Culture

Synthesizing chemical-sensing cells from scratch

image: A study published in Journal of the American Chemical Society, synthesized artificial cells to detect histamine. When histamine was detected the artificial cells expressed an enzyme that digests the cell membrane, resulting in self-destruction.

Image: 
OIST

Baking a cake from scratch is a task deemed difficult for many. Constructing an artificial cell-like system from scratch, well that's another story.

"Synthesizing cells from scratch is of fundamental importance to understand what life is," said Prof. Yohei Yokobayashi, leader of the Okinawa Institute of Science and Technology Graduate University (OIST) Nucleic Acid Chemistry and Engineering Unit.

Scientists around the world are beginning to create simple artificial cells that conduct some basic biological functions and that contain small strands of DNA or RNA. However, getting these snippets of genetic material to express their encoded proteins in response to precise signals has been a challenge.

Now, Yokobayashi and other researchers from OIST and Osaka University have found a way to make artificial cells interact with a wide range of chemicals. They developed a riboswitch - a gene switch that senses chemical signals - that can respond to histamine, a chemical compound that is naturally produced in the body. In the presence of this chemical, the riboswitch turns on a gene inside the artificial cells. Such a system, could one day be used as a new way of administering medicine, said Yokobayashi, a corresponding author on a recent study in Journal of the American Chemical Society, which describes the approach.

"We want the cells to release drugs based on their detection of histamine," Yokobayashi said. "The ultimate goal is to have cells in your gut use histamine as a signal to release the appropriate amount of drug to treat a condition."

Signal selection

The scientists chose histamine as the chemical signal for their artificial cells because it is an important biological compound in the immune system. If you feel an itch, histamine is the likely culprit. It is also released by the body during allergic reactions and helps defend against foreign pathogens by spurring inflammation.

To detect histamine, they created a molecule called an RNA aptamer. RNA aptamers are small segments of RNA building blocks that can be engineered to act as binding agents to specific target molecules. It took Yokobayashi and his colleagues, former OIST postdocs Dr. Mohammed Dwidar and Dr. Shungo Kobori and OIST PhD student Charles Whitaker, two years to create an aptamer that targeted histamine.

Next, the team developed a so-called riboswitch that would turn this signal detection into action - specifically, translating a gene to produce a protein. Normally, cells produce proteins when templates made of messenger RNA (mRNA) bind to cellular structures called ribosomes. Here, the scientists used the histamine aptamer to design a riboswitch that alters the shape of the mRNA upon binding histamine. In the absence of histamine, the shape of the mRNA prevents the ribosome from binding, and no protein is produced. Histamine-bound mRNA, however, allows ribosome to bind and synthesize proteins.

"We demonstrated that riboswitches can be used to make artificial cells respond to desired chemical compounds and signals," Yokobayashi said.

The next step resulted from a collaboration with senior author Prof. Tomoaki Matsuura and graduate student Yusuke Seike of the Department of Biotechnology at Osaka University. Matsuura and Seike put the cell-free riboswitch created by Yokobayashi's team into lipid vesicles to create artificial cells. The Osaka team attached the riboswitch to a gene expressing a fluorescent protein, so that when the riboswitch was activated by histamine, the system glowed. Then, they controlled another protein by the riboswitch - one that makes nanometer-scale pores on the cell membrane. When the aptamer sensed histamine, a fluorescent compound encapsulated in the vesicles was released out of the cells through the pores, modeling how the system would release a drug.

The scientists also created a 'kill switch', which instructs the cell to self-destruct - creating a control for the technology.

The technology is in the early stages of development. The next step is to make the artificial cells more sensitive to a smaller amount of histamine. Medical use may be in the distant future, but the potential exists, the scientists say.

Credit: 
Okinawa Institute of Science and Technology (OIST) Graduate University

Genetic variation linked to response to anxiety could inform personalised therapies

A new study in marmoset monkeys suggests that individual variation in genes alters our ability to regulate emotions, providing new insights that could help in the development of personalised therapies to tackle anxiety and depression.

Some individuals are at greater risk of developing anxiety and depression than others and this depends in part upon the interaction between our genes and our environment, such as stressful or adverse events in our lives. Moreover, some of those who develop anxiety or depression may respond better to treatment while others struggle to benefit.

Although much research has been dedicated to finding effective treatments, we still have a poor understanding of how mental health disorders such as these develop and of the underlying brain mechanisms.

A study published today in PNAS has identified specific brain mechanisms that may underlie how genetic variation in the serotonin transporter gene, a key gene that regulates mood and stress responses, can influence the way we respond to perceived threat.

In a previous study working with marmoset monkeys, Dr Andrea Santangelo in the laboratory of Professor Angela Roberts at the University of Cambridge showed that the particular variant of the gene carried by a monkey will influence whether it perceives an ambiguous stimulus as being high or low threat. This characteristic of an individual's personality is called 'trait anxiety'.

High trait anxiety is a risk factor in humans for developing anxiety and mood disorders, and genetic variation in the serotonin transporter gene has been linked with an increased likelihood of developing these disorders.

In this earlier study, the researchers showed that variants of the gene also affected how a monkey responds to certain medicines. Specifically, individuals carrying the variant of the gene associated with high anxiety actually increased their anxiety towards a threat immediately after treatment with a commonly-used antidepressant known as a 'selective serotonin re-uptake inhibitor', or SSRI. This so called 'anxiogenic' effect is often seen in patients in the early stages of treatment and is thought to be part of the reason why these patients do not respond favourably to SSRIs.

