Culture

Gum bacteria implicated in Alzheimer's and other diseases

image: The mouth of a person with severe gum disease. Bacteria involved in periodontitis have been linked with Alzheimer's disease, aspiration pneumonia, rheumatoid arthritis and other common disorders.

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Image courtesy of Jan Potempa, University of Louisville.

Orlando, Fla. (April 7, 2019) - Researchers are reporting new findings on how bacteria involved in gum disease can travel throughout the body, exuding toxins connected with Alzheimer's disease, rheumatoid arthritis and aspiration pneumonia. They detected evidence of the bacteria in brain samples from people with Alzheimer's and used mice to show that the bacterium can find its way from the mouth to the brain.

The bacterium, Porphyromonas gingivalis, is the bad actor involved in periodontitis, the most serious form of gum disease. These new findings underscore the importance of good dental hygiene as scientists seek ways to better control this common bacterial infection.

"Oral hygiene is very important throughout our life, not only for having a beautiful smile but also to decrease the risk of many serious diseases," said Jan Potempa, PhD, DSc, a professor at the University of Louisville School of Dentistry and head of the department of microbiology at Jagiellonian University in Krakow, Poland. "People with genetic risk factors that make them susceptible to rheumatoid arthritis or Alzheimer's disease should be extremely concerned with preventing gum disease."

While previous researchers have noted the presence of P. gingivalis in brain samples from Alzheimer's patients, Potempa's team, in collaboration with Cortexyme, Inc., offers the strongest evidence to date that the bacterium may actually contribute to the development of Alzheimer's disease. Potempa will present the research at the American Association of Anatomists annual meeting during the 2019 Experimental Biology meeting, held April 6-9 in Orlando, Fla.

The researchers compared brain samples from deceased people with and without Alzheimer's disease who were roughly the same age when they died. They found P. gingivalis was more common in samples from Alzheimer's patients, evidenced by the bacterium's DNA fingerprint and the presence of its key toxins, known as gingipains.

In studies using mice, they showed P. gingivalis can move from the mouth to the brain and that this migration can be blocked by chemicals that interact with gingipains. An experimental drug that blocks gingipains, known as COR388, is currently in phase 1 clinical trials for Alzheimer's disease. Cortexyme, Inc. and Potempa's team are working on other compounds that block enzymes important to P. gingivalis and other gum bacteria in hopes of interrupting their role in advancing Alzheimer's and other diseases.

The researchers also report evidence on the bacterium's role in the autoimmune disease rheumatoid arthritis, as well as aspiration pneumonia, a lung infection caused by inhaling food or saliva.

"P. gingivalis's main toxins, the enzymes the bacterium need to exert its devilish tasks, are good targets for potential new medical interventions to counteract a variety of diseases," said Potempa. "The beauty of such approaches in comparison to antibiotics is that such interventions are aimed only at key pathogens, leaving alone good, commensal bacteria, which we need."

P. gingivalis commonly begins to infiltrate the gums during the teenage years. About one in five people under age 30 have low levels of the bacterium in their gums. While it is not harmful in most people, if it grows to large numbers the bacteria provoke the body's immune system to create inflammation, leading to redness, swelling, bleeding and the erosion of gum tissue.

Making matters worse, P. gingivalis even causes benign bacteria in the mouth to change their activities and further increase the immune response. Bacteria can travel from the mouth into the bloodstream through the simple act of chewing or brushing teeth.

The best way to prevent P. gingivalis from growing out of control is by brushing and flossing regularly and visiting a dental hygienist at least once a year, Potempa said. Smokers and older people are at increased risk for infection. Genetic factors are also thought to play a role, but they are not well understood.

Jan Potempa will present this research on Sunday, April 7, from 1-1:30 p.m. in Room W208A, Orange County Convention Center (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

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Experimental Biology

Blocking opioid receptors could reduce hormone-therapy-fueled increases in sugar intake

Orlando, Fla. (April 7, 2019)--Estradiol is a commonly prescribed estrogen therapy. Previous research has found that rats treated with the hormone experience an increase in sugar consumption. But according to new research, blocking the body's opioid receptors can reverse this effect. The findings will be presented today at the American Physiological Society's (APS) annual meeting at Experimental Biology 2019 in Orlando, Fla.

Estradiol is a naturally occurring estrogen hormone and common medication used in various hormone treatments, such as menopausal hormone therapy and birth control. Previous studies by this research team found giving estradiol replacement in a rat model of menopause caused the rats to consume more of an offered sugar solution.

Because the opioid system is known to contribute to overindulgence of highly palatable foods, the researchers decided to examine its role in estradiol's impact on sugar intake. Rats were assigned to either estradiol treatment or a control. Researchers then continuously infused rats with either naltrexone, which blocks opioid receptors, or saline. In a second experiment, the research team injected naltrexone or DAMGO, a synthetic compound that stimulates the opioid system, into an area of the brain associated with reward (the nucleus accumbens). In the first experiment, naltrexone treatment reversed the estradiol-related increase in sugar consumption. Injection of DAMGO stimulated sugar intake in both treated and control rats, but the effect was smaller in estradiol-treated rats than in control rats. These suggests that the opioid system plays a role in the estrogen-induced enhancement of sugar intake, but opioid receptors in the nucleus accumbens is not likely to be directly involved in the estrogen-induced enhancement of sugar intake.

