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Higher vitamin A intake linked to lower skin cancer risk

PROVIDENCE, R.I. [Brown University] -- People whose diets included high levels of vitamin A had a 17 percent reduction in risk for getting the second-most-common type of skin cancer, as compared to those who ate modest amounts of foods and supplements rich in vitamin A.

That's according to researchers from Brown University, who unearthed that finding after analyzing data from two long-term observational studies.

Cutaneous squamous cell carcinoma is the second-most-common type of skin cancer among people with fair skin. Vitamin A is known to be essential for the healthy growth and maturation of skin cells, but prior studies on its effectiveness in reducing skin cancer risk have been mixed, said Eunyoung Cho, an associate professor of dermatology and epidemiology at Brown.

"Our study provides another reason to eat lots of fruits and vegetables as part of a healthy diet," said Cho, who is also an associate epidemiologist at Brigham and Women's Hospital. "Skin cancer, including squamous cell carcinoma, is hard to prevent, but this study suggests that eating a healthy diet rich in vitamin A may be a way to reduce your risk, in addition to wearing sunscreen and reducing sun exposure."

The findings were published on Wednesday, July 31, in the Journal of the American Medical Association Dermatology.

The research team led by Cho looked at the diet and skin cancer results of participants in two large, long-term observational studies: the Nurses' Health Study, which followed 121,700 U.S. women from 1984 to 2012, and the Health Professionals Follow-Up Study, which followed 51,529 U.S. men from 1986 to 2012.

Between the two studies, some 123,000 participants were white (and thus had significant risk of developing skin cancer), had no prior history of cancer and completed the dietary reports multiple times. Among these individuals included in the team's subsequent analysis, a total of 3,978 cases of squamous cell carcinoma were reported and verified within the 24- or 26-year follow-up periods.

Both studies also asked the participants about hair color, the number of severe sunburns they had received in their lifetime and any family history of skin cancer, and the researchers adjusted for these and other factors. The studies did not, however, ask participants about their avoidance of mid-day sun, known to be a major risk factor for skin cancer.

After grouping the study participants into five categories by vitamin A intake levels, the researchers found that people in the category with the highest average daily total vitamin A intake were 17 percent less likely to get skin cancer than those in the category with the lowest total vitamin A intake.

Those in the highest category reported eating on average the amount of vitamin A equivalent to one medium baked sweet potato or two large carrots each day. Those in the lowest category reported eating a daily average amount of vitamin A equivalent to one-third cup of sweet potato fries or one small carrot, which is still above the U.S. Recommended Dietary Allowance of vitamin A.

The team also found that the majority of vitamin A came from the participants' diets, particularly from fruits and vegetables, rather than from animal-based foods or vitamin supplements. Plant-based sources of vitamin A include not only sweet potatoes and carrots, but leafy green vegetables and fruits like apricots and cantaloupe. Milk, some types of fish and liver are rich sources of animal-based vitamin A.

Cho cautioned that too much vitamin A, particularly from supplements and animal sources, can lead to nausea, liver toxicity, increased risk of osteoporosis and hip fracture, and even birth defects. Side effects from high levels of plant-based vitamin A are minimal, she added.

The researchers also found that eating high levels of other plant-based pigments similar to vitamin A -- such as lycopene, commonly found in tomatoes and watermelon -- was associated with decreased risk of skin cancer.

Because the analysis was based on studies surveying a large number of people about the foods they ate and observing whether or not they got skin cancer, rather than a randomized clinical trial, it cannot establish cause and effect. It's possible that another factor may have led to the differences -- such as the fact that people who consumed more vitamin A also tended to drink less alcohol.

As a next step, Cho would like to conduct a clinical trial to see if vitamin A supplements can prevent squamous cell carcinoma. However, she added, conducting a dietary clinical trial is quite challenging on a technical level, as is ensuring that participants actually stick to the diet.

"If a clinical trial cannot be done, then a large-scale prospective study like this is the best alternative for studying diet," Cho said.

Credit: 
Brown University

For children born with HIV, adhering to medication gets harder with age

Boston, MA - Children born with HIV in the U.S. were less likely to adhere to their medications as they aged from preadolescence to adolescence and into young adulthood, according to a new study led by researchers at Harvard T.H. Chan School of Public Health. Additionally, the prevalence of detectable viral load--an indication that the virus is not being managed by medications and a factor that's often associated with nonadherence--also increased with age.

The study is one of the first to examine why different age groups stop adhering to treatment (nonadherence). While the factors related to nonadherence varied by age group, youth who were concerned about side effects of the drugs were less likely to be adherent at most ages.

"As they approach adulthood, many youth face challenges, such as entering new relationships, managing disclosure of their HIV status, and changing to an adult HIV care provider. Ensuring successful HIV medication adherence before and throughout adolescence is critical," said lead author Deborah Kacanek, research scientist in Harvard Chan School's Department of Biostatistics. "We found that the factors that either supported adherence and a suppressed (undetectable) viral load, or made it harder for youth to adhere to treatment, varied depending on their age."

The study was published online ahead of print in AIDS.

In the U.S., approximately 12,000 children, adolescents, and young adults are living with perinatally acquired HIV, meaning that they have lived with HIV since birth. Globally, 1.8 million adolescents live with HIV. Adhering to regimens of antiretroviral therapy (ART) is key to managing the disease and reducing the risk of transmission. Sticking to a daily regimen of medicine, however, is especially challenging for adolescents and young adults, who are navigating a range of physical, cognitive, social, and emotional changes.

Adherence can be more complicated for youth growing up with perinatal HIV, whose lifelong experiences with HIV, stigma, and multiple antiretroviral medications may pose challenges to achieving viral suppression that are different from youth who acquire HIV later in life.

To better understand these challenges and why young people may not adhere to their medications, researchers followed 381 youth with perinatally acquired HIV for an average of 3.3 years. The youth were participants in the Pediatric HIV/AIDS Cohort Study, which follows children and youth born with HIV or born exposed at birth to HIV to determine the impact of lifelong HIV and the long-term safety of antiretroviral regimens.

