Culture

CATONSVILLE, MD, January 8, 2020 - Live chat tools allow for communication between sellers and buyers. They are popular instruments for e-commerce sites that don't have the advantage of face-to-face communication that brick-and-mortar stores do. New research in the INFORMS journal Information Systems Research says these live chats can actually increase sales and boost profits.

The study, "Impact of Live Chat on Purchase in Electronic Markets: The Moderating Role of Information Cures," looked at data from Alibaba on consumers' purchase decisions of Apple and Samsung tablets from March through June 2013.

"We found live chat can increase purchase probability of tablets by 15.9%," said Xue (Jane) Tan of Indiana University. "We see that human interaction results in better sales performance."

Tan, Youwei Wang of Fudan University and Yong Tan of the University of Washington say the fact that sellers and buyers cannot speak in person, like brick-and-mortar stores, leads to uncertainty about product quality and seller credibility. Live chat tools allow e-vendors to communicate with customers in real time.

The data source, Alibaba, has a reputation of being similar to eBay, where feedback is collected after each transaction. The data consisted of consumer browsing, live chat and purchase histories. The live chat tool is moderated by existing information cues: product sales volume and seller feedback score.

"Sellers with limited feedback benefit more from live chat conversations than sellers with a lot of feedback. And products with high past sales volume sell better after live chat, indicating a reinforcement effect," continued Tan. "It is interesting that a seller can sell multiple products with varying levels of sales performance, and the seller feedback is measured based on all products."

Media coverage is more likely to influence jurors to vote for acquittal than for conviction. This new finding challenges arguments that pretrial publicity is of greater concern to defendants due to their Sixth Amendment right to a fair trial.

Researchers at the University of South Florida studied the verdicts of juries exposed to news articles perceived to weaken the prosecution's case (anti-prosecution), such as those that question whether the right person is on trial, and compared them to stories that strengthen the likelihood of a defendant's guilt (anti-defendant). They found juries purely exposed to anti-prosecution stories ahead of deliberation delivered 'not guilty' verdicts 100 percent of the time. However, those whom solely read anti-defendant articles delivered 'guilty' verdicts just 38 percent of the time. This research also discovered that pretrial publicity has a strong impact on how jurors interpret evidence and their impressions of key trial players, such as witnesses and defendants.

The study published in Psychology, Public Policy, and Law is based on CA v. Debra Cummings. The then-babysitter was charged in the 1990 murder of a nine-month-old boy placed in her care. Researchers formed 96 mock juries comprised of 500 people between ages 18 and 58 whom were unfamiliar with the case. Prior to the trial, the authors provided 67 percent of participants six news articles. Half were edited to appear anti-prosecution and included information about the victim's parents' prior criminality and lack of concern for the baby's injuries. The others mentioned how the babysitter had another child die in her care, alluding to the defendant's guilt. The remaining 33 percent of jurors were not exposed to any pretrial publicity.

The jurors were broken into six groups of 16 juries, each group with a specific composition based on familiarity with the case. They watched recordings of the actual trial, which included opening and closing arguments, testimony from four doctors, direct and cross-examination of the victim's mother and the defendant, direct examination of the victim's father and testimony from the defendant's sister.

Study participants issued jury verdicts and provided their personal verdicts before and after the trial to determine the influential power of deliberation. Researchers discovered that deliberating on juries consisting of only anti-prosecution jurors resulted in an increase in anti-prosecution bias, with jurors being more likely to render a 'not guilty' verdict after deliberations than prior to them. In addition, jurors exposed to anti-prosecution publicity swayed their fellow jurors without background on the case to vote 'not guilty' 81 percent of the time, while those whom read anti-defense-slanted stories influenced the others to vote 'guilty' 38 percent of the time.

"These findings suggest that the courts, in high-profile cases, should not rely on jury deliberation to correct the bias associated with pretrial publicity exposure - doing so may result in an increase or spread of bias," said Christine Ruva, PhD, psychology professor at the University of South Florida Sarasota-Manatee. "In addition, juror exposure to pretrial publicity should not only be the concern of the defense's efforts to be granted a fair trial but should also be the concern of prosecutors as it can challenge their ability to prove guilt."

Other remedies to prevent bias include judges granting a change of venue, yet that rarely happens. The jury selection process is also designed to eliminate potential jurors influenced by pretrial publicity. However, it's difficult for the defense to prove their client won't receive a fair trial. The Fourteenth Amendment's Due Process Clause does not require potential jurors to be questioned about their knowledge on specific case information and the Sixth Amendment's impartial jury requirement is satisfied when prospective jurors refrain from stating they've been prejudiced by pretrial publicity.

CA v. Cummings resulted in a retrial, in which Cummings was acquitted of all charges in 1994.

DALLAS - Jan. 8, 2020 - In work that could have clinical implications, UT Southwestern researchers find that humans and mice with pancreatitis are deficient in a stress hormone called FGF21. Normally, FGF21 is more abundant in the pancreas than in any other organ in the body. They also show that replacement therapy reverses the condition in mouse models in about 24 hours and may even prevent it.

The study published today in Science Translational Medicine also reports success with a second treatment strategy. A potential drug called a PERK inhibitor targets a different step in the integrated stress response, the cellular pathway affecting the amount of fibroblast growth factor 21 (FGF21) available in the pancreas.

"Given that several FGF21 drug candidates are or soon will be in clinical trials for conditions related to metabolic disease, it may be possible to test fibroblast growth factor 21 for treating human pancreatitis in the near future," says David Mangelsdorf, Ph.D. In addition to being chair of pharmacology, Mangelsdorf is an investigator in the Howard Hughes Medical Institute (HHMI). He adds that he knows of no current investigations of PERK inhibitors for clinical use.