Lead author Kurumi Iida noted that these findings suggest that extra sugar intake caused by estradiol "is possibly mediated by the opioid system." However, a potential site of the action for this phenomenon remains unknown.

Kurumi Iida, an undergraduate student at Nara Women's University in Nara, Japan, will present "Involvement of the opioid system in the 17β-estradiol-induced enhancement of sucrose intake in ovariectomized rats" Sunday, April 7, at a poster session in West Hall B of the exhibit hall of the Orange County Convention Center.

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American Physiological Society

Fresh guidance to fill 'information vacuum' on new cannabis products for medicinal use

A clinical review, published today (Saturday 6 April 2019) for the BMJ, provides new interim advice for doctors and clinicians in prescribing cannabis-based products and cannabinoids to treat certain conditions.

Since a policy change in November 2018, specialist doctors registered with the General Medical Council (GMC), have been permitted to prescribe new medicines which derive from cannabis. Yet, research into these products has, to date, been limited creating an 'information vacuum' about these medicines, their benefits or harms.

A new review authored by leading scientists and clinicians from the University of Bath and University College London (UCL) points to the array of different cannabis-based products and cannabinoids available, and a clear need to educate both patients and clinicians into what these different products do and how they might help.

In particular, it points to important differences between products containing THC (the main psychoactive and intoxicating constituent of cannabis) versus CBD (the non-intoxicating element). Although in certain medicines CBD and THC are combined for clinical benefit, in others these components can work independently, playing different roles in improving certain symptoms.

For example, several studies have found that a combination of THC and CBD can alleviate symptoms of chronic pain, while CBD alone may be effective for treatment-resistant epilepsy. By contrast THC alone may be effective for treating nausea and vomiting caused by chemotherapy. THC and CBD are both 'cannabinoids' that act in different ways on the body's endogenous cannabinoid system.

The cannabis plant produces over 144 different cannabinoids such as THC or CBD. Some medicinal products contain THC and/or CBD derived from the cannabis plant, while others contain synthetically produced cannabinoids. CBD is also available in non-medicinal products such as oils and tinctures.

Lead author, Dr Tom Freeman of the University of Bath's Addiction and Mental Health Group explains: "In this complex and rapidly evolving field, there are several different cannabis-based and cannabinoid medicinal products. These differ in their THC and CBD content, who can prescribe them, and the conditions they may be used to treat. Here we provide an update for clinicians in advance of forthcoming NICE guidelines.

"A key message is that CBD products widely sold online and in health food shops lack quality standards and should not be treated as medicinal products."

Research on cannabis was previously restricted because it was listed in Schedule 1, implying that it had no medical value. Cannabis was recently moved to Schedule 2 in the UK.

Dr Freeman adds: "Research on unlicensed cannabis products has been limited to date. The rescheduling of cannabis and allocation of dedicated UK research funding will improve the evidence we have to guide clinical decision-making."

Co-author, Dr Michael Bloomfield Head of Translational Psychiatry at University College London (UCL) added: "There have been leaps and bounds in our scientific knowledge in recent years, which combined with confusing claims about the medicinal uses of these drugs can be potentially perplexing for doctors and patients. We hope that our new guidance is helpful to doctors and patients worldwide. Much more research is needed into this new class of medicine."

Co-author Dr Chandni Hindocha of the Clinical Psychopharmacology Unit at UCL added: "Resources must be made available to update and educate clinicians about cannabis and cannabinoid based medicines. We would like to encourage doctors to maintain a compassionate and evidence-based approach when engaging with their patients in this rapidly developing field, in order to provide the best standard of care."

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University of Bath

Scientists find new therapy target for drug-induced liver failure

image: Findings from a new mouse study suggest that treatments that increase levels of the protein thrombospondin-1 could help the liver recover from an overdose of acetaminophen.

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Matthew McMillin

Orlando, Fla. (April 6, 2019) - Acetaminophen -- a commonly used pain reliever and fever reducer -- is the leading cause of quickly developing, or acute, liver failure in the U.S. Findings from a new mouse study suggest that treatments that increase levels of the protein thrombospondin-1 could help the liver recover from an overdose of acetaminophen.

"The only treatment available now for acetaminophen overdose must be administered early, before significant liver injury occurs," said Matthew McMillin, PhD, who performed the research. "We are working to identify new drug targets to improve treatment options and reduce the need for liver transplantation, which is often the only option for patients with acute liver failure due to drug toxicity."

McMillin, an assistant professor at the University of Texas at Austin and research biologist at Central Texas Veterans Health Care System, will present the research at the American Society for Investigative Pathology annual meeting during the 2019 Experimental Biology meeting to be held April 6-9 in Orlando, Fla.

