Category: Health

{Scientists at The Scripps Research Institute (TSRI) have found a way to tether HIV-fighting antibodies to immune cells, creating a cell population resistant to the virus. Their experiments under lab conditions show that these resistant cells can quickly replace diseased cells, potentially curing the disease in a person with HIV.}

“This protection would be long term,” said Jia Xie, senior staff scientist at TSRI and first author of the study published today in the journal Proceedings of the National Academy of Sciences.

The researchers, led by study senior author Richard Lerner, M.D., Lita Annenberg Hazen Professor of Immunochemistry at TSRI, plan to collaborate with investigators at City of Hope’s Center for Gene Therapy to evaluate this new therapy in efficacy and safety tests, as required by federal regulations, prior to testing in patients.

“City of Hope currently has active clinical trials of gene therapy for AIDS using blood stem cell transplantation, and this experience will be applied to the task of bringing this discovery to the clinic,” said John A. Zaia, M.D., director of the Center for Gene Therapy in the Hematological Malignancy and Stem Cell Transplantation Institute at City of Hope. “The ultimate goal will be the control of HIV in patients with AIDS without the need for other medications.”

“We at TSRI are honored to be able to collaborate with physicians and scientists at City of Hope, whose expertise in transplantation in HIV patients should hopefully allow this therapy to be used in people,” added Lerner.

The new TSRI technique offers a significant advantage over therapies where antibodies float freely in the bloodstream at a relatively low concentration. Instead, antibodies in the new study hang on to a cell’s surface, blocking HIV from accessing a crucial cell receptor and spreading infection.

Xie called it the “neighbor effect.” An antibody stuck nearby is more effective than having many antibodies floating throughout the bloodstream. “You don’t need to have so many molecules on one cell to be effective,” he said.

Before testing their system against HIV, the scientists used rhinovirus (responsible for many cases of the common cold) as a model. They used a vector called lentivirus to deliver a new gene to cultured human cells. This gene instructed cells to synthesize antibodies that bind with the human cell receptor (ICAM-1) that rhinovirus needs. With the antibodies monopolizing that site, the virus cannot enter the cell to spread infection.

“This is really a form of cellular vaccination,” said Lerner.

Because the delivery system can’t reach exactly 100 percent of cells, the finished product was a mix of engineered and unengineered cells. The researchers then added rhinovirus to these cell populations and waited to see what would happen.

The vast majority of cells died in about two days. In dishes with only unengineered cells, the population never recovered. There was an initial die-off in the mixed engineered/unengineered populations, too, but their numbers quickly bounced back. After 125 hours, these cell populations were back up to around the same levels as cells in an undiseased control group.

In essence, the researchers had forced the cells to compete in Darwinian, “survival-of-the-fittest” selection in a lab dish. Cells without antibody protection died off, leaving protected cells to survive and multiply, passing on the protective gene to new cells.

This success led the researchers to test the same technique against HIV. To infect a person, all strains of HIV need to bind with a cell surface receptor called CD4. So the scientists tested antibodies that could potentially protect this receptor on the very immune cells normally killed by HIV. “This research is possible because of the ability to select specialized antibodies from combinatorial antibody libraries,” said Lerner.

Again, their technique worked. After introducing cells to the virus, the researchers ended up with an HIV-resistant population. The antibodies recognized the CD4 binding site, blocking HIV from getting to the receptor.

The scientists further confirmed that these tethered antibodies blocked HIV more effectively than free-floating, soluble antibodies in experiments led by study co-authors Devin Sok of the International AIDS Vaccine Initiative (IAVI) and TSRI Professor Dennis R. Burton, who is also scientific director of the IAVI Neutralizing Antibody Center and of the National Institutes of Health’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) at TSRI.

Joseph Alvarnas, M.D., director of Value-Based Analytics at City of Hope, explained how the TSRI technique could help patients, who–despite treatment with anti-retroviral drugs–still suffer from higher rates of diseases, such as cancers. “HIV is treatable but not curable–this remains a disease that causes a lot of suffering. That makes the case for why these technologies are so important,” he said.

