approaches such as radiation and chemotherapy.

"Our transducer, designed and built at U-M, delivers high amplitude microsecond-length ultrasound pulses -- acoustic cavitation -- to focus on the tumor specifically to break it up," Xu said. "Traditional ultrasound devices use lower amplitude pulses for imaging."

The microsecond long pulses from UM's transducer generate microbubbles within the targeted tissues -- bubbles that rapidly expand and collapse. These violent but extremely localized mechanical stresses kill cancer cells and break up the tumor's structure.

Since 2001, Xu's laboratory at U-M has pioneered the use of histotripsy in the fight against cancer, leading to the clinical trial #HOPE4LIVER sponsored by HistoSonics, a U-M spinoff company. More recently, the group's research has produced promising results on histotripsy treatment of brain therapy and immunotherapy.

The study was supported by grants from the National Institutes of Health, Focused Ultrasound Foundation, VA Merit Review, U-M's Forbes Institute for Discovery and Michigan Medicine-Peking University Health Sciences Center Joint Institute for Translational and Clinical Research.

Source: ScienceDaily

How do our eyes stay focused on what we reach for?

 Keeping our eyes focused on what we reach for, whether it be an item at the grocery store or a ground ball on the baseball field, may appear seamless, but, in fact, is due to a complex neurological process involving intricate timing and coordination. In a newly published study in the journal Nature, a team of researchers sheds additional light on the machinations that ensure we don't look away from where we are reaching.

The work centers on a form of coordinated looking and reach called "gaze anchoring" -- the temporary stoppage of eye movements in order to coordinate reaches.

"Our results show that we anchor our gaze to the target of the reach movement, thereby looking at that target for longer periods," explains Bijan Pesaran, a professor at NYU's Center for Neural Science and one of the paper's authors. "This is what makes our reaches much more accurate. The big question has been: How does the brain orchestrate this kind of natural behavior?"

The study, conducted with Maureen Hagan, a neuroscientist at Australia's Monash University, explores the frequently studied but not well understood process of gaze anchoring -- in particular, how different regions of the brain communicate with each other.

To examine this phenomenon, the scientists studied brain activity in the arm and eye movement regions of the brain at the same time as non-human primates performed a sequence of eye and arm movements. The first movement was a coordinated look-and-reach to a target. Then, as little as 10 milliseconds later, a second target was presented that subjects needed to look at as quickly as possible. This second eye movement revealed the gaze anchoring effect. These movements are similar to those made when changing the radio while driving and attending to a traffic light -- if you quickly look away from the radio to the traffic light, you might not select the right channel.

Their results showed that, during gaze anchoring, neurons in the part of the brain -- the parietal reach region -- used for reaching work to inhibit neuron activity in the part of the brain -- the parietal saccade region -- used for eye movements. This suppression of neuron firing serves to inhibit eye movement, keeping our eyes centered on the target of our reach, which then enhances the accuracy of what we're grasping for. Importantly, the scientists note, the effects were tied to patterns of brain waves at 15-25 Hz, called beta waves, that organize neural firing across the different regions of the brain.

"Beta waves have been previously linked to attention and cognition, and this study reveals how beta activity may control inhibitory brain mechanisms to coordinate our natural behavior," explains Pesaran.

By further illuminating the neurological processes of coordinated looking and reaching, tying them to inhibitory beta waves, this study offers the potential to better understand afflictions of attention and executive control that orchestrate natural behaviors like coordinated looking and reaching.

Source: ScienceDaily

Scientists identify potential new 'soldier' for cancer immunotherapy

 Despite the success of immunotherapy in helping many people with cancer, the majority of patients still do not respond to these treatments. There is need for continued research.

On April 20, 2022, researchers at the Sloan Kettering Institute reported in the journal Nature that a recently discovered new immune cell "soldier" could be a good target for immunotherapy, raising hopes that it might help narrow the gap between people who respond and those who do not.

The new cells, which the scientists have dubbed killer innate-like T cells, differ in notable ways from the conventional target of many immunotherapies -- the cytotoxic (aka "killer") T cells. For one, they don't get exhausted from extended activity like cytotoxic T cells do. And two, they can penetrate more deeply into tissues where cancer is hiding. These unique attributes make them attractive as a target for immunotherapy.

"We think these killer innate-like T cells could be targeted or genetically engineered for cancer therapy," says Ming Li, an immunologist in SKI and the lead author of the new study. "They may be better at reaching and killing solid tumors than conventional T cells."

