Culture

Virginia Tech scientists uncover how a molecule improves appearance of surgery scars

image: In a new study, Fralin Biomedical Research Institute at VTC scientists discovered that the alphaCT1 molecule may help repair the skin's collagen matrix. Microscopic imaging of 29-day scar biopsies from the same patient reveals the molecule's effects on collagen organization. Collagen bundles in the untreated scar, right, are more aligned compared to the alphaCT1-treated tissue's collagen, which is more randomly arranged in swirls that resemble unwounded skin.

Image: 
(Gourdie Lab /Virginia Tech)

Surgical scars treated with a molecule called alphaCT1 showed a long-term improvement in appearance when compared to control scars, according to multicenter, controlled Phase II clinical trials - a finding that could help surgeons improve patient outcomes.

Now, a public-private research team led by Rob Gourdie, professor and director of the Center for Vascular and Heart Research at the Fralin Biomedical Research Institute at VTC, has revealed clues about why and how it improves the appearance of scars.

The study, to be published in the August issue of the Federation of American Societies for Experimental Biology (FASEB) Journal, describes how the drug influences the behavior of collagen-producing cells called fibroblasts.

The findings reveal a previously unreported feature of scar formation, and could help advance wound healing treatments for patients undergoing surgical procedures.

The researchers analyzed scars from 49 healthy volunteers in a randomized, double-blind Phase I clinical study. Each volunteer had 5-milimeter punches of skin biopsied from each of their inner biceps. One arm's wound was treated with the alphaCT1 molecule in a gel, and the other received a non-medicated control gel. The wounds healed for 29 days, at which point the scars were photographed and biopsied again.

Under the microscope, the untreated scars' collagen - a protein produced by cells called fibroblasts - formed parallel strips, which makes the tissue less pliable. By contrast, scars that were applied with the drug had a collagen matrix resembling unwounded skin. Related experiments were repeated using guinea pig and rat models and yielded similar results.

The researchers also analyzed human skin cells cultured in a dish to watch how the drug influenced cellular activity in real-time. They discovered that the presence of the molecule caused fibroblasts to stretch out like a rubber band, then snap back into shape and change direction.

"We call it the fibroblast dance," said Gourdie, who is also the Commonwealth Research Commercialization Fund Eminent Scholar in Heart Reparative Medicine Research and a professor of biomedical engineering and mechanics in Virginia Tech's College of Engineering.

This unusual fibroblast behavior in the treated tissue appears to have a positive effect on scar formation, Gourdie says.

"In unwounded skin, the collagen is enmeshed, allowing the tissue to move and stretch in all directions. The fibroblasts' directional changes appear to influence how the collagen matrix forms during scarring," Gourdie said.

More than 300 million surgical procedures are performed in the United States each year - often resulting in noticeable scarring on patients. Methods to reduce scarring after operations are sought after.

"This is some of the most exciting basic science research in wound healing I've seen in a long time," said Kurtis Moyer, chief of plastic and reconstructive surgery for Carilion Clinic and a professor of surgery at the Virginia Tech Carilion School of Medicine. Moyer was not involved in the study, but has collaborated with the Gourdie lab on wound healing research for 20 years.

"This shows real promise and could potentially revolutionize what we do in plastic surgery," Moyer said.

AlphaCT1 influences wound healing by temporarily interrupting cell signaling functions of connexin 43, a gap junction channel protein.

Gourdie and his lab invented the molecule and discovered its useful effects on wound healing with his former postdoctoral associate, Gautam Ghatnekar, a decade ago. Together they formed a biopharmaceutical company, FirstString Research Inc., to bring alphaCT1 to market.

The molecule is currently being evaluated in Phase III clinical testing in bilateral breast surgery patients.

"These findings validate that the drug's mechanism is playing out as we thought it would," said Ghatnekar, FirstString's president and chief executive officer.

The company has closed $55 million in Series B, C, and D Funding since 2018, and is evaluating the drug's use in a variety of applications, including surgical wound healing, chronic wound healing, radiation therapy wound healing, and corneal tissue repair.

"We alter how the human body responds to injury by shifting the balance from healing by scarring to healing by regeneration. The medical applications for our technology are far-ranging," Ghatnekar said.

Credit: 
Virginia Tech

A foot tumor and two tail fractures complicated the life of this hadrosaur

video: Life of the hadrosaur

Image: 
José Antonio Peñas (SINC)

When it was discovered in the 1980s in Argentina, this hadrosaur was diagnosed with a fractured foot. However, a new analysis now shows that this ornithopod commonly known as the duck-billed dinosaur actually had a tumour some 70 million years ago, as well as two painful fractures in the vertebrae of its tail, despite which, it managed to survive for some time.

This dinosaur, called Bonapartesaurus rionegrensis, was discovered in Argentinean Patagonia in the 1980s, and the first analyses of its fossils indicated an ailment of the foot, possibly a fracture, as the Argentinean palaeontologist Jaime Powell pointed out at the time. The study of this animal then came to a standstill until 2016, when Powell invited another team of scientists to resume the research.

"In addition to the ailment of the foot, there were other possible fractures in several neural spines of the vertebrae of the tail," as Penélope Cruzado-Caballero, the lead author of the study, now published in the journal Cretaceous Research, and a scientist at the Research Institute of Palaeobiology and Geology of CONICET and the National University of Río Negro (Argentina), as well as a professor at the University of La Laguna (Tenerife, Spain), has told SINC.

The researchers decided to analyse them all to see this hadrosaur, also known as duck-billed dinosaur, "during its lifetime" and to see how it was able to interact with the environment, with its fellows, and with predators while suffering from these problems.

Scientists were particularly surprised by the condition of the foot. "We were struck by the large overgrowth of bone that gave it a cauliflower-like appearance and covered almost the entire metatarsal," the researcher points out. When studying the histology and CT scans of the fossil, the team did not find a fracture. Instead, the indicators showed a reduction in bone density and several areas where cortical tissue had been destroyed.

"We were probably looking at a cancer or a neoplasm, such as an osteosarcoma," specifies Cruzado-Caballero. The presence of diseases such as tumours confirms that they already existed at a very early age and among a very diverse group of animals.

