Culture

PTSD partners feel invisible, study finds

Recognition of the needs of wives and intimate partners in supporting the recovery of veterans and front-line emergency workers affected by post-traumatic stress disorder (PTSD) has been highlighted in a new study led by Flinders University.

Their contribution to trauma recovery, and their own need for support, are not well understood by military and emergency service organisations, healthcare providers and government, the researchers found when they interviewed 22 partners of Australian veterans, paramedics, fire and police officers.

"We looked at partners in these groups because of the occupational exposure to trauma they experience," says Flinders Behavioural Health researcher Professor Sharon Lawn, project lead and author of a new article published in Health and Social Care in the Community.

"The key finding was that partners feel invisible in recovery. They live with the trauma that their partners experience but are still not acknowledged by health services or professional organisations (such as Department of Veterans' Affairs, Police, etc) as a vital part of the person's support system."

Feeling invisible was the barrier respondents felt to receiving the support they crave, says co-investigator Paula Redpath, a consultant psychotherapist and discipline lead - Flinders Behavioural Health.

"The participants' key concerns were to protect their family unit and relationship with their partner, showing many ways in which they managed, coped and adapted to myriad changes brought by the PTSD," she says.

However, many perceive that the strength of their commitment to their relationship, their contribution to the recovery of the veteran, and to what they do every day for the family, is largely invisible to the organisations and healthcare providers available to these occupations, the researchers conclude.

The article, ' " Why do you stay?": The lived-experience of partners of Australian veterans and first responders with Posttraumatic Stress Disorder' (April 2020) by E Waddell, S Lawn, L Roberts, J Henderson, A Venning and P Redpath has been published by Wiley DOI 10.1111/hsc.12998

The research, funded by veteran support network The Road Home, used a qualitative phenomenological approach, and inductive thematic analysis was undertaken on data collected in 2017-2018 through individual interviews with a purposive sample of 22 partners of veterans, paramedics, fire and police officers living in Australia.

Behavioural Health, based at Flinders University, has developed a wide range of tools and outreach services to facilitate support for self-management, so that health professionals can become truly collaborative with people with chronic conditions.

Credit: 
Flinders University

A study finds neuropeptide somatostatin enhances visual processing?

image: PV+ neurons receive perisomatic excitatory synaptic inputs that are innervated by axons of SST neurons.

Image: 
Professor Seung-Hee Lee, KAIST

Researchers have confirmed that neuropeptide somatostatin can improve cognitive function in the brain. A research group of Professor Seung-Hee Lee from the Department of Biological Sciences at KAIST found that the application of neuropeptide somatostatin improves visual processing and cognitive behaviors by reducing excitatory inputs to parvalbumin-positive interneurons in the cortex.

This study, reported at Science Advances on April 22nd (EST), sheds a new light on the therapeutics of neurodegenerative diseases. According to a recent study in Korea, one in ten seniors over 65 is experiencing dementia-related symptoms in their daily lives such like memory loss, cognitive decline, and motion function disorders. Professor Lee believes that somatostatin treatment can be directly applied to the recovery of cognitive functions in Alzheimer's disease patients.

Professor Lee started this study noting the fact that the level of somatostatin expression was dramatically decreased in the cerebral cortex and cerebrospinal fluid of Alzheimer's disease patients

Somatostatin-expressing neurons in the cortex are known to exert the dendritic inhibition of pyramidal neurons via GABAergic transmission. Previous studies focused on their inhibitory effects on cortical circuits, but somatostatin-expressing neurons can co-release somatostatin upon activation. Despite the abundant expression of somatostatin and its receptors in the cerebral cortex, it was not known if somatostatin could modulate cognitive processing in the cortex.

The research team demonstrated that the somatostatin treatment into the cerebral cortex could enhance visual processing and cognitive behaviors in mice. The research team combined behaviors, in vivo and in vitro electrophysiology, and electron microscopy techniques to reveal how the activation of somatostatin receptors in vivo enhanced the ability of visual recognition in animals. Interestingly, somatostatin release can reduce excitatory synaptic transmission to another subtype of GABAergic interneurons, parvalbumin (PV)-expressing neurons.

As somatostatin is a stable and safe neuropeptide expressed naturally in the mammalian brain, it was safe to be injected into the cortex and cerebrospinal fluid, showing a potential application to drug development for curing cognitive disorders in humans.

Professor Lee said, "Our research confirmed the key role of the neuropeptide SST in modulating cortical function and enhancing cognitive ability in the mammalian brain. I hope new drugs can be developed based on the function of somatostatin to treat cognitive disabilities in many patients suffering from neurological disorders."

Credit: 
The Korea Advanced Institute of Science and Technology (KAIST)

Atmospheric tidal waves maintain Venus' super-rotation

image: Venus - Computer Simulated Global View Centered at 90 Degrees East Longitude (NASA/JPL).

Image: 
NASA/JPL

Images from the Akatsuki spacecraft unveil what keeps Venus's atmosphere rotating much faster than the planet itself.

An international research team led by Takeshi Horinouchi of Hokkaido University has revealed that this 'super-rotation' is maintained near the equator by atmospheric tidal waves formed from solar heating on the planet's dayside and cooling on its nightside. Closer to the poles, however, atmospheric turbulence and other kinds of waves have a more pronounced effect. The study was published online in Science on April 23.

Venus rotates very slowly, taking 243 Earth days to rotate once around its axis. Despite this very slow rotation, Venus' atmosphere rotates westward 60 times faster than its planetary rotation. This super-rotation increases with altitude, taking only four Earth days to circulate around the entire planet towards the top of the cloud cover. The fast-moving atmosphere transports heat from the planet's dayside to nightside, reducing the temperature differences between the two hemispheres. "Since the super-rotation was discovered in the 1960s, however, the mechanism behind its forming and maintenance has been a long-standing mystery," says Horinouchi.