Pinning Down What Makes the Cells Distinct

Dr. Li's team first reported the existence of this unusual cell population in 2016. At that time, it was clear to his team that these cells had the power to kill cancer cells, but they knew little about where the cells come from or how they work.

For this new study, Dr. Li and colleagues used a variety of techniques, including single-cell analysis and CRISPR genome editing, to further characterize the cells.

They made several startling discoveries. For one, killer innate-like T cells don't make the immune checkpoint molecule PD-1 and, as a consequence, do not appear to become exhausted the way typical killer T cells do. This is an attractive feature in a potential immune cell therapy.

The cells also appear to recognize different markers, or antigens, on cancer cells. Whereas conventional killer T cells recognize specific mutated antigens (called neoantigens), the killer innate-like T cells recognize a much broader range of non-mutated (that is, normal) antigens.

Killer innate-like T cells also don't depend on antigen-presenting cells, such as dendritic cells, to alert them to the presence of dangerous-looking antigens. In this way, they behave more like innate immune cells that are always primed and ready for attack.

Lastly, unlike conventional T cells, they don't recirculate throughout the blood and lymph fluid, making stops in lymph nodes. Rather, they appear to home directly to tissues throughout the body, where they seek out danger.

All of these make them of particular interest as a target of immunotherapy, Dr. Li says.

A Unique Fate That Avoids Autoimmunity and Suppresses Cancer

The fact that killer innate-like T cells recognize unmutated antigens in the body raises the question of why these cells don't cause autoimmunity -- when the immune system attacks normal parts of the body. Dr. Li says it's because they get reprogrammed during their development.

Typically, developing T cells that react strongly to normal antigens are proactively killed off by the body to prevent autoimmune reactions. But the killer innate-like T cells escape that fate. Instead, their T cell receptor machinery gets tamped down, rendering these cells harmless to normal cells in the body.

At the same time, they become much more sensitive to a molecule called IL-15 that is produced by many cancer cells and is recognized as an "alarmin" -- a danger signal that prods the immune system into action. The team found that if they delete IL-15 from cancer cells, then the protection provided by the killer innate-like T cells was eliminated and tumor growth increased.

Because IL-15 isn't highly produced in healthy tissues, the killer innate-like T cells would not be spurred into action there, and therefore would not cause unwanted damage.

Dr. Li's team did most of their experiments in mice, but they confirmed that these killer innate-like T cells are present in human tumors, including colon cancer tumors from patients at MSK. They are excited about the possibility of working with doctors at MSK to translate these findings from the lab to the clinic, where they might ultimately help patients.

This work was supported by the National Institute of Health (R01 CA243904-01A1, F30 AI29273-03, and F31 CA210332), the Howard Hughes Medical Institute, the Cancer Research Institute, the Ludwig Center for Cancer Immunotherapy and the Functional Genomic Initiative grants, and the Memorial Sloan Kettering Cancer Center (MSKCC) Support Grant/Core Grant (P30 CA08748), the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center of MSK.

MSK has filed a patent application regarding use of killer innate-like T cells in cancer immunotherapy. Dr. Li is a scientific advisory board member of and holds equity or stock options in, Amberstone Biosciences Inc, and META Pharmaceuticals Inc.

Source: ScienceDaily

Got food cravings? What's living in your gut may be responsible

 Eggs or yogurt, veggies or potato chips? We make decisions about what to eat every day, but those choices may not be fully our own. New University of Pittsburgh research on mice shows for the first time that the microbes in animals' guts influence what they choose to eat, making substances that prompt cravings for different kinds of foods.

"We all have those urges -- like if you ever you just feel like you need to eat a salad or you really need to eat meat," said Kevin Kohl, an assistant professor in the Department of Biology in the Kenneth P. Dietrich School of Arts and Sciences. "Our work shows that animals with different compositions of gut microbes choose different kinds of diets."

Despite decades of speculation by scientists about whether microbes could influence our preferred diets, the idea has never been directly tested in animals bigger than a fruit fly. To explore the question, Kohl and his postdoc Brian Trevelline (A&S '08), now at Cornell University, gave 30 mice that lacked gut microbes a cocktail of microorganisms from three species of wild rodents with very different natural diets.

The duo found that mice in each group chose food rich in different nutrients, showing that their microbiome changed their preferred diet. The researchers published their work today in the Proceedings of the National Academy of Sciences.