The preadolescents, adolescents, and young adults in the study ranged from age 8 to 22 and were recruited from 15 different clinical sites in the U.S, including Puerto Rico. As part of the study, the researchers examined results from blood tests that measured viral loads, and they examined nearly 1,200 adherence evaluations in which study participants or their caregivers self-reported any missed doses of medication in the prior seven days.

The researchers found that from preadolescence to young adulthood, the prevalence of nonadherence increased from 31% to 50%. In addition, the prevalence of detectable viral load among the same age groups increased from 16% to 40%.

For each age group, different factors were associated with nonadherence. For example, during middle adolescence (15-17 years old), alcohol use, having an unmarried caregiver, indirect exposure to violence, stigma, and stressful life events were all associated with nonadherence.

"It is important to talk with youth about how to take medications properly, but our study highlights the need for those who care for these youths to focus also on age-related factors that may influence adherence," Kacanek said. "Services to help support adherence need to address both the age-related risks and build on the sources of strength and resilience among youth at different stages of development."

Credit: 
Harvard T.H. Chan School of Public Health

The urbanization of the beach

To most people, a beach is a beach. You could likely take an image of almost any urban beach in Southern California -- the flat, mostly featureless expanse of sand against blue-green water and blue skies -- swap it with one of nearly any other urban beach in Southern California, and chances are that only a trained eye would notice the difference. Some of these differences lie just beneath the surface, however, and are actually quite important ecologically.

Dig just few inches into the sand on many beaches in Southern California -- home to some of the most biologically diverse sandy beaches in the world -- and you'll find it teeming with life such as sand crabs, clams and beach hoppers. But for about a third of the sandy beaches extending from Santa Barbara to San Diego, only a small subset of these highly specialized beach animals remain, and in reduced numbers at that.

This lack of biodiversity, say researchers at UC Santa Barbara's Marine Science Institute (MSI), is an unintended consequence of the quest to maintain the Instagram-ready, tourist-accommodating, iconic look of Southern California's urban beaches. Cities up and down the coast have flattened dunes, destroyed native vegetation and groomed the sand with heavy equipment such that what many of us have come to call "natural beauty" is in fact about as natural as a sand parking lot.

All of this, the scientists write in a paper in the journal Ecological Indicators, has massive impacts on the larger beach ecosystem. Further, it could already be having negative effects in terms of erosion, sea level rise and the health of the surrounding ocean and coastal ecosystems.

"After studying mainland beaches in Los Angeles and San Diego, one of the big a-ha moments for me occurred when I went out to the Channel Islands to study sandy beaches that have never had vehicles driving on them and have never been subjected to grooming, filling or bulldozers," said coastal marine ecologist and study co-author Jenny Dugan. On those beaches, she noted, coastal vegetation comes right down to the winter high-tide mark, sand collects in dunes of all sizes and shapes, and kelp washes onshore and accumulates in piles, providing food for an amazing variety and abundance of invertebrates, which, in turn, are food for shorebirds and fish.

This well-tuned ecosystem has been disrupted on Southern California's urban beaches, say Dugan and her co-researchers. Heavy machinery is often employed to rake trash and debris out of the sand -- and large quantities of sand from elsewhere are brought in to replenish sand washed away by storm and wave action. Some beaches are groomed daily, often twice. The frequency of disturbance to many beaches by these widespread activities is greater than any known farming or land management practice.

"We observed strong negative responses to these intense widespread practices on urban beaches in the biodiversity, structure and function across all the intertidal zones of beach ecosystems," said Nicholas Schooler, a postdoctoral reseacher within MSI and the study's lead author, He conducted the research when he was a Sea Grant trainee.

Some of these results came as no surprise to the researchers. In previous studies, the team found disturbance from beach grooming caused strong negative impacts to upper intertidal biodiversity on Southern California beaches and in one study those impacts persisted for more than three decades. The current study, funded by Sea Grant and the National Science Foundation, took a much wider and deeper look at the diversity of beach ecosystems affected by these management practices, revealing the scale of impacts across the entire intertidal zone as well as the region.

"We explored how disturbance from these management practices affected ecological communities on different spatial scales," Schooler said, "including that of littoral cells, which are basically compartments of the coast that contain a sand source, usually rivers, alongshore transport of sand by waves and currents, and a sink where sand exits the system, such as a submarine canyon."

The results are sobering. In comparisons between select urban beaches in Carpinteria, Malibu, Santa Monica, Redondo Beach, Huntington Beach and Carlsbad, and neighboring, minimally disturbed "reference" beaches within the same littoral cells, the scientists found that up to half of the natural inhabitants were missing on the urban beaches. The ones that remained tended to be the same few species across all littoral cells.

"Beaches within a littoral cell can often support very similar intertidal communities, but those communities vary distinctly from cell to cell," Schooler explained. However, the disturbance to the sand caused by grooming and filling on urban beaches has homogenized the intertidal communities of those beaches across littoral cells in Southern California, he added.

One reason for the impacts, according to Dugan, is that in addition to the habitat destruction and disturbance by the heavy machinery used for grooming, beaches are often nourished or filled with the "wrong" sand.

"Many beach species are very sensitive to sand grain-size," she explained. Beach clams, for instance, require fine-grained sand in order to flourish. But the sand brought in by the dump truck to fill urban beaches comes from harbor dredging or quarries miles away and is coarser than the long-lived, slow-growing beach clams can handle. An increase in sand grain-size from beach filling can exclude a great variety of species of beach animals from living on an urban beach.

The severe drop in intertidal species diversity documented in this study is a cause for concern -- and not only because of the loss of unique intertidal species. It also renders the urban beach ecosystem more susceptible to collapse, the scientists said. Fewer species occupying important roles in the food web means that the system is more likely to be thrown out of balance should one species disappear. Reduced diversity and abundance of invertebrates in the sand could also mean less food for the fish and shorebirds that depend on beaches.

Although sandy beach ecosystems are generally thought of as highly resilient given their conditions of constantly moving sand and water, the study results show how sensitive these ecosystems are to human disturbance. This was particularly apparent for wrack-associated species -- the small invertebrates that inhabit the upper intertidal zone and rely on stranded kelp wrack for food and shelter. This group typically represents around 40% of the biodiversity on Southern California beaches.