Horinouchi and his colleagues from the Institute of Space and Astronautical Science (ISAS, JAXA) and other institutes developed a new, highly precise method to track clouds and derive wind velocities from images provided by ultraviolet and infrared cameras on the Akatsuki spacecraft, which began its orbit of Venus in December 2015. This allowed them to estimate the contributions of atmospheric waves and turbulence to the super-rotation.

The group first noticed that atmospheric temperature differences between low and high latitudes are as small as it cannot be explained without a circulation across latitudes. "Since such circulation should alter the wind distribution and weaken the super-rotation peak, it also implies there is another mechanism which reinforces and maintains the observed wind distribution," Horinouchi explained. Further analyses revealed that the maintenance is sustained by the thermal tide -- an atmospheric wave excited by the solar heating contrast between the dayside and the nightside -- which provides the acceleration at low latitudes. Earlier studies proposed that atmospheric turbulence and the waves other than the thermal tide may provide the acceleration. However, the current study showed that they work oppositely to weakly decelerate the super-rotation at low latitude, even though they play an important role at mid- to high latitudes.

Their findings uncovered the factors that maintain the super-rotation while suggesting a dual circulation system that effectively transports heat across the globe: the meridional circulation that slowly transports heat towards the poles and the super-rotation that rapidly transports heat towards the planet's nightside.

"Our study could help better understand atmospheric systems on tidally-locked exo-planets whose one side always facing the central stars, which is similar to Venus having a very long solar day," Horinouchi added.

Credit: 
Hokkaido University

Conservation research on lynx

image: Scientists at the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) and the Leibniz Institute for Molecular Pharmacology (Leibniz-FMP) discovered that selected anti-oxidative enzymes, especially the enzyme superoxide dismutase (SOD2), may play an important role to maintain the unusual longevity of the corpus luteum in lynxes. It is highly likely that SOD2 not only detoxifies the reactive oxygen radicals in the cells, but also inhibits programmed cell death.

Image: 
Iberian lynx Ex-Situ Conservation Programme

Another piece of the puzzle about the longevity of the corpus luteum in lynxes has been uncovered. Scientists at the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) and the Leibniz Institute for Molecular Pharmacology (Leibniz-FMP) discovered that selected anti-oxidative enzymes, especially the enzyme superoxide dismutase (SOD2), may play an important role to maintain the unusual longevity of the corpus luteum in lynxes. It is highly likely that SOD2 not only detoxifies the reactive oxygen radicals in the cells, but also inhibits programmed cell death. The results were recently published in the scientific journal Scientific Reports of the Nature Group.

In contrast to other felids, Eurasian lynx, Canada lynx and Iberian lynx can only become pregnant once a year within a short period of conception. This restriction in terms of reproductive period is particularly observed in animals that live in strongly seasonal habitats, e.g. in the north with long winters or in southern Europe with hot and dry summers. The restriction ensures that the young are born at the optimal time of year, increasing their chances of survival. For endangered species such as the Iberian lynx this restriction of the reproductive season is a challenge for breeding in human care. In 2004, the Iberian lynx conservation breeding programme was established on the Iberian Peninsula to support the survival of the Iberian lynx. If a female Iberian lynx does not become pregnant or lose their young in the breeding programme, she can only contribute to the breeding programme one year later. It is therefore remarkable that husbandry and breeding success has been improved to such an extent that currently about 40 animals from the breeding programme are being released into the wild every year to support the decimated wild population of only a few hundred animals.

In order to understand why lynxes can only become pregnant once a year and how a new cycle is induced, it is necessary to study the mechanism of female reproduction. After the ovulation of egg cells, corpora lutea - hormone glands - are formed on the ovaries. They produce the hormone progesterone which prevents a new ovulation, an effect also used in the contraceptive pill. If a corpus luteum regresses at the end of the cycle or after birth, a new cycle can start. As the Leibniz-IZW reproduction team found out in previous studies, the lynx corpora lutea remain present and active for several years, they persist. "We suspect that the longevity of the corpus luteum and their release of progesterone are responsible for the strong seasonality of lynx reproduction," explains Beate Braun, scientist of the Department of Reproduction Biology at Leibniz-IZW.

Until now it was unclear how the longevity of the corpus luteum comes about. The scientists have now succeeded in solving part of this mystery. "We could show that anti-oxidative enzymes, especially superoxide dismutase (SOD2), is likely to contribute in a significant way to the regulation of corpus luteum longevity," says Beate Braun. The research team investigated ten anti-oxidative enzymes in fresh and older, at least one year old, corpora lutea of Iberian lynxes (Lynx pardinus) and Eurasian lynxes (Lynx lynx). The scientists recorded for different stages of the corpus luteum which enzyme was being produced, present and active. "The expression profiles of SOD2 showed remarkable differences between older corpora lutea of lynxes, fresh lynx corpora lutea and the corpora lutea of the domestic cat," explains Braun. SOD2 was conspicuous in the older lynx corpus luteum with very high expression and enzyme activity, whereas it played a subordinate role in the domestic cat in all corpus luteum stages. "We suspect that SOD2 in the older, long-lived/persistent, lynx corpora lutea has a classic anti-oxidative effect by transforming poisonous reactive oxygen radicals," says Katarina Jewgenow, head of the Department of Reproductive Biology. "During that process, SOD2 produces hydrogen peroxide, which is then broken down and converted into water by other enzymes. In addition, the hydrogen peroxide can function as a signaling molecule that protects the corpus luteum from programmed cell death and thus ensures its survival for several years," adds Jewgenow.

These new findings contribute to a better understanding of lynx reproduction and provide an important basis for further investigations into the regulation of corpus luteum development and longevity. The aim is to elucidate the complex mechanisms of female reproduction in lynxes step by step and provide lasting support for the conservation breeding of lynxes in human care through the use of assisted reproduction techniques such as ovulation induction and artificial insemination.