While the idea of the microbiome affecting your behavior may sound far-fetched, it's no surprise for scientists. Your gut and your brain are in constant conversation, with certain kinds of molecules acting as go-betweens. These byproducts of digestion signal that you've eaten enough food or maybe that you need certain kinds of nutrients. But microbes in the gut can produce some of those same molecules, potentially hijacking that line of communication and changing the meaning of the message to benefit themselves.

One such messenger will be familiar to anyone who's had to take a nap after a turkey dinner: tryptophan.

"Tryptophan is an essential amino acid that's common in turkey but is also produced by gut microbes. When it makes its way to the brain, it's transformed into serotonin, which is a signal that's important for feeling satiated after a meal," Trevelline said. "Eventually that gets converted into melatonin, and then you feel sleepy."

In their study, Trevelline and Kohl also showed that mice with different microbiomes had different levels of tryptophan in their blood, even before they were given the option to choose different diets -- and those with more of the molecule in their blood also had more bacteria that can produce it in their gut.

It's a convincing smoking gun, but tryptophan is just one thread of a complicated web of chemical communication, according to Trevelline. "There are likely dozens of signals that are influencing feeding behavior on a day-to-day basis. Tryptophan produced by microbes could just be one aspect of that," he said. It does, however, establish a plausible way that microscopic organisms could alter what we want to eat -- it's one of just a few rigorous experiments to show such a link between the gut and the brain despite years of theorizing by scientists.

There's still more science to do before you should start distrusting your food cravings, though. Along with not having a way to test the idea in humans, the team didn't measure the importance of microbes in determining diet compared to anything else.

"It could be that what you've eaten the day before is more important than just the microbes you have," Kohl said. "Humans have way more going on that we ignore in our experiment. But it's an interesting idea to think about."

And it's just one behavior that microbes could be tweaking without our knowledge. It's a young field, Kohl points out, and there's still lots to learn.

"I'm just constantly amazed at all of the roles we're finding that microbes play in human and animal biology," Kohl said.

Source: ScienceDaily

 

Good' cholesterol may decrease your risk of Alzheimer's disease

• Good cholesterol or high-density lipoprotein (HDL) is essential to health. Still, the impact of HDL on the brain is not fully understood.
• Alzheimer’s disease is a disorder that impacts people’s ability to think and function in everyday life. Researchers are still working on developing treatments and understanding the condition.
• A recent study suggests that higher levels of small high-density lipoproteins might decrease the risk for Alzheimer’s disease.

Alzheimer’s disease is a debilitating condition that primarily affects older adults. People who have it can become forgetful and become unable to carry out tasks of daily living. Currently, the disorder has no cure. Researchers are still trying to understand how the disease develops, how to prevent it, and how to best treat it.

A recent study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s AssociationTrusted Source offers new insight. Researchers studied the connection between small HDLs or “good” cholesterol in the cerebrospinal fluid and the risk for Alzheimer’s disease. The results suggest that higher levels of small HDL were associated with a lower risk of developing Alzheimer’s disease.

  What is “good” cholesterol?

Cholesterol is a substance that your body needs. For example, the body uses cholesterol to make certain hormones, properly digest food, and make new cells. The body makes cholesterol, but people can also get it from food sources.

As noted by the American Heart AssociationTrusted Source, cholesterol exists in the body in two primary forms: low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDLs can build up in the bloodstream and increase the risk of strokes and heart attacks, so it is essential for your LDL count not to be too high.

The body’s HDL or “good” cholesterol helps to carry cholesterol back to the liver so that the liver can break it down. But HDLs can impact other areas of health in ways researchers do not fully understand. For example, researchers are still trying to understand how HDL levels affect the brain. The study authors note that the HDL in the brain is slightly different from the HDL in the rest of the body.

         What is Alzheimer’s disease?

Alzheimer’s diseaseTrusted Source is a disorder that impacts the brain, and it typically occurs in adults over the age of sixty. It impacts the brain’s nerves and is related to the buildup of specific proteins in the brain. Ultimately, the neurons in the brain die and lose their ability to communicate with other brain cells.

This damage causes people with Alzheimer’s disease to have memory, language, and decision-making problems. It can be debilitating, and those with Alzheimer’s disease often slowly lose their ability to function independently.

Research is ongoing about what causes Alzheimer’s disease and how we can best develop treatments.

          Good cholesterol and Alzheimer’s disease

The study in question included 180 participants aged 60 or older. Participants engaged in the study through the University of Southern California (USC) Alzheimer Disease Research Center (ADRC) and the Huntington Memorial Research Institute (HMRI) Aging Program.