"Despite the large development of the cancer, it did not significantly affect the muscle insertion zone, so we cannot be sure that the lesion affected its locomotion," says the palaeontologist. The study has allowed us to determine that the tumour did not spread to other bones - since this ornithopod preserved almost half of its skeleton -, "so, although it severely affected the metatarsus, it did not cause its death," she adds.

Tail fractures followed by infections

In addition to the foot tumour, other pathologies were identified in the neural spines of two vertebrae in Bonapartesaurus rionegrensis's tail. According to the scientists, one of the vertebrae had a displaced fracture that had almost healed. "It was probably related to an injury resulting from a strong blow that caused the bone to be displaced and to heal in this manner, giving the spine a curved appearance," Cruzado-Caballero stresses.

The other vertebra had an almost completely healed fracture also produced by a stress event (it is not known if it was due to impact), which did not lead to the displacement of the bone. Although the spine maintains its straight shape, the researchers observed a swelling that formed a callus on the bone as it healed.

"These fractures, especially in the case of the displaced fracture, must have been associated with infections following the rupture of the muscles surrounding the bone," says the researcher, who considers that they must have been painful not only because of the blow, but also because of the infections that could have impeded the mobility of the tail and caused this specimen a great deal of discomfort when it moved.

However, despite the severity of the ailments, the death of Bonapartesaurus rionegrensis did not follow immediately after its injuries, the authors point out. "But we cannot quantify how long it lived afterwards, which means that it could have lived for months or years. Nor can we confirm that these injuries were the final cause of its death," comments the scientist.

This hadrosaur, although badly injured, therefore managed to survive and continued to interact with its fellows, despite the initial pain caused by fractures and infections. These could have been caused by falling, hitting an object or another animal to defend itself from predators, or even by being trampled on the tail by another hadrosaur.

Credit: 
Spanish Foundation for Science and Technology

Spinal fluid biomarkers detect neurodegeneration, Alzheimer's disease in living patients

PHILADELPHIA--Alzheimer's disease and related diseases can still only be confirmed in deceased patients' brains via autopsy. Even so, the development of biomarkers can give patients and their families answers during life: Alzheimer's disease can be accurately detected via peptides and proteins in a patient's cerebrospinal fluids (CSF), which can be collected through a lumbar puncture and tested while the patient is alive. In 2018, a new framework suggested combining three Alzheimer's disease biomarkers in CSF - pathologic amyloid plaques (A), tangles (T), and neurodegeneration (N), collectively called ATN. According to recent research from the Perelman School of Medicine at the University of Pennsylvania, the ATN framework can be extended to detect another neurodegenerative condition: frontotemporal degeneration.

Patients with frontotemporal degeneration can experience a range of symptoms, including behavioral changes, executive dysfunction, and language impairments. Distinguishing frontotemporal degeneration from Alzheimer's disease can be a challenge for clinicians: the symptoms of frontotemporal degeneration can sometimes overlap with Alzheimer's disease, and a subset of patients can even have both pathologies. Biomarkers can fill the gap by providing evidence of whether Alzheimer's pathology underlies a patient's symptoms.

"CSF biomarkers work similarly to a pregnancy test, offering a simple positive or negative result when enough of a substance is detected. But like a pregnancy test, biomarkers for Alzheimer's disease can provide false negatives or positives," said lead investigator Katheryn A.Q. Cousins, PhD, a research associate in the Frontotemporal Degeneration Center in the Department of Neurology at Penn Medicine. "Alzheimer's is a diverse disease, and it is common for other conditions to also be present in the brain. The ATN framework may provide a more complete look at a person's diagnosis and give us a much richer understanding of not only Alzheimer's disease, but other co-occurring neurodegenerative conditions. However, to accomplish this, additional biomarkers that can detect other neurodegenerative conditions are critically needed."

The findings, published in Alzheimer's and Dementia: The Journal of the Alzheimer's Association, show that ATN incorporating neurofilament light chain (NfL) may provide a more accurate and precise diagnosis for patients with frontotemporal degeneration. NfL is a protein abundant in the brain, whose levels increase as degeneration progresses. Cousins' work shows that CSF NfL may be a more accurate marker of neurodegeneration for patients with frontotemporal degeneration, including for Alzheimer's disease.

"While the ATN framework is very exciting and offers much opportunity for patients with Alzheimer's disease, these biomarkers don't capture every case of the disease. We want to be able to detect and treat every patient with neurodegenerative disease as early as possible, and more research is needed to fully understand how biofluids track with the disease process," said Cousins. "I am eager to conduct additional research into which patients might be missed by these markers, what they have in common, and what causes the pathological and clinical differences in the disease."

Credit: 
University of Pennsylvania School of Medicine

Automobile class society

In order to correctly separate vehicles into classes, for instance for mobility pricing, one must be able to clearly distinguish mid-sized cars from upper class cars or small cars from compact cars. But this is becoming increasingly difficult: On photos, an Audi A4 looks almost the same as an Audi A6, a Mini One looks similar to a Mini Countryman. To date, there is no independent procedure for doing this.

Thus far, the classes in each country have been determined by experts - to a large extend at their own discretion. Empa researcher Naghmeh Niroomand has now developed a system that can classify cars worldwide based on their dimensions. Purely mathematical and fair. Thanks to it, the current classification by experts could soon be a thing of the past. At the same time, car classes could be compared worldwide in an easier and more objective way. After all, a "mid-size car" is something different in Italy than it is in the US.

Credit: 
Swiss Federal Laboratories for Materials Science and Technology (EMPA)

Fish friends help in a crisis

image: Fish on Coral Reef

Image: 
Amy Cox

FORT LAUDERDALE/DAVIE, Fla. - It's good to have friends.

Most humans have experienced social anxiety on some level during their lives. We all know the feeling - we show up to a party thinking it is going to be chock full of friends, only to find nearly all total strangers. While we typically attribute the long-lasting bonds of social familiarity to complex thinkers like humans, growing evidence indicates that we underestimate the importance of friendship networks in seemingly "simple" animals, like fish, and its importance for survival in the wild. To better understand how familiarity impacts social fishes, a group of research scientists studied this idea using schooling coral reef fish.

"We studied how the presence of 'friends' versus 'strangers' affected how fish responded to a predator threat," said lead author Lauren Nadler, Ph.D., an assistant professor in Nova Southeastern University's (NSU) Halmos College of Arts and Sciences. "The presence of 'strangers' seemed to distract fish, making them react more slowly and greatly increasing the chance that they would become lunch for a hungry predator when in the wrong social scene."