In this new study, Dr Santangelo and Professor Roberts, along with colleagues including those at the Wolfson Brain Imaging Centre and Translational Neuroimaging Laboratory, have revealed how variation in the serotonin transporter gene has an impact on the number of a specific type of serotonin receptor, known as the type 2A receptor, in a specific brain area. Receptors are proteins in the brain that enable particular molecules - in this case serotonin - to affect the function of nerve cells. Monkeys carrying the variant of the gene associated with high anxiety had lower numbers of this receptor, hence changing the way in which serotonin-based drugs act upon them.

Medicines targeting these receptors have recently been used in the treatment of anxiety and mood disorders, so these findings suggest that it could be important in the future to know what variant of the serotonin transporter gene an individual is carrying when deciding on a treatment strategy.

The specific brain area where the number of receptors was reduced was the insula cortex, an important site for integrating information about sensations coming from the body with cognitive information processed in other areas to generate feelings and self-awareness, and to help guide decision-making.

This new finding suggests that those cognitive behavioural therapies (CBT) that focus on controlling sensations from the body could help patients in whom SSRI drugs are not effective.

"As many as one in three people affected by anxiety and depression does not respond to anti-depressants, so we need to find better treatments to help improve their quality of life," says Dr Santangelo from the Department of the Physiology, Development and Neuroscience at the University of Cambridge.

"Our research suggests that differences in our DNA may help predict which of us will respond well to these medicines and which of us require a different approach. This could be assessed using genetic testing."

Credit: 
University of Cambridge

Millet farmers adopted barley agriculture and permanently settled the Tibetan Plateau

The permanent human occupation on the Tibetan Plateau was facilitated by the introduction of cold-tolerant barley around 3600 years before present (BP), however, how barley agriculture spread onto the Tibetan Plateau remains unknown. Now by using both genetics and archaeological data, researchers from Kunming Institute of Zoology, CAS and Lanzhou University revealed that the barley agriculture was mainly brought onto the plateau by the millet farmers from northern China. Moreover, the genetic contribution from millet farmers largely promoted the formation of genetic landscape of the contemporary Tibetans. The work was reported on-line in the journal National Science Review.

According to archaeological evidence, before the permanent settlement of modern humans on the high altitudes of the plateau, the lower altitudes in the northeast Tibetan plateau was extensively occupied by the millet farmers during 5200 to 3600 BP. Interestingly, towards the end of this period (since about 4000 BP), a coexistence of indigenous millet and exotic barley-wheat cultivation appeared in the area, making it probable that the millet farmers adopted barley agriculture and further migrated onto the high altitudes. To test this possibility, the team analyzed large-scale mitochondrial DNA (mtDNA) data of current Tibetans (8277 samples) and the surrounding populations (58514 samples). Together with radiocarbon dating of cereal remains at different elevations, they identified two haplogroups (M9a1a1c1b1a and A11a1a), whose originations and migrations well matched the dispersal history of millet farming from northern China. Moreover, these components were also found in ancient DNA of human samples excavated from Neolithic sites in which millet was the most important crop (e.g., Yangshao and Majiayao cultural sites), thus would represent the genetic legacy of millet farmers that still retained in the contemporary Tibetans.

Additionally, these millet farmers' genetic components are common in contemporary Tibetans (20.9%), and were probably even more common (40%-50%) in early Tibetans at about 3300 BP (when the barley farmers had already settled on the high altitudes). Meanwhile, these components also contributed to the genetic differentiation between contemporary Tibetans and other East Asians. Therefore, the genetic contribution from Neolithic millet farmers played important roles in the formation of genetic landscape of the current Tibetans.

These results demonstrated substantial genetic components in the Tibetans could trace their ancestry back to the Neolithic millet farmers. The most probable explanation for this observation is that the millet farmers adopted and brought barley agriculture to the Tibetan Plateau and finally occupied the high altitudes permanently. This work thus provide deeper insights into dispersal model of barley agriculture onto the Tibetan Plateau, as well as the origin and migration history of the Tibetans.

Credit: 
Science China Press

Airless worms: A new hope against drug-resistant parasites

image: Parasitic nematodes, such as whipworms and hookworms, disproportionately affect developing nations with more than one billion people suffering from infections that can cause lasting damage and can also be lethal. This illustration of a whipworm is from an 1830 French zoology textbook.

Image: 
WikiMedia Commons

Over one billion people, including 880 million children, are infected with intestinal nematode worms, such as roundworms, hookworms and tapeworms, according to the World Health Organization. The infections are especially common in the developing world due to a lack of clean water and sanitation. If left untreated, they can leave a lasting mark on health and can also be lethal.

"We serendipitously discovered a new way to kill these parasites without harming the human host," says Andy Fraser, a professor of molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research at the University of Toronto.

"These parasites pose a major global health burden and as their resistance to the available drugs continues to grow, so does the need to develop new therapies," he says.

Learn more about how Donnelly Centre teams are tackling neglected parasitic diseases.

The work was led by three graduate students, Samantha Del Borrello, Margot Lautens and Kathleen Dolan, and in collaboration with Amy Caudy, also a professor of molecular genetics in the Donnelly Centre. Their findings are described in a study published online in eLife, an open-access journal.