Researchers looked at participants’ cognitive functions through a variety of cognitive tests. They took cerebrospinal fluid (CSF), the fluid surrounding the brain and the spinal cord, and plasma samples from participants and isolated the DNA. Researchers tested for the APOE ε4 gene from the DNA, a potential risk factorTrusted Source for Alzheimer’s disease.

Researchers then examined the levels of small HDL particles in the CSF. They found that higher levels of the small HDL particles were associated with better cognitive function among participants. They found this result to be the same even after accounting for the APOE ε4 gene, age, sex, and amount of education.

Results of the study may lead to the development of new treatments for Alzheimer’s disease. Study author Hussein Yassine noted the following to Medical News Today:

The discovery of lipid particles (LDL, HDL) in [the] blood led to several advances in drug discovery for cardiovascular disease treatment and prevention. Here for the first time, we measure HDL particles in cerebrospinal fluid as a surrogate of brain HDL and find that greater levels of small HDL correlate with better performance on cognitive measures.

Now that we have this biomarker, our next step is to figure out what promotes the formation of these small HDL particles in the brain. Such new discoveries could then lead to a new list of medications in our fight against Alzheimer’s.

         Study limitations and continued research

The study authors noted that their study had several limitations. First, it is difficult to identify which of these particles has the protective properties because there are many subtypes of the small HDLs. They acknowledge that more research is needed to understand the interactions and differences between the HDLs in the brain and those in general circulation.

Researchers further acknowledge that the study’s findings cannot be generalized, and the study does not show cause. Further research can look at whether HDL levels can predict the development of cognitive problems and if increasing HDL levels could help prevent Alzheimer’s disease. Researchers note that future studies could include more participants and have more long-term follow-ups.

The Alzheimer’s Association was optimistic about the study’s results. Percy Griffin, Ph.D., the Director of Scientific Engagement for the Alzheimer’s Association, noted the following to MNT:

This work is interesting and adds to the growing body of research examining different species in the cerebrospinal fluid. These findings on small high-density lipoprotein particles are intriguing and may inform the development of biomarkers that can help predict how quickly people will progress through Alzheimer’s disease. However, the sample size is pretty small and more research is needed.

 

Sleep deprivation may lower 'good' cholesterol

Previous studies have suggested that lack of sleep may increase the risk for cardiovascular disease, and a new study may help explain why; researchers found that sleep deprivation may have a negative impact on cholesterol levels.

Published in the journal Scientific Reports, the study found that sleep loss leads to changes in genes that are responsible for regulating cholesterol levels.

What is more, two population cohorts reveal that people who experience sleep deprivation may have fewer high-density lipoproteins (HDL) – known as the “good” cholesterol – than those who have sufficient sleep.

HDL cholesterol is responsible for removing low-density lipoproteins (LDL) – the “bad” cholesterol – from the arteries.

LDL cholesterol contributes to atherosclerosis – a build-up of plaque in the arteries that can increase the risk for heart attack and stroke – so a robust HDL cholesterol level is important for protecting heart health.

The team reached its findings by conducting experimental and epidemiological analyses.

For the experimental analysis, the researchers enrolled 21 participants who were required to sleep in a laboratory-controlled condition for 5 nights

The sleep duration for 14 of these participants was restricted to just 4 hours a night, while the remaining seven participants enjoyed sufficient sleep each night.

Lack of sleep reduced activity in lipoprotein-regulating genes

Blood samples were taken from all subjects during the study period, which the team analyzed for gene expression and lipoprotein levels.

Compared with participants who had sufficient sleep, the researchers found that those who experienced sleep loss had reduced expression for genes that encode for lipoproteins – that is, there was reduced activity in genes that are responsible for regulating cholesterol levels.

For the epidemiological analysis, the researchers assessed the data of 2,739 participants from one of two Finnish population studies: Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) study, and the Cardiovascular Risk in Young Finns Study (YFS).

In the DILGOM study, participants completed questionnaires in which they were asked whether they got enough sleep each night. Subjects who answered “seldom” or “never” were deemed as having “subjective sleep insufficiency.”

In the YFS study, subjects were asked how many hours they slept each night and how many hours they need each night to fell well-rested. Their subjective sleep duration was then subtracted from their subjective sleep need in order to determine which participants could be deemed as having sleep deprivation.