You can find the study published online in the journal Communications Biology.

Nadler and her colleagues believe that their results come down to trust. In social animals living in the wild, individuals rely on their buddies to alert them if a predator is lurking, but they need to balance the risk of being eaten against the wasted energy of reacting to inaccurate information. So, individuals will alter their sensitivity to social information based on the level of familiarity in the group, and hence trust in the information's accuracy.

"Trust among individuals is critical. This is true for humans as well as many other species, including fishes," said co-author Jacob Johansen, Ph.D., assistant professor at University of Hawaii Manoa. "Our research in fishes show that when accurate information transfer breaks down, so too does the chance of survival for the individual and the group as a whole."

Further, the researchers' results seemed to be driven by a combination of greater vigilance by the first fish to detect the predator, as well as more effective information sharing among neighboring fish.

"Our work shows that readiness to react to a threat depends on who is around you, if you are a fish," said Dr. Paolo Domenici, Research Director with the Institute of Biophysics at the Italian National Research Council "If you are in an unfamiliar social environment, this is already something you need to pay attention to. If you are surrounded by familiar individuals, then you will be able to pay attention to any external threat more readily."

As escape performance underpins survival from predator attacks, these results help us to understand why animals have evolved to prefer associating with "friends" rather than "strangers", due to the implications for both individual and group-level survival in the wild.

"Friendship networks matter, both for humans and for less evolved taxa like fishes," said Mark McCormick, Ph.D., of the ARC Centre of Excellence for Coral Reef Studies. "The more you can rely on your friends, the easier and more fulfilling your life will be."

Credit: 
Nova Southeastern University

SARS-CoV-2: Achilles' heel of viral RNA

FRANKFURT, GERMANY. When SARS-CoV-2 infects a cell, it introduces its RNA into it and re-programmes it in such a way that the cell first produces viral proteins and then whole viral particles. In the search for active substances against SARS-CoV-2, researchers have so far mostly concentrated on the viral proteins and on blocking them, since this promises to prevent, or at least slow down, replication. But attacking the viral genome, a long RNA molecule, might also stop or slow down viral replication.

The scientists in the COVID-19-NMR consortium, which is coordinated by Professor Harald Schwalbe from the Institute of Organic Chemistry and Chemical Biology at Goethe University, have now completed an important first step in the development of such a new class of SARS-CoV-2 drugs. They have identified 15 short segments of the SARS-CoV-2 genome that are very similar in various coronaviruses and are known to perform essential regulatory functions. In the course of 2020 too, these segments were very rarely affected by mutations.

The researchers let a substance library of 768 small, chemically simple molecules interact with the 15 RNA segments and analysed the result by means of NMR spectroscopy. In NMR spectroscopy, molecules are first labelled with special types of atoms (stable isotopes) and then exposed to a strong magnetic field. The atomic nuclei are excited by means of a short radio frequency pulse and emit a frequency spectrum, with the help of which it is possible to determine the RNA and protein structure and how and where small molecules bind.

This enabled the research team led by Professor Schwalbe to identify 69 small molecules that bound to 13 of the 15 RNA segments. Professor Harald Schwalbe: "Three of the molecules even bind specifically to just one RNA segment. Through this, we were able to show that the SARS-CoV-2 RNA is highly suitable as a potential target structure for drugs. In view of the large number of SARS-CoV-2 mutations, such conservative RNA segments, like the ones we've identified, are particularly interesting for developing potential inhibitors. And since the viral RNA accounts for up to two thirds of all RNA in an infected cell, we should be able to disrupt viral replication on a considerable scale by using suitable molecules." Against this background, Schwalbe continues, the researchers have now already started follow-up trials with readily available substances that are chemically similar to the binding partners from the substance library.

Credit: 
Goethe University Frankfurt

Brain 'noise' keeps nerve connections young

image: Adult Drosophila neuromuscular synaptic terminals. Motor neurons (blue), synaptic boutons (red) and neurotransmitter release sites (green).

Image: 
© Laboratory of Neural Genetics and Disease / EPFL

Neurons communicate through rapid electrical signals that regulate the release of neurotransmitters, the brain's chemical messengers. Once transmitted across a neuron, electrical signals cause the juncture with another neuron, known as a synapse, to release droplets filled with neurotransmitters that pass the information on to the next neuron. This type of neuron-to-neuron communication is known as evoked neurotransmission.

However, some neurotransmitter-packed droplets are released at the synapse even in the absence of electrical impulses. These miniature release events -- or minis -- have long been regarded as 'background noise', says Brian McCabe, Director of the Laboratory of Neural Genetics and Disease and a Professor in the EPFL Brain Mind Institute.

But several studies have suggested that minis do have a function -- and an important one. In 2014, for example, McCabe and his team showed that minis are important for the development of synapses. If neurons in the brain were a network of computers, evoked releases would be packets of data through which the machines exchange information, whereas minis would be pings -- brief electronic signals that determine if there is a connection between two computers, McCabe says. "Minis are the pings that neurons use to say 'I am connected.'"

To assess whether minis could play a role in the mature nervous system, Soumya Banerjee, a postdoc in McCabe's group, and his colleagues set out to study a set of neurons that control movement in fruit flies. As the insects aged, their synapses started to break up into smaller fragments, the researchers found. (A similar process occurs in aging mammals, including people.) As nerve junctions broke down, both evoked and miniature neurotransmission were dampened, and the flies showed motor problems such as a reduced ability to climb the walls of a plastic vial.

Next, the team assessed the effects of stimulating or inhibiting evoked and miniature neurotransmission. When both types of neurotransmission were blocked, synapses aged prematurely, suggesting that during aging or in neurological diseases associated with old age, changes in neurotransmission happen before synapses start to crumble. This finding, McCabe says, upends a longstanding idea in neuroscience. "The idea has long been that the structure of the synapse breaks down, and that causes a functional change in the synapse, but we found it is the other way around," he says.

Stimulating evoked neurotransmission alone had no effect on aging synapses, the researchers found. However, increasing the frequency of minis kept synapses intact and preserved the motor ability of middle-aged flies at levels comparable to those of young flies. "Motor ability declines in all aging animals, including humans, so it was a delightful surprise to see that we could change that," McCabe says.