McMillin and his colleagues found that mice with acute liver failure from acetaminophen toxicity had higher levels of thrombospondin-1 than mice with normal liver function. When they administered acetaminophen to genetically modified mice that lack thrombospondin-1, the liver injury and loss of liver function was more severe compared to unmodified mice. The researchers also observed impaired liver regeneration and increased cell death in the mice without thrombospondin-1.

"Our study is the first to investigate thrombospondin-1 during acetaminophen toxicity," said McMillin. "We were able to identify cell communication pathways that do not work properly during acetaminophen-induced liver injury and thus lead to worse outcomes."

Next, the researchers plan to give mice different drug treatments that manipulate thrombospondin-1 to find out which treatment might be suited for potential clinical studies. They also plan to examine patients with acetaminophen-induced acute liver failure to determine if their thrombospondin-1 findings from mice hold true in people.

Matthew McMillin will present this research on Saturday, April 6 at 7 p.m. during the Experimental Biology Welcome Reception in Valencia Ballroom ABCD, Orange County Convention Center and on Monday, April 8, from 11:45 a.m.-12:45 p.m. in room Exhibit Hall-West Hall B (poster A62 662.62 ) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

Image available.

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Experimental Biology

Heart attack victims over 65 treated differently; suffer worse outcomes but have lower hospital charges, new research finds

ARLINGTON, Virginia, April 6, 2019 -- Heart attack victims over age 65 are less likely than younger patients to receive timely percutaneous coronary intervention to open their blocked heart arteries, according to preliminary research presented at the American Heart Association's Quailty of Care and Outcomes Research Scientific Sessions 2019, a premier global exchange of the latest advances in quality of care and outcomes research in cardiovascular disease and stroke for researchers, healthcare professionals and policymakers.

In the study, older heart attack patients suffered more complications, such as shock and heart failure, had longer hospital stays and an increased chance of death. Despite staying in the hospital on average a half-day longer, older patients had lower total charges, something the researchers said could be attributed to the lack of undergoing more costly interventions such as percutaneous coronary intervention (PCI).

PCI, often referred to as angioplasty, is a non-surgical procedure used to treat narrow or blocked coronary arteries. During the procedure, special tubing with an attached deflated balloon is inserted into the blockage and the balloon is inflated to push open the blockage. Sometimes a stent may be placed during the procedure to keep the blood vessel open.

"Our study found that seniors were less likely to undergo PCI for a heart attack and if they do receive the procedure it's not within the optimal time for the best possible outcome," said Wojciech Rzechorzek, M.D., lead study author and a resident at Mount Sinai St. Luke's and Mount Sinai West Hospital in New York. "Their prognosis is worse than for younger patients with the same conditions, and this lack of treatment or delay in treatment could be a factor."

Researchers used the 2014 Nationwide Inpatient Sample to review records of 115,042 heart attack patients, 54 percent of whom were over 65.

The average age of the older group was 78. They were more likely than their younger counterparts to have high blood pressure, heart failure, chronic kidney disease and diabetes.

Researchers found, compared to younger patients, older patients were:

34 percent less likely to receive PCI to open blocked arteries;

36 percent less likely to have a stent inserted to keep the artery open after the blockage is removed;

34 percent less likely to have stents placed within 48 hours.

There appeared to be no difference between the two groups in the use of drugs or surgery to open blocked arteries.

Older patients were more likely to fare worse. Compared to younger counterparts they were:

62 percent more likely to develop heart failure;

28 percent more likely to go into shock;

21 percent more likely to experience cardiac arrest; and

10 percent more likely to need assistance from a breathing machine.

Despite older patients having to stay in the hospital longer, their adjusted total hospital charges were lower by approximately $3,231 per stay compared to younger patients.

"I am surprised that the costs of stay are lower despite the increased length of stay, but this could be primarily driven by decreased use of PCI, which is an expensive procedure," Rzechorzek said.

The researchers said because this was a retrospective analysis based on a very limited data set, further research is needed.

"Elderly patients are underrepresented in clinical trials, and we need more prospective studies evaluating the impact of PCI on outcomes," Rzechorzek said.

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American Heart Association

Anti-inflammatory drugs ineffective for prevention of Alzheimer's disease

Researchers have known for decades that inflammation accompanies Alzheimer's disease (AD) brain lesions. Several early studies suggested that "super-aspirins" or Nonsteroidal anti-inflammatory drugs (NSAID) could help avoid the disease. However, after clinical trials showed that NSAIDs don't help patients who already have AD symptoms, doctors wondered whether these drugs could still be helpful to people who were at risk of developing the disease, but weren't yet showing symptoms.

