Culture

Better prognosticating for dogs with mammary tumors

image: Karin Sorenmo (left) and colleagues created a practical tool for assessing prognoses for dogs with mammary tumors. The research emerged from Penn Vet's Shelter Canine Mammary Tumor Program, which assists in treating and then finding homes for dogs like Brownie, pictured with former oncology intern, Kiley Daube.

Image: 
John Donges/School of Veterinary Medicine/University of Pennsylvania

Mammary tumors in dogs are the equivalent of breast cancers in people, and, as in the human disease, the canine tumors can manifest in a variety of ways. Some are diagnosed early, others late, and they can be either slow growing or aggressive.

Yet current prognostic tools, which provide information about the tumor stage--how large or dispersed it is--and grade--how likely it is to grow quickly--don't always give veterinarians or owners clear picture of how a tumor is going to progress, and what treatments might be most appropriate.

A new "bio-scoring" system, devised by a team led by Karin Sorenmo, a veterinary oncologist at Penn's School of Veterinary Medicine, equips clinicians with a more reliable prognosticating method. The researchers shared their work in the journal Veterinary and Comparative Oncology.

"Mammary gland carcinomas are the most common tumors in intact dogs around the world," says Sorenmo. "Yet we still haven't made great progress in deciding which dogs are fine with just surgical treatment, which dogs might require chemotherapy, and which dogs might benefit from hormonal treatment. In testing this new approach, we found it helps identify the dogs that develop metastasis better than other methods. I'm very excited about it."

To develop and assess this new scoring method, Sorenmo relied on a unique dataset that emerged from Penn Vet's Shelter Canine Mammary Tumor Program. This initiative, spearheaded by Sorenmo, enables shelter dogs to receive treatment for their mammary tumors, then finds foster or permanent homes for each animal. Researchers such as Sorenmo and others benefit from studying the dogs, including how they respond to treatment.

The current work took data from 96 dogs treated through the program, as well as an additional 31 dogs treated in a similar fashion at the Norwegian University of Life Sciences. The records they used including the pets' disease stage, grade, treatments received, and outcome--specifically, the time to metastasis, or spread of their disease within the body.

The "golden rule" for determining treatment currently, Sorenmo says, is to look at tumor stage, from stage I when the tumor is localized and small, up to stage IV when it has spread to distant organs.

"That's fine for some tumors that tend to behave in a certain way," Sorenmo notes, "but with mammary tumors it can be such a diverse disease."

Dogs can have advanced stage disease but, if their tumor has a low grade--that is, it is not fast-growing--they may have a better outcome than a dog with a lower stage but a more advanced grade. In addition, a tumor's histology, or the molecular markers that characterize the cancer cells, can further influence its behavior and the eventual outcome of treatment.

"We really didn't have a system to pull all the data together," Sorenomo says.

Looking to human oncology, Sorenmo and colleagues decided to borrow the idea of a scoring method that has been used to categorize breast cancers. They pulled together three pieces of information to attempt to more accurately determine a dog's prognosis: stage, grade, and histological type.

Some interesting findings arose from the statistical analysis. "We found that if you had a grade 1 tumor, no matter how large it gets, the vast majority of the time it doesn't cause any trouble," she says.

Since a good number of the dogs in the study had experienced long delays in receiving care due to being abandoned or in shelters, and thus had larger tumors than one would expect to see in the pet populations, the researchers were able to detect this size-independent effect.

"It's the same thing with lymph node involvement," says Sorenmo. "Everyone thinks that is a sign that the cancer has already started to move, but again we found that with a grade 1 tumor it doesn't matter. Those dogs didn't develop distant metastasis."

Using the overall bio-score, the researchers were able to differentiate dogs at lower risk of developing metastasis from those at a higher risk. If a pet has a higher bio-score, Sorenmo says, then a veterinarian or an owner may want to consider more aggressive treatment options, including chemotherapy. Dogs with a lower bio-score, on the other hand, may do just as well with surgical intervention alone.

In future work, Sorenmo would like to build on these findings by isolating the effect of hormones on mammary tumor and disease progression. Since the standard of care for treating dogs in the program is to spay them, she notes that doing so may remove a source of hormones that could be contributing to the dogs' disease in many cases.

For now, she is glad to have developed a system that can be implemented easily and immediately into treatment planning decisions.

"I try not to publish on things that most practicing veterinarians are not going to be able to use, like fancy tests that they won't routinely order," Sorenmo says. "This is practical. You look at three different things, given them a number and add it up."

Credit: 
University of Pennsylvania

Virus genes help determine if pea aphids get their wings

image: Jennifer Brisson, an associate professor of biology at the University of Rochester, and her former postdoctoral student Benjamin Parker uncovered genes that influence whether aphids produce wingless (aphid on the left) or winged (aphid on the right) offspring in response to crowding in their environment.

Image: 
University of Rochester photo / Omid Saleh Ziabari

Many of an organism's traits are influenced by cues from the organism's environment. These features are known as phenotypically plastic traits and are important in allowing an organism to cope with unpredictable environments.

But what are the genetic mechanisms underlying these traits?