Credit: 
Forschungsverbund Berlin

Breakthrough in genome visualization

Kadir Dede and Dr. Enno Ohlebusch at Ulm University in Germany have devised a method for constructing pan-genome subgraphs at different granularities without having to wait hours and days on end for the software to process the entire genome. Scientists will now be able to create visualizations of pan-genomes on different scales much more rapidly.

The research article "Dynamic construction in pan-genome structures", was published in De Gruyter's open access journal Open Computer Science.

In order to analyze specific parts of a genome, scientists must be able to "see" the parts they are investigating, and this requires a large amount of processing power and time. The Computational Pan-Genomics Consortium encourages researchers to ensure that all information within a data structure is easily accessible for human eyes by visualization support on different scales. However, a pan-genome graph can have thousands to millions of nodes, which are not very easy for human eyes to visualize.

In an experiment, Dede and Ohlebusch used 10 human genomes and computed a graph that contains part of the large repetitive central exon of the human MUC5AC gene. Formerly, researchers had to create an entire index structure of the genomes, which takes about 8.5 hours and requires 38.5 GB of memory. Using the method developed by Dede and Ohlebusch, the researcher simply has to compute two bit-vectors (on which the construction of the subgraph is based) and the subgraph ? containing the reference path and its ?-neighborhood.

Instead of over eight hours, the software constructed the subgraph (including the computation of the bitvectors, which requires about 10 minutes) in only 24.5 minutes and required 39.6 GB of main memory; the subgraph itself required merely 15 KB of memory.

"Based on solid theory, Dede and Ohlebusch present a new method for the flexible and efficient exploration of suspicious genomic regions, highlighting for example pathogenic genes that distinguish new variants of a virus from all previously known genomes," said Prof. Dr. Jens Stoye, head of the Genome Informatics team, Faculty of Technology, Bielefeld University.

The open access paper can be found here: https://doi.org/10.1515/comp-2020-0018

Credit: 
De Gruyter

Wiring the quantum computer of the future: A novel simple build with existing technology

video: Scientists from Japan and Sydney have collaborated and proposed a novel two-dimensional design for a Quantum Computer that can be constructed using existing integrated circuit technology

Image: 
Tokyo University of Science, Japan

Quantum computing is increasingly becoming the focus of scientists in fields such as physics and chemistry, and industrialists in the pharmaceutical, airplane, and automobile industries. Globally, research labs at companies like Google and IBM are spending extensive resources on improving quantum computers, and with good reason. Quantum computers use the fundamentals of quantum mechanics to process significantly greater amounts of information much faster than classical computers. It is expected that when error-corrected and fault-tolerant quantum computation is achieved, scientific and technological advancement will occur at an unprecedented scale.

But, building quantum computers for large-scale computation is proving to be a challenge in terms of their architecture. The basic units of a quantum computer are the "quantum bits" or "qubits." These are typically atoms, ions, photons, subatomic particles such as electrons, or even larger elements that simultaneously exist in multiple states, making it possible to obtain several potential outcomes rapidly for large volumes of data. The theoretical requirement for quantum computers is that these are arranged in two-dimensional (2D) arrays, where each qubit is both coupled with its nearest neighbor and connected to the necessary external control lines and devices. When the number of qubits in an array is increased, it becomes difficult to reach qubits in the interior of the array from the edge. The need to solve this problem has so far resulted in complex three-dimensional (3D) wiring systems across multiple planes in which many wires intersect, making their construction a significant engineering challenge.

A group of scientists from Tokyo University of Science, Japan, RIKEN Centre for Emergent Matter Science, Japan, and University of Technology, Sydney, led by Prof Jaw-Shen Tsai, proposes a unique solution to this qubit accessibility problem by modifying the architecture of the qubit array. "Here, we solve this problem and present a modified superconducting micro-architecture that does not require any 3D external line technology and reverts to a completely planar design," they say. This study has been published in the New Journal of Physics.

The scientists began with a qubit square lattice array and stretched out each column in the 2D plane. They then folded each successive column on top of each other, forming a dual one-dimensional array called a "bi-linear" array. This put all qubits on the edge and simplified the arrangement of the required wiring system. The system is also completely in 2D. In this new architecture, some of the inter-qubit wiring--each qubit is also connected to all adjacent qubits in an array--does overlap, but because these are the only overlaps in the wiring, simple local 3D systems such as airbridges at the point of overlap are enough and the system overall remains in 2D. As you can imagine, this simplifies its construction considerably.

The scientists evaluated the feasibility of this new arrangement through numerical and experimental evaluation in which they tested how much of a signal was retained before and after it passed through an airbridge. Results of both evaluations showed that it is possible to build and run this system using existing technology and without any 3D arrangement.

The scientists' experiments also showed them that their architecture solves several problems that plague the 3D structures: they are difficult to construct, there is crosstalk or signal interference between waves transmitted across two wires, and the fragile quantum states of the qubits can degrade. The novel pseudo-2D design reduces the number of times wires cross each other, thereby reducing the crosstalk and consequently increasing the efficiency of the system.

At a time when large labs worldwide are attempting to find ways to build large-scale fault-tolerant quantum computers, the findings of this exciting new study indicate that such computers can be built using existing 2D integrated circuit technology. "The quantum computer is an information device expected to far exceed the capabilities of modern computers," Prof Tsai states. The research journey in this direction has only begun with this study, and Prof Tsai concludes by saying, "We are planning to construct a small-scale circuit to further examine and explore the possibility."

Credit: 
Tokyo University of Science

Falling visibility shows African cities suffering major air pollution increases -- study

Falling visibility in three major African cities reveals that air pollution has increased significantly over the last 45 years - leaving citizens facing further short-term increases in man-made pollution due to increasing urbanization and economic development, a new study reveals.