To test this hypothesis, researchers at McGill University's Faculty of Medicine developed a new approach to AD prevention trials, and used it to test whether the common NSAID naproxen could indeed stop the disease in its tracks, before people developed AD symptoms. Sadly, the results were not encouraging, according to research published in the April 5, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"To give the NSAID story one more chance to end well, we enrolled trial participants at the earliest stages of disease development, before they exhibited cognitive impairment," explains Dr. John Breitner, Professor of Psychiatry at McGill and the study's senior author. "The resulting trial, known as INTREPAD, examined the effects of naproxen in people who had a strong family history of AD but 'squeaky-clean' memory and other cognitive abilities."

Developing a new method to assess effectiveness

Many researchers have noted the special challenge of measuring disease development at a time when they could not rely on symptoms to assess effects of a treatment. To deal with this challenge the McGill team collaborated in developing a new Alzheimer Progression Score (APS) that was shown elsewhere to predict the onset of clinical disease over the coming decade or more. The APS measures the early development of disease by combining many little changes into a composite score.

Applying the APS to a trial sample of 200 people (100 assigned to naproxen and 100 to placebo), the INTREPAD results showed real changes over the two-year trial period. However, there was no evidence that the APS change was reduced in those taking naproxen. "The usual side effects were there," notes Pierre- François Meyer, a PhD candidate in Dr. Breitner's lab and the study's first author, "but there was not the slightest suggestion of any benefit."

"We think this is the end of the road for the use of NSAIDs for treatment or prevention of Alzheimer's disease, and it suggests a need for caution about using other anti-inflammatory drugs for this purpose," adds Dr. Breitner, who is Founding Director of the Centre for Studies on Prevention of Alzheimer's Disease at the Research Centre of the Douglas Mental Health University Institute. "The world desperately needs a way to prevent this horrible disease," he says, "and many other avenues are being investigated." In this process, researchers argue ever more strongly for the importance of publishing negative or "null" trial results like this one.

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McGill University

Older adults with blood cancers: How they fare

Although the majority of patients who have blood cancers are older adults, they make up only a small percentage of participants in the clinical trials that lead to new therapies. That's because the standard research methods used in oncology (cancer medicine) are not ideal for identifying certain vulnerabilities linked to aging, such as having multiple chronic diseases and being frail.

To help remedy that situation, the American Society of Clinical Oncology (ASCO) issued a guideline recommending that older adults who have cancer receive a geriatric assessment to see if they are at increased risk for experiencing side effects from medication and other complications from cancer and its treatment. Recently, a team of researchers examined older adults who have cancer to see whether their ability to manage daily activities as measured by these assessments was linked to staying alive longer. The team published their study in the Journal of the American Geriatrics Society.

A key part of the geriatric assessment is to determine how well an older adult performs the basic activities of daily living (ADLs). These include bathing, dressing, getting themselves from a chair to the bed (and vice versa), eating, grooming, and using the toilet. The geriatric assessment also takes into account an older adult's ability to perform instrumental activities of daily living (IADLS), or activities necessary for them to live on their own in the community. These activities include shopping, preparing meals, housework, taking medication, and handling their finances.

The researchers studied how performing daily activities was linked to survival and also to the use of medical care for adults living with cancer and aged 75 years and older. The researchers suspected that being unable to perform their daily activities would mean higher rates of death and unexpected visits to the Emergency Department (ED) and admissions to the hospital.

Participants included 464 people who on average were nearly 80 years old; 65 percent were male. All the participants were treated for blood cancers, including leukemia, multiple myeloma, and lymphoma, at the Dana-Farber Cancer Institute in Boston. About 38 percent of the participants had an aggressive form of blood cancer.

Of the participants, 11 percent reported they had trouble with at least one ADL and almost 27 percent had trouble performing at least one IADL.

The researchers also looked at a group of 318 participants who had visited the ED or had unplanned hospitalizations. Of them, 17 percent had at least one ED visit and 19 percent had at least one unplanned hospitalization. The five most common causes of hospitalization were pneumonia, fever, sepsis (the medical term for a blood infection), pain, and congestive heart failure.

For their main findings, the researchers reported that participants who had trouble performing at least one IADL had a higher risk for death, ED visits, and unplanned hospitalizations. This risk was not affected by how old they were, whether they had other chronic illnesses, how aggressive their cancers were, or the intensity of their cancer treatment.

What's more, the researchers found that many of the patients who were dependent in performing their IADLS (meaning they relied on help from others) also had higher rates of age-related conditions, such as memory issues, problems with mobility, and feelings of loneliness or depression. The researchers concluded from their study that it is not only important to ask about function for older adults with blood cancer but to also screen for age-related conditions that could limit functioning. Treating these other conditions to improve function might help older adults better tolerate the stress of blood cancers and their treatment, the researchers suggested.

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American Geriatrics Society

Tailoring lactation education to the cultural needs of orthodox Jewish families

image: Diane L. Spatz, PhD, RN-BC, FAAN, the Helen M. Shearer Term Professor of Nutrition at University of Pennsylvania School of Nursing

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Eric Sucar, Univ. of Penn. Communications

PHILADELPHIA (April 5, 2019) -Breastfeeding is an accepted practice for millions of women worldwide and strongly endorse by the World Health Organization. To provide appropriate counseling about human milk and breastfeeding, it is important to understand cultural beliefs and customs related to the practice.