"For one of our urban study beaches, wrack-associated species were completely undetectable in our surveys, representing a major loss in both diversity and ecosystem function," explained Schooler. The extreme vulnerability of wrack-associated species follows a theme in their continued research on sandy beach ecosystems.

"This study will force us to make critical choices about whether we value well-groomed beaches or healthy natural ecosystems," said David Garrison, a program director in the National Science Foundation's Division of Ocean Sciences, which co-funded the research. "Shorebirds and other marine life we value are critically dependent on resources provided by thriving ecosystems."

"We started out doing ecology for ecology's sake, asking basic questions on the diversity and functioning of sandy beach ecosystems," study co-author David Hubbard, of MSI, said of this study. "The more we worked in Southern California, the more we realized how altered many of the beach ecosystems were."

With this new information, however, they hope to turn some of that around. Managers of urban beaches, such as those in the Beach Ecology Coalition, have been receptive, the researchers said. It will take more education, they noted, but if the managers better understand, for instance, that native dune plants can prevent beach erosion and buffer against sea level rise, or that a healthy beach invertebrate population could take care of kelp wrack without help from heavy grooming equipment, some unique species richness and ecosystem resilience could be restored to sandy beaches.

Credit: 
University of California - Santa Barbara

Going green? Not so easy for mainstream brands

Did you know that Nike makes a line of clothing and shoes created from recycled plastic bottles? Did you know that consumer products giant, Procter & Gamble, made eco-friendly industrial products for commercial use? Or that outdoor clothing manufacturer, Patagonia, made fleece products and jackets from used soda bottles and recycled fabric?

If you answered no, it's probably for good reason: Recent research shows that when mainstream brands advertise using visual cues suggesting the product is environmentally friendly or "green" consumers may actually evaluate the product as being less effective and switch to a more niche green brand.

San Diego State University marketing professor, Dr. Morgan Poor, along with Dr. Stacy Wood and Dr. Stefanie Robinson, both of North Carolina State University, conducted a survey of 565 consumers from across the U.S. to determine their choice among three real pesticide brands and whether a green cue (an earth image) on the product label of the largest mainstream competitor influenced this choice. Four hundred and twenty of the individuals surveyed identified themselves as consumers of pesticides and 352 responded "yes" when asked if they considered themselves "a consumer who prioritizes 'environmental friendliness' in purchase decisions."

The study, recently published in the Journal of Advertising Research, focused on one mainstream product from a large multinational company (the target brand), a second mainstream product with significant market share (the mainstream competitor), and one brand that sold only eco-friendly products (green competitor).

Survey participants were shown the full-size packages for all three brands and asked to evaluate them, however, there were three different product labels used for the target brand. One group of participants saw the standard target brand packaging with no added cue. A second group saw the target brand's packaging with a safety cue (an image of a home-in-hands). The final group saw the target brand's packaging with a green cue (an image of an earth).

The results showed that the choice share of the target brand differed based on the product label used on the package. When the survey participants were shown the package with the standard label with no cue or the safety cue, choice share was similar at 43.6 percent and 43.4 percent respectively. In comparison, when participants were shown the package with the green cue label, choice share dropped to 33 percent.

Upon further questioning, the researchers found that when survey participants were shown the package with a green cue, they perceived the product to be more environmentally friendly and less effective in its performance, thus leading them to be less inclined to purchase it.

The researchers noted that while packaging isn't the only attribute prompting consumer behavior, the colors, images and verbiage used on packaging labels seem to have a noteworthy impact on influencing consumer's decisions when considering a "green product."

"At one point, Clorox removed some of the environmental-friendly cues from the labels of their Green Works product line when sales started to decline. While Clorox didn't say why they took these steps, it certainly mirrors the results of our study," said Poor. "Our findings seem to indicate that mainstream green brands should consider keeping information about environmental friendliness under the radar and promote their products' performance instead."

Credit: 
San Diego State University

Neuroimaging essential for Zika cases

image: This is Sarah B. Mulkey, M.D., Ph.D., a fetal-neonatal neurologist in the Division of Fetal and Transitional Medicine at Children's National in Washington, D.C.

Image: 
Children's National in Washington, D.C.

Seventy-one of 110 Brazilian infants at the highest risk for experiencing problems due to exposure to the Zika virus in the womb experienced a wide spectrum of brain abnormalities, including calcifications and malformations in cortical development, according to a study published July 31, 2019 in JAMA Network Open.

The infants were born at the height of Brazil's Zika epidemic, a few months after the nation declared a national public health emergency. Already, many of the infants had been classified as having the severe form of congenital Zika syndrome, and many had microcephaly, fetal brain disruption sequence, arthrogryposis and abnormal neurologic exams at birth.

These 110 infants "represented a group of ZIKV-exposed infants who would be expected to have a high burden of neuroimaging abnormalities, which is a difference from other reported cohorts," Sarah B. Mulkey, M.D., Ph.D., writes in an invited commentary published in JAMA Network Open that accompanies the Rio de Janeiro study. "Fortunately, many ZIKV-exposed infants do not have abnormal brain findings or a clinical phenotype associated with congenital Zika syndrome," adds Dr. Mulkey, a fetal-neonatal neurologist in the Division of Fetal and Transitional Medicine at Children's National in Washington, D.C.

Indeed, a retrospective cohort of 82 women exposed to Zika during their pregnancies led by a research team at Children's National found only three pregnancies were complicated by severe fetal brain abnormalities. Compared with the 65% abnormal computed tomography (CT) or magnetic resonance imaging (MRI) findings in the new Brazilian study, about 1 in 10 (10%) of babies born to women living in the continental U.S. with confirmed Zika infections during pregnancy had Zika-associated birth defects, according to the Centers for Disease Control and Prevention.

"There appears to be a spectrum of brain imaging abnormalities in ZIKV-exposed infants, including mild, nonspecific changes seen at cranial US [ultrasound], such as lenticulostriate vasculopathy and germinolytic cysts, to more significant brain abnormalities, such as subcortical calcifications, ventriculomegaly and, in its most severe form, thin cortical mantle and fetal brain disruption sequence," Dr. Mulkey writes.