Jennifer Brisson, an associate professor of biology at the University of Rochester, and her former postdoctoral student Benjamin Parker, now an assistant professor of microbiology at the University of Tennessee, studied phenotypically plastic traits in pea aphids and uncovered, for the first time, genes that influence whether aphids produce wingless or winged offspring in response to their environment. In a new paper in the journal Current Biology, the researchers shed light on how phenotypically plastic traits evolve and address critical questions about the evolution of environmentally sensitive traits.

Pea aphids are insects that reproduce rapidly and typically give birth to offspring that do not have wings. As many gardeners know, aphids can quickly overwhelm and kill the host plants on which they live and feed. When an environment becomes too crowded with other aphids, the females begin producing offspring that have wings, rather than the typical wingless offspring. The winged offspring can then fly to and colonize new, less crowded plants.

"Aphids have been doing this trick for millions of years," Brisson says. "But some aphids are more sensitive to crowding than others. Figuring out why is key to understanding how this textbook example of phenotypic plasticity works."

The researchers used techniques from evolutionary genetics and molecular biology to identify genes that determine the degree to which aphids respond to crowding. Surprisingly, the genes they uncovered are from a virus that then became incorporated into the aphid genome. The virus, which is from a group of insect viruses called densoviruses, causes its host to produce offspring with wings. Researchers believe the virus does this in order to facilitate its own dispersal. As Brisson and Parker found, the gene from the virus retained the same function of producing winged offspring even after it was transferred and incorporated into the aphid genome.

"This is a novel role for viral genes that are co-opted by the genome for other purposes, like modulating plastic phenotypes," Parker says. "Microbial genes can become incorporated into animal genomes, and this process is important to evolution."

Most laterally transferred DNA--DNA that is inherited from other organisms, like viruses--is not expressed by its hosts because it is quickly inactivated or eliminated. However, there are examples in most organisms--even humans--where genomes co-opt genes laterally; in humans, for instance, the gene that creates a membrane between the placenta and the fetus was co-opted from a retrovirus.

Brisson and Parker found a clear case in which genes from outside an organism were co-opted by the organism's genome to modify the strength of a plastic response to environmental cues. Microbial genes like those from viruses can, therefore, play an important role in insect and animal evolution, Brisson says. "Even in ancient traits like the one studied here, new genes can start to play a role in shaping plastic traits and can help organisms cope with an unpredictable world."

Credit: 
University of Rochester

The current Nor­we­gian Bar­ents Sea risk governance frame­work would need con­sid­er­able

image: This is Norway's Barents Sea.

Image: 
Tuuli Parviainen

A recent case study from the University of Helsinki examines different ways of framing oil spill risks with regard to the Norwegian Barents Sea where new areas have been recently opened for oil exploration and exploitation. The study demonstrates that there is an urgent need for new ways of integrating different risk frames and multiple ways of knowing into the risk governance processes of complex socio-ecological risks, such as oil spill risks.

The different, often conflicting, perceptions of risks as well as societal values present challenges in the governance of environmental risks. The opening of new areas for offshore drilling in the Arctic is highly controversial. As the ice cover in the region is melting at an alarming rate, new areas have been opened for the petroleum industry in the Norwegian Barents Sea.

The decision of the Norwegian government to open new areas for maritime operations closer to the ice edge remains highly controversial as the oil spill risks of offshore operations are exacerbated due to, e.g., the possible presence of ice, harsh weather conditions, and the ineffectiveness of current response measures. Considering the contribution of fossil fuels to climate change, opening new areas for the petroleum industry impedes reaching the goals of the Paris climate agreement.

The study indicates that the current governance framework is unapt for integrating the multiple risk frames and knowledge systems into decision-making processes.

"We suggest that social learning and collaborative knowledge production are needed to move towards developing a shared understanding of the problem situation and the solutions", says Tuuli Parviainen, doctoral student in the Ecosystem and Environment Research Programme, University of Helsinki.

Considerable differences in how risks were defined and perceived by the participants were revealed by the study. The participants emphasised a wide range of environmental, economic and social risks, including both the long-term local and global consequences of offshore drilling operations, e.g., how offshore drilling contributes to climate change. In addition, the respondents identified different knowledge sources as important when assessing the risks, including, e.g., interdisciplinary research and traditional knowledge.

Therefore, questions - such as who should take part in identifying and evaluating risks; who are seen as relevant or as "experts" in assessing risks and who are not; what governance measures are considered important; and who should be involved in ensuring the legitimacy of the decisions - need to be explored as part of oil spill risk governance processes.

In their paper, Parviainen et al. (2019) demonstrate the multiple ways in which risks with regard to the Norwegian Barents Sea are perceived and defined, and analyse the types of knowledge that the risk frames are based on. Risk frames were elicited using semi-structured interviews to construct qualitative mental models: mental modelling can be used to bring forward and illustrate the extent of uncertainties as well as the ambiguity related to evaluating and assessing oil spill risks.

"The current risk governance framework, including, e.g., the Barents Sea ecosystem-based management plan and the industry risk assessments, have largely focused on natural sciences and engineering studies, and risks are understood principally in terms of probabilities and consequences. We would