Understanding Orthodox Jewish customs regarding breastfeeding is especially important for health care providers because the Orthodox population in the United States is growing. Orthodox women get married younger and have twice as many children as non-Orthodox Jews. Some of these families are at higher risk for conceiving infants with genetic disorders, who may require special care and continued hospitalization after the mother has been discharged.

In a new article published in The American Journal of Maternal/Child Nursing, nurse researchers examine Orthodox Jewish practices related to the provision of human milk and breastfeeding for a sick newborn. The article guides nurses in providing culturally competent lactation education, and evidence based guidance to meet the individual needs of each Orthodox Jewish infant and family. It is critical for the family to have conversations with their Rabbi ideally before delivery or at time of birth to determine needs for saving colostrum and milk, as well as, milk expression during Shabbat or religious holidays.

"Personalized, culturally and religiously tailored care, education, and counseling can ensure that Orthodox mothers are able to meet their personal breastfeeding goals even if their infant requires hospitalization at birth," says Diane L. Spatz, PhD, RN-BC, FAAN, the Helen M. Shearer Term Professor of Nutrition at University of Pennsylvania School of Nursing (Penn Nursing), one of the article's co-authors.

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University of Pennsylvania School of Nursing

Study measures gluten in gluten-free labeled restaurant food

April 5, 2019 -- Even tiny amounts of gluten in foods are troublesome for people with celiac disease, and restaurants may be the hardest places to avoid the protein, finds a study by Benjamin Lebwohl, MD, MS, Celiac Disease Center at NY-Presbyterian Hospital and assistant professor of medicine and epidemiology at Columbia Mailman School. More than half of gluten-free pizza and pasta dishes in restaurants tested positive for the presence of gluten; about one-third of supposedly gluten-free foods had detectable gluten. Results are published in the American Journal of Gastroenterology.

"Patients have long suspected that gluten contamination in restaurant foods is a frequent occurrence, and these results support that," said Lebwohl. "Our findings suggest that pizza, pasta and foods served at dinner were more likely to have a problem."

Lebwohl used data uploaded by users of the portable device Nima Gluten Sensor which restaurant patrons use to test foods. The manufacturer supplied 5,624 food tests by 804 users over 18 months. The research showed 32 percent of tests revealed detectable gluten in dishes that were supposed to be gluten-free.

Gluten-free pasta samples were positive in 51 percent of tests; gluten-free pizza contained gluten for 53 percent. Gluten was detected in 27 percent of breakfasts, 29 percent of lunches and 34 percent of dinners.

There are limitations to the data, notes Lebwohl. "Users may have uploaded results that surprised them the most." Also, the device is very sensitive. To be labeled gluten-free in the U.S., a product must contain less than 20 parts per million. "The device can detect levels as low as 5 to 10 ppm, which most do not consider clinically significant, so a 'gluten found' result does not necessarily mean 'unsafe for celiac disease.' The device also does not detect certain forms of gluten, such as fermented gluten. So both false positives and false negatives will affect this estimate."

Lebwohl suspects that gluten-free foods are inadvertently contaminated, and "the solution may be better education for food preparers."

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Columbia University's Mailman School of Public Health

Digging ancient signals out of modern human genomes

With new genome analysis tools, scientists have made significant advances in our understanding of modern humans' origins and ancient migrations.

But trying to find ancient DNA, let alone prove that the ancient DNA is ancestral to a population living today is extremely challenging.

A new study in Molecular Biology and Evolution (MBE) adds to this understanding by reconstructing artificial genomes with the analyses of the genome of 565 contemporary South Asian individuals to extract ancient signals that recapitulate the long history of human migration and admixture in the region.

"All in all, our results provide a proof-of-principle for the feasibility of retrieving ancient genetic signals from contemporary human subjects, as if they were genomes from the past embedded in amber," said Luca Pagani, the research coordinator of the study.

The study was led by Burak Yelmen and Mayukh Mondal from the Institute of Genomics of the University of Tartu, Estonia and coordinated by Luca Pagani from the same institution and from the University of Padova, Italy.

"The genetic components we managed to extract from modern genomes are invaluable, given the shortage of ancient DNA available from South Asian human remains, and allow us to elucidate the genetic composition of the ancient populations that inhabited the area," said Burak Yelmen, co-first author of the study.

While studying the mixing events that brought ancient human populations to form contemporary South Asians, the researchers also noted that some portion of the genomes had not mixed as expected, as if the genetic variants that evolved in South Asia or the ones that arrived from West Eurasia were important for adapting to the local lifestyle through admixture.

"Among these variants, we found genes important for immunity and for dietary changes, as one may expect for human populations adapting to new sets of pathogens or food," said Mayukh Mondal, joint first author of this work.

The human evolution of skin pigmentation also revealed many genetic variants for the population studied.