Fraser's team were testing their new method for unpicking how drugs affect the movement of a nonparasitic nematode, Caenorhabditis elegans, used as a stand-in for humans by researchers across the world. But a fluke finding prompted them to use this lab worm as a model for parasites instead.

The first drug they tried was cyanide because its effects are well known and they wanted to make sure the new system works. Cyanide blocks respiration and, as expected, when added to the lab dish containing the worms, it quickly paralyzed them. But to the researchers' surprise, the worms did not die. They resumed wriggling about as if nothing happened when the drug was washed out 24 hours later.

"Our worms were clearly doing something very different to everything we knew about respiration in other animals," says Del Borrello.

It turned out that the cyanide made the worms switch to another, unusual form of metabolism that makes energy without needing oxygen. This type of anaerobic metabolism has been known to occur in parasitic worms, allowing them to survive for long periods of time in the airless confines of the gut. Instead of oxygen, these parasites rewire their metabolism to produce energy using a molecule called rhodoquinone, or RQ.

Crucially, humans do not make RQ. That makes it a perfect target for drug development because the drugs will selectively kill the parasites without touching their human host.

Having tricked the lab worm into making energy like a parasite, the team could now apply all the genetic and molecular tools that have been developed for C. elegans to begin to work out how RQ is made. This has remained an outstanding question in a field that has seen little progress since RQ was first discovered 50 years ago in parasitic worms, for which such tools still do not exist.

But first, they needed oysters. Oysters, and other coastal mollusks, are among the few organisms beside the nematodes that produce RQ, probably as an adaptation to changing oxygen levels brought about by tide turns. Because RQ is not commercially available, Dolan had to extract it from the oysters she bought at the store and use it to optimize the mass spectrometry instrument that was later used to detect RQ in worms.

Then began the hunt for the genes responsible. They tested about 80 different mutant worm strains before finding one unable to make the molecule--and thus unable to survive in cyanide-- indicating that the mutated gene is required for RQ biosynthesis. The gene, called kynu-1 (pronounced as 'kai-noo 1') turned out to code for an enzyme that carries out an early step in RQ synthesis. This finding upended widely accepted ideas about how RQ is made. Most importantly, it also showed them clear ways to try to block RQ synthesis with drugs.

Del Borello is now testing thousands of compounds to find candidates that kill C.elegans when it's using RQ and which could be developed into new drugs against parasites.

"It's great that we figured out the science behind it, but what I am most excited about is finding drugs that target the RQ-dependent metabolism," she says. "We haven't reached the tipping point quite yet in terms of drug resistance, but we also don't have anything in the pipeline to help out when we do."

They already have several promising candidates, which will next be tested on animals, such as mice and sheep, before moving on to human trials. But even if a drug for livestock could be found, it would help save agricultural industry billions of dollars estimated to be lost from lower productivity that is caused by nematode infections in farm animals.

From testing new equipment to solving parasite metabolism, the way the project turned out took everyone by surprise. "This was not at all what we expected when we started out," says Lautens who credits the whole team for their success. "That we've been able to contribute to a field that has not seen much progress in many years is a testament to how hard everyone's been working on it with a lot of different perspectives."

Credit: 
University of Toronto

Few US higher education campuses have gone completely smoke and/or tobacco-free

Just one in six accredited US colleges and universities have gone completely smoke and/or tobacco free, reveals the first study of its kind, published in the journal Tobacco Control.

As smoke-free environments have increased in the US and across the globe, so have smoke-free policies at colleges and universities. But, to date, it's not clear how many, and what proportion of, institutions have gone completely smoke or tobacco-free.

To try and find out, the researchers drew on data from the American Nonsmokers' Rights Foundation and the National Center for Education Statistics Integrated Postsecondary Education Data System.

They calculated the number and proportion of completely smoke-free and tobacco-free accredited institutions in the US that award degrees, and the number and proportion of US college and university students, faculty, and admin staff protected by campus policies and state laws.

They found that while some progress has been made, only 1 in 6 higher education institutions had gone completely smoke or tobacco free by 2017--equal to 823 institutions, representing 1816 individual campuses.

Four states--the District of Columbia, New Mexico, Nevada, Wyoming--and six territories, including the US Virgin Islands and Puerto Rico, had no known institutions that were fully protected.

Only three states and two territories had comprehensive policies in place in over half of their accredited, higher education institutions: Iowa (almost 86.5%); Arkansas (just under 62%); and North Dakota (55%); Guam (just under 67%); and the Northern Mariana Islands (100%).

The researchers estimated that 14.9 million full and part time college/university students (just under 27%) and 8.9 million (25.4%) faculty and admin staff were covered by strict smoke or tobacco free campus policies or state laws.

Despite some progress, efforts to implement comprehensive smoke and tobacco free policies at higher education institutions need to be stepped up, say the researchers.

"Continued success in increasing the adoption of comprehensive smoke free and tobacco free protections at institutions of higher learning will strengthen smoking prevention among non-smokers, increase quitting among current smokers, and protect youth and young adults from the negative health effects of exposure to secondhand smoke," they conclude.

Credit: 
BMJ Group

It's dog eat dog on the canine social ladder

image: The study focussed on a group of wild dogs living on the outskirts of Rome.