Pancreatitis, a debilitating and sometimes deadly inflammation of the pancreas, can be acute or chronic. It accounts for about 275,000 U.S. hospitalizations each year, with its incidence on the rise for reasons that are unclear. The many causes of pancreatitis include long-term alcohol abuse, gallstones, and certain inherited conditions, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH). Pancreatitis also can occur as a complication of endoscopic retrograde cholangio-pancreatography, or ERCP, a procedure in which a camera, contrast dye, and X-rays are used to view the bile duct, gall bladder, and pancreatic ducts.

Treatment for acute pancreatitis is generally supportive. Most patients recover after a few days in the hospital, where they are given intravenous fluids and pain relief. Chronic pancreatitis, which is more common in those with alcohol use disorder, worsens over time. The progressive damage to the pancreatic tissue can affect the ability to digest food and sometimes requires prescription enzymes to avoid malnutrition.

The pancreas, an organ near the small intestine, creates the hormone insulin that helps keep blood sugar in balance. The organ also creates enzymes that normally get released into the small intestine to aid digestion, says Mangelsdorf, who runs a joint laboratory with Steven Kliewer, Ph.D., professor of molecular biology and pharmacology. For nearly two decades the researchers have studied FGF21, learning valuable information about this important metabolic hormone.

In 2017, the researchers reported the hormone's role in keeping digestive enzymes from damaging the pancreas. "We found that FGF21 stimulates the pancreas to secrete digestive enzymes into the small intestine," Mangelsdorf says. "If this mechanism fails, the enzymes remain in the pancreas, where they damage the tissue and cause inflammation."

Mangelsdorf says his and other labs have shown that loss of FGF21 magnifies damage and slows recovery in animal models of pancreatitis. That led him and collaborators at the University of Pittsburgh, Stanford University in California, and Shanghai Jiao Tong University in China to wonder whether the stress hormone might hold promise as a pancreatitis therapy.

To answer that question, the researchers studied the effect of pancreatitis on the FGF21 pathway by analyzing samples from the pancreata of mice and humans with acute and chronic forms of the disease. They found in mice that pancreatic levels of FGF21 rose during the first four hours of pancreatitis and, unexpectedly, dropped at the 12-hour mark, becoming nearly undetectable after 18 hours. FGF21 was also reduced in human pancreatitis.

They were able to verify FGF21 behaves similarly in three different mouse models of the disease: pancreatitis induced by the drug cerulein, which causes excessive secretion of pancreatic enzymes; alcohol-induced pancreatitis; and ERCP-induced pancreatitis. The experiments confirmed that loss of FGF21 is a hallmark of the illness. Next, they wanted to know if FGF21 replacement therapy would work, using these same three mouse models of pancreatitis.

The researchers conducted several experiments using each of the three mouse models, repeating each investigation three to four times with three to eight mice per test group. They also ran experiments on 66 human tissue samples: 14 from healthy people and 52 from people with pancreatitis.

Injecting 1 milligram per kilogram of mouse body weight of FGF21 four times over a 12- to 16-hour period after inducing pancreatitis increased the amount of FGF21 in the bloodstream and caused inflammation, necrosis, and swelling to mostly disappear within 24 hours in the mice with drug- or alcohol-induced pancreatitis.

To see if they could somehow prevent ERCP-induced pancreatitis, the researchers mixed FGF21 with the contrast dye normally used in the procedure and found that by doing so, they were able to maintain normal FGF21 levels and prevent them from dropping, thereby preventing procedure-induced inflammation.

Mangelsdorf cautions that the study's limitations include that the models mimicked but fell short of completely reproducing human disease, and that a definitive conclusion about pancreatitis in humans will require an analysis of a greater number of test subjects.

"Nevertheless, we show that pancreatitis is broadly characterized as an FGF21-deficient state and restoring FGF21 pharmacologically reverses or prevents it," he says.

JUPITER, FL -- Jan. 8, 2020 -- A sophisticated new screening platform developed by scientists at Scripps Research has enabled them to discover a set of drug-like compounds, including an ingredient found in sore throat lozenges, that may powerfully protect brain cells from dangerous stresses found in Alzheimer's and other neurodegenerative diseases.

The screening platform, described in a paper in Science Advances, allows researchers for the first time to rapidly test "libraries" of thousands of molecules to find those that provide broad protection to mitochondria in neurons. Mitochondria are tiny oxygen reactors that supply cells with most of their energy. They are especially important for the health and survival of neurons. Mitochondrial damage is increasingly recognized as a major factor, and in some cases a cause, for diseases of neuronal degeneration such as Alzheimer's, Parkinson's, and ALS.

The scientists, in an initial demonstration of their platform, used it to rapidly screen a library of 2,400 compounds, from which they found more than a dozen that boost the health of neuronal mitochondria and provide broad protection from stresses found in neurodegenerative disorders.

The researchers are now testing the most potent of these mitochondria-protectors in animal models of Alzheimer's, amyotrophic lateral sclerosis, and other diseases, with the ultimate goal of developing one or more into new drugs.

"It hasn't yet been emphasized in the search for effective therapeutics, but mitochondrial failure is a feature of many neurodegenerative disorders and something that must be corrected if neurons are to survive," says principal investigator Ronald Davis, PhD, professor in the Department of Neuroscience at Scripps Research. "So I'm a big believer that finding mitochondria-protecting molecules is the way to go against these diseases."