In addition to potentially collaborating with City of Hope, Xie said the next step in this research is to try engineering antibodies to protect a different receptor on the cell surface.

Additional authors of the study, “Immunochemical Engineering of Cell Surfaces to Generate Virus Resistance,” were Nicholas Wu and Tianqing Zheng of TSRI. The study was supported by Zebra Biologics and the JPB Foundation.

{{About The Scripps Research Institute}}

The Scripps Research Institute (TSRI) is one of the world’s largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists–including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine–work toward their next discoveries. The institute’s graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www.scripps.edu.

{{About City of Hope}}

City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 47 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout Southern California. It is ranked as one of “America’s Best Hospitals” in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and numerous breakthrough cancer drugs based on technology developed at the institution. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

Source:Science Daily

{Exercise enthusiasts often wonder whether it’s better to eat or fast before a workout. A new study is the first of its kind to show the effects of eating versus fasting on gene expression in adipose (fat) tissue in response to exercise. This study highlights the different roles fat plays in powering and responding to exercise. The study is published ahead of print in the American Journal of Physiology — Endocrinology and Metabolism.}

Researchers from the University of Bath in the U.K. studied a group of overweight males. The volunteers walked for 60 minutes at 60 percent maximum oxygen consumption on an empty stomach and, on another occasion, two hours after consuming a high-calorie carbohydrate-rich breakfast. The research team took multiple blood samples after eating or fasting and after exercising. The researchers also collected adipose tissue samples immediately before and one hour after walking.

Gene expression in the adipose tissue differed significantly in the two trials. The expression of two genes, PDK4 and HSL, increased when the men fasted and exercised and decreased when they ate before exercising. The rise in PDK4 likely indicates that stored fat was used to fuel metabolism during exercise instead of carbohydrates from the recent meal. HSL typically increases when adipose tissue uses stored energy to support increased activity, such as during exercise, explained Dylan Thompson, corresponding author of the study.

These results reinforce the view that “adipose tissue often faces competing challenges,” Thompson wrote. After eating, adipose tissue “is busy responding to the meal and a bout of exercise at this time will not stimulate the same [beneficial] changes in adipose tissue. This means that exercise in a fasted state might provoke more favorable changes in adipose tissue, and this could be beneficial for health in the long term,” he noted.

Source:Science Daily

{The fertility of women drops as a woman ages. It starts dropping significantly when a woman is around age 35 but why do this happen?
}
According to a research published in the Daily Mail, chromosomal defect in the eggs of older women could be the cause behind fertility problems in older women.

Scientists claim a biological structure that separates chromosomes in the eggs of older women sends the chromosomes all over the place instead of distributing them evenly to each egg.

“An egg typically has 46 chromosomes, and having more than 46 is the cause behind Down syndrome, while having too few will likely end in miscarriage,” a report in Daily Mail claims.

An egg that has more than 46 chromosomes is called an aneuploid egg and eggs are more likely to be aneuploid with age because the “glue” that keeps the chromosomes together works poorly in older eggs.

The report also revealed that “women are born with a fixed number of eggs, which remain dormant in the ovaries until the release of a single egg per menstrual cycle.”

Source:Elcrema

{Scientists at Lund University in Sweden have developed a new understanding of how the first blood cells form during human development as they transition from endothelial cells to form blood cells of different types.}

Using a laboratory model of human stem cell development and by looking at the expression of blood cell and endothelial cell genes in each individual cell, they found a progression from an endothelial state, to a mixed endothelial/blood state, to a blood-only state. This is the first study showing the molecular processes of this transition in the human developmental context.

“Understanding how the first human blood cells develop will provide missing clues for us to generate blood stem cells in the laboratory for use in the treatment of blood disorders and malignancies,” says Niels-Bjarne Woods, in charge of the study.