Image: 
Simona Cafazzo

Climbing the social ladder is a ruff business for dogs, new research shows.

Top dogs in a pack are known to assert their dominance, but scientists studied a group of free-roaming mongrels and found high levels of aggression in the middle of the dominance hierarchy.

Most theories predict more aggression higher up the ladder. However, the researchers say the difficulty of working out the pecking order in the crowded middle leads to aggression.

The research was carried out by the University of Exeter (UK) and by the Veterinary Service of the Local Health Unit Rome 3 (Italy).

"Our results reveal the unavoidable costs of climbing a dominance hierarchy," said Dr Matthew Silk, of the Environment and Sustainability Institute on the University of Exeter's Penryn Campus in Cornwall.

"In the middle of the hierarchy - where it's harder to predict which animal should be dominant - we see lots of aggression."

Professor Robbie McDonald said: "Fighting over food and mates uses energy and time and can lead to injuries, so hierarchies play an important role because animals know their place without needing to fight."

The year-long study examined a pack of 27 mongrel dogs that roamed freely in the suburbs of Rome.

The dogs did not live with humans, although they relied on humans for food.

Their hierarchy was based on age and sex, with adults dominant over younger dogs and males dominant over females of the same age group.

"Although fights within a social group of free-roaming dogs are usually characterised by low-intensity aggression, the middle of the hierarchy is occupied by young males of similar size and age, among whom nothing is definitive and for whom the challenge is to gain rank," said Dr Simona Cafazzo, of the University of Veterinary Medicine, Vienna.

"Our results confirm that these dogs have an age-graded dominance hierarchy similar to that of wolves," added Dr Eugenia Natoli, of the Veterinary Service of the Local Health Unit Rome 3.

Dominant behaviour included a stiff, upright body, holding the head and tail high and laying a paw on another dog's back.

Submissive behaviour included avoiding eye contact, holding the head and ears low and lying down with the chest and stomach exposed.

Credit: 
University of Exeter

Black hole brings down curtain on jellyfish galaxy's star turn

image: This is jellyfish galaxy JO201.

Image: 
Callum Bellhouse and the GASP collaboration

The role of an excited black hole in the death of an exotic 'jellyfish' galaxy will be presented today (3 July) by Callum Bellhouse of the University of Birmingham at the RAS National Astronomy Meeting in Lancaster. The supermassive black hole at the centre of jellyfish galaxy JO201 is stripping away gas and throwing it out into space, accelerating suppression of star formation and effectively 'killing' the galaxy. 

Jellyfish galaxies are spectacular objects that undergo a dramatic process of transformation as they plunge through the dense core of a galaxy cluster at supersonic speeds. External drag forces tear away the galaxy's gas, in a process known as ram-pressure stripping, leaving extended tentacles of trailing material. 

The fate of JO201 has been revealed as part of a study of 114 jellyfish galaxies by the GASP (GAs Stripping Phenomena) collaboration, an international team of researchers led by Dr Bianca Poggianti.

To explore the structure of the jellyfish galaxies in 3D and estimate the timescales of their transformation, Bellhouse has createdinteractive models that can also be experienced in virtual reality.

The study shows that JO201, originally a large spiral galaxy, has been diving through the massive cluster Abell 85 at supersonic speeds for around a billion years. As the jellyfish galaxy is travelling along the line of sight, its tentacles appear foreshortened in the model, but the team estimates that they trail 94 kiloparsecs behind JO201 -- about three times the diameter of our Milky Way.

"A galaxy sustains itself by constantly forming new stars from gas, so understanding how gas flows into and out of a galaxy helps us learn how it evolves. The example of JO201 shows how the balance tips towards then away from star-formation as it plunges through the galaxy cluster and faces increasingly extreme stripping of its gas," said Bellhouse.

JO201's transformation into a jellyfish galaxy has caused a brief increase in star formation due to the ram-pressure stripping process. Compressed clouds of gas have collapsed and formed a ring of stars in the disk of the galaxy. Dense knots in tentacles have condensed like rainclouds to begin forming new stars in the galaxy's wake.

However, the over the last few hundred million years, the black hole appears to have ripped away gas to leave a large void around the centre of the galaxy disc. The team believes that the ram-pressure stripping may have funnelled gas into the central parts of the galaxy, where it has provoked the black hole into blasting out material and creating a shock-wave that has left a cavity behind.

"An important balancing act occurs between processes which either boost or diminish the star formation rate in jellyfish galaxies. In the case of JO201, the central black hole becomes excited by the ram-pressure stripping and starts to throw out gas. This means that the galaxy is being hollowed out from the inside, as well as torn away from the outside," said Bellhouse.

"JO201 is, so far, a unique example of a supermassive black hole and ram-pressure stripping in quenching star formation in a jellyfish galaxy. Studying these curious objects gives us an insight into the complex processes that galaxies experience," said Bellhouse.

Interactive models

An interactive visualisation showing a 3D model of the distribution of stars and gas in the Jellyfish Galaxy JO201/JW100/JO194. The model is made using the spatial distribution of stars and gas on the sky, with the velocity along the line-of-sight giving the depth. Red=Hydrogen, Blue=Nitrogen, Green=Oxygen, White=stars. Credit: Callum Bellhouse and the GASP collaboration.