About three years ago, Zika virus emerged as a newly recognized congenital infection, and a growing body of research indicates the damage it causes differs from other infections that occur in utero. Unlike congenital cytomegalovirus infection, cerebral calcifications associated with Zika are typically subcortical, Dr. Mulkey indicates. What's more, fetal brain disruption sequence seen in Zika-exposed infants is unusual for other infections that can cause microcephaly.

"Centered on the findings of Pool, et al, and others, early neuroimaging remains one of the most valuable investigations of the Zika-exposed infant," Dr. Mulkey writes, including infants who are not diagnosed with congenital Zika syndrome. She recommends:

Cranial ultrasound as the first-line imaging option for infants, if available, combined with neurologic and ophthalmologic exams, and brainstem auditory evoked potentials

Zika-exposed infants with normal cranial ultrasounds do not need additional imaging unless they experience a developmental disturbance

Zika-exposed infants with abnormal cranial ultrasounds should undergo further neuroimaging with low-dose cranial CT or brain MRI.

Credit: 
Children's National Hospital

Multi-state switchable stationary phase opens new doors in chiral separation

image: Schematic illustration of three-state switchable chiral stationary phase based on macromolecular helicity modulation in a poly(phenylacetylene) derivative using metal cations in the column.

Image: 
Kanazawa University

Kanazawa, Japan - The concept of chirality can be challenging for the layperson, with "chemical handedness" seeming a very minor distinction. However, as the consequences of the notorious thalidomide disaster illustrate, understanding chiral materials is a major concern. The continued development of chiral separation techniques therefore remains a key research area. A team involving researchers from Kanazawa University has reported a three-state switchable chiral stationary phase (CSP) that provides new opportunities in chiral separation. Their findings are published in the Journal of the American Chemical Society.

Chiral high performance liquid chromatography (HPLC) remains the most effective method for separating chiral molecules. HPLC involves running samples through a tube--known as a column--containing chiral material (the CSP) that can differentiate between pairs of chiral molecules (enantiomers). However, owing to the numerous enantiomers that cannot be separated using currently available CSPs, research in this area remains ongoing.

The researchers report a CSP based on a helical polymer material containing a chiral pendant group that causes the polymer to adopt different conformations in response to metal ions. When Na+ ions are present the polymer is forced to adopt a left-handed helix so that the ions can interact with the aromatic component of the group. In contrast, when Cs+ ions are present the polymer is forced into a right-handed helix to facilitate bonding between the ions and the two oxygen atoms of the group. In the absence of ions the structure is a deactivated mixture of the two helices.

"Our experiments used a CSP based on a poly(phenylacetylene) derivative that can be altered using an achiral external stimulus," study lead author Daisuke Hirose explains. "This allowed us to control the chirality of the column, and hence the retention of enantiomers, simply by introducing metal salts. The metal ions caused the polymer switch to a particular chiral conformation; however, the effect could be reversed by eluting the column with methanol."

The stability of the ion-induced states was demonstrated over 4 days of continuous flow through the column, and the separation performance was exhibited by switching between the active and deactivated state numerous times.

"As far as we are aware, our system is the first reported example of a CSP that can be switched between three different recognition states using a stimulus that is not chiral," study corresponding author Katsuhiro Maeda explains. "We hope to build on our findings to extend the range of enantiomers that can be separated, which we believe will benefit numerous research areas such as drug discovery."

Credit: 
Kanazawa University

Psychotherapy should be first-line treatment for depression in young people, trial finds

video: Associate Professor Christopher Davey speaking on his research that shows that should be first-line treatment for depression in young people.

Image: 
Orygen, the National Centre of Excellence in Youth Mental Health

Young people seeking support for depression should be offered psychotherapy as the first line of treatment, a clinical trial by researchers at Orygen, the National Centre of Excellence in Youth Mental Health, has found.

Associate Professor Christopher Davey, head of mood disorder research at Orygen, said the clinical trial results emphasised the importance of a multi-faceted approach to treating depression in young people.

"The results suggest that we should really be focusing on providing good quality psychotherapy, such as cognitive behavioural therapy, to young people and keeping medication as the second line of treatment," Associate Professor Davey said.

Psychotherapy refers to a range of psychological therapies provided by a counsellor, psychologist or psychiatrist. Cognitive behavioural therapy is the most common psychotherapy for treating depression in young people.

The randomised, double blind, placebo-controlled clinical trial involved 153 young people aged 15-25 who had been diagnosed with depression and were being treated at youth mental health services in north-west Melbourne. All trial participants received cognitive behaviour therapy for 12 weeks coupled with either the common antidepressant fluoxetine or a placebo medication.

The trial results have been published in The Lancet Psychiatry.

Associate Professor Davey said at the end of treatment there were no significant differences in symptom improvement between the two groups, suggesting that the addition of fluoxetine did not affect the participants' mental health outcomes.

However, this does not suggest that antidepressants should not be used in treating depression.

"Antidepressants can be very useful for some people," Associate Professor Davey said. "Anyone considering the role of antidepressants in their treatment should discuss this with their doctor or clinician.

"Our study found some evidence to suggest that if antidepressants have a role, they have more of a role in people at the older end of our age range.

"The take-home message from the study is that the first-line treatment for young people with depression should be psychotherapy."

Credit: 
Orygen

Encapsulated Indian medicinal herb shows anti-diabetic properties in mice

Extracts of the herb Withania coagulans, or Paneer dodi, are used in traditional Indian medicine. Although some healers claim that W. coagulans can help treat diabetes, the bitter-tasting plant hasn't been studied extensively by scientists. Now, researchers have found that herbal extracts packaged in polymers derived from natural substances can reduce blood glucose levels in diabetic mice. They report their results in ACS Omega.

Alternative medicines are becoming increasingly popular for the treatment of chronic illness, primarily because of people's perception that plant-based medicines are less toxic and have fewer side effects. However, this is not always the case, and even so-called "natural" therapies must be carefully tested for efficacy, dose-related toxicity and interactions with other drugs. In addition, scientists must find ways to effectively deliver the medicines into the body in controlled ways. Many plant extracts, like W. coagulans, are bitter and unpalatable at the doses needed to have beneficial effects. Also, when taken orally, the medicinal components in plant extracts are often destroyed by the acidic conditions of the stomach. That's why Say Chye Joachim Loo and colleagues wanted to find a way to encapsulate W. coagulans extract in a delivery system based on natural components that could safely transport the extract to the small intestine, where the cargo would be released and absorbed.