The blood running through our veins is composed of billions of specialized cells, responsible for many important functions required for life, including providing oxygen to all tissues in our body and providing immune responses against viruses, bacteria, and even cancer cells. During a narrow window of time in embryonic development, the first blood stem cells form. These give rise to all the blood cells you will produce in your lifetime. The birth of these blood stem cells is a transition from another cell type into blood cells — a process known as endothelial to hematopoietic transition.

The cells undergoing the transition to blood in the embryo start as endothelial cells that make up the walls of the developing arteries. During a short temporal window in development, a small number of tightly packed spindle shaped endothelial cells round up forming nascent blood, detach, and are released into the circulation. In this process, the endothelial cells undergoing the transition to blood show dramatic changes in their size and shape (from spindle shaped to the round cells of the blood).

However, what happens inside the cell during this time, as it changes shape and identity, had until now never been described at a molecular level. Thanks to single-cell molecular analysis, the scientists in Lund have now analyzed individual cells from an in vitro model of human blood development, known to comprise endothelial cells that transition to blood. The analysis revealed new populations of endothelial cells undergoing transition. These new cell populations showed differences in the repertoire of blood cell types that could be produced. which is a critically important finding in the understanding of origins of blood. Niels-Bjarne Woods explains:

“Most cell types are believed to result from a linear sequence of undifferentiated stages, progressively restricting their potential until they are restricted to the mature state. Cells arising from a transitioning process may not need to follow this rule, giving wider flexibility to which blood cell types can be produced.”

This is a significant step towards understanding how the first blood cells are formed and how numbers and types of blood cells is regulated in development.

“It would also be interesting to find out if there are any endothelial cells in the adult that can still be “triggered” to produce new blood stem cells,” says Niels-Bjarne Woods.

Source:Science Daily

{Twice-weekly yoga led to better physical, sexual, emotional, and social health, study finds}

Men who attended a structured yoga class twice a week during prostate cancer radiation treatment reported less fatigue and better sexual and urinary function than those who didn’t, according to a clinical trial led by the Perelman School of Medicine at the University of Pennsylvania. It is the first randomized trial to look at the effect of twice-weekly yoga on the side-effects and quality of life issues caused by prostate cancer treatment. The results published this week in the International Journal of Radiation Oncology, Biology, and Physics.

All of the patients in the trial underwent between six and nine weeks of external beam radiation therapy for prostate cancer. The patients were randomized into two groups: one arm participated in a yoga class that met twice a week and the other arm served as a control group. Patients who already practiced yoga on their own were not eligible for the study, nor were patients with a history of prior radiation therapy or those with metastatic disease.

Only two instructors led classes for this study, with the lead instructor teaching 75 percent of the classes. Each session lasted 75 minutes, beginning with five minutes of breathing and centering techniques and ending with five minutes of Savasana, a common yoga position. Typical sessions incorporated sitting, standing, and reclining positions that were modified using props to adapt to each patient’s needs and restrictions.

Patients were primarily evaluated on their level of fatigue. Each man filled out a nine-item questionnaire assessing fatigue severity and impact on daily life. The first questionnaire was given between two and three weeks before the start of radiotherapy, then twice a week while receiving radiotherapy, with a final survey filled out within a week of their last yoga class or last radiation treatment, depending on the assigned study arm.

“At their baseline, before patients started treatment, patients in both groups were on the lower end of the scale, meaning they reported lower amounts of fatigue,” said the trial’s principal investigator Neha Vapiwala, MD, an associate professor of Radiation Oncology. “But as treatment went on, we observed a difference in the two groups.” Patients in the yoga group reported lower fatigue scores over time, as they attended more yoga sessions, relative to where they started. Patients who did not participate in yoga trended in the opposite direction, reporting greater fatigue as treatment progressed.

“Levels of patient-reported fatigue are expected to increase by around the fourth or fifth week of a typical treatment course, but that did not happen in the yoga group,” Vapiwala said. “Both the severity of the fatigue as well as the patients’ ability to go about their normal lives appeared to be positively impacted in the yoga group.”