The findings, published in Nature Communications, could have important implications for human health: minis have been found at every type of synapse studied so far, and defects in miniature neurotransmission have been linked to range of neurodevelopmental disorders in children. Figuring out how a reduction in miniature neurotransmission changes the structure of synapses, and how that in turn affects behavior, could help to better understand neurodegenerative disorders and other brain conditions.

Credit: 
Ecole Polytechnique Fédérale de Lausanne

DNA assay aids in identifying and protecting North American wolves, coyotes

Forensics specialists can use a commercial assay targeting mitochondrial DNA to accurately discriminate between wolf, coyote and dog species, according to a new study from North Carolina State University. The genetic information can be obtained from smaller or more degraded samples, and could aid authorities in prosecuting hunting jurisdiction violations and preserving protected species.

In the U.S., certain wolf subspecies or species are endangered and restricted in terms of hunting status. It is also illegal to deliberately breed wolves or coyotes with domesticated dogs.

"If it's a case where you have a whole specimen, authorities can typically identify it based on physical characteristics, though similarity between some species makes that method less than ideal," says Kelly Meiklejohn, assistant professor of forensic science at NC State and corresponding author of the research. "If you're working with cross-bred animals, or incomplete specimens, you need DNA-based methods to accurately determine what species you have."

Although some U.S. federal laboratories perform DNA-based identification of wolves and coyotes, their methods and genetic reference databases aren't publicly available. Meiklejohn partnered with the U.S. Fish and Wildlife Service to see if it was possible to use a commercially available assay designed for dogs as a way to recover the mitochondrial genome from diverse North American canid species.

The mitochondrial genome is one of two genomes inherited from an animal's parents. Specifically, the mitochondrial genome is inherited from the mother. It is useful for species identification both because its circular shape makes it less prone to degradation, and because there are more copies of this genome per cell, increasing the chance of retrieving useful material from small or damaged samples.

The team used a method, called a 'hybridization capture,' in which about 80 base-pair long RNA fragments are used to isolate DNA for sequencing. Samples are incubated with the RNA fragments, and if there's a match, the fragment will bind with the sample's DNA. The bound DNA can be isolated and sequenced. In this case, the team used a hybridization capture panel designed for the dog mitochondrial genome.

"The fragments will bind if there is about 80% similarity, which is why we felt the dog kit would be useful for sequencing wolves and coyotes," Meiklejohn says. "Dogs only diverged from wolves around 20,000 years ago, so the mitochondrial genomes aren't that different."

They sequenced 51 samples, and were able to recover full mitochondrial genomes and successfully differentiate between four species of interest: dog, wolf, Mexican wolf, and coyote.

"Essentially, this finding means we can do more with less," Meiklejohn says. "In forensics we rarely have high quality DNA samples; they've usually been exposed to the environment and are degraded. The flexibility of this kit allows us to determine the species we're looking at, which in turn may aid in prosecuting hunting or breeding violations and protecting endangered canid species."

Credit: 
North Carolina State University

Child with rare genetic syndrome successfully treated in less than two years

EAST LANSING, Mich. - Diagnosing a rare medical condition is difficult. Identifying a treatment for it can take years of trial and error. In a serendipitous intersection of research expertise, an ill patient in this case a child and innovative technology, Bachmann-Bupp Syndrome has gone from a list of symptoms to a successful treatment in just 16 months.

The paper chronicling this lightning-fast scientific response to the Bachmann-Bupp Syndrome was published in the open-access journal, eLife.

For more than 25 years, André Bachmann, professor of pediatrics in Michigan State University College of Human Medicine, had been studying the ODC1 gene. This gene and its protein product ODC, which produces polyamines are crucial for cell survival and contribute to many developmental processes, including muscle tone and motor skills in children.

Through Bachmann's research, he also knew that the drug difluoromethylornithine, or DFMO, (sometimes referred to as eflornithine), had already been successful and approved by the Food and Drug Administration for treating other diseases linked to problems with ODC like African sleeping sickness and hirsutism (excessive hair growth). It was also studied in cancer clinical trials of colon cancer and pediatric neuroblastoma.

In 2018, Caleb Bupp, a medical geneticist at Helen DeVos Children's Hospital in Grand Rapids and clinical assistant professor in the Department of Pediatrics and Human Development in Michigan State University College of Human Medicine, had an unusual patient. Three-year-old Marley Berthoud's symptoms included a large head size, complete hair loss, low muscle tone and developmental delays. She could not hold her head up, feed herself, crawl or communicate.

When Bupp sequenced Marley's exome (the part of the human genome that contains the genetic code for making proteins), he discovered a mutation on her ODC1 gene. Bupp recalled a presentation by Surender Rajasekaran, a pediatric ICU physician at Helen DeVos and assistant professor in the Department of Pediatrics and Human Development in the Michigan State University College of Human Medicine, and Bachmann about ODC1, and he reached out to them.

Marley's ODC1 gene mutation caused her body to accumulate lots of ODC protein which was building up in her system. Bachmann knew from his previous work that DFMO deactivates ODC proteins.

"We can't stop her body from accumulating ODC protein, but we can make the protein inactive," Bachmann said.

Bupp was encouraged by Bachmann's previous research showing that DFMO was safe and had minimal side effects on patients, especially children. With her family's approval, Marley started taking DFMO in 2019. This was the first FDA-approved single-patient study in the world to treat a patient with an ODC1 mutation using DFMO.

"From the discovery of the syndrome until the patient's first dose it took less than two years," Bachmann said. "That doesn't usually happen so quickly."

While Bachmann, Bupp, Rajasekaran and Berthoud's family waited to see if DFMO would work, Marley's list of symptoms was given the official name of Bachmann-Bupp Syndrome by the Online Mendelian Inheritance in Man, an online database of human genes and genetic disorders.

"This rarely happens," Bachmann said. "As of today, and still many years from now, medical students will be learning about Bachmann-Bupp Syndrome and this all started at MSU."

Since she started taking DFMO, Marley has made tremendous progress. She has gained muscle tone which means she can hold her head up, feed herself with a spoon and crawl, but the most visible sign of success has been a full head of new hair growth.