Scientists in prior studies have developed screens for molecules that can enhance mitochondrial function, but only by focusing on mitochondria in cells from outside the brain. A screening system that measures mitochondrial health in mature neurons requires cultures of such neurons, which are relatively difficult to maintain--in part because they do not divide to make new neurons. Davis was convinced, however, that only this more difficult approach, which others including pharmaceutical researchers have avoided, would enable the discovery of compounds that protect brain cells by protecting their mitochondria.

The screening system developed by Davis and his team uses cultured neurons from mouse brains in which mitochondria are labeled with fluorescent tags. Sophisticated microscope imaging and semi-automated image analysis enables the researchers to quickly record mitochondrial numbers, shapes and other visible markers of health in the neurons before and after exposure to different compounds.

In an initial test, the team found that compounds with reported benefits for mitochondria in other cell types had no obvious positive effects for mitochondria in neurons. The researchers then screened their library of 2,400 compounds, which included many existing drug compounds, and found 149 with significant positive effects on neuronal mitochondria.

With further tests the scientists winnowed these "hits" down to a much smaller number, and found several that could robustly protect mouse neuron mitochondria from three stresses known to harm mitochondria in Alzheimer's: small, toxic clusters of the amyloid beta protein; the neurotransmitter glutamate, which can excite neurons to death; and peroxide, a highly reactive molecule that can be released from damaged mitochondria and go on to harm healthy mitochondria.

The compounds with beneficial effects protected the neuronal mitochondria in some ways more than others, and evidently worked via a variety of biological mechanisms. For example, dyclonine, an anesthetic found in some sore-throat products, protected cultured neurons against glutamate and peroxide toxicity. Dyclonine also increased the energy production of healthy mitochondria as well as the activity of their host neurons' synapses--connection points to other neurons. Dyclonine seemed so promising that the researchers put it in the water supply of live mice, and again found evidence that it powerfully boosted the health of the mitochondria in the animals' brains.

"It remains a mystery why dyclonine and other local anesthetics have such effects on mitochondria in neurons--we certainly didn't anticipate this," Davis says. "But the compounds we identified give us strong hope that we'll see beneficial effects when we test them in animal models of specific neurodegenerative diseases, as we're now doing."

BIRMINGHAM, Ala. - Your fingerprints stay the same all your life. But what about the "fingerprint" of microbial strains that are shared in the guts of childhood twins?

Using a genomics strain-tracking bioinformatics tool developed at the University of Alabama at Birmingham, researchers investigated whether those shared bacterial strains remain stable and resilient to changes in diet or environment after adult twins -- who had lived together for decades -- began to live apart.

The UAB study, published in the journal PLOS ONE, analyzed two metagenomic sequencing databases from pairs of twins -- one for children who were still living together and the other from adult twins, ages 36 to 80, who then lived apart for periods from one to 59 years.

"Adult twins, ages 36 to 80 years old, showed that a certain strain or strains between a pair of twins was shared post-separation," said Casey Morrow, Ph.D., professor emeritus in UAB's Department of Cell, Developmental and Integrative Biology. "While we do not know the origin of these shared microbes in the twins, these results suggest the possibility of strains shared between non-cohabitating twins for decades. As a corollary to these studies, our studies establish a time line for stability of microbial strains in the human gut."

The study used a strain-tracking bioinformatics tool previously developed by UAB, called Window-based Similarity Single-nucleotide-variant, or WSS. Hyunmin Koo, Ph.D., UAB Department of Genetics and Genomics Core, led the informatics analysis. The research generated about six terabytes of data, which was analyzed with the help of the Cheaha UABgrid supercomputer and the UAB Information Technology's Research Computing group.

Morrow and colleagues have used this microbe fingerprint tool in several previous strain-tracking studies. In 2017, they found that fecal donor microbes -- used to treat patients with recurrent Clostridium difficile infections -- remained in recipients for months or years after fecal transplants. In 2018, they showed that changes in the upper gastrointestinal tract through obesity surgery led to the emergence of new strains of microbes, and in 2019, they analyzed the stability of new strains in individuals after antibiotic treatments.

The current study used metagenomic sequencing databases from fecal samples of eight twin child individuals and 50 twin adult individuals.

The UAB researchers found significantly more shared strain pairs in child-aged twins who still lived together, as compared with adult twins after living apart for periods of time. Among the adult twins, those who had lived apart less than 10 years shared significantly more related strain pairs than twins living apart for longer periods, from 10 to 60 years.

Specifically, 80-year-old twins who had lived together for 79 years then were apart for 1 year showed the highest number of related strain pairs. The next highest numbers of related strain pairs were found in 56-year-old twins who had lived together for 51 years then apart for five years, in 73-year-old twins who lived together for 66 years and then apart for seven years, and in 36-year-old twins separated for 19 years.

Single-shared strains were seen in three twin sets who had lived apart between 22 to 54 years, but these sporadic shared strains did not show a correlation with the length of living apart.

"While certain gut microbial strains can be stable in people, in some cases for decades, changes in the host environmental conditions over time can impact the stability landscape of the gut microbial community," Morrow said. "This might result in the appearance of new strains that could potentially impact the microbial interactions that are essential for function in human health."

Want to sway the opinion of climate deniers? Start by acknowledging and respecting people's beliefs. That's one of four suggestions a Stanford researcher unearthed in a review of the psychology behind why some people reject climate change despite knowledge or access to the facts.