From the berries of W. coagulans, the team extracted plant steroid compounds that increased insulin secretion by mouse pancreatic cells in a dish. The researchers encapsulated the steroids in chitosan nanoparticles made from shellfish exoskeletons and coated the particles with starch, which delayed release of the herbal extract under acidic conditions. Finally, diabetic mice that were fed the nanoparticles for 5 days showed about 40% lower blood glucose levels compared to their starting amounts. Surprisingly, even 5 days after the treatment ended, the mice showed a 60% reduction in blood glucose compared to their starting levels. This effect could arise from the ability of the delivery system to prolong the release of extract over an extended period of time, the researchers say.

Credit: 
American Chemical Society

Biosynthesized fibers inspired strong and tough artificial nanocomposite fibers

image: Schematic illustration of the fabrication process (a), structural characterization (b) and mechanical investigation (c) of the bioinspired hierarchical helical nanocomposite fibers.

Image: 
©Science China Press

High-performance biomass-based nanocomposites are emerging as promising materials for future structural and functional application due to their environmentally friendly, renewable and sustainable characteristics. Bio-sourced nanocelluloses (a kind of nanofibers) obtained from plants and bacterial fermentation are the most abundant raw materials on earth. They have attracted tremendous attention recently due to their attractive inherent merits including biodegradability, low density, thermally stability, global availability from renewable resources, as well as impressive mechanical properties. These features make them very appropriate building blocks for spinning the next generation of advanced macrofibers for practical applications.

In past decades, various strategies have been pursued to gain cellulose-based macrofibers with improved strength and stiffness. However, nearly all of them have achieved at the expense of elongation and toughness, because strength and toughness are always mutually exclusive for man-made structural materials. Therefore, this dilemma is quite common for previously reported cellulose-based macrofibers, which greatly limited their practical applications.

In a new article published in the National Science Review, Recently, a bionics research team led by Prof. YU Shuhong from the University of Science and Technology of China (USTC) sought an inspiration to solve this problem from biological structures. They found that the widespread biosynthesized fibers, such as some plant fibers, spider silk and animal hairs, all have some similar features. They are both strong and tough, and have hierarchical helical structures across multiple length scales with stiff and strong nanoscale fibrous building blocks embedded in soft and energy dissipating matrices.

Inspired by these structural features in biosynthesized fibers, they presented a design strategy to make nanocellulose-based macrofibers with similar structural features. They used bacterial cellulose nanofibers as the strong and stiff building blocks, sodium alginate as the soft matrix. By combining a facile wet-spinning process with a subsequent multiple wet-twisting procedure, they successfully obtained biomimetic hierarchical helical nanocomposite macrofibers, and realized impressive improvement of their tensile strength, elongation and toughness simultaneously as expected.

This achievement certifies the validity of their bioinspired design and provides a potential route for further creating many other strong and tough nanocomposite fiber materials for diverse applications.

Credit: 
Science China Press

Fragrance-releasing fabric could help neutralize sweaty gym clothes

Hot summer weather, stressful situations and intense workouts can produce unpleasant sweaty odors. But what if clothing could cover up these embarrassing smells with a burst of fragrance? Now, researchers have modified cotton fabric to emit a lemony citronella aroma upon contact with sweat. They report their body-odor-fighting strategy in ACS Applied Materials & Interfaces.

In recent years, scientists have developed smart fabrics that react to stimuli such as light, temperature or mechanical stress and respond in certain ways, such as by changing color or conducting an electrical signal. Researchers have also explored different methods to release fragrances from fabrics. Carla Silva, Artur Cavaco-Paulo and colleagues wanted to develop and compare two new strategies for releasing a fragrance -- β-citronellol, a lemongrass-derived scent used in some insect repellants -- from cotton fabric in response to sweat. 

The first approach involved an odorant-binding protein (OBP) found in pigs' noses that binds to β-citronellol and other scent molecules. To the OBP, the researchers attached a protein domain, called a carbohydrate-binding module (CBM), that binds to cotton. In their second strategy, the researchers packaged the fragrance in liposomes that displayed CBMs, which anchored the lipid carriers and their cargo to the fabric. The team exposed the modified cotton fabrics to an acidic sweat solution, and the low pH of the simulated perspiration caused the OBP and liposomes to release β-citronellol. Comparing the two strategies revealed that the OBP released a quick burst of scent, while the liposomes showed a slower, controlled release. The liposomes could also hold more fragrance than the other approach. The two strategies could prove useful for different clothing applications, the researchers say.

Credit: 
American Chemical Society

'Promising' antibody therapy extends survival in mice with pancreatic cancer

image: Professor John Marshall, Barts Cancer Institute, Queen Mary University of London

Image: 
Pancreatic Cancer Research Fund

Scientists have found a way to target and knock out a single protein that they have discovered is widely involved in pancreatic cancer cell growth, survival and invasion.

Called αvβ6, the protein is present on the surface of more than 80 per cent of pancreatic ductal adenocarcinoma (PDAC) - the most common form of pancreatic cancer - and is vital to increase the successful growth and spread of the tumour cells.

In a new study, published today in the Journal of Pathology, a team of researchers at Barts Cancer Institute, Queen Mary University of London, were able to confirm the prevalence of αvβ6 not only in primary cancer, but also in metastasised tumours that had spread from the pancreas to other organs in the body.

The study reports how a particular antibody, used in combination with leading pancreatic cancer drug, gemcitabine, successfully reduced tumour growth in the mice and delivered up to a sixfold increase in survival time, compared to the control.

The team say their results confirm that αvβ6 should be a focus for research into new antibody therapies for pancreatic cancer.

The study, funded by the national charity Pancreatic Cancer Research Fund, was led by Professor John Marshall. Key to its success was the University of Nebraska's Rapid Autopsy Programme, which allowed the researcher to access tissue samples from metastasised tumours as well as from primary tumours.