"It's astounding," Bachmann said. "When I first saw a picture of her, I couldn't believe she had grown that much hair in a year, and she managed to sled down a hill by herself."

Seeing all of this external progress was promising but Bupp wanted to go a step further to learn more about the internal changes happening inside Marley's body from the DFMO treatment. Bupp contacted Metabolon, a health technology company based in Morrisville, North Carolina, that has developed a tool for the detecting biological markers of rare diseases and response to treatment.

Metabolon's Precision Metabolomics technology could test Marley's blood samples before and during treatment to find out exactly how her body's metabolism responded to DFMO treatment and the effect the drug was having on her body.

"There is not really a regular lab test you can do to look at that, so working with Metabolon gave us that window into Marley's biochemistry that wouldn't have been possible otherwise," Bupp said. "What we saw in the numbers agreed with what we were observing with our eyes -- Her body was changing on the inside too."

The result of what was happening inside Marley's body confirmed that DFMO works and was just as impressive as what was happening on the outside.

"Now Marley is using some sign language, where previously she couldn't communicate," Bupp said. "My heart melted when she was able to give me a high five for the first time."

Credit: 
Michigan State University

Public trust in CDC, FDA, and Fauci holds steady, survey shows

image: Public confidence in Dr. Anthony Fauci providing trustworthy information about preventing and treating Covid-19 -- by reliance on different media sources. Source: Annenberg Science Knowledge survey, June 2-22, 2021, among 1,719 U.S. adults.

Image: 
Annenberg Public Policy Center of the University of Pennsylvania

With more than two-thirds of American adults vaccinated with at least one dose of an authorized Covid-19 vaccine, the top U.S. health agencies retain the trust of the vast majority of the American public, as does Dr. Anthony Fauci, the public face of U.S. efforts to combat the virus, according to a new survey from the Annenberg Public Policy Center (APPC) of the University of Pennsylvania.

The survey revealed growing public confidence in both the safety and effectiveness of vaccines to prevent Covid-19.

But after months of attacks on Fauci in conservative and social media, the survey found that people who said they rely on conservative and very conservative media rather than other sources were more likely to have less confidence in Fauci's trustworthiness on Covid-19 and more likely to accept misinformation about him and misinformation and conspiracy theories about the authorized Covid-19 vaccines and the novel coronavirus.

The survey also found that a growing number of Americans - more than 1 in 3 - believes that the coronavirus was created by the Chinese government as a biological weapon.

"Our analysis of the data shows that there is good news and bad news here," said Kathleen Hall Jamieson, director of the Annenberg Public Policy Center. "Those who underestimate the lethality of Covid-19 or the safety of Covid-19 vaccination are less likely to accept a Covid-19 vaccination. The same is true of those who believe Covid-19 conspiracy theories. By contrast, those who trust health authorities are more likely to seek vaccination. Deceptive messages that undermine trust in a health expert such as Dr. Fauci are deeply worrisome."

The latest Annenberg Science Knowledge (ASK) survey was conducted among 1,719 U.S. adult respondents from June 2 - June 22, 2021. Data were weighted to represent the target U.S. adult population. The margin of error is ± 3.2 percentage points at the 95% confidence level. The panel survey is a follow-up to an April 2021 ASK survey with 1,941 respondents. (See the Appendix for additional data.)

Confidence in U.S. health authorities

The ASK survey found that the most trustworthy source of information for treating and preventing Covid-19 is the doctor or nurse who is an individual's primary health care provider:

Primary health care provider: 83% are confident their primary health care provider is providing trustworthy information about Covid-19;

Food and Drug Administration: 77% are confident that the FDA, which authorized emergency use of the Covid-19 vaccines available in the United States, is providing trustworthy information about treating and preventing Covid-19 - statistically about the same as the 75% in April and up significantly from 71% in August 2020 in an earlier Annenberg Public Policy Center survey;

Centers for Disease Control and Prevention: 76% are confident that the CDC is providing trustworthy information on Covid-19, about the same as in April (75%) and August 2020 (72%);

Dr. Anthony Fauci: 68% overall are confident that Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, is providing trustworthy advice on Covid-19, statistically about the same as in April (71%) and August 2020 (68%).

Conservative media and lower confidence

For more than a year, some prominent hosts in the conservative media have attacked Fauci's credibility. Fox News's Laura Ingraham falsely claimed on June 2, 2021, "Much of what Fauci said about this virus, the drugs that could treat it, and the measures that could be taken to slow the spread was untrue. He knew it was untrue."

The survey found that those who indicated that they rely on conservative and very conservative media have less confidence in U.S. health authorities providing trustworthy information about Covid-19 - especially Fauci.

Among people who said they rely all the time or often on ...

Very conservative media sources such as Newsmax, One America News (OAN), Gateway Pundit, Parler, or Telegram: 55% are confident about trustworthiness of the FDA, 52% are confident about the trustworthiness of the CDC, and only 38% are confident in the trustworthiness of Fauci.

Conservative media such as Fox News: Nearly 7 in 10 are confident that the CDC (68%) and FDA (69%) are providing the public with trustworthy information on Covid-19, but just over half (51%) have confidence that Fauci is doing so.

Mainstream broadcast and print news media such as CBS, ABC, and NBC News, the New York Times, the Wall Street Journal news pages, and the Associated Press: 87% are confident in trustworthiness of the CDC and FDA, and 84% in Fauci.

Social media such as Facebook: 80% are confident that the CDC and FDA are providing the public with trustworthy information on Covid, and 71% have confidence that Fauci is providing trustworthy information.

Confidence in Covid-19 vaccines

In June, a growing majority of the U.S. public said the Covid-19 vaccines are safe and effective:

78% of the U.S. public believes it is definitely or probably true that Covid-19 vaccines are effective in preventing Covid-19, up significantly from 74% in April;

o Those who say this is definitely true grew to 46%, from 38% in April. (NOTE: THESE UNFILLED-IN BULLETS ARE INDENTED UNDER A REGULAR BULLET)

76% of the U.S. public believes it is definitely or probably true that it is safer to get the Covid-19 vaccine than to get Covid-19, about the same as the 75% in April;

o Those who say this is definitely true grew to 54%, from 49% in April, a significant change.

o In the presence of statistical controls, the more ideologically conservative that people described themselves as, the less likely they are to believe that it is true that it is safer to get the Covid-19 vaccine than to get Covid-19.