Denying the effects of climate change serves as a barrier to taking the actions needed to mitigate the worst effects, including rising seas, more intense hurricanes and increased droughts and heatwaves. However, the researchers found that those who deny human causes for climate change can be swayed through conversations that appeal to their different identities, reframe solutions - or even embrace their climate views.

"I think in the climate change sphere there's this thinking of, 'there's the deniers over there, let's just not even engage with them - it's not worth it,'" said behavioral scientist Gabrielle Wong-Parodi, lead author of the paper published in Current Opinion in Environmental Sustainability Jan. 8. "A lot of the tactics and strategies start from the point that something is wrong with the climate deniers, rather than trying to acknowledge that they have a belief and opinion and it matters. But I think there is an opportunity to keep trying to understand one another, especially now."

The researchers focused on what is referred to as "motivated denial" - knowing or having access to the facts, but nevertheless denying them. For some people, accepting that humans cause climate change questions self-worth, threatens financial institutions and is accompanied by an overwhelming sense of responsibility.

Although efforts to sway climate deniers may seem futile, the researchers found four approaches in peer-reviewed studies from the past two years that could be most effective:

1. Reframing solutions to climate change as ways to uphold the social system and work toward its stability and longevity

2. Reducing the ideological divide by incorporating the purity of the Earth, rather than how we harm or care for it

3. Having conversations about the scientific consensus around climate change with trusted individuals

4. Encouraging people to explicitly discuss their values and stance on climate change prior to engaging with climate information

Wong-Parodi said she found the fourth approach to be the most intriguing because less research has been done in that area than the other three - and it seems to have a lot of potential for behavior change. Self-affirmation is challenged when people face climate change because it requires them to consider their contribution to the problem, which can threaten their sense of integrity and trigger self-defense.

"A good portion of people who deny climate change recognize that there is some change, but the change is so threatening because it basically could affect your quality of life. It could affect your income. It could affect a number of different things that you care about," said Wong-Parodi, an assistant professor of Earth system science at Stanford's School of Earth, Energy & Environmental Sciences (Stanford Earth).

Some preliminary studies suggest that rather than trying to get around people's identities and denial of climate change, conversations should instead embrace their views. We should not try to ignore who people are, but rather acknowledge their views so that they can be dealt with and the conversation can move on to behavioral changes - such as finding solutions that match their values and do not threaten a person's sense of identity or quality of life, according to Wong-Parodi.

"I think we often forget that people can have many identities - there might be a political identity, but there is also an identity as a mother, or an identity as a friend or an identity as a student," said Wong-Parodi, who is also a fellow at the Stanford Woods Institute for the Environment. "You can elicit other identities when you're talking about climate change that may be more effective."

Only a tiny minority of people at risk for an opioid overdose actually are prescribed a drug that could save their lives, a new study suggests. And the odds of having a dose of the rescue drug were very low among some of the most at-risk groups, including those who had already survived a previous opioid overdose.

In all, less than 2% of people who had at least one of the main risk factors for opioid overdose had filled a prescription for the life-saving drug naloxone by the last 6 months of the study period. Naloxone prescribing may be missing a large proportion of those at highest risk, the authors say.

Naloxone can help reverse an overdose of any type of opioid, from prescription pain medicines to heroin.

The new study, performed by a team from the University of Michigan and VA Ann Arbor Healthcare System, is published in the Journal of General Internal Medicine. It uses data from a national sample of people covered by private health insurance.

National guidelines issued in 2016 by the Centers for Disease Control and Prevention call for physicians to prescribe naloxone to anyone who takes high doses of opioid pain medicine and to anyone who has other major overdose risk factors including a history of opioid use disorder or opioid overdose. People who take opioids at the same time they're taking a type of sedative called a benzodiazepine should also receive it, because the two drugs can interact.

Opioid overdose can occur when someone takes too much of an opioid-containing drug accidentally or on purpose, or when an opioid interacts with another prescription drug, alcohol or an underlying health condition. Naloxone, given by injection or nasal spray, can reverse the effects of the opioid.

Rising, but still low, rates

While the new study shows that naloxone prescription fills by adults with private health insurance rose during the study period from January 2014 to mid-2017, the percentage of patients receiving it was still very low.

Only 1.6% of those taking high doses of prescription opioids had filled a naloxone prescription in the last six months of the study period, and the percentage was no higher for those who had already survived an opioid overdose or had a formal diagnosis of opioid use disorder, some of the most concerning risk factors for overdose.

"The vast majority of naloxone prescribing is to patients who have received opioid prescriptions, but there are other groups at high risk for overdose but not receiving prescription opioids, including people using only street drugs, that warrant further attention," says Lewei (Allison) Lin, M.D., M.Sc., an addiction psychiatrist at the U-M Addiction Center and the VAAAHS who led the research team.

"Over the course of the entire study period, we also found that although both high-dosage opioid prescriptions and having an opioid use disorder were associated with receiving naloxone, the same wasn't true for those with a history of overdose or those with other substance use disorders," she explains. "Further work is needed to help guide naloxone prescribing to patient populations at highest risk for overdose."

Lin notes that during the study period, many states enacted 'standing orders' for naloxone that allow anyone to receive a dose of it from a pharmacist, to have on hand in case they or someone near them experiences an opioid overdose.

Community-based naloxone distribution programs also grew during the study period.

More about the study

Lin and her colleagues used anonymous insurance data, including outpatient pharmacy prescription fills, to do the study.

In addition to documenting overall trends in naloxone prescription fills, they performed a detailed comparison of two subsets of patients: nearly 4,000 people who had filled both an opioid prescription and a naloxone prescription during the entire study period, and more than 19,815 who had filled only an opioid prescription during that time.