Researchers also evaluated both groups in terms of their sexual health. Sexual dysfunction — including but not limited to erectile dysfunction (ED) — is reported by up to 85 percent of radiation therapy patients during treatment, often due to the concurrent use of androgen deprivation therapy (ADT). The study utilized the International Index of Erectile Function (IIEF) questionnaire, in which scores range from 0-25. Scores greater than 21 are considered normal and scores below 12 indicate moderate to severe ED. Both groups started out with scores of around 11, and were balanced in terms of ADT exposure; but while the yoga group’s score ended up largely unchanged from baseline, the non-yoga group saw a decline over the course of treatment.

“Yoga is known to strengthen pelvic floor muscles, which is one of several postulated theories that may explain why this group did not demonstrate declining scores, as seen in the control group,” Vapiwala said. “That may also explain the yoga patients’ improved urinary function scores, another finding of this trial.” Vapiwala pointed out that the findings on improved or stable urinary function are consistent with other research on the effects of physical therapy on pelvic floor muscles.

The trial also found that while the emotional well-being of both groups increased as patients progressed through treatment, the evaluation scores in the yoga group rose more rapidly than in the control group. An evaluation of physical well-being showed a similar pattern.

Source:Science Daily

{Research identifies a new potential way to help cardiac muscle recover from procedures}

Cedars-Sinai Heart Institute investigators have learned how cardiac muscle cells react to a certain type of injury that can be caused by open-heart surgery. The findings point to a new potential way to help these hearts recover more completely.

The cells, known as cardiomyocytes, can be damaged by the process of stopping and starting the heart during surgeries that use cardiopulmonary bypass machines to take over the heart’s functions. Hundreds of thousands of these operations are performed each year in the U.S. to replace failing hearts, bypass clogged arteries, fix leaky valves and more.

While most patients recover easily enough, some patients suffer long-term effects or even fatal heart failure from the stresses of the surgery.

In their study, published in the JCI Insight journal of the American Society for Clinical Investigation, the investigators scrutinized cardiac muscle cells in tissue samples taken from patients before and after open-heart surgeries. Their work demonstrates for the first time in human hearts that cardiac muscle cells react to this type of injury by both destroying and creating new mitochondria, the tiny energy factories inside each cell.

“By accelerating beneficial aspects of this process, doctors one day may be able to speed up healing from open-heart surgery,” said Roberta Gottlieb, MD, director of Molecular Cardiobiology and professor of Medicine at the Cedars-Sinai Heart Institute. She was the principal investigator of the study.

Currently, physicians try to protect the cardiac muscle during open-heart surgery by cooling it and infusing it with potassium to stop its contractions. The goal is to reduce the trauma produced by the one-two punch of first depriving the heart of blood (ischemia) and then flooding it with blood (reperfusion).

“Despite these measures, ischemia/reperfusion injury remains a major cause of complications after heart surgery,” said Allen Andres, PhD, a research scientist in Gottlieb’s laboratory and assistant professor of Medicine. He was the first author of the study, working with Robert Mentzer, MD, professor of Medicine, who initiated and designed the study.

Investigators for decades have tried to develop drugs to treat ischemia/reperfusion injury associated with cardiac surgeries, with little success, according to Gottlieb. “There have been wonderful results in animal tests, but not in people,” she said. “We need to have a better understanding of the beneficial and deleterious processes that characterize the human heart’s response to ischemia and reperfusion.”

Prior to beginning the study, the Cedars-Sinai investigative team had expected to find that cardiac muscle cells would dismantle some of the mitochondria after ischemia/reperfusion injury. This process was known to occur in the hearts of laboratory animals. Cells and cell structures in various parts of the body often self-destruct after their genetic material gets damaged by stress or other events.

The investigators were gratified to confirm that self-destruction of mitochondria occurred in the human heart too. But they were surprised to learn that human cardiac muscle cells also assembled new mitochondria in response to ischemia/reperfusion injury. “We don’t know if this mitochondrial production is good or bad news for the heart,” Gottlieb said. “These could be better mitochondria or carry genetic defects. We intend to find out.”