Conspiracy beliefs

The survey asked respondents about misinformation and conspiracy theories.

Bioweapon conspiracy theory: Over 1 in 3 people (35%) said it was true that the coronavirus was created by the Chinese government as a biological weapon, up slightly from 31% in April. Another 42% said that statement was false and 23% were not sure. (Although the origin of the coronavirus is still uncertain, there currently is no evidence it was created by the Chinese as a bioweapon.)

o In the presence of statistical controls, those who say they rely on conservative media such as Fox News or very conservative media such as OAN are more likely to believe this conspiracy theory. Those who say they rely on mainstream media are more likely to reject this theory.

Among the instances in which a conservative media outlet legitimized the Chinese bioweapon theory was Tucker Carlson's Fox News show on June 30, 2021, which featured an interview with a Chinese "coronavirus whistleblower" who claimed that Covid-19 was a "biologically engineered weapon that got out of control... " And on June 8, 2021, conservative personality Steve Bannon hosted Rep. Marjorie Taylor Greene (R., Ga.) on his podcast "War Room: Pandemic," where she claimed that Fauci was sending "American tax dollars" to the Chinese lab in Wuhan "to fund this research that was creating ... a virus that can spread rapidly among a population, make people sick and kill them... [with] these viruses that they experiment with like some sort of Dr. Frankenstein experiments: These are bioweapons."

In addition, while most respondents knew that a vaccine conspiracy theory involving Bill Gates and microchips was false, a worrisome number either thought it was true or were unsure:

Gates/microchip conspiracy theory: 75% correctly said it was false that the vaccine against Covid-19 developed with support from Microsoft founder Bill Gates contains microchips that can track the person who has been vaccinated, but 1 in 4 people either said this conspiracy theory was true (11%) or were not sure (14%). None of the authorized Covid-19 vaccines contain microchips and while the Gates Foundation has a partnership with BioNTech, the foundation says it did not directly invest in either the Pfizer/BioNTech or Moderna Covid-19 vaccines.

o In the presence of statistical controls, those who say they rely on conservative media or very conservative media are more likely to believe this claim.

Misinformation

Fauci and vaccines: Asked if it was true that Dr. Anthony Fauci of the NIH "has NO financial stake" in any Covid-19 vaccine, only 37% said it was true - a decline from the 42% who said it was true in April. Another 32% thought it was false to say Fauci had no financial stake in a Covid vaccine, and 30% were not sure. (There is no evidence Fauci has a financial stake in a Covid-19 vaccine.)

o In the presence of statistical controls, those who indicate that they rely on conservative media or very conservative media are more likely to say this is false - in other words, to reject the idea that Fauci has no financial stake in any vaccine. Those who say they rely on mainstream news are more likely to say this is true.

Give you Covid-19: 75% correctly said it was false that taking a Covid-19 vaccine can give you Covid-19 - it can't - but 1 in 4 people said it was true (14%) or were not sure (11%);

Change your DNA: 71% correctly said it was false that the Covid-19 vaccine changes people's DNA - it does not - but nearly 3 in 10 people thought it was true (12%) or were not sure (17%).

The lab leak theory

As scientists search for the origins of SARS-CoV-2, more than half the survey respondents said they believe the virus came from a lab in Wuhan, China - and got out through either a deliberate or an accidental leak. When asked which statement was closest to their view:

20% said the coronavirus was deliberately leaked from a Wuhan, China, laboratory;

33% said the coronavirus accidentally escaped through carelessness or incompetence from the Wuhan lab;

13% said the coronavirus did not originate in a lab in Wuhan, China;

34% said they were not sure.

Vaccination and prevention

Asked about prevention and vaccination, 70% of respondents said they have gotten a Covid-19 vaccine, up from 47% in April. The other 30% (442 people) said they have not been vaccinated.

Of those 442 people who have not been vaccinated,

76% said they had the information they need to decide if they want to get vaccinated, and 24% said they did not have it;

75% said they were not likely to get vaccinated (333 people) and 25% said they were likely to be vaccinated.

Those who were not likely to be vaccinated (333 people) were asked to give their reasons why and select all that applied. Due to multiple responses, the results total over 100%. Their top five reasons:

o 61% said the vaccines were still too untested or they were waiting to see what happens - which increased significantly from the 48% who gave this reason in April;

o 44% are worried about allergies and side effects;

o 43% don't trust the government;

o 36% don't trust the scientists and companies that make the vaccines;

o And 32% are "just not concerned" about coronavirus/Covid-19.

For the survey Appendix containing the methodology and additional data, click here.

The Annenberg Public Policy Center was established in 1993 to educate the public and policy makers about communication's role in advancing public understanding of political, science, and health issues at the local, state, and federal levels.

Credit: 
Annenberg Public Policy Center of the University of Pennsylvania

New insight into "training" highly reactive chemical compounds

image: Dr Jonas Warneke explains the chemistry of highly reactive molecules, which are being researched at the Wilhelm Ostwald Institute

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Photo: private

Led by Dr Jonas Warneke, researchers at the Wilhelm Ostwald Institute of Physical and Theoretical Chemistry at Leipzig University have made a decisive advance in the study of one type of highly reactive particles. Based on their research, they now understand the "binding preferences" of these particles.

Their research serves as the basis for the targeted use of these highly reactive molecules, for example, to generate new molecular structures or to bind hazardous chemical "waste" and in this way dispose of it. The researchers have now published their findings in the journal Chemistry - A European Journal, and their research was featured on the cover thanks to the excellent review they received.

What molecules and people have in common

Molecules and people actually have a lot in common. There are those who are lethargic and prefer to keep to themselves, and there are those who are very active and outgoing. And then there are those who are so dissatisfied with their situation that they haphazardly attack everyone in their surroundings. If you want to get them to behave in a social manner, you must first understand the reason for their attacks. Chemists work with highly reactive compounds in a similar way. Given their exceptional reactivity, targeted syntheses (the production of a specific molecule) with these compounds are extremely difficult. If you want these highly reactive compounds to react with a specific molecule, this usually fails because they instead react with the solvent in their environment. They bind with everything that comes across their path. "But this is, in fact, the huge opportunity that these compounds offer. They are able to induce even very unreactive small molecules and atoms to react in ways that would not have been otherwise possible", explains Warneke.