JO201: https://sketchfab.com/3d-models/3fb078406b6648a08f34869e7029fc3f

JW100: https://skfb.ly/6LyYp

JO194: https://skfb.ly/6LyY6

Credit: 
Royal Astronomical Society

Proliferation of JUUL-related content on Instagram likely to appeal to the young

There has been a proliferation of JUUL-related content on the photo and video sharing social media service, Instagram, that is likely to appeal to young people, reveals research published online in the journal Tobacco Control.

The posts feature product promotion, nicotine and addiction content, and references to youth culture, the analysis shows.

In the US, digital marketing of e-cigarettes on social media is unregulated, leaving the way clear for the vaping industry to aggressively market products like JUUL to young people, who are the heaviest users of social media platforms, say the researchers.

JUUL is a high tech vaping device that resembles a computer flash drive. It comprises a rechargeable battery and detachable pods--nicotine cartridges that come in various flavours.

Amid growing concerns about the increasing popularity of JUUL and other e-cigarette products and their potential to addict a new generation to nicotine, the researchers set out to analyse the amount and characteristics of JUUL-related posts on Instagram.

In all, they retrieved 14,838 relevant posts from 5201 individual users between 1 March and 15 May 2018, including all posts on the official JUUL account before it was deleted in November 2018.

Using a combination of machine learning methods, keyword algorithms, and human coding, primary posts were classified as featuring content related to product promotion; nicotine and addiction; youth culture, including memes, celebrities and music; and lifestyle, including social activities or identities.

A third of the posts (34%) contained overt promotional content that highlighted ways to obtain products at reduced cost, such as freebies and incentivised friend-tagging.

Around one in 10 (11%) of the posts contained information related to nicotine and addiction. These featured memes and hashtags about the positive effects of nicotine and compared nicotine's addictive nature to chocolate cravings or binge-watching Netflix.

Over half the posts (55%) featured youth culture or lifestyle-related (57%) content.

Youth-related content or lifestyle appeals were obvious within promotional posts and nicotine- and addiction-related posts.

"These findings bear a striking resemblance to the tactics used by the traditional tobacco industry to promote smoking as a socially acceptable behaviour and normalise the 'positive aspects of smoking and nicotine'," they write.

JUUL recently closed its official Instagram account, but voluntary action alone might not be enough, say the researchers, given the burgeoning category of JUUL-like e-cigarettes coming to market.

"Strong regulatory action is needed to restrict promotional efforts for e-cigarette products, particularly within social media platforms where youth participation is high," they conclude.

Credit: 
BMJ Group

Researchers identify maximum weight children should carry in school backpacks

image: Scientists carry out tests on schoolchildren with trolleys and backpacks.

Image: 
University of Granada

Researchers from the University of Granada (UGR) and UK-based Liverpool John Moores University have determined for the first time the maximum weight a child should carry using a school backpack trolley: a maximum of 20% of their body weight.

In an article published in the prestigious Applied Ergonomics journal, ranked second in the Ergonomics area of Journal Citation Reports, the scientists describe how they have established--in a worldwide first--recommendations on the appropriate load that primary school-age children should carry when using a backpack trolley.

To date, weight recommendations have been established for ordinary school backpacks, as they are the most widely used type in the school context worldwide. However, in Spain, more than 40% of children use backpacks on wheeled trolleys, and until now there have been no studies making weight recommendations for this type of backpack.

This research was conducted via a collaborative project involving researchers from the UGR (the Department of Physical Education and Sports and the Laboratory for the Analysis of Movement and Human Behaviour, Ceuta campus, or HubemaLab) and from Liverpool John Moores University.

Study focuses on Primary School pupils

In this study, 49 primary school pupils were assessed. A kinematic analysis of the children (posture of the trunk and lower limbs) was conducted while (i) they walked freely, carrying no weight, (ii) carrying a traditional backpack, and finally (iii) pulling a backpack trolley with different loads (10%, 15%, and 20% of their respective body weights).

For the analysis, a three-dimensional optical motion capture system was used, similar to those used in animation films and video games. In collaboration with the researchers from Liverpool John Moore University, the UGR researchers used statistical techniques to analyse the full kinematics curves, based on tracing point trajectories.

The main findings of the study indicate that the greatest alterations when using trolleys or backpacks are produced in the proximal extremities (hip and trunk), while there is little difference in the kinematics of the distal extremities (knee and ankle). However, pulling the backpack trolley produces fewer changes in the child's kinematics and, therefore, resembles more closely their movement when walking free of any load, compared to carrying the backpack, even when it weighs very little.

As an overall conclusion, the study corroborates that schoolchildren who use backpacks should avoid carrying loads greater than 10% of their body weight. Furthermore, in a new finding, when pulling a school backpack trolley, the child should avoid carrying any load greater than 20% of their body weight.

Credit: 
University of Granada

Long-term follow up is required to help maintain bone health in childhood cancer survivors

Advances in the treatment of children and adolescents with cancer have led to substantial improvements in survival, with a 5-year survival rate of childhood cancer close to 80%.

However, treatments such as chemotherapy and radiation can have long-term effects on bone health, potentially impacting on the attainment of peak bone mass, predisposing to premature onset of low bone mineral density, or causing other bone-related side-effects, such as impairment of bone quality or avascular necrosis of bone.