Africa is not well-equipped with air quality monitoring, so scientists have used visibility data for capital cities in Ethiopia, Kenya and Uganda as a substitute measurement.

They discovered a significant reduction in visibility since the 1970s, where Nairobi shows the greatest loss (60%), compared to Kampala (56%) and Addis Ababa (34%) - due to increased particulate matter (PM) emissions from vehicles and energy generation.

Correspondingly, PM pollution levels in the three cities are estimated to have increased by 182%, 162% and 62% respectively since the 1970s to the current period.

University of Birmingham experts published their findings in Environmental Research Letters. They are now calling for a systematic approach to understand the causes and effects of air pollution in urban East Africa - allowing improvements in air quality to co-exist with sustainable future economic development.

Report co-author Dr. Ajit Singh commented: "Evidence indicates that ambient air quality in urban African locations is often poor, because of high rates of urbanisation and population growth leading to large-scale construction, increased energy use, vehicle emissions and industrialisation.

"PM air pollution is a major concern in East Africa because of its impact on human health. There are few air quality monitoring networks, resulting in little long-term air quality data, but visibility measured at major cities can be used as a proxy for PM pollution.

"We're tremendously proud of our work in East Africa and the analysis techniques we developed to study Nairobi, Kampala and Addis Ababa are translatable to other parts of the world where air quality data is limited."

The Birmingham team's work is funded by the UK Department for International Development (DFID) through the East Africa Research Fund (EARF) grant 'A Systems Approach to Air Pollution (ASAP) East Africa' and Digital Air Quality (DAQ) - East Africa funded via EPSRC Global Challenges Research Fund.

Co-author Dr. William Avis commented: "Air pollution poses a major health, economic and social threat to cities around the world - inextricably linked to how we plan, manage and live in urban areas. East Africa is no exception to this, but lacks robust air quality data."

Co-author and ASAP lead Professor Francis Pope said: "We need to understand the causes and effects of air pollution in these three cities, which are rapidly developing and will likely experience further increases in PM. Poor air quality acts as a brake on development through increasing expenditure on health, loss of labour productivity, and the impact of illness on education.

"To date, no studies have been able to assess the role of socio-economic factors upon the evolution of air pollution in East Africa. Our work provides data that helps us understand this relationship and provides a much needed baseline for East African urban air quality that can help assess future air quality improvement interventions in the region."

The researchers compared changes in pollution to population growth and GDP statistics - finding increased PM levels linked to increases in national GDP and populations in all three study cities.

They also discovered distinct variations in seasonal visibility, which are largely explained by changing PM sources and sinks in rainy and dry seasons. Visibility was lowest during the dry months and highest in wet months. At all study sites, visibility was higher on Sundays - due to reduced traffic and industrial emissions.

Credit: 
University of Birmingham

Key nose cells identified as likely COVID-19 virus entry points

Two specific cell types in the nose have been identified as likely initial infection points for COVID-19 coronavirus. Scientists discovered that goblet and ciliated cells in the nose have high levels of the entry proteins that the COVID-19 virus uses to get into our cells. The identification of these cells by researchers from the Wellcome Sanger Institute, University Medical Centre Groningen, University Cote d'Azur and CNRS, Nice and their collaborators, as part of the Human Cell Atlas Lung Biological Network, could help explain the high transmission rate of COVID-19.

Reported today (23rd April) in Nature Medicine, this first publication with the Lung Biological Network is part of an ongoing international effort to use Human Cell Atlas data to understand infection and disease. It further shows that cells in the eye and some other organs also contain the viral-entry proteins. The study also predicts how a key entry protein is regulated with other immune system genes and reveals potential targets for the development of treatments to reduce transmission.

Novel coronavirus disease - COVID-19 - affects the lungs and airways. Patient's symptoms can be flu-like, including fever, coughing and sore throat, while some people may not experience symptoms but still have transmissible virus. In the worst cases, the virus causes pneumonia that can ultimately lead to death. The virus is thought to be spread through respiratory droplets produced when an infected person coughs or sneezes, and appears to be easily transmitted within affected areas. So far the virus has spread to more than 184 countries and claimed more than 180,000 lives*.

Scientists around the world are trying to understand exactly how the virus spreads, to help prevent transmission and develop a vaccine. While it is known that the virus that causes COVID-19 disease, known as SARS-CoV-2, uses a similar mechanism** to infect our cells as a related coronavirus that caused the 2003 SARS epidemic, the exact cell types involved in the nose had not previously been pinpointed.

To discover which cells could be involved in COVID-19 transmission, researchers analysed multiple Human Cell Atlas§ (HCA) consortium datasets of single cell RNA sequencing, from more than 20 different tissues of non-infected people. These included cells from the lung, nasal cavity, eye, gut, heart, kidney and liver. The researchers looked for which individual cells expressed both of two key entry proteins that are used by the COVID-19 virus to infect our cells.

Dr Waradon Sungnak, the first author on the paper from Wellcome Sanger Institute, said: "We found that the receptor protein - ACE2 - and the TMPRSS2 protease that can activate SARS-CoV-2 entry are expressed in cells in different organs, including the cells on the inner lining of the nose. We then revealed that mucus-producing goblet cells and ciliated cells in the nose had the highest levels of both these COVID-19 virus proteins, of all cells in the airways. This makes these cells the most likely initial infection route for the virus."

Dr Martijn Nawijn, from the University Medical Center Groningen in the Netherlands, said, on behalf of the HCA Lung Biological Network: "This is the first time these particular cells in the nose have been associated with COVID-19. While there are many factors that contribute to virus transmissibility, our findings are consistent with the rapid infection rates of the virus seen so far. The location of these cells on the surface of the inside of the nose make them highly accessible to the virus, and also may assist with transmission to other people."

The two key entry proteins ACE2 and TMPRSS2 were also found in cells in the cornea of the eye and in the lining of the intestine. This suggests another possible route of infection via the eye and tear ducts, and also revealed a potential for fecal-oral transmission.