Lower circulating HDL with sleep deprivation in population cohorts

On analyzing the blood samples of the participants, once again, the researchers found that subjects who were not getting sufficient sleep had reduced expression of lipoprotein-encoding genes, compared with those who were getting enough sleep.

Additionally, subjects who were experiencing lack of sleep had lower levels of circulating HDL.

The team says the findings from both analyses suggest that just a short period of sleep deprivation may have a big impact on health, and they may explain why people who fail to get enough sleep may be at greater risk for cardiovascular disease.

Study co-author Vilma Aho, from the University of Helsinki Sleep Team, says:

“The experimental study proved that just 1 week of insufficient sleep begins to change the body’s immune response and metabolism. Our next goal is to determine how minor the sleep deficiency can be while still causing such changes.”

Medical Myths: All about cholesterol

Cholesterol is an essential component of animal cell membranes; as such, it is synthesized by all animal cells. Regardless of its bad name, cholesterol is essential for life.

However, when present in high levels in the blood, it increasesTrusted Source the risk of cardiovascular disease.

Cholesterol, along with other substances, such as fat and calcium, builds up in plaques on the walls of arteries. Over time, this narrows the blood vessels and can lead to complications, including stroke and heart attack.

According to the Centers for Disease Control and Prevention (CDC), in 2015–2016, 12%Trusted Source of people aged 20 years or older in the United States had high cholesterol.

The World Health Organization (WHO) estimates that raised cholesterol levels are responsible for 2.6 millionTrusted Source deaths each year.

Given such prevalence, it is no surprise that misinformation about cholesterol is rife. So, to help us separate fact from fiction, Medical News Today enlisted the help of three experts:

• Dr. Edo Paz, a cardiologist and vice president of Medical at K Health
• Dr. Robert Greenfield, a board-certified cardiologist, lipidologist, and internist at MemorialCare Heart & Vascular Institute at Orange Coast Medical Center in Fountain Valley, CA
• Dr. Alexandra Lajoie, a noninvasive cardiologist at Providence Saint John’s Health Center in Santa Monica, CA

1. All cholesterol is bad

As mentioned in the introduction, cholesterol is a vital component of cell membranes. Aside from its structural role in membranes, it is also vitalTrusted Source in the production of steroid hormones, vitamin D, and bile acid.

So, although high levels are a risk factor for disease, without any cholesterol, we could not survive.

As Dr. Greenfield explained to MNT: “Cholesterol isn’t bad. It’s an innocent bystander that is being mishandled in our modern lifestyle today.”

“Our bodies weren’t designed to live in an environment where food was in excess, and so when cholesterol is in excess, it will be deposited in our body. And that deposit center can often be our blood vessels, and that’s when it’s bad for us.”

– Dr. Robert Greenfield

Beyond cholesterol’s functions in the body, the way in which it is transported also makes a difference to whether it is detrimental to health.

Cholesterol is moved aroundTrusted Source the body by lipoproteins, which are substances that consist of fat and protein. This transport occurs in two main ways.

Low-density lipoprotein (LDL) carries cholesterol from the liver to cells, where it is used in several processes. People sometimes term LDL “bad” cholesterol, because high levels of LDL cholesterol in the bloodstream increase the risk of cardiovascular disease.

High-density lipoprotein (HDL) is often referred to as “good” cholesterol, because it transports cholesterol back to the liver. Once there, cholesterol is removed from the body, thereby reducing cardiovascular risk. 

2. I am a healthy weight, so I can’t have high       cholesterol

“Oh, yes you can!” according to Dr. Greenfield. “Cholesterol balance is really a function of what we eat but also our genetics. For example, a person can be born with a genetic tendency to not process cholesterol efficiently.”

“Because it’s genetic,” he explained, “it has been called familial hypercholesterolemia, and it might be as common as 1 in 200Trusted Source people. Weight is more a function of your inherited metabolism and the balance between calories consumed and calories expended.”

Dr. Paz concurred: “Even if you have a healthy weight, your cholesterol can be abnormal. Other factors that impact your cholesterol are the foods you eat, your exercise habits, whether you smoke, and how much alcohol you drink.”

Additionally, as Dr. Lajoie told us, people who have a healthy weight might have high cholesterol levels, while some people who have overweight may not have high cholesterol. “Cholesterol levels are affected by genetics, thyroid function, medications, exercise, sleep, and diet,” she explained.

“There are also factors that you cannot modify and which can contribute to high cholesterol, like your age and your genetics,” she continued.

Medical News Today