Directing highly reactive compounds

For several years now, researchers at the Wilhelm Ostwald Institute have investigated a special type of highly reactive compound with twelve boron atoms that can bind even the very unreactive noble gases. Eleven boron atoms have a binding partner (called a substituent), while the twelfth boron atom carries out the attack. How can we direct these highly reactive compounds so that targeted syntheses will be possible in the future? To answer this question, the researchers produced these highly reactive compounds in the solvent-free and airless environment of a mass spectrometer and thus isolated the compounds in such a way that there were no compounds in their environment for them to attack.

In a second step, the highly reactive compounds were selectively fed reaction partners that they attacked. The researchers found that the "aggressiveness" of the compounds changed when the substituents were altered. "This wasn't surprising at first", Warneke says. "However, we then found that the propensity to attack did not simply become stronger or weaker as a result of this exchange of atoms, but instead it depended strongly on which reaction partner was present." The researchers were able to show that the substituents have a strong influence on the reactivity and trace the reaction preferences back to a very specific chemical bond that forms to varying degrees depending on the reaction partner.

This finding surprised the researchers because in chemistry this type of bond is more commonly found with metal compounds and not with the boron compounds studied, which belong to the non-metal compounds. This hypothesis was finally proven beyond reasonable doubt by special experimental and theoretical methods carried out by the early career research group under Warneke in partnership with the working groups led by Prof. Dr. Knut Asmis and Prof. Dr. Ralf Tonner, both from the Wilhelm Ostwald Institute. The group will continue its research together with its partners from Wuppertal. They hope to be able to use molecules such as carbon monoxide or nitrogen from the air in this way for targeted syntheses. But Warneke says there is still a long way to go before that happens.

Credit: 
Universität Leipzig

Mind and matter: Modeling the human brain with machine learning

video: Modeling the Human Brain with Machine Learning

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Shibaura Institute of Technology

We all like to think that we know ourselves best, but, given that our brain activity is largely governed by our subconscious mind, it is probably our brain that knows us better! While this is only a hypothesis, researchers from Japan have already proposed a content recommendation system that assumes this to be true. Essentially, such a system makes use of its user's brain signals (acquired using, say, an MRI scan) when exposed to a particular content and eventually, by exploring various users and contents, builds up a general model of brain activity.

"Once we obtain the 'ultimate' brain model, we should be able to perfectly estimate the brain activity of a person exposed to a specific content," says Prof. Ryoichi Shinkuma from Shibaura Institute of Technology, Japan, who was a part of the team that came up with the idea. "This could provide powerful solutions in the commercial field, such as reduce the costs of targeted advertising."

However, a major drawback presents itself at the outset: acquiring MRI scans is expensive. A typical brain scan would involve deployment and maintenance costs of an MRI, the labor costs of specialists, and the recruitment costs of a large number of participants. Faced with this challenge, Prof. Shinkuma and his team has come up with an ingenious solution: using profile information of people to infer their brain model.

In a new study published in the IEEE Transactions on Systems, Man, and Cybernetics: Systems, the team proposes a scheme that attempts to mitigate the trade-off between the performance associated with inferring the brain model from profile information and the cost of acquiring that information. "Our scheme utilizes machine learning (ML) to create a brain model based on inference of profile model," explains Prof. Shinkuma. "To reduce the cost of information collection, we make use of the feature selection capability of ML to narrow down the number of questionnaire items by estimating the extent to which each item contributes to the inference performance."

Specifically, the feature selection process quantified the contribution of a questionnaire item by attributing to it an "importance score" and then retained only those with top importance scores for the inference. This allowed the team to maintain a high inference performance while limiting the information cost at the same time.

To validate the effectiveness of their scheme, the team evaluated its performance accuracy using a brain model obtained experimentally and a profile model based on real profile information. They found that the scheme achieved nearly the same level of inference accuracy of the brain model as the case employing 209 questionnaires by using only 15-20 topmost items. This suggested that only the top 10% questionnaire items were enough for inferring the brain model.

"An important next step will be to determine the best combination of ML and feature selection method for optimizing the performance of our scheme," says an excited Prof. Shinkuma, contemplating future research directions of their work. "At the same time, we will need to reduce the total computation cost for real-world applications involving large number of users."

Looks like, in a not too distant future, our knowledge of who we are might come from the outside!

Credit: 
Shibaura Institute of Technology

American Board of Urology outlines processes to ensure diversity in leadership

July 19, 2021 - At the organization responsible for certifying the training and skills of US urologists, achieving and maintaining diversity, equity and inclusion is more than just a "numbers game," according to a special article in Urology Practice®, an Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.

In the new article, the American Board of Urology (ABU) points out that the practice of diversity and inclusion has been a cornerstone of its values for years. However, the Board acknowledges that while progress has been made, more work remains to be done. The authors included ABU Trustees Douglas A. Husmann, MD, Martha K. Terris, MD, and Cheryl T. Lee, MD, and Executive Director J. Brantley Thrasher, MD.

Building and sustaining diversity and inclusion at ABU
The report focuses on informing ABU diplomates about initiatives to evaluate and strengthen diversity and representation on three Committees central to the ABU's mission: The Board of Trustees and the Written and Oral Examinations Committees. For several years it has been the ABU's standard of practice to perform a yearly GAP analysis, comparing and contrasting the membership of their committees to the characteristics of their constituents: practicing urologists within the United States, as defined by the American Urology Association's 2019 annual National Census.

The selection of new Committee members is subsequently based on both the individual's merit and an attempt to match or exceed the diversity ratios defined within the Census regarding gender, race, ethnicity, geography of practice, and subspecialty area. This year's evaluation revealed the ABU committee structure consisted of 85% men and 15% women, compared to 90% and 10% in the 2019 National Census, respectively.

Regarding race and ethnicity, proportions of Committee members compared to the National Census of practicing urologists were non-Hispanic White, 74% versus 81%; Asian, 22% versus 12%; Black/African American, 3% versus 2%; and Hispanic, 1% versus 4%. Regarding region of practice, the ABU assesses the proportion of US urologists practicing within a given section, and attempts to achieve a Committee structure that is equivalent or within 1 to 4 percentage points.