A new publication by the International Osteoporosis Foundation (IOF) Cancer and Bone Working Group reviews the latest knowledge in this area of clinical research and provides succinct recommendations for essential long-term follow-up of bone health in childhood cancer survivors. The review 'Bone health in childhood cancer: review of the literature and recommendations for the management of bone health in childhood cancer survivors' aims to help clinicians define specific groups at higher risk of long-term bone complications, identify unrecognized long-term adverse effects, and ultimately improve patient care. It includes a concise diagnostic-therapeutic algorithm which outlines a clinical pathway to aid physicians in the long-term care of their patients.

Professor Maria-Luisa Brandi, Head of the Bone Metabolic Diseases Unit, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Italy, and lead author of the study, states: "In children and adolescents treated for cancer, the attainment of peak bone mass, which is a fundamental factor affecting bone mass in adulthood, can be negatively affected. Lower bone mineral density and microarchitectural deterioration can persist during adulthood, thereby increasing fracture risk. That is why the bone health of children and adolescents with a cancer history should be carefully monitored, and patients should be informed of possible late complications of their previous medical treatment."

As well as cancer treatments such as chemotherapy, radiotherapy and stem-cell transplantation, factors which contribute to bone mass impairment in childhood cancer survivors include an inadequate diet (especially calcium and vitamin D deficiency); prolonged treatments with glucocorticoids; hormone alterations involving growth hormone and/or gonadal hormones; reduced or absent physical activity, and inflammation and altered secretion of cytokines due to cancer cells.

The review also points to areas where there are substantial knowledge gaps and identifies the need for further research to clarify whether improving bone health in childhood cancer survivors differs from the management of bone disorders in the general population.

Professor René Rizzoli, Chair of the IOF Cancer and Bone Working Group, added: "Cancer treatments in youth have a multifactorial impact on bone fragility and a core objective, both during treatment and once the patient is in remission or cured, is to reduce the impact on future adult bone health. This requires long-term follow up, involving effective transition from pediatric to adult care, as well as good communication between pediatric oncology and primary care. As clinicians we must work together to help to maintain and protect our young patients' skeletal health."

Credit: 
International Osteoporosis Foundation

Glow reveals dangerous bacteria

Salmonella and listeria are among the most widely distributed and deadliest causes of foodborne infections. Their rapid and reliable detection on food and industrial food processing equipment is very important. In the journal Angewandte Chemie, scientists have introduced a new, ultrasensitive, chemiluminescence-based method for the direct detection of Salmonella and Listeria monocytogenes. Because of the simplicity and sensitivity, this test is significantly faster than conventional methods and can be carried out in the field.

It is estimated that about a million people per year are infected with salmonella infections in the USA alone. Of these, 380 die. Infections with listeria can also often be fatal. Current testing methods usually require the growth of bacterial cultures in a containment laboratory. A conclusive result based on standard diagnostic techniques generally takes two to six days.

Researchers working with Urs Spitz and Doron Shabat at the University of Tel Aviv, Nemis Technologies AG (Zurich, Switzerland), Zurich University of Applied Sciences, and Biosynth AG (Staad, Switzerland) have now introduced a new and efficient method for the ultrasensitive and significantly faster detection of Salmonella and Listeria. The method is based on chemiluminescence--the emission of light resulting from a chemical process. The simplicity of the tests allows for both enrichment of the bacteria and their detection in a test tube, with no further sample preparation, so no containment laboratory is required. The chemiluminescence probes have proven to be about 600 times more sensitive than conventional fluorescence probes.

The success of this technique is due to two specially developed probe molecules made by combining a luminescent substance (a phenoxy-dioxetane) with a "trigger". In this form the probe does not light up. The trigger is tailored to the bacteria to be detected: it is recognized by a specific enzyme produced by the pathogen--a special esterase in the case of Salmonella and a special phospholipase C for Listeria--that splits it from the luminescent part. This initiates a chemical reaction that causes the luminescent molecule to split off more pieces. The energy released by the reaction is emitted in the form of a very intense green glow. Tests with various bacteria demonstrated that the probe tailored to Listeria test only reacts to Listeria monocytogenes, not to other, non-pathogenic, strains of listeria. The intensity of the glow can be used to quantify the concentration of bacteria. The tests are so sensitive that, for example, a count of ten salmonella can be detected within six hours of enrichment. Even dried bacteria can be swabbed from surfaces and detected.

The researchers are confident that their new method can be used more broadly to develop specific chemiluminescence probes for other bacteria.

Credit: 
Wiley

High brightness mid-infrared laser expands horizon of spectroscopic analytical technique

WASHINGTON -- Researchers have used an extremely bright mid-infrared laser to perform an analytical technique known as spectroscopic ellipsometry. The new approach captures high-resolution spectral information in less than a second and could offer new insights into quickly changing properties of a variety of samples from plastics to biological materials.

Spectroscopic ellipsometry measures how the polarization of light changes after interacting with a sample. When performed in the infrared portion of the spectrum, this approach can reveal detailed information about a sample's chemical composition and molecular orientation.

In The Optical Society (OSA) journal Optics Letters, researchers from the Research Center for Non Destructive Testing (RECENDT) GmbH and Johannes Kepler Universität, both in Austria, describe how they incorporated a mid-infrared quantum cascade laser (QCL) into a spectroscopic ellipsometry setup. This relatively new type of laser is at least 10,000 times brighter than the traditional light sources used for spectroscopic ellipsometry.