"Analysing these samples gave much richer data than in previous studies," explains Professor Marshall. "Previously we only looked at samples from tumours which had been surgically removed which, by definition, were not as far advanced. Using samples from the Rapid Autopsy Programme we were able to confirm the αvβ6 protein is retained when the cancer spreads and confirms its importance."

The team then developed PDAC tumours containing the αvβ6 protein which were put into mice and treated with a specific antibody called 264RAD, that was developed by the team in partnership with biopharmaceutical company, AstraZeneca.

Using a strain of mouse whose tumours closely mimic the human form of the disease, the team showed that they could increase the survival of the mice from an average of 10 days to up to 60 days using a combination of 264RAD and gemcitabine.

In particular, the researchers noted that the number of blood vessels in the tumour had decreased, and so had the number of fibroblasts - a type of cell that helps produce the framework of tissue, including tumours, and which also plays a critical role in wound healing. The tumour produces blood vessels and fibroblasts via a cell signalling protein called TGFβ - a protein that is normally activated by the body as part of its wound healing process.

Based on these results, the team have speculated that the protein αvβ6 is responsible for continually activating TGFβ and driving the production of blood vessels and fibroblasts to help the tumour grow.

Professor Marshall says: "When you cut yourself and the wound heals, it is this same αvβ6 activating TGFβ that tells blood vessels and fibroblasts to heal the wound. Cancer cells re-use these same skills from αvβ6 to help themselves.

"A scientist called Harold Dvorak at Harvard Medical School described cancer as a 'wound that does not heal'. Although he didn't know it, he could have been talking about αvβ6. So by targeting αvβ6, we also reduce TGFβ, which slows the cancer from developing."

Credit: 
Pancreatic Cancer Research Fund

First pictures of enzyme that drives new class of antibiotics

video: A multi-part enzyme called a nonribosomal peptide synthetase produces the highly reactive beta-lactone ring that is responsible for obafluorin's antimicrobial activity. Understanding how antibiotic scaffolds are constructed in nature can help scientists prospect for new classes of antibiotics through DNA sequencing and genome mining. For more information: doi.org/10.1038/s41467-019-11383-7

Image: 
Timothy Wencewicz, Washington University in St. Louis

Understanding how antibiotic scaffolds are constructed in nature can help scientists prospect for new classes of antibiotics through DNA sequencing and genome mining. Researchers have used this knowledge to help solve the X-ray crystal structure of the enzyme that makes obafluorin -- a broad spectrum antibiotic agent made by a fluorescent strain of soil bacteria. The new work from Washington University in St. Louis and the University at Buffalo is published July 31 in the journal Nature Communications.

A multi-part enzyme called a nonribosomal peptide synthetase produces the highly reactive beta-lactone ring that is responsible for obafluorin's antimicrobial activity.

"Obafluorin has a novel structure compared to all FDA-approved antibiotics," said Timothy Wencewicz, assistant professor of chemistry in Arts & Sciences. "In the long term, we really need new structural classes of antibiotics that have never been contaminated by clinical resistance from established antibiotic classes."

These chemicals could be used as next-generation antibiotics for humans, or even to benefit the agriculture sector, Wencewicz noted -- as researchers strive to engineer seed treatments and biopesticides to support plant systems capable of making enough food to feed the 9.6 billion people projected to live on this planet by 2050.

The new work provides a useful road map that shows how individual protein domains in the ObiF1 enzyme are stitched together in three-dimensional space. An enzyme's structure is fundamental to almost every function it performs.

"The solution of this structure expands on previous discoveries to provide views of the molecular interactions between catalytic domains in a brand new way," said Andrew M. Gulick, associate professor in the department of structural biology in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo. "This is a brand new class of compounds, and we've never had the molecular vision to appreciate how they are produced."

Pinning down a new antibiotic from nature

Obafluorin is made by a fluorescent strain of soil bacteria that forms biofilms on plant roots. Obafluorin was originally discovered in 1984, but it wasn't until 2017 that Wencewicz uncovered the genetic blueprint of the enzyme that makes the molecule's bio-active components. That discovery marked the first time that anyone had been able to pin down a beta-lactone forming enzyme from nature, and recreate it in the laboratory.

Like penicillin, obafluorin has a four-membered ring -- sometimes called an enchanted ring. A four-membered ring puts strain on bond angles that carbon prefers to adopt. But because a four-member ring is unstable, these molecules are also short-lived and difficult to make. For example, it took years for chemists to learn how to synthesize penicillin from chemicals and then figure out how fungi make it. This ultimately led to the global production of penicillin by fermentation.

Researchers in the Wencewicz laboratory were able to fast-track the discovery process using genetics to zero in on the biosynthetic machinery that bacteria use to make obafluorin, and then to reconstruct that multi-step, enzyme-catalyzed process in the laboratory.

Captured 'in the act'

For their new work, Wencewicz and Gulick, along with postdoctoral researcher Dale F. Kreitler (UB) and graduate students Jason E. Schaffer and Erin M. Gemmell (Washington University), mapped the full-length nonribosomal peptide synthetase (NRPS) that makes the bio-active components of obafluorin.

Gulick is an expert in NRPS systems and has published many of the seminal crystal structures of core pieces of these enzymes, as well as structures for full-length systems such as the one presented in this work.

The result is a comprehensive, detailed molecular structure at 3 Angstrom resolution that allows one to identify the atoms in the protein chain, see their location and points of contact along the chain, and determine how the pieces are assembled to produce useful molecules from start to finish.

"We were able to catch some of the building blocks of the molecules captured inside some of the enzyme-active sites -- in the act of doing the chemistry," Wencewicz said. "This helped us to connect small molecules to the protein, and fill in some of the mechanistic gaps in how the molecules are created."

This type of view is particularly important for the future goal of creating a chemical library, populated with related beta-lactone compounds that have been engineered for beneficial uses.

"We also got a very interesting glimpse at how the domains of the protein actually talk to each other," Wencewicz said. The crystal structures allowed them to see how key components of the enzyme dock to each other, and how molecules are efficiently moved through the entire NRPS assembly line.