While counting and comparing gender and racial/ethnic representation is a necessary first step, establishing ratios has not been found to change societal behavior or attitudes substantially - and indeed may have significant negative unintended consequences. Dr. Husmann and coauthors outline a series of "continuous and structural processes" to promote a lasting culture of diversity and inclusion. Specific aims include:

Educating ABU diplomates and Committee members regarding the benefits of diversity
Educating Committee members about the concept of unconscious bias
Performing rigorous assessments of the ABU written and oral examinations to verify the absence of implicit bias
Stressing the need to mentor today's diverse constituency of young urologists to participate and eventually take over leading roles in state, regional and national committees - giving them the experience they will need to succeed as ABU Committee members
Anticipating the changing demographics of the next generation of urologists - for example, whereas only 10 percent of urologists currently in practice are women, they account for 30 percent of residents in training
Above all else, encouraging frank and open discussions regarding diversity, equity, and inclusion

Dr. Husmann and coauthors conclude: "The ability to achieve and maintaining diversity, equity, and inclusion is an imperative requiring regular attention and discussion to ensure that we continually strive to reflect the values and principles of both the public and the diplomates we serve."

Click here to read "The American Board of Urology: In Pursuit of Diversity, Equity, and Inclusion."

DOI: 10.1097/UPJ.0000000000000244

Credit: 
Wolters Kluwer Health

Tomato fruits send electrical warnings to the rest of the plant when attacked by insects

A recent study in Frontiers in Sustainable Food Systems shows that the fruits of a type of tomato plant send electrical signals to the rest of the plant when they are infested by caterpillars. Plants have a multitude of chemical and hormonal signaling pathways, which are generally transmitted through the sap (the nutrient-rich water that moves through the plant). In the case of fruits, nutrients flow exclusively to the fruit and there has been little research into whether there is any communication in the opposite direction--i.e. from fruit to plant.

"We usually forget that a plant's fruits are living and semiautonomous parts of their mother-plants, far more complex than we currently think. Since fruits are part of the plant, made of the same tissues of the leaves and stems, why couldn't they communicate with the plant, informing it about what they are experiencing, just like regular leaves do?" says first author Dr Gabriela Niemeyer Reissig, of the Federal University of Pelotas, Brazil. "What we found is that fruits can share important information such as caterpillar attacks--which is a serious issue for a plant--with the rest of the plant, and that can probably prepare other parts of the plant for the same attack."

A tomato's defense

To test the hypothesis that fruits communicate by electrical signals, Niemeyer Reissig and her collaborators placed tomato plants in a Faraday's cage with electrodes at the ends of the branches connecting the fruits to the plant. They then measured the electrical responses before, during and after the fruits had been attacked by Helicoverpa armigera caterpillars for 24 hours. The team also used machine learning to identify patterns in the signals.

The results showed a clear difference between the signals before and after attack. In addition, the authors measured the biochemical responses, such as defensive chemicals like hydrogen peroxide, across other parts of the plant. This showed that these defenses were triggered even in parts of the plant that were far away from the damage caused by the caterpillars.

The authors emphasize that these are still early results. Their measurements provide a "big picture" view of all of the electrical signals, rather than distinguishing individual signals more precisely. It will also be interesting to see whether this phenomenon holds true for other plant species, as well as different types of threats.

That said, this novel use of machine learning appears to have very high potential for answering these and other future questions. The technique may also provide new--and possibly more environmentally friendly--approaches for insect control in agriculture.

"If studies like ours continue to advance and the techniques for measuring electrical signals in open environments continue to improve, it will be possible to detect infestation of agricultural pests quite early, allowing for less aggressive control measures and more accurate insect management," explains Niemeyer Reissig. "Understanding how the plant interacts with its fruits, and the fruits among themselves, may bring insights about how to 'manipulate' this communication for enhancing fruit quality, resistance to pests and shelf life after harvest."

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Frontiers

Public health summer program increases STEM career interests in high schoolers

High school students who participated in summer programs about public health increased their interest in pursuing careers in science, technology, engineering and mathematics (STEM), according to a Rutgers study.

Published in the journalPedagogy in Health Promotion, the study explored whether increasing public health awareness would motivate high school students to pursue public health careers.

Researchers found that the summer program, Public Health: Outbreaks, Communities, and Urban Studies (PHocus) offered in 2018 and 2019 increased the students' knowledge in public health, epidemiology, urban public health and global public health.

"Including interdisciplinary, authentic learning experiences in our summer program enabled students to personally connect public health disciplines with their personal experiences, as well as with population health in general," said Laura E. Liang, co-director of the PHocus Summer Experience and associate dean of academic affairs at the Rutgers School of Public Health.

While the students who went through the course in 2018 researched the 2018 influenza pandemic and those in 2019 investigated measles outbreaks in 2019, Liang says she expects future groups to examine public health through the lens of the COVID-19 pandemic.

"These personally relevant topics, supplemented by exposure to academic research practices, not only personally interested students but also aided in student learning and retention," she said.

Researchers, who point to a decline in an interest in the STEM field by middle and high school students, developed the summer program to address these issues and offer students seeking health science careers alternatives beyond becoming doctors or nurses.

Researchers said 130 students from 63 high schools participated in the week-long program, which provided insights into college plans, helped set professional goals and offered tips to taking control of their own health.

The students gave the program, which provided an overview of public health, epidemiology, and health issues particularly relevant to adolescents, such as sleep hygiene, alcohol and tobacco, as well as the careers available in the field, a 100 percent rating. More specifically, nearly 90 percent of participants in the Summer 2018 cohort and 96 percent of participants in the Summer 2019 cohort felt PHocus provided valuable insight that will assist in their collegiate and career planning. Further, approximately 65 percent of participants from each summer cohort strongly agreed that PHocus provided high-quality information and strategies.

"Through our integration of current public health faculty and community sector partners, students can create interpersonal connections with public health professionals while also experiencing these professions through their immersion in simulations and activities," said Marian Passannante, co-director of PHocus and associate dean for Education Program Development and Global Programs at the Rutgers School of Public Health. "This allows students to explore the breadth of career opportunities in public health and encourages them to begin to think about their future."

Researchers said the easily replicable program demonstrated the value in hosting similar summer programming at other institutions to address students' declining interest in STEM fields.

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Rutgers University