The study data included all prescriptions filled and billed to the private insurance plans that contribute data to the Clinformatics database the researchers used. So it would not include naloxone received from community locations or pharmacists but not billed to insurance. The Clinformatics database draws from all 50 states.

January 8, 2020 -- Researchers at Columbia University Mailman School of Public Health assessed the time trends in alcohol and marijuana detected in homicide victims and found that the prevalence of marijuana almost doubled, increasing from 22 percent in 2004 to 42 percent in 2016. Alternately, the prevalence of alcohol declined slightly from 40 percent in 2004 to 35 percent in 2016. The findings are published in Injury Epidemiology.

"Despite the growing body of evidence linking alcohol and marijuana to homicide victimization, until now there was little information about the contemporary trends in the prevalence of alcohol and marijuana among homicide victims in the United States," said Guohua Li, MD, DrPH, professor of Epidemiology at Columbia Mailman School.

The researchers analyzed toxicological data for homicide victims from the 2004-2016 National Violent Death Reporting System (NVDRS), a population-based surveillance system for violent deaths occurring in the U.S. and administered by the Centers for Disease Control and Prevention. The study sample included homicide victims in 9 states that have been participating in the NVDRS since 2004: Colorado, Georgia, Massachusetts, New Jersey, Oregon, Rhode Island, South Carolina, Virginia, and Wisconsin. The NVDRS recorded a total of 30,433 homicide victims in the 9 states, of which there were 12,638 homicide victims aged 15 years and older with toxicological testing results available for analysis.

Of the 12,638 homicide victims, 37.5 percent tested positive for alcohol, 31 percent were positive for marijuana, and 11 percent were positive for both substances.

The results also showed that male victims were more likely than female victims to test positive for alcohol, marijuana, and both substances. Over two-thirds of adolescent victims aged 15-20 years in 2016 tested positive for marijuana. "We observed marked increases in the prevalence of marijuana in both sexes and across age and racial groups," said Li, who is also a professor of anesthesiology at Columbia University Vagelos College of Physicians and Surgeons.

As of June 2019, 34 states and the District of Columba have legalized marijuana for medical use; of them, 11 states and the District of Columbia have also legalized recreational marijuana for adults aged 21 years and older.

"Our findings are of public health significance because previous research has established marijuana use as an important risk factor for homicide victimization. The impact of increased permissibility and availability of marijuana on violence and injuries needs to be closely monitored and rigorously studied," said Dr. Li.

San Antonio, Texas (January 8, 2020) - New technology employing single cell genome sequencing of the parasite that causes malaria has yielded some surprising results and helps pave the way for possible new intervention strategies for this deadly infectious disease, according to Texas Biomedical Research Institute Assistant Professor Ian Cheeseman, Ph.D. Dr. Cheeseman was Principal Investigator of a three-year study published in the January 2020 edition of Cell Host & Microbe, a high-impact peer-reviewed publication.

Malaria is caused by Plasmodium parasites spread to people by the bite of infected Anopheles mosquitoes.

"We don't know what is inside malaria infections," Dr. Cheeseman said. "We don't know how many different genetically distinct strains of parasites there are. We don't know how related they are to each other. We don't know how many mosquitoes they came from."

To help answer these questions, Dr. Cheeseman and his collaborators turned to single cell genome sequencing. Using this technology, individual malaria parasite cells are isolated and their genome amplified before being analyzed by a genome sequencer. Single cell sequencing allows researchers to capture the genetic mutations present in a single cell, and has been adopted by cancer researchers to understand how tumors evolve. This is the first time the technology was used to study malaria transmission.

Dr. Cheeseman and his international team studied single malaria-infected cells from malaria patients in Malawi, a country heavily burdened by this infectious disease. Malaria patients, who donated malaria-infected blood samples used in this study reside in Chikhwawa, a region with a large mosquito population. In this region, people may be bitten by a malaria-infected mosquito every 48 hours.

The single cell sequencing approach applied in this study provides a fresh picture of how often bites from an infected mosquito lead to a malaria infection. What researchers discovered went against conventional wisdom. Nearly all the infections they studied likely came from one mosquito bite.

"We found that complex malaria infections are predominantly caused by a single mosquito bite transmitting many genetically diverse but related parasites into the blood stream of a patient," Dr. Standwell Nkhoma, lead author on the study and a Malawian national, stated.

Knowing this enables scientists to design more effective interventions to block mosquitoes from spreading malaria and build more sophisticated models to predict the spread of antimalarial drug resistance and malaria transmission patterns. The rise of antimalarial drug resistance is a major threat to malaria control globally as resistance to the antimalarial drugs artemisinin and piperaquine continue to spread.

Malaria infects an estimated 200 million people worldwide each year and kills more than 400,000 people, most of them children, according to the World Health Organization. "Any strides we can make in understanding this disease will make an enormous impact," Dr. Cheeseman concluded.

BAR HARBOR, MAINE — Scientists at the MDI Biological Laboratory, in collaboration with scientists from the Buck Institute for Research on Aging in Novato, Calif., and Nanjing University in China, have identified synergistic cellular pathways for longevity that amplify lifespan fivefold in C. elegans, a nematode worm used as a model in aging research.

The increase in lifespan would be the equivalent of a human living for 400 or 500 years, according to one of the scientists.