"Intriguingly we also noted that some genetic variants implicated in the skin pigmentation of West Eurasians were under opposite selective forces, some becoming highly frequent and others being almost lost after the admixture events. Skin pigmentation is surely a fascinating and complex subject and we are still trying to understand what, if any, would be the adaptive implications of the signal we detected."

The study will add to the growing picture of the diversity of South Asians, and future studies of modern human population origins.

"These signals can complement the picture emerging from the booming field of ancient DNA by providing high quality genomic sequences especially for areas of the world where archaeological human remains are scarce or poorly preserved."

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SMBE Journals (Molecular Biology and Evolution and Genome Biology and Evolution)

Like old photographs, memories fade over time

image: Much like opaque filters we apply to pictures on social media, the vibrancy of our memories dims and fades over time, Boston College researchers report in the journal Psychological Science. The image reflects 12 levels of visual salience, or vibrancy, used to rate how memories fade.

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Psychological Science

Chestnut Hill, Mass. (4/5/2019) - Like old photographs, memories fade in quality over time - a surprising finding for a team of Boston College researchers who expected recollections would become less accurate, but found people also report declines in the vibrancy and visual qualities of their memories.

When people remember the past, they remember it with varying degrees of clarity, said Boston College Assistant Professor of Psychology Maureen Ritchey, a cognitive neuroscientist and co-author of the study, published in an online edition of the journal Psychological Science.

Sometimes people remember lots of details about an event, as if they are reliving the moment as it happened, said Ritchey. Other times, it seems like the memory has faded, and the details are fuzzy. Prior memory research has shown that emotionally significant events-- like a car accident-- are remembered more vividly than everyday events.

"We wanted to know whether this feeling of memory vividness is related to not just what is remembered, but how it is remembered - the visual quality of the memory," said Ritchey, who conducted the study with Boston College Professor of Psychology Elizabeth Kensinger and post-doctoral researcher Rose Cooper.

As events are stored in memory or forgotten, the team asked, how do their visual features change? Ritchey said people reported changes to their memories akin to using a filter to edit a picture.

"A simple analogy is what happens when you post a photo on Instagram," Ritchey said. "You're cued to apply a filter that changes the brightness or color saturation of the image. In our study, we asked if forgetting is like applying a filter to past experience, and whether or not the emotional significance of the event would change which filter you apply."

In three experiments, participants studied emotionally negative and neutral images that varied in visual quality -- luminance and color saturation. They then reconstructed the visual qualities of each image in a subsequent test.

The findings revealed that memories were recollected as less visually vibrant than they were encoded, demonstrating a novel memory-fading effect, the researchers reported.

Negative emotions subjects experienced when viewing the images increased the likelihood that images would be accurately remembered but did not influence memory fading. In addition, subjective ratings of memory vividness were lower for less accurate memories and for memories that had visually faded, the team found.

These findings provide evidence that the vibrancy of low-level details - such as colors and shapes associated with an event -- fade in memory while the gist of the experience is retained.

People may remember going to a music festival and watching their favorite band, but the intensity of that sensory experience, including the bright stage lights and strength of the bass, will slowly fade.

"We found that memories seem to literally fade: people consistently remembered visual scenes as being less vibrant than they were originally experienced," said Cooper. "We had expected that memories would get less accurate after a delay, but we did not expect that there would be this qualitative shift in the way that they were remembered."

The fading effect happened less for memories that were rated as subjectively stronger. "We were also surprised to find that emotional memories did not influence the amount of fading, only the likelihood with which people remembered the images at all," she added.

Cooper and Ritchey said the team's next steps are to figure out what exactly drives the memory fading effect - does it stem from forgetting over time or interference from new information? How is it influenced by individual differences in memory for other kinds of event details?

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Boston College

US Medical guidelines biased, overly aggressive, and lead to high health care costs

ITHACA, N.Y. - Dr. Sunita Sah practiced general medicine for several years in the United Kingdom's National Health Service. When she came to the United States, she noticed something strange.

The U.K. guidelines for tests such as mammograms and colon cancer screenings drastically differed from those in the U.S. - even though they were based on the same medical evidence.

"Having colonoscopy at the age of 50 - that struck me as rather odd when I moved to the U.S., because you don't really hear about people having colonoscopies as a screening procedure in the U.K.," said Sah. "It's much less invasive to test for blood in the stool. It's also less costly and doesn't have the risks of undertaking a colonoscopy."

Now an assistant professor of management and organizations at Cornell, Sah and Ismail Jatoi of the University of Texas Health, San Antonio, say the treatment guidelines recommended by medical specialist organizations are more likely to call for greater use of health care services and exacerbate overdiagnosis, overtreatment and spiraling health care costs. Their commentary, "Clinical Practice Guidelines and the Overuse of Health Care Services: Need for Reform," appeared March 18 in the Canadian Medical Association Journal.

The implications are significant, she said, because guidelines are supposed to provide standard evidence-based treatment practices for all doctors.