They showed that the QCL greatly improved the signal quality of the spectroscopic measurements and shortened the spectral acquisition time from several hours to less than a second, with further improvements possible as the new laser technology progresses. They also demonstrated that the technique can be used for real-time monitoring of molecular reorientation as a plastic film is stretched.

"Our method provides access to sample properties that couldn't be observed in real-time before," said Markus Brandstetter, head of the research team from RECENDT. "QCL ellipsometry could help improve manufacturing processes and the quality of the resulting product. It might also reveal previously unobservable physical and biological processes that would lead to new scientific discoveries."

A very bright light source

The mid-infrared QCL used by the researchers features a brightness level that exceeds even that of synchrotron sources, which are only available in specialized facilities. The laser's brightness means it can be used for mid-infrared spectroscopic ellipsometry of highly absorbing materials or substances, including those dissolved in water. "Because of the high mid-infrared absorbance of water, this has been very difficult or even unconceivable up to now," said Brandstetter.

The laser's emission wavelengths can be tuned over a broad mid-infrared range that matches perfectly with commercially available mid-infrared detectors. Another advantage is that it can be used for spectroscopic measurements without expensive and complex optical components such as monochromators or interferometers.

"The laser we used also offers the possibility of spot sizes that are restricted only by the diffraction-limit of light," said Jakob Kilgus, a member of the research team from RECENDT. "This can be exploited for ellipsometric measurements with high spatial resolutions, which will be of interest for both science and industry."

Making real-time measurements

To test their new system, the researchers compared it to an instrument considered the gold standard of commercial infrared spectroscopic ellipsometers. They also performed real-time measurements of the re-alignment of molecular chains as a polypropylene film was stretched.

"The new setup outperformed the standard acquisition time and signal-to-noise ratio by orders of magnitude," said Kilgus. "Our measurement of the polypropylene film was only limited by the speed of the stage used to apply the force. Much faster processes could be monitored with the setup."

The researchers point out that these are very promising, but preliminary, results. They plan to develop the instrument further and want to fully exploit the possibility of diffraction limited laser spots to acquire hyperspectral mid-infrared ellipsometry images -- which would contain the entire spectrum for each pixel of the image -- with reasonable acquisition times.

"We believe there will be a strong interest in this novel technique and the possibility of developing it for commercial use," said Brandstetter. "The sub-second time resolution combined with the high brightness of the laser will be useful for numerous industrial and scientific applications."

Credit: 
Optica

New epidemic forecast model could save precious resources

image: Taking into account the way an individual changes their behavior when faced with an outbreak can help researchers advise communities of the best use of their resources.

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Texas A&M Engineering

When governments and institutions deploy epidemic forecast models when facing an outbreak, they sometimes fail to factor in human behavior and over-allocate precious resources as a result. Thanks to new research authored by a Texas A&M University engineering professor, that may no longer be the case.

Dr. Ceyhun Eksin, lead author and assistant professor in the Texas A&M Department of Industrial & Systems Engineering and his colleagues at the University of California Santa Barbara and the Georgia Institute of Technology have published an article in the journal Epidemics that focuses on incorporating behavior change criteria into disease outbreak models.

Adding these criteria will allow professionals and communities to mobilize adequate resources during epidemic outbreaks and reduce public mistrust caused by the overallocation of resources.

"Our goal was to adapt these findings to forecast the disease trajectory, even if the initial information the model received was inaccurate," Eksin said. "The findings show there is value to incorporating a behavior aspect into forecast models."

A modified SIR model

The current models used to predict the impact of an outbreak, called simple susceptible-infected-recovered (SIR) models, do not take the changes in an individual's behavior into account and can over predict the number of infected individuals during an outbreak. This can lead to an overuse of resources.

The research team hypothesized that individuals would take action during an outbreak to reduce their exposure by avoiding infected individuals and as a result would change the number of individuals infected during the outbreak. To put this idea to the test, the researchers created a modified SIR model that included the ability to pick up a change in an individual's behavior.

By testing their modified model against the simple SIR model, Eksin and his colleagues were able to show that the modified model more accurately predicted outbreak numbers. By inputting past outbreak data into the modified models, they were able to predict the number of infected individuals more accurately.

Putting resources to better use

Predicting the number of individuals who will become infected during an outbreak is valuable to determine how to use limited resources, and interdisciplinary research can help understand the link between a public health response and behavior change. If a community is better able to plan for an outbreak, without over-preparing, it can save resources and reduce the possibility of losing public support during future outbreaks.

Credit: 
Texas A&M University

Carbohydrate in the heart seems to help regulate blood pressure

New research suggests that a particular type of carbohydrate plays an important role in regulating the blood pressure in the human body. This has been shown by researchers from the University of Copenhagen and Rigshospitalet in a new study using rats. The researchers believe that the finding may have a vast potential for improved medications for high blood pressure.

Both hypertension and hypotension can have adverse consequences for the health and lead to cardiovascular diseases and syncope, respectively. Now, researchers from the University of Copenhagen and Rigshospitalet know a little more about the factors that help regulate the blood pressure. The new research results have been published in the scientific journal, Journal of Biological Chemistry.