To learn more, the investigators are developing proposals to collect data on mitochondria from heart transplant patients over a period of months. And they are already investigating a pharmacological agent that shows promise in stimulating mitochondrial creation in animal models.

Source:Science Daily

{Cortex of super-aged brain deteriorated much slower than average elderly brain over time.}

Donald Tenbrunsel is 89 years old, but he is just as likely to talk to you about Chance the Rapper as reminisce about Frank Sinatra.

The highly engaged and delightful conversationalist, who reads, volunteers and routinely researches questions on the Internet, is part of a new path-breaking Northwestern Medicine study that shows that SuperAgers’ brains shrink much slower than their age-matched peers, resulting in a greater resistance to “typical” memory loss and dementia.

Over the course of the 18-month study, normal agers lost volume in the cortex twice as fast as SuperAgers, a rare group of people aged 80 and above whose memories are as sharp as those of healthy persons decades younger.

“Increasing age is often accompanied by ‘typical’ cognitive decline or, in some cases, more severe cognitive decline called dementia,” said first author Amanda Cook, a clinical neuropsychology doctoral student in the laboratory of Emily Rogalski and Sandra Weintraub. “SuperAgers suggest that age-related cognitive decline is not inevitable.”

The study was published in JAMA. Senior author Emily Rogalski will present the findings at the 2017 Cognitive Aging Summit in Bethesda, Maryland, April 6.

SuperAger Tenbrunsel, who lives with his daughter’s family, is intent on being a good conversationalist with his three grandchildren.

“I have to adapt to that kind of life,” Tenbrunsel said. “They don’t know much about Frank Sinatra or Franklin Delano Roosevelt, so I have to keep saying, ‘Is the Chance the Rapper coming this week or is it Taylor Swift?’”

The researchers already knew SuperAgers’ brains tended to retain more brain volume and typically don’t show the same wear-and-tear as normal agers.

“For this study we explored whether SuperAgers’ brains were on a different trajectory of decline,” said Rogalski, associate professor at the Cognitive Neurology and Alzheimer’s Disease Center (CNADC) at Northwestern University Feinberg School of Medicine. “We found that SuperAgers are resistant to the normal rate of decline that we see in average elderly, and they’re managing to strike a balance between life span and health span, really living well and enjoying their later years of life.”

Using magnetic resonance imaging (MRI), the scientists measured the thickness of the cortex in 24 SuperAgers and 12 same-age, educationally and cognitive average peers (control group) to determine the approximate health of the brain over 18 months. The annual percent decline in thickness between the first and second visit for the SuperAgers was 1.06 and 2.24 for the control group.

Previous research showed that SuperAgers have a thicker cortex than those who age normally. By studying what makes SuperAgers unique, the scientists said they hope to undercover biological factors, such as the reduced cortical brain atrophy demonstrated here, that might contribute to the maintenance of memory ability in advanced age.

SuperAger research at Northwestern is flipping the traditional approach to Alzheimer’s research of focusing on brains that are underperforming to instead focusing on outperforming brains.

“Sometimes it’s useful to turn a complex problem on its head and look from a different vantage point,” Rogalski said. “The SuperAging program studies people at the opposite end of the spectrum: those with unexpectedly high memory performance for their age.”

Source:Science Daily

{Eating potassium-rich foods like sweet potatoes, avocados, spinach, beans, bananas — and even coffee — could be key to lowering blood pressure, according to Alicia McDonough, PhD, professor of cell and neurobiology at the Keck School of Medicine of the University of Southern California (USC).}

“Decreasing sodium intake is a well-established way to lower blood pressure,” McDonough says, “but evidence suggests that increasing dietary potassium may have an equally important effect on hypertension.”

Hypertension is a global health issue that affects more than one billion people worldwide. The World Health Organization estimates that hypertension is responsible for at least 51 percent of deaths due to stroke and 45 percent of deaths due to heart disease.