"The recommendations put out by specialty organizations - like the American College of Cardiology or the American College of Radiology - show specialty bias in recommending more aggressive and/or more frequent screening procedures," said Sah, an expert on conflict of interest. "In the U.S. in particular, where the fee-for-service compensation model dominates medicine, which is different from countries like the U.K., you see even more recommendations for greater use of health care services."

Specialty bias refers to the tendency of physicians to recommend the treatments in which they are trained to deliver. For example, localized prostate cancer can be treated with either surgery or radiation.

"If you go to a surgeon, chances are that they are more likely to recommend that you have surgery; if you go to a radiation oncologist, they are more likely to recommend that you have radiation," she said. "They each often believe that the treatment that they're trained in is the better one."

In the case of screening for colorectal cancer, the American College of Gastroenterology's panel - all of whom were gastroenterologists - recommended colonoscopy as the best strategy.

But the United States Preventive Task Force, with no gastroenterologists or gastrointestinal surgeons, recommended testing the stool, sigmoidoscopy (an exam of only the lower part of the colon) or colonoscopy as a last resort. Stool testing was also recommended by the European Society of Medical Oncology panel, which consisted of six medical oncologists, no gastroenterologists and one gastrointestinal surgeon. The panel said there was limited evidence that screening colonoscopy is effective.

"Colonoscopies are more invasive than stool testing and come with potentially greater risks and costs for patients - but increased clinical volume and profits for gastroenterologists," Sah said.

Specialty guidelines are also subject to fee-for-service bias, according to the commentary. Doctors who receive a payment for each treatment may tend to recommend that treatment more often, because they have a financial interest in it.

"The bias is not necessarily malicious or intentional," Sah said. "In a fee-for-service environment, they may be biased to do more rather than less, so it becomes a habit."

But more is not necessarily better, she said. "Sometimes the risks of those procedures are just not worth the benefits."

The authors call for a reduction in conflicts of interest in the fee-for-service model, and more professional diversity in the makeup of the guideline committees. "You need a variety of different voices on those committees," Sah said.

And patients could ask their doctors which guidelines they follow and why. "Ask them questions," she said. "Ask your doctor to explain their thought process in recommending the particular guideline and the advantages or disadvantages of one guideline versus another."

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Cornell University

Noncoding DNA drives the convergent loss of flight in flightless birds

Tucked away in the noncoding regions of bird DNA, researchers have discovered molecular roots of the loss of flight seen in so many disparate paleognathous birds. In contrast with previous work, which emphasized changes to protein-coding DNA as driving flightlessness, this study associates loss of flight more strongly with regulatory evolution in noncoding DNA. The results provide an example for future genome studies of so-called convergent phenotypes throughout the animal kingdom. Over time, species of divergent lines of the tree of life can develop similar evolutionary traits. Various species of birds, for example, have experienced the loss of flight many times independently in the course of bird evolution. However, what drives convergent evolution is not well understood; in particular, the underlying genetic changes responsible are a question, with many previous studies implicating changes in protein-coding regions of bird DNA, as opposed to those in regulatory regions. To better understand genetic drivers of the convergent evolution of flightlessness, Timothy Sackton and colleagues investigated the genomes of various ratites, a group of flightless birds that includes the ostrich, kiwi, emu and extinct moa, among others. Sackton et al. combined phylogenetic, developmental and epigenomic analyses of the genomes of ratites, including eleven new genomes, with similar analyses of closely related, flight-capable tinamous. The researchers' analyses suggest that the loss of flight is more strongly associated with changes in noncoding regulatory regions of the DNA, and less so with changes in protein-coding genes, contradicting the results of previous studies. Furthermore, the results indicate that changes in regulatory regions could result in rapid, convergent changes across taxa.

Credit: 
American Association for the Advancement of Science (AAAS)

Microglia, cells thought restricted to central nervous system, are redefined in new study

image: Microglia thought to be restricted to the central nervous system, enters the peripheral nervous system at the site of brachial plexus injury.

Image: 
University of Notre Dame

Inside the body, disease and injury can leave behind quite the mess -- a scattering of cellular debris, like bits of broken glass, rubber and steel left behind in a car accident.

Inside the central nervous system (CNS), a region that includes the brain and spinal cord, it is the job of certain cells, called microglia, to clean up that cellular debris. Microglia have counterparts called macrophages that serve similar function outside the CNS in the peripheral nervous system (PNS), the region that contains most of the sensory and motor nerves.

Scientists have long believed that microglia are restricted to the CNS, and in cases of injury the two cells clean up their own sides of the highway, so to speak.

In a new study published in PLOS Biology, scientists at the University of Notre Dame discovered microglia actually squeeze through the spinal boundary, crossing into the peripheral nervous system in response to injury. The surprising result could have broad implications in the area of nervous system diseases, while opening the door to a completely new set of questions in the study of both systems.