The research draws on the discovery of two major pathways governing aging in C. elegans, which is a popular model in aging research because it shares many of its genes with humans and because its short lifespan of only three to four weeks allows scientists to quickly assess the effects of genetic and environmental interventions to extend healthy lifespan.

Because these pathways are “conserved,” meaning that they have been passed down to humans through evolution, they have been the subject of intensive research. A number of drugs that extend healthy lifespan by altering these pathways are now under development. The discovery of the synergistic effect opens the door to even more effective anti-aging therapies.

The new research uses a double mutant in which the insulin signaling (IIS) and TOR pathways have been genetically altered. Because alteration of the IIS pathways yields a 100 percent increase in lifespan and alteration of the TOR pathway yields a 30 percent increase, the double mutant would be expected to live 130 percent longer. But instead, its lifespan was amplified by 500 percent.

“Despite the discovery in C. elegans of cellular pathways that govern aging, it hasn’t been clear how these pathways interact,” said Hermann Haller, M.D., president of the MDI Biological Laboratory. “By helping to characterize these interactions, our scientists are paving the way for much-needed therapies to increase healthy lifespan for a rapidly aging population.”

The elucidation of the cellular mechanisms controlling the synergistic response is the subject of a recent paper in the online journal Cell Reports entitled “Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity.” The authors include Jarod A. Rollins, Ph.D., and Aric N. Rogers, Ph.D., of the MDI Biological Laboratory.

“The synergistic extension is really wild,” said Rollins, who is the lead author with Jianfeng Lan, Ph.D., of Nanjing University. “The effect isn’t one plus one equals two, it’s one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways.”

The discovery of the synergistic interaction could lead to the use of combination therapies, each affecting a different pathway, to extend healthy human lifespan in the same way that combination therapies are used to treat cancer and HIV, Pankaj Kapahi, Ph.D., of the Buck Institute, has said. Kapahi is a corresponding author of the paper with Rogers and Di Chen, Ph.D., of Nanjing University.

The synergistic interaction may also may explain why scientists have been unable to identify a single gene responsible for the ability of some people to live to extraordinary old ages free of major age-related diseases until shortly before their deaths.

The paper focuses on how longevity is regulated in the mitochondria, which are the organelles in the cell responsible for energy homeostasis. Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysregulation and aging. Rollins’ future research will focus on the further elucidation of the role of mitochondria in aging, he said.

PHILADELPHIA--A new Penn Medicine study puts researchers within closer reach of vaccines that can protect infants against infections by overcoming a mother's antibodies, which are known to shut down immune defenses initiated by conventional vaccines. That hurdle largely explains why vaccinations for infectious diseases like influenza and measles not given until six to 12 months of age. Findings from the preclinical study were published online today in Science Translational Medicine.

The research team, led by Scott E. Hensley, PhD, an associate professor of Microbiology, and Drew Weissman, MD, PhD, a professor of Infectious Diseases in the Perelman School of Medicine at the University of Pennsylvania, found that a specialized modified-RNA (mRNA) influenza vaccine developed at Penn successfully protected young mice against the infection in the presence of maternal antibodies. The study suggests this protection occurred because the vaccine programs cells to constantly churn out new antigens for a prolonged period of time, rather than delivering a one-time shot of a viral protein.

"Around the world, every year, many young infants become infected and often die from infections because of a lack of effective vaccines to protect them earlier in life," Weissman said. "mRNA-based vaccines could potentially help prevent that. What's more, it would not only be effective against influenza but also other pathogens, as the vaccine's platform is easily adaptable to different antigens."

Elinor Willis, a doctoral student in the department of Microbiology and Penn Vet, served as first author on the paper.

Developing effective vaccines that protect infants in the presence of maternal antibodies has proven difficult because the antibodies can bind to vaccines and prevent them from eliciting good immune responses.

"Maternal antibodies are kind of a double-edged sword: they are great to have around when you are young because they can protect you from infection, but it's tough to vaccinate when there are high levels of them," Hensley said. "Today's strategy is to wait awhile for these antibodies to decline. This isn't ideal because the timing can be imprecise, so there is almost always a period where the young infant is susceptible to disease."

mRNA vaccines have emerged as leading candidates for protection against pathogens in adult clinical studies. Instead of delivering lab-grown viral proteins like a traditional vaccine, mRNA vaccines introduce an mRNA sequence that programs cells to produce antigens to mimic the disease. The result is a more powerful immune response and broader protection.

For this study, the Penn lab turned to the what is known as a nucleoside-modified mRNA encapsulated in lipid nanoparticles (mRNA-LNP) vaccine. In the past, Hensley and Weissman showed that this vaccine, which expresses hemagglutinin (HA) proteins, elicited robust antibody responses and protected adult animals from influenza.

To determine its ability to overcome maternal antibodies, the researchers first established a mouse model to show how the antibodies protect young mice against influenza and how they inhibit immune responses elicited by conventional vaccinations. Next, the researchers tested the mRNA vaccine platform in the mouse model and found that it elicited very strong antibody responses, both in the presence and absence of maternal antibodies, and protected the mice from the virus.

The vaccine essentially "slips under the radar," Hensley said, gets into cells, and then starts continuously producing the antigen for the immune system to respond to in what's called "prolonged germinal center reactions." The finding suggest that maternal antibodies eventually drop below a certain level and the antigen is still there to generate an immune response from the child.

The researchers continue to investigate the vaccine in mouse models to better understand mechanistically why this vaccine works so well in the presence of a mother's antibodies and hope to translate the promising results into human studies in the future.