McDonough explored the link between blood pressure and dietary sodium, potassium and the sodium-potassium ratio in a review article published in the April 2017 issue of the American Journal of Physiology — Endocrinology and Metabolism. The review looked at population, interventional and molecular mechanism studies that investigated the effects of dietary sodium and potassium on hypertension.

McDonough’s review found several population studies demonstrating that higher dietary potassium (estimated from urinary excretion or dietary recall) was associated with lower blood pressure, regardless of sodium intake. Interventional studies with potassium supplementation also suggested that potassium provides a direct benefit.

McDonough reviewed recent studies in rodent models, from her own lab and others, to illustrate the mechanisms for potassium benefit. These studies indicated that the body does a balancing act that uses sodium to maintain close control of potassium levels in the blood, which is critical to normal heart, nerve and muscle function.

“When dietary potassium is high, kidneys excrete more salt and water, which increases potassium excretion,” McDonough says. “Eating a high potassium diet is like taking a diuretic.”

Increasing dietary potassium will take a conscious effort, however. McDonough explains that our early ancestors ate primitive diets that were high in fruits, roots, vegetables, beans and grains (all higher in potassium) and very low in sodium. As a result, humans evolved to crave sodium — but not potassium. Modern diets, however, have changed drastically since then: processed food companies add salt to satisfy our cravings, and processed foods are usually low in potassium.

“If you eat a typical Western diet,” McDonough says, “your sodium intake is high and your potassium intake is low. This significantly increases your chances of developing high blood pressure.” When dietary potassium is low, the balancing act uses sodium retention to hold onto the limited potassium, which is like eating a higher sodium diet, she says.

But how much dietary potassium should we consume? A 2004 Institute of Medicine report recommends that adults consume at least 4.7 grams of potassium per day to lower blood pressure, blunt the effects of dietary sodium and reduce the risks of kidney stones and bone loss, McDonough says. Eating ¾ cup of black beans, for example, will help you achieve almost 50 percent of your daily potassium goal.

McDonough recommends developing public policies to increase intake of dietary potassium from plant-based sources. She also advocates adding potassium content to nutrition labels to help raise consumers’ awareness of economical sources of potassium.

Source:Science Daily

{University of Queensland School of Public Health researcher Akilew Adane said women who gained more than 2.5 per cent of their body weight each year had almost triple the risk of gestational diabetes compared to women who maintained a stable weight.}

“Women with only a small weight gain each year (1.5 to 2.5 per cent of body weight) doubled their risk of gestational diabetes,” Mr Adane said.

“Surprisingly, even women who were underweight or in the normal BMI range had an increased risk of gestational diabetes when they gained weight — even if they remained within the healthy weight category.

“Women with small weight gains within the healthy BMI range doubled their risk of gestational diabetes compared to women whose weight remained stable.”

Obesity is a known risk factor for gestational diabetes, which can lead to large babies, birth complications and long-term health risks for mothers and children.

Mr Adane said researchers set out to see what impact weight change had in the years leading up to pregnancy.

They tracked more than 3000 participants from the Women’s Health Australia study (also known as the Australian Longitudinal Study on Women’s Health).

The women, aged between 18 and 23 when they joined the study in 1996, have answered regular surveys on their weight, physical activity, lifestyle, health issues, and pregnancies ever since.

“It’s important for women and their clinicians to be aware that, even in the healthy BMI range, gaining a kilogram or two a year can be a health risk,” Mr Adane said.

“For instance, a 60-kilogram, 166-centimetre woman is in a healthy BMI range, but if she gains 1.14kg each year for seven years (about two per cent of her body weight) her risk of gestational diabetes would double compared to a woman whose weight remained stable.

“It’s likely that women who continue to gain weight through early adulthood may experience a modest, progressive insulin resistance, which is further exacerbated by pregnancy, even though their weight is still within the normal range.”

The research is published in Diabetes Research and Clinical Practice and will be presented at the 15th World Congress of Public Health this week.

Source:Science Daily