In interdisciplinary collaboration between researchers at the University of Copenhagen and Rigshospitalet, PhD student Lasse Holst Hansen found a particular form of carbohydrate or sugar on a particular peptide hormone in humans. In addition, in tests with rats the research team found that the peptide hormone with that particular form of sugar affects the regulation of the blood pressure. They hope that in the long term, their results can be used to develop better medications for hypertension.

'It may be a really good bet for a modern way to treat hypertension without side effects, such as syncope. It has long been known that this peptide hormone is extremely important for the blood pressure, but so far it has not been possible to use it in the treatment. This finding was only possible because we collaborated across disciplines and combined basic and clinical research,' says Professor Jens Peter Gøtze, Rigshospitalet, the Department of Clinical Biochemistry.

About one in five Danes has hypertension. This increases the risk of cardiovascular diseases, such as coronary thrombosis and heart failure. According to the Danish Heart Association, one in four Danes will die from cardiovascular diseases.

New Insight into Physiological Processes

The cells of the body use sugar to decorate proteins - a process also called glycosylation - in order to control the function and stability of the proteins. In the study, the researchers show how a particular type of sugar attach to a peptide hormone called atrial natriuretic peptide (ANP). This peptide hormone is secreted from the heart and is important for regulation of the blood pressure and the fluid balance in the body.

'We can see that when that particular sugar is located on the peptide hormone, it regulates the fluid balance and blood pressure differently than if the sugar is not located there. In our animal models, we could see that the peptide hormone with and without sugar behaves differently. It gives us an insight into a new mechanism for regulation of these important physiological processes in the body,' says Associate Professor Katrine Schjoldager, Copenhagen Center for Glycomics.

The next step for the researchers will now be in-depth studies of the function of that particular sugar and studies as to how the heart regulates the attachment of the sugar. At the same time, the researchers wish to investigate the function in humans to find out whether the phenomenon is more prevalent in some patient groups than in others, such as patients with heart failure.

Credit: 
University of Copenhagen - The Faculty of Health and Medical Sciences

DNA from tooth in Florida man's foot solves 25-year-old shark bite mystery

image: In the summer of 2018, Florida resident Jeff Weakley noticed a blister-like bulge on his foot. Chalking it up to a recent increase in running miles, he ignored it, but it continued to grow. When he finally tweezed it open, he found a tooth fragment from a shark that bit him in 1994. DNA from the tooth revealed he was bitten by a blacktip.

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Florida Museum photo by Kristen Grace

GAINESVILLE, Fla. --- When Jeff Weakley tweezed open a blister-like bulge on his foot, he was not expecting to find a piece of tooth from a shark that bit him while he was surfing off Flagler Beach in 1994.

He also did not imagine that a DNA test of the tooth, conducted by scientists at the Florida Museum of Natural History, would reveal the kind of shark that had nabbed his foot nearly a quarter century ago: a blacktip.

Weakley was planning to turn the small sliver of tooth into a pendant when he read about how researchers in the Florida Program for Shark Research identified the shark species responsible for a bite off New York by analyzing DNA from a tooth retrieved from the victim's leg.

He decided to offer the tooth to science.

"I was very excited to determine the identity of the shark because I'd always been curious," said Weakley, editor of Florida Sportsman magazine. "I was also a little bit hesitant to send the tooth in because for a minute I thought they would come back and tell me I'd been bitten by a mackerel or a houndfish - something really humiliating."

But Weakley's bite was the real deal, caused by Carcharhinus limbatus, a shark species commonly involved in bites in Florida.

The result came as no surprise to Weakley, who had always suspected a blacktip. But to Gavin Naylor, director of the shark research program, the fact that any viable DNA was left in the tooth fragment to analyze - after 24 years in Weakley's foot where it would have been attacked by his immune system - was a shocker.

"I had put our odds of success at slim to none," he said.

His doubts were shared by his laboratory manager Lei Yang who said he thought "it was kind of weird" to test the tooth, but was also intrigued to try.

"It was a mystery waiting for us to uncover," he said.

Yang cleaned the tooth of contaminants, removed part of the enamel and scraped pulp tissue from the tooth's cavity. He extracted DNA from the tissue, purified it, broke it into small pieces and then added molecular "bookends" on either side of each piece. These bookends made a genomic "library" out of the DNA, which Yang could then search for the sequences he needed to identify the shark. He compared the target sequences against two databases of shark and ray genetic information to determine Weakley had been bitten by a blacktip.

About 70 percent of shark bites are caused by unidentified species, and more precise data on which species are involved could improve bite mitigation strategies, Yang said. He also understood Weakley's personal curiosity.

"If I was bitten by a shark, I would want to know what it was," Yang said.

Weakley, who was bitten while surfing at a college beach mixer, said he was back in the water - foot encased in a waterproof bandage and bootie - within a couple of weeks. Twenty-five years later, he surfs and fishes weekly and regards the sharks he frequently sees in the same light as dogs that menace him when he jogs.

"I've been lucky to have not been bitten by a dog, but I would regard that interaction I had with that shark as being no different or more destructive than a dog bite," he said. "I certainly don't have a hatred of sharks or any feeling of vindictiveness toward them. They're part of our natural world."

But he doesn't wax romantic about them either.

"I've consumed blacktip shark and thought it was delicious."

Credit: 
Florida Museum of Natural History