When cells are damaged or fighting an infection, various immune genes are activated. The study showed that ACE2 receptor production in the nose cells is probably switched on at the same time as these other immune genes.

The work was carried out as part of the global Human Cell Atlas consortium which aims to create reference maps of all human cells to understand health and disease. More than 1,600 people across 70 countries are involved in the HCA community, and the data is openly available to scientists worldwide.

Dr Sarah Teichmann, a senior author from the Wellcome Sanger Institute and co-chair of the HCA Organising Committee, said: "As we're building the Human Cell Atlas it is already being used to understand COVID-19 and identify which of our cells are critical for initial infection and transmission. This information can be used to better understand how coronavirus spreads. Knowing which exact cell types are important for virus transmission also provides a basis for developing potential treatments to reduce the spread of the virus."

The global HCA Lung Biological Network continues to analyse the data in order to provide further insights into the cells and targets likely to be involved in COVID-19, and to relate them to patient characteristics.

Professor Sir Jeremy Farrar, Director of Wellcome, said: "By pinpointing the exact characteristics of every single cell type, the Human Cell Atlas is helping scientists to diagnose, monitor and treat diseases including COVID-19 in a completely new way. Researchers around the world are working at an unprecedented pace to deepen our understanding of COVID-19, and this new research is testament to this. Collaborating across borders and openly sharing research is crucial to developing effective diagnostics, treatments and vaccines quickly, ensuring no country is left behind."

Credit: 
Wellcome Trust Sanger Institute

Dietary counselling introduced in infancy leads to better cardiovascular health in adults

The Special Turku Coronary Risk Factor Intervention Project (STRIP) of the University of Turku, Finland, examines the benefits of promoting cardiovascular health by dietary counselling from infancy to early adulthood. Altogether 1,116 children and their families from Turku participated in the study starting when the children were 7 months of age.

Half of the children were randomly assigned to a group that received dietary counselling promoting a heart-healthy diet according to the nutritional recommendations. Other half were assigned to the control group who received only the basic health education given at Finnish maternity and child health clinics and school health care. The regular counselling that started in infancy ended when the participants turned 20.

"The research shows that regular dietary counselling starting in infancy has positive impact on the quality of fat in the diet, as well as on the serum cholesterol level, insulin sensitivity, and blood pressure. In addition, the clustering of adverse cardiovascular health markers is less common is the group that participated in the dietary counselling than in the control group", says Assistant Professor and vice principal investigator Katja Pahkala from the University of Turku.

After the dietary counselling aiming at better cardiovascular health ended, the participants were invited to a follow-up study at the age of 26. In 2015-2018, 551 people participated in the follow-up.

"The aim of the study was to investigate whether the persons who participated in the dietary counselling continued to have a more heart-healthy diet and a lower serum cholesterol level than the control group", says Pahkala.

Better cardiovascular health due to counselling

The first results of the follow-up study have now been published demonstrating that the diets of the people in the intervention group continue to be more heart-healthy. In addition, sustained beneficial effects are seen in the serum total and LDL serum cholesterol levels, which are still lower in the intervention than in the control group.

Furthermore, the insulin sensitivity of the persons who participated in the counselling was also better than in the control group.

"As a whole, the results support the idea that counselling on a heart-healthy diet starting in childhood has a positive impact on cardiovascular health, which is sustained after discontinuation of the active counselling", sums Pahkala.

Credit: 
University of Turku

Giant teenage shark from the Dinosaur-era

image: Hypothetical outlines of †Ptychodus showing the minimum and maximum size estimations for the sub-adult specimen from Spain.

Image: 
© Patrick L. Jambura

In 1996, palaeontologists found skeletal remains of a giant shark at the northern coast of Spain, near the city Santander. Here, the coast comprises meter high limestone walls that were deposited during the Cretaceous period, around 85 million years ago, when dinosaurs still roamed the world. Scientists from the University of Vienna examined this material now and were able to assign the remains to the extinct shark family, Ptychodontidae, a group that was very specious and successful in the Cretaceous but suddenly vanished mysteriously before the infamous end-Cretaceous extinction event.

Shark vertebrae are rare in the fossil record, but precious

Ptychodontid sharks are mainly known from their teeth, which are flattened and allowed them to crush hard-shelled prey, like bivalves or ammonites, similar to some of today's ray species. However, the find of Spain consists only of parts of the vertebral column and placoid scales (teeth-like scales), which are much rarer than teeth in the fossil record.

In contrast to teeth, shark vertebrae bear important information about a species' life history, such as size, growth and age, which are saved as growth rings inside the vertebra, like in the stem of trees. Statistical methods and the comparison with extant species, allowed the scientists to decode these data and reconstruct the ecology of this enigmatic shark group.

Ptychodontid sharks grew big and old

"Based on the model, we calculated a size of 4-7m and an age of 30 years for the examined shark. Astonishing about this data is the fact that this shark was not yet mature when it died despite its rather old age." states Patrick L. Jambura, lead author of the study. Sharks follow an asymptotic growth curve, meaning that they grow constantly until maturation and after that, the growth curve flattens resulting from a reduced growth rate. "However, this shark doesn't show any signs of flattenings or inflections in the growth profile, meaning that it was not mature, a teenager if you want. This suggests that these sharks even grew much larger (and older)!"

The study suggests that ptychodontid sharks grew very slow, matured very late, but also showed high longevity and reached enormous body sizes. "This might have been a main contributor to their success, but also, eventually, demise."

Do modern sharks face a similar fate?

Many living sharks, like the whale shark or the great white shark, show very similar life history traits, a combination of low recruitment and late maturation, which makes them vulnerable to anthropogenic threats, like overfishing and pollution.