One particular component -- something called an MbtH-like protein, or MLP, because it was first identified in a related system to produce mycobactin in the bacteria that causes tuberculosis -- was shown to play a critical role in facilitating protein-to-protein interactions between catalytic domains.

"Turns out, the (overall) protein suffers largely when you take away this very little protein that provides the critical handshake," he said. "It showed us once and for all that the coordination of these domains is absolutely critical to the function of making antibiotics with this enzyme."

Taken as a whole, the new paper is unique in its reach, the researchers said, presenting the X-ray crystal structure of the complete obafluorin-synthesizing enzyme ObiF1, probing the molecular mechanism for various key steps in the catalytic cycle, and establishing the conserved residues that enable formation of the reactive beta-lactone ring.

A key step in a long process

Finding an antibiotic from a source in nature is only a first step in a long process of drug development. With the structure and techniques reported in this new paper, it is now possible to quickly and easily create analogs of the natural product in the laboratory -- to optimize its molecular properties and bioactivity.

Gulick and Wencewicz plan to continue to apply their knowledge of the obafluorin biosynthetic pathway to discover new beta-lactone natural products using genomic and biochemical approaches.

"Given the structural diversity of known beta-lactone natural products, we believe that novel beta-lactone synthases remain to be discovered," Wencewicz said.

Washington University has filed for a U.S. utility patent covering this technology.

Credit: 
Washington University in St. Louis

Many North American indigenous youth experience symptoms of depression during adolescence

Studies of youth and their experiences with depression have tended not to include Indigenous youth. A new study that analyzed data on the development of depressive symptoms among Indigenous youth in the United States and Canada found that many of the youth had experienced these symptoms during adolescence. The study also identified the risks associated with developing symptoms of depression and how depressive symptoms were associated with alcohol use disorder.

The analyses were conducted by researchers at the University of Missouri and are published in Child Development, a journal of the Society for Research in Child Development.

"Our findings provide insight into the unique developmental patterns of symptoms of depression for Indigenous youth," notes Miriam M. Martinez, assistant research professor of human development and family science at the University of Missouri, who conducted the analyses.

"Since Indigenous youth may be at greater risk for psychological problems like depression due to their disproportionate exposure to stressful experiences, such as poverty, substance use and abuse, physical illness, and trauma from maltreatment, our findings can help clinicians and other mental health practitioners, including counselors and social workers, identify at-risk adolescents for targeted prevention and intervention."

Researchers interviewed 674 North American Indigenous adolescents annually from 2002 to 2009, starting when they were 11 to 12 years old and continuing until they were 17 to 18 years old. The youth were part of a longitudinal study by researchers at the University of Nebraska-Lincoln that examined culture-specific risk and resilience factors among Indigenous adolescents. That study was designed in partnership with three U.S. American Indian reservations and four Canadian First National reserves. Participants were youth who were part of Indigenous groups that were the original settlers of their regions, including Native Americans and Canadian First Nations. About half the participants reported a gross annual household income below $25,000.

Symptoms of depression were measured with a standardized diagnostic test that was adapted for cultural appropriateness. The study took into account the youth's gender, early puberty-related development, perceived experiences with discrimination, and a history of major depression in the youth's caregivers. The researchers also assessed the youth's use of alcohol.

The study found that the following Indigenous youth were at greater risk of experiencing high levels of depressive symptoms:

Girls and youth who perceived that they had experienced discrimination in early adolescence,

Teens who had early puberty-related development, and

Adolescents who had a primary caretaker with a history of major depression.

Youth who experienced sustained high levels of symptoms of depression had the greatest risk of developing an alcohol-use disorder during adolescence; almost 33% of the study's participants met the diagnostic criteria for this disorder by the time they were 17 and 18 years old.

Researchers also identified four developmental patterns of depressive symptoms in the participants:

Almost 37% of the youth had relatively low levels of depressive symptoms that decreased slightly over time,

7.6% of the youth had low initial levels of depressive symptoms that increased sharply after ages 13 and 14,

34% of the youth had high initial levels of symptoms of depression that increased slightly between ages 11 and 12 and ages 13 and 14, but decreased steadily after that, and

21% of the youth had high levels of symptoms of depression that were relatively stable across time.

The authors of the study caution that because they looked at youth from a single cultural group and because Indigenous populations differ, it is not possible to generalize their findings to Indigenous youth from other cultural groups.

"Our findings show that youth who felt they had been discriminated against when they were 12 were more likely to experience high levels of depression in early and later adolescence," explains Brian E. Armenta, assistant research professor of psychological sciences at the University of Missouri, who coauthored the study. "They also suggest that the mental health of Indigenous youth may be improved by addressing the ways they understand and respond to such discrimination."

"When parents or other caregivers, teachers, and mental health professionals teach ethnic-minority adolescents directly and indirectly to take pride in their heritage and how to cope with discrimination, it can reduce the negative consequences of these experiences." Armenta adds. "These lessons can also be integrated into existing prevention and intervention programs aimed at improving the well-being of Indigenous youth."

Credit: 
Society for Research in Child Development

How humans and chimpanzees travel towards a goal in rainforests

image: Chimpanzee inspecting a tree during a foraging trip on her own in the tropical rainforest of Taï National Park, Ivory Coast.

Image: 
Karline Janmaat

The human ranging style is unique among hominoids. The Mbendjele BaYaka people move from camp to camp every few months, and thus have a large lifetime range of approximately 800 square meters. Human foragers collect food and take it back to their camp to process and share. Furthermore, the Mbendjele BaYaka have created a trail system and walk mostly on trails. In contrast, one of our closest living relatives, chimpanzees, live in a relatively smaller area (25 square meters) and spend most of their adult lives within the same home range.

Chimpanzees consume food as they encounter it and make sleeping nests at variable locations within their home range. In addition, chimpanzees (especially, the chimpanzees living in the Taï National Park, Ivory Coast, where this research was conducted) rarely use the same paths when travelling on the ground. These different ranging styles between humans and chimpanzees might shape their different spatial experience and thus the way they travel through the forest to find food in their natural habitats.