"It could be a real game changer," Hensley said. "Imagine a world where an infant is born or comes into the clinic very early in life and can receive vaccines that have antigens not just for the flu but a multitude of different pathogens. Wouldn't that be something?"

URBANA, Ill. - Affirmative action policies (AAP) such as quota systems based on racial or socio-economic criteria are often recommended as a way to increase enrollment of underrepresented students in higher education. But those policies can be controversial and their results are sometimes questioned.

A new study from the University of Illinois looks at comprehensive data from Brazilian universities to understand the effect of AAPs on minority enrollments. In the United States, universities are not required to disclose their affirmative action criteria, which makes it difficult to evaluate their effectiveness. However, in Brazil, such data are publicly available.

"We are looking at whether those programs were effective in their goals, which was to increase the enrollment of underrepresented students," says Mary Arends-Kuenning, associate professor of agricultural and consumer economics at the U of I, and co-author of the study, published in the Economics of Education Review.

The researchers found that the policies do work as intended. "We show that these quotas worked towards their goals. They did increase enrollment of students from the groups that they were supposed to. There were more students from poor backgrounds and from public high schools; there were more black students and more under-represented students."

Arends-Kuenning and co-author Renato Schwambach Vieira, a recent graduate of the U of I Department of Agricultural and Consumer Economics, also looked at whether quotas based on socio-economic criteria can be used as a substitute for race-based criteria. The study was part of Vieira's doctoral dissertation.

"Racial quotas can be very controversial. Sometimes people argue you could get similar effects by having a quota based on socio-economic status," Vieira says.

However, the study found that was not the case. "If you want to achieve racial equality, you can't have quotas that are based on socio-economic background; that did not work to increase the number of black or brown students in Brazil," he notes.

Arends-Kuenning explains that Brazil historically has been one of the most unequal societies in the world. Large socio-economic and racial inequalities remain, in part due to gaps in educational opportunities.

To counteract those gaps, Brazil implemented a National Law of Quotas in 2012, requiring half of undergraduate positions to be reserved for students from underrepresented groups.

However, many Brazilian universities already started implementing either race-based or socio-economic AAPs in the early 2000. This made it possible to compare schools with different types of AAPs in the study, while schools with no such policy could serve as a control group.

"Between 2004 and 2010, 34 out of 49 federal universities adopted some type of AAP. Twenty universities adopted race-neutral policies and 14 adopted race-targeted AAPs," the researchers explain in their paper.

The study examined AAPs and enrollment from 2004 to 2012, analyzing data from a national entrance exam that all freshmen are required to take. That exam also contains a section on socioeconomic characteristics and racial affiliation, based on students' self-identification. The study included data from 163,889 freshmen enrolled in more than 1,000 academic programs at 48 different federal universities.

The researchers analyzed the effect of AAPs in relation to four student demographics: race, gender, socio-economic background, and whether the student attended public or private secondary school.

The result showed significant increases in enrollment of students from disadvantaged groups; specifically, increases of 9.8% for black and mixed-race students, 10.7% for public high school students, and 14.9% for students from lower socio-economic backgrounds. There was no difference for gender, which was not a target criterion for any of the policies.

The researchers found that both types of AAPs increased enrollment of lower socioeconomic groups, but only the race-targeted criteria increased enrollment of blacks and mixed-race students.

They also looked at whether the results were associated with certain types of programs. Arends-Kuenning says one might suspect that schools that were reluctant about quotas would implement them only for less competitive programs, but the results debunked that assumption.

"We find strongly that the quotas are more effective in the most competitive programs," she says. "You might think that schools would focus on certain programs and channel the underrepresented students to easier programs, but we found that wasn't happening. In the most competitive programs, we find bigger effects."

Arends-Kuenning says future research might look beyond student enrollment effects.

"That could include looking closely issues of performance and drop-out rates; how well these students did while they were in school. It will also be interesting to look at how they do after they graduate. The quotas have been in place long enough to do that," she says.

More than half of cancer cases worldwide are associated with genetic mutations in p53, the protein responsible for protecting DNA from changes that can lead to cancer. When this protein deforms, it not only loses its protective capacity, but can also gain new functions, acting as a "traitor", and contributing to the spread of the tumor by forming protein clusters that may be resistant to chemotherapy. The mechanisms by which this "betrayal" occurs and how it causes drug resistance are not yet fully understood.

A group of Brazilian researchers led by biochemist Jerson Lima Silva, professor at the Federal University of Rio de Janeiro (UFRJ), uncovered part of the mystery. In a new study, the scientists identified the presence of a large amount of the protein's traitor version in chemotherapy-resistant cells derived from glioblastoma, a super aggressive brain tumor. They also found how the deformed protein are organized inside the cell to exert resistance: they form clumps larger than those found in healthy individuals, some with amyloid properties, that is, when mutation leads to clumps. These structures were observed in the nucleus of living cells for the first time. The results are published in iScience.

The use of living cells makes important contributions to research in the field. "Unlike other studies, we identified small oligomers (structures a little larger than the healthy version of p53) in living cells, contributing to the identification of p53 aggregates more closely to what should occur in the human organism. This was possible because of the collaboration with researcher Enrico Gratton, who developed fluorescence fluctuation spectroscopy analysis," explains Murilo Pedrote, a graduate student at the National Institute of Science and Technology for Structural Biology and Bioimaging (INBEB) and first author of the study.

The research was conducted using a p53-specific mutation (M237I). "This is important because the native protein (without mutation) and other mutations are not capable of conferring the same drug resistance," says Guilherme A. P. de Oliveira, professor at UFRJ and one of the study's coordinators.