"It might be the case that similar to today's sharks, ptychodontid sharks faced changes in their environment, to which they could not adapt quick enough and, ultimately, led to their demise before even dinosaurs went extinct. However, unlike in the Cretaceous period, it is up to us now, to prevent this from happening to modern sharks again and to save the last survivors of this ancient and charismatic group of fishes!"

Credit: 
University of Vienna

'Designer virus' is first new polio vaccine in 50 years

Before being halted due to the COVID-19 pandemic, a relentless vaccination campaign had nearly succeeded in eradicating polio from the world. Between 2000 and 2017, the World Health Organization (WHO) estimated that its campaign had reduced the burden of the disease by 99 percent, preventing more than 13 million children from becoming infected and risking potentially debilitating paralysis.

But in recent years, the eradication effort has been plagued by outbreaks of vaccine-derived polio -- in which the weakened virus used in oral polio vaccines evolved the ability to escape from vaccinated individuals and spread in communities with poor vaccination rates.

Now, with support from the Bill and Melinda Gates Foundation, UC San Francisco virologist Raul Andino, PhD and Andrew Macadam, PhD, of the UK's National Institute for Biological Standards and Control (NIBSC) report promising Phase 1 clinical results for the first new oral polio vaccine in 50 years, which they have designed to be incapable of evolving the ability to cause disease in humans.

In a 2017 study, Andino and colleagues discovered that in every vaccine-derived polio outbreak they studied, the virus had used the same three evolutionary steps to mutate from harmless vaccine into a regional menace.

In their new study, published April 23, 2020 in Cell Host and Microbe, Andino, Macadam, and colleagues at the Gates Foundation, the Center for Vaccine Innovation and Access in Seattle, and the Centre for the Evaluation of Vaccination at the University of Antwerp have employed clever genetic wizardry based on decades of study of the poliovirus's biology to redesign the vaccine to ensure that is incapable of following this three-step pathway to re-evolve virulence. Specifically, they stabilized a region of the viral genome that is required for it to re-evolve the ability to infect humans, and ensured that the virus could not get rid of this modification even by exchanging genetic material with related viruses.

"To my knowledge, this is the first effort to rationally design a live attenuated virus based on detailed understanding on its biology, as opposed to the standard approach of blindly passaging the virus in animal cells to eliminate human virulence through poorly understood mechanisms," said Andino, a professor of microbiology and immunology at UCSF.

The new study presents results of a double blinded phase 1 clinical trial conducted in 15 adult volunteers at the University of Antwerp, all of whom had previously been vaccinated with an inactive vaccine composed of shredded virus particles to ensure they could not be made sick by the live vaccine.

The trial found that the new designer polio vaccine was both more stable and more effective than the 50-year old Sabin vaccine from which it was derived. Specifically, the new vaccine caused participants to generate plentiful antibodies against the poliovirus, and despite shedding viral particles in their stool, those particles were unable to infect or cause paralysis in mice. In contrast, previous studies have found that when mice are exposed to viral samples shed by people vaccinated with the standard Sabin oral polio vaccine, as many as 90 percent develop paralysis.

A phase 2 trial is currently underway and shows promise, Andino said, and the WHO is planning a phase 3 trial, hoping to fast-track development of the vaccine as an emergency measure to contain these outbreaks of vaccine-derived polio.

Applying Polio's Lessons to Search for COVID-19 Vaccine

In the wake of the suspension of the WHO's polio eradication efforts during the COVID-19 crisis, Andino's lab is now applying all they've learned designing polio vaccines to the search for new approaches for a SARS-CoV-2 vaccine, including developing a mouse model to better understand exactly how the virus spreads and causes disease.

Dozens of other COVID-19 vaccine efforts are going after the low-hanging fruit of traditional vaccination using isolated viral particles or more advanced RNA-based vaccination, but Andino is working to understand the biological pathways within the virus that might be most amenable to transformation into a safe but effective live attenuated vaccine that could be rapidly produced for worldwide distribution.

"I believe the lesson of polio is that it will take time to develop an optimal vaccine against SARS-CoV-2, and early efforts are likely to meet with unexpected challenges," Andino said. "Once we do have safe and effective vaccines, they'll need to be produced at global scale, which will probably require the use of older technologies that are already in place. Given how little we know about this new coronavirus, I'm betting we'll need all the weapons we can muster."

Credit: 
University of California - San Francisco

Study shows fewer kids enrolling in cancer clinical trials

image: Kelly Faulk, MD, and colleagues show lower clinical trial enrollment for pediatric cancer patients.

Image: 
University of Colorado Cancer Center

Historically, pediatric cancer patients have been much more likely than adult cancer patients to enroll in clinical trials as part of their treatment. Now a study by University of Colorado Cancer Center researchers working at Children's Hospital Colorado shows pediatric oncology clinical trial enrollment may be down, from 40-70 percent seen in studies completed in the 1990s, to 20-25 percent in the early 2000s, to 19.9 percent in the current study.

"Childhood cancer is rare overall," says the study's first author, Kelly Faulk, MD, CU Cancer Center investigator and pediatric oncologist at Children's Hospital Colorado, "so historically high enrollment rates to clinical trials has been integral to improving outcomes for our patients."

The study used the Surveillance, Epidemiology, and End Results (SEER) database to estimate the overall number of pediatric cancer cases from 2004-2015, and then compared overall cancer numbers to the number of patients enrolled in clinical trials with the Children's Oncology Group (COG), the largest pediatric oncology cooperative group.

"The potential reduction in enrollment isn't all bad news," says Faulk. "One reason trial enrollment may be decreasing is that good treatments have been developed for some of the most common childhood cancers, thereby shifting the focus and resources toward opening trials for higher risk, but often more rare cancers."

Additionally, pediatric cancers tend to have fewer mutations than adult cancers, offering fewer genetic targets for the kinds of new drugs being tested in many clinical trials. And, Faulk points out, historically low funding for pediatric cancer research limits the ability to open new trials.