"Microglia are defined as central nervous system cells. So if they're seen outside in the peripheral nervous system -- that was surprising to us -- that opens up a ton of new questions," said Cody J. Smith, the Elizabeth and Michael Gallagher Assistant Professor of Biological Sciences at Notre Dame and at the University's Center for Stem Cells and Regenerative Medicine. "It has been shown during different disease states that the macrophages in the peripheral can get into the CNS, but we certainly didn't know or really expect for the central nervous system cells to cross over, because there was little literature that suggested that was likely." Smith co-authored the study with Lauren Green, who is currently studying biology at Notre Dame and led the study.

In the study, Smith and his team modeled a brachial plexus injury in zebrafish and observed how microglia and macrophages responded. Brachial plexus injuries take place at the intersection of the central and peripheral nervous systems, affecting nerves that connect the brain and spinal cord to the shoulders, arms and hands. According to the National Institutes of Health, brachial plexus injuries occur in one to three out of every 1,000 births.

Once inside the peripheral nervous system, Smith said, microglia do their job of clearing cellular debris at the point of injury, but they return to the CNS with that debris, and could potentially carry it straight to the brain.

The study also showed the microglia return to the CNS in an altered state, which makes the results of this research of particular concern to the study of post-injury development and function.

Altered microglia have been seen widespread in countless neurodegenerative diseases, Smith said, and have been implicated in autism spectrum disorder.

In disease, altered microglial cells can clear too much cellular material -- including material they normally do not clear -- in the brain. If microglia are altered, the suggestion is that it could cause neuropathic pain, disorder or disease-type states, because the cells are clearing or removing cellular material that's necessary for proper nervous system function.

"There was little thought these cells could leave the central nervous system, so there are few studies of microglia in the context of diseases and function within both central and peripheral nervous system diseases," Smith said. "What happens when they do go into the brain after being in the PNS? What else are they capable of doing? Our study shows the full function, the full capability of these cells is not limited to the central nervous system. It opens up so many more exciting questions than it answers."

Credit: 
University of Notre Dame

Ready, steady, go: 2 new studies reveal the steps in plant immune receptor activation

image: The upper image depicts the pentameric wheel-like structure of the ZAR1 resistosome from above. In the lower panel depicting the resistosome in the side view, the funnel can be seen in light brown.
PBL2 is colored in green and RKS1 in mustard. All other colors denote different domains of the ZAR1 protein.

Image: 
Jijie Chai

Although separated by more than one billion years of evolution, plants and animals have hit upon similar immune strategies to protect themselves against pathogens. One important mechanism is defined by cytoplasmic receptors called NLRs that, in plants, recognize so-called effectors, molecules that invading microorganisms secrete into the plant's cells. These recognition events can either involve direct recognition of effectors by NLRs or indirect recognition, in which the NLRs act as 'guards' that monitor additional host proteins or 'guardees' that are modified by effectors. Host recognition of effectors, whether direct or indirect, results in cell death to confine microbes to the site of infection. However, until now, a detailed understanding of the mechanisms of action of plant NLRs has been lacking, and much of our understanding of how these molecules function in plants has been based on comparison with animal counterparts.

In two new studies published in the journal Science, Jijie Chai who is affiliated with Tsinghua University in Beijing as well as the University of Cologne and the Max Planck Institute for Plant Breeding Research together with the groups of Hong-Wei Zhang and Jian-Min Zhou at Tsinghua University and the Chinese Academy of Sciences in Beijing have now pieced together the sequence of molecular events that convert inactive NLR molecules into active complexes that provide disease resistance.

The authors focused their attentions on a protein called ZAR1, an ancient plant molecule that is likely to be of broad importance since it interacts with multiple 'guardees' to recognize unrelated bacterial effectors.

Using cryo-electron microscopy, Chai and co-authors observed that in the absence of bacterial effectors, ZAR1, together with the plant protein RKS1, is maintained in a latent state through interactions involving multiple domains of the ZAR1 protein. Upon infection, a bacterial effector modifies the plant 'guardee' PBL2, which then activates RKS1 resulting in huge conformational changes that first allow plants to swap ADP for ATP and then result in the assembly of a pentameric, wheel-like structure that the authors term the 'ZAR1 resistosome'.

One striking feature of this structure is its similarity with animal NLR proteins, which, once activated, also assemble into wheel-like structures that act as signaling platforms for cell death execution and immune signaling. However, one important difference between the structures offers a tantalizing clue as to how ZAR1 induces cell death. The authors could identify a highly ordered funnel-like structure in ZAR1 that tethers the resistosome to the plasma membrane and is required for cell death and disease resistance. The authors speculate that ZAR1 may form a pore in the plasma membrane and in this way perturb cellular function leading to immune signaling and cell death.

Other plant NLRs also assemble into complexes that associate with the plasma membrane and it is thus highly likely that Chai's findings have important general implications for understanding plant immunity. MPIPZ director Paul Schulze-Lefert, who was not involved in the studies, is in no doubt about the importance of the new studies: "This will become textbook knowledge."

Credit: 
Max Planck Institute for Plant Breeding Research