Haneul Jang and her colleagues from the Max Planck Institute for Evolutionary Anthropology set out to study how human foragers and chimpanzees compare in their spatial movement patterns in similar rainforest environments. To this aim, the researchers measured travel linearity and speed of five Mbendjele BaYaka women from the Republic of Congo and five female chimpanzees from Taï forest when they travelled off-trail areas to out-of-sight food locations during their daily search for food in the rainforest.

Jang and her colleagues found that both the Mbendjele BaYaka people and Taï chimpanzees had, on average, similarly high levels of linearity when they travelled towards out-of-sight locations. However, the Mbendjele BaYaka and Taï chimpanzees clearly differed in the manner in which their travel linearity and speed changed with group size and familiarity with a foraging area. The Mbendjele BaYaka travelled with higher linearity in familiar areas compared to less familiar areas. This pattern was reversed in Taï chimpanzees - they moved with higher linearity and speed in less familiar areas compared to familiar areas.

"One possible explanation of these differences can be their different ranging style. The Mbendjele BaYaka people stay in several seasonal camps in their lifetime range, and walk 90 percent of their travel distance on human-made trails during their foraging trips in the forest. They may therefore have less experience in less familiar off-trail areas. Hence, when the Mbendjele BaYaka people forage in these areas, their travel linearity decreases due to their searching effort", says Haneul Jang, lead author of the study. On the contrary, chimpanzees decreased travel linearity and speed in more familiar areas. "Since chimpanzee groups can be highly hostile towards each other, they might need to travel more efficiently and faster in less familiar areas, where they are more likely to encounter other chimpanzee groups", says Jang.

In addition, Jang and her colleagues found that travel linearity increased in the Mbendjele BaYaka people and decreased in Taï chimpanzees when they travelled in a larger as compared to a smaller foraging group. "When I followed the chimpanzees, I often saw them wait for each other and have apparent disagreements about where to go", says Karline Janmaat, the main supervisor of the study. "With more individuals joining the group, disagreement seemed to increase. It is therefore perhaps not surprising that when group size increased, their travel became less linear. For the Mbendjele BaYaka people we found the opposite pattern. This can have many reasons, but I like to think that it is because humans can discuss, evaluate and eventually agree about where the best food sources are, by using language, and that this helped them to travel more efficiently."

According to the authors, this study is the first necessary step needed to compare long-range spatial movement patterns of human and chimpanzee populations in their natural habitats. "Our study provides insights into how two closely related species living in similar environments can differ in their spatial movement patterns, which possibly results from their different ranging styles", says Jang. "We hope our study can contribute to expanding comparative research on spatial movement patterns to a wide range of primate species and populations, including humans, in natural environments."

Credit: 
Max Planck Institute for Evolutionary Anthropology

Autonomic nervous system appears to function well regardless of mode of childbirth

image: This is Sarah B. Mulkey, M.D., Ph.D., a fetal-neonatal neurologist in the Division of Fetal and Transitional Medicine at Children's National and the study's lead author.

Image: 
Children's National in Washington, D.C.

Late in pregnancy, the human body carefully prepares fetuses for the rigors of life outside the protection of the womb. Levels of cortisol, a stress hormone, ramp up and spike during labor. Catecholamines, another stress hormone, also rise at birth, helping to kick start the necessary functions that the baby will need to regulate breathing, heartbeat, blood pressure and energy metabolism levels at delivery. Oxytocin surges, promoting contractions for the mother during labor and stimulating milk production after the infant is born.

These processes also can play a role in preparing the fetal brain during the transition to life outside the womb by readying the autonomic nervous system and adapting its cerebral connections. The autonomic nervous system acts like the body's autopilot, taking in information it needs to ensure that internal organs run steadily without willful action, such as ensuring the heart beats and eyelids blink at steady intervals. Its yin, the sympathetic division, stimulates body processes while its yang, the parasympathetic division, inhibits them.

Infants born preterm have reduced autonomic function compared with their full-term peers and also face possible serious neurodevelopmental impairment later in life. But is there a difference in autonomic nervous system function for full-term babies after undergoing labor compared with infants delivered via cesarean section (C-section)?

A team from the Children's National Inova Collaborative Research Program (CNICA) - a research collaboration between Children's National in Washington, D.C., and Inova Women's and Children's Hospital in Virginia - set out to answer that question in a paper published online July 30, 2019, in Scientific Reports.

They enrolled newborns who had experienced normal, full-term pregnancies and recorded their brain function and heart performance when they were about 2 days old. Infants whose conditions were fragile enough to require observation in the neonatal intensive care unit were excluded from the study. Of 167 infants recruited for the prospective cohort study, 118 newborns had sufficiently robust data to include them in the research. Of these newborns:

62 (52.5%) were born by vaginal delivery

22 (18.6%) started out with vaginal delivery but ultimately switched to C-section based on failure to progress, failed labor induction or fetal intolerance to labor

And 34 (28.8%) were born by elective C-section.

The CNICA research team swaddled infants for comfort and slipped electrode nets over their tiny heads to simultaneously measure heart rate variability and electrocortical function through non-invasive techniques. The team hypothesized that infants who had been exposed to labor would have enhanced autonomic tone and higher cortical electroencephalogram (EEG) power than babies born via C-section.

"In a low-risk group of babies born full-term, the autonomic nervous system and cortical systems appear to function well regardless of whether infants were exposed to labor prior to birth," says Sarah B. Mulkey, M.D., Ph.D., a fetal-neonatal neurologist in the Division of Fetal and Transitional Medicine at Children's National and the study's lead author.

However, infants born by C-section following a period of labor had significantly increased accelerations in their heart rates. And the infants born by C-section during labor had significantly lower relative gamma frequency EEG at 25.2 hours old compared with the other two groups studied.

"Together these findings point to a possible increased stress response and arousal difference in infants who started with vaginal delivery and finished delivery with C-section," Dr. Mulkey says. "There is so little published research about the neurologic impacts of the mode of delivery, so our work helps to provide a normal reference point for future studies looking at high-risk infants, including babies born preterm."

Because the research team saw little differences in autonomic tone or other EEG frequencies when the infants were 1 day old, future research will explore these measures at different points in the newborns' early life as well as the role of the sleep-wake cycle on heart rate variability.

Credit: 
Children's National Hospital