Unlike many studies of adult trial enrollment, the current study found no significant racial, ethnic, or socioeconomic disparities within pediatric trial enrollment. Faulk says this highlights the accessibility of COG trials to U.S. patients and also points out that children may be more likely than adult patients to be covered by public insurance options like Medicaid.

However, the study does reveal a group of cancer patients that has historically and continues to under-enroll in clinical trials, namely adolescent and young adult (AYA) patients from ages 15 to twenty-nine.

"They can feel lost between pediatric and adult cancer care, and unfortunately these AYA patients represent a population that has failed to see the same improvements in outcomes that their younger counterparts have," Faulk says. "Given their age and other socioeconomic factors, they may not see doctors as often and commonly suffer from suboptimal health insurance coverage."

To respond to this need, COG trials have increased age eligibility limits on many trials to include patients in this AYA population. Likewise, Faulk would continue to encourage adult cooperative groups to lower their age restrictions to provide more overlap with the upper range of pediatric trials.

"We feel this study is a useful evaluation of pediatric and AYA trial enrollment, representing important shifts in the way we design and test new treatments, and highlighting areas where we can continue to improve our use of clinical trials to give our patients the best possible options," Faulk says.

Credit: 
University of Colorado Anschutz Medical Campus

New test for COVID-19 may deliver faster results to more people

Philadelphia, April 23, 2020 - The COVID-19 pandemic has resulted in over 2.5 million confirmed cases worldwide and nearly over 170,000 deaths as of April 21 according to the World Health Organization1. Early identification of potential patients and diagnosis followed by isolation are critical for controlling the current pandemic and flattening the curve. This study describes a novel method that may enable decentralized facilities to deliver faster test services for COVID-19 to more people, reports the Journal of Molecular Diagnostics, published by Elsevier.

Diagnostic testing for SARS-CoV-2, the causative viral pathogen of COVID-19, is critical to detecting the virus, understanding its epidemiology, informing case management, and suppressing transmission. Diagnosis currently relies mainly on methods involving RT-qPCR (reverse transcription quantitative PCR), but their capacity is limited by the availability of high-level facilities and instruments.

Lead investigator Jin-Soo Maeng, PhD, Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, and Research Group of Food Processing, Korea Food Research Institute, Wanju-gun, Republic of Korea, and colleagues developed and evaluated RT-LAMP (reverse transcription loop-mediated isothermal amplification) assays to detect genomic RNA (ribonucleic acid) of SARS-CoV-2. RT-LAMP is a one-step nucleic acid amplification method that is used in the diagnosis of infectious diseases caused by bacteria or viruses.

The investigators first designed LAMP primer sets targeting genomic regions specific to SARS-CoV-2 compared to other human pathogenic coronaviruses. Through subsequent screening for sensitivity and reaction time, they found two promising LAMP primer sets. They then optimized RT-LAMP reactions for each of the two sets and evaluated the limit of detection and the specificity to other coronaviruses.

The RT-LAMP assays in this study were able to detect as low as 100 copies of SARS-CoV-2 RNA. Cross-reactivity of RT-LAMP assays to other human coronaviruses was not observed. The primer sets were used as the starting point and coupled with crystal violet colorimetric detection, which may increase test throughput. The reaction can be performed and interpreted with a very simple instrument such as a drying oven or water bath. The performance of assays may be further modified by adopting other detection methods and using other enzyme systems.

"Isothermal nucleic acid amplification tests such as RT-LAMP have the potential to be used at the point-of-care with sensitivity comparable to that of the current RT-qPCR tests," noted Dr. Maeng. "Although the proper extraction of sample RNA is still required, our RT-LAMP method has the potential to be run in decentralized test facilities to provide faster test services to more people."

"Although RT-qPCR is the gold standard for detection of pathogens because of their high sensitivity and specificity, there are still some caveats," explained Dr. Maeng. "Centralized testing laboratories, with facilities such as a reliable supply of electricity, expensive instruments, and trained personnel, are required to properly perform RT-qPCR tests. Ideally, screening tests have to be not only sensitive, but also simple and fast so that they can be performed at point-of-care. The main goal of our research was to identify a method with high diagnostic potential that may operate in decentralized facilities."

RT-qPCR measures the amount of a specific RNA, a polymeric molecule essential in various biological roles in coding, decoding, regulation, and expression of genes. Other molecular assays that detect the pathogen are also in development.

Credit: 
Elsevier

Icelandic DNA jigsaw-puzzle brings new knowledge about Neanderthals

image: DNA of Icelanders provides new knowledge about extinct human species

Image: 
Astrid Reitzel, Aaarhus University

An international team of researchers has put together a new image of Neanderthals based on the genes Neanderthals left in the DNA of modern humans when they had children with them about 50,000 years ago. The researchers found the new pieces of the puzzle by trawling the genomes of more than 27,000 Icelanders. Among other things, they discovered that Neanderthal women gave birth when they were older than the Homo-Sapien women at that time, and Neanderthal men became fathers when they were younger.

It is well-known that a group of our ancestors left Africa and, about 50,000 years ago, met Neanderthals in Europe, and then had children with them.

Now, a new analysis shows that the Neanderthals may have had children with another extinct species of human (Denisovans), before they met Homo Sapiens, and that these children have been fertile and transferred genes from both species further on to modern people.

The analysis also shows that the Neanderthal women living 100,000 - 500,000 years ago on average became mothers at a later age than the contemporary Homo-Sapien women living in Africa. On the other hand, Neanderthal men fathered at a younger age than their Homo-Sapien cousins in Africa.

How can an analysis show all that?

Neanderthals may well be extinct, but small pieces of their DNA live on in us. All living people outside Africa have up to two per cent Neanderthal genes in their DNA.