Lima Silva's group has been studying p53 mutations for over 15 years. His laboratory was the first to identify the propensity of the deformed protein to form amyloid aggregates, and that they play a crucial role in cancer development through loss of function, negative dominance (when mutated versions of the protein bind to healthy ones, altering their behavior) and gain of function. After that, it was observed by different scientists that mutated p53 amyloid aggregates are present in breast, ovarian and prostate cancer. Due to their characteristics, these amyloid clusters have become a new target for anticancer therapy.

In the new study, Lima Silva, de Oliveira and the other authors found that, in glioblastoma, an aggressive, invasive brain tumor with low survival (14 months), the deformed protein is involved not only in the formation of amyloid aggregates, but also in the resistance to temozolomide, the main drug used to treat the disease. The results are expected to enable the development of more effective treatments against various types of cancer. "Our study indicates that misfolded p53 and p53 aggregates are formidable targets for the development of new cancer treatment strategies," Lima Silva concludes.

The brain undergoes dramatic change during the first years of life. Its circuits readily rewire as an infant and then child encounters new sights and sounds, taking in the world and learning to understand it. As the child matures and key developmental periods pass, the brain becomes less malleable--but certain experiences create opportunities for parts of the adult brain to rewire and learn again.

Cold Spring Harbor Laboratory (CSHL) scientists have been studying one such period of transformation in mice: the time during which an adult female first learns to recognize and respond to the distress cries of young mouse pups. The research, reported January 7, 2020 in the Journal of Neuroscience, suggests that the same mechanisms that enable rapid learning during early development come into play when a period of heightened learning is triggered during adulthood. The findings hint at potential therapeutic strategies for a rare neurodevelopmental disorder called Rett syndrome, in which the adult brain may be unable to benefit from the rewiring opportunities.

A few years ago, CSHL Associate Professor Stephen Shea and colleagues discovered that female mice that lack two functional copies of a gene called Mecp2 failed to learn to retrieve distressed young. The scientists traced this parental neglect to the abnormal behavior of a group of neurons in the brain's auditory cortex called parvalbumin (PV) neurons. PV neurons are inhibitory neurons: their signals dampen the activity of other brain cells. During development, the signals of PV neurons help close the critical periods during which the brain is most receptive to change.

The latest work from the Shea team, led by postdoctoral researchers Billy Lau and Keerthi Krishnan, and conducted in collaboration with CSHL Professor Josh Huang, took a closer look at how exposure to the young pups changes signaling within the auditory cortex of female mice. By monitoring the activity of individual cells in this part of the brain, the researchers found that when Mecp2 is intact, inhibitory signaling from PV neurons decrease following exposure to an encounter with pups. This inhibitory signaling allows other neurons in the circuit to become more responsive to the young animals' cries. "The inhibitory networks sort of back off and allow the excitatory activity to be stronger," Shea explains.

It's not yet known exactly how pups trigger these changes in the female mice, but they occurred as long as MECP2 was present--even in mice that had never been pregnant. In female mice whose Mecp2 genes were impaired, however, the PV neurons' signals remained strong.

In humans, mutations in Mecp2 cause Rett syndrome. Children with Rett syndrome appear develop normally for the first several months of life, but later begin to lose language and motor skills. The new findings from Shea's team support previous evidence that PV neurons are particularly vulnerable to loss of MECP2. This suggests that these cells or the circuits they are involved in may be appropriate targets for drug development.

It also suggests that patients with Rett syndrome may be most responsive to treatment during certain developmental periods. Shea says prior to pup exposure, cells in the auditory cortex behaved the same in the brains of mice with impaired Mecp2 as they did in other mice. "That suggests that Mecp2 is specifically important during windows of heightened learning. That principle might guide treatments that are focused in time, at certain developmental milestones."

The way consumers use vapour and tobacco heating products (THPs) can affect the levels of harmful and potentially harmful constituents they are exposed to, and a new study has analysed how the use of these products compares with cigarette smoking.

Emissions from a number of tested vapour and THPs were shown to contain far fewer and lower levels of certain toxicants than cigarette smoke.*1,2 However, the way consumers actually use these products can have a significant bearing on the levels of harmful and potentially harmful constituents they are exposed to.

To investigate this, scientists at British American Tobacco (BAT) carried out an 'actual use study' in Italy, where it is common for people to smoke cigarettes as well as vape and use THPs. The study compared how consumers used BAT's THP glo, and vapour product iSwitch, as well as another commercially available THP and a reference cigarette.

"Understanding how a product is being used, and how often, allows for a holistic approach to risk assessment," says Joshua Jones, Human Studies Scientist at BAT.

As well as the average daily consumption of the products, the study determined puffing topography (puffing frequency, duration and volume) and corresponding mouth level exposure (MLE) to the aerosol.

The study found overall consumption of THPs was less than cigarettes, and MLE to dry particulate matter was significantly lower compared to cigarettes. On average, Italian consumers took puffs of similar volume and duration on both the vapour product and the reference cigarette.

The results have been published today in Scientific Reports.

"As an example, glo THP emissions contain around 90% less of certain toxicants than a cigarette* -- a reduction that is amplified by the reduced average daily consumption by consumers," says Jones.

"This data adds to growing evidence that Italian consumers are exposed to much lower levels of certain toxicants when using THPs and vapour products compared with traditional cigarettes, suggesting these products have the potential to be reduced risk compared with smoking."

The data will be used to ensure that laboratory-based product testing is realistic and reflective of real-world consumers, aiding in the development of potentially reduced-risk products.