However, this two per cent is scattered as small fragments in our genomes, and not all individuals have inherited the same fragments. The fragments are like pieces of a jigsaw puzzle, and if they are put together correctly, they will show a picture of the genome in the Neanderthal population that the modern Homo Sapiens had children with.

New method to find the pieces

First, of course, we have to find these pieces. And this is precisely what the group of researchers from Denmark, Iceland and Germany did to produce their results, published today in the scientific journal Nature.

One of them, Laurits Skov, postdoc from the Bioinformatics Research Centre (BiRC) at Aarhus University, has developed a method for tracing Neanderthal fragments in our DNA. Laurits and PhD student Moisès Coll Macià took the method to Iceland, where the genetics firm deCODE has amassed genetic data and health information for more than half of the Icelandic population.

"We spent several months at deCODE in Reykjavik on what can be called field studies for a computational biologist. By combining my method with deCODE's data and expertise, we have analysed 27,566 genomes, and this makes our study 10-times larger than previous studies of Neanderthal genes in human DNA," says Laurits Skov.

Together, the many fragments account for approximately half of a complete Neanderthal genome.

Denisovan genes gone astray?

However, the researchers also found significant fragments of genetic material from another archaic species of human, Denisovans, in the DNA of the Icelanders, and this was something of a surprise. Up to now, Denisovan genes have primarily been found in Australian Aborigines, East Asians and people in Papua New Guinea. So how did these genes end up in Islanders' DNA? And when?

Based on the distribution of genes and mutations, the researchers came up with two possible explanations.

Either Neanderthals had children with Denisovans before they met the Homo Sapiens. This would mean that the Neanderthals with whom Homo Sapiens had children were already hybrids, who transferred both Neanderthal and Denisovan genes to the children.

"Up to now, we believed that the Neanderthals modern people have had children with were "pure" Neanderthals. It's true that researchers have found the remnants of a hybrid between Denisovans and Neanderthals in a cave in East Asia, but we have not known whether there were more of these hybrids and whether, thousands of years later, they had children with modern humans," explains Professor Mikkel Heide Schierup from BiRC.

Or Homo Sapiens met Denisovans long before they met Neanderthals. So far, it has been thought that modern humans met Neanderthals and had children with them first, and not until tens of thousands of years later did they have children with Denisovans.

"Both explanations are equally likely, and both explanations will be scientific news," says Mikkel Heide Schierup.

Neandertal genes of little importance

The study also shows that the Neanderthal DNA has no great importance for modern humans.

"We have previously thought that many of the Neanderthal variants previously been found in modern human DNA were associated with an increased risk of diseases. However, our study shows that the human gene variants located directly beside the Neanderthal genes are better explanations for the risk. We have also found something that can only be explained by Neanderthal genes, but this doesn't mean that much," says Mikkel Heide Schierup.

The properties and risks of diseases that can be linked to Neanderthal DNA are: slightly lower risk of prostate cancer, lower levels of haemoglobin, lower body length (one millimetre) and slightly faster blood plasma clotting.

Credit: 
Aarhus University

New study takes the pulse of a sleeping supervolcano

image: The llamas of the Andes' high plateau are unaware of the enormous amount of magma below their hooves.

Image: 
Osvaldo González-Maurel

Under the volcanoes in the Andes where Chile, Argentina and Bolivia meet, there is a gigantic reservoir of molten magma. For several million years, it has been there without fully solidifying or causing a supervolcanic eruption. Geologists have long wondered how this is possible. Researchers from Uppsala University, among others, have now discovered that the secret may be hidden tributaries of hot magma from inside the Earth.

The study is published in the journal Scientific Reports.

"Huge volcanic eruptions from so-called supervolcanoes are very unusual, but when they happen they are extremely devastating. It's incredibly important for volcanologists to clarify what keeps this sleeping giant alive and what can cause it to awaken," says Valentin Troll, Professor of Petrology at the Department of Earth Sciences at Uppsala University.

The giant so-called Altiplano-Puna magma body is estimated to contain 500,000 cubic kilometers of molten and semimolten magma. In order to provide a picture of how much volume is involved, it can be said that the entire island of Gran Canaria would fit inside - more than ten times over. The last really large volcanic eruption here occurred 4 million years ago and was the last in a series of very large explosive eruptions that began 10 million years ago. Some of them can be classified as supervolcanic eruptions.

In order to look for answers as to how the magma could stay molten for millions of years, the researchers studied lavas that were ejected from the magma reservoir during smaller volcanic eruptions after the last major eruption. The chemical composition of such material can provide an indication of how a magma reservoir works, how far down from inside the Earth the material originates, how long it remained in the reservoir and what different processes the magma underwent before it was ejected by the volcano.

In this case, the researchers wants to find out if new magma forces its way into the reservoir and therefore needed to find material that, after forming in the Earth's mantle, was not affected by interaction with the magma that was already in the reservoir.

"This was a demanding task. Under these particular volcanoes in the Central Andes is the Earth's thickest crust, 70 kilometers thick, which means that the magma is given many chances to change and react with the material it comes into contact with when it forces its way up to the surface," says Frances Deegan, a researcher at Uppsala University.

The researchers therefore searched several years for lava that was as "original" as possible. Finally, they found what they were looking for. They have now analyzed the composition of the oxygen isotopes in their samples to find out how lavas were formed and where they originate from. The results showed that the lavas came from deep within the Earth and that they represent the material that feeds the volcanoes of the Central Andes, keeping them alive.

This new knowledge is important to understanding how large, complex volcanoes work.

"Supervolcanic eruptions can cause gigantic disasters. The last one that happened on the Earth was Toba's super eruption in Indonesia 73,000 years ago and it is considered to have almost led to the extinction of mankind. Even if we can't prevent a super eruption from happening, it would be smart to use the time until the next eruption to learn as much as possible to increase the chances for our communities to survive such an event," says Valentin Troll.

Credit: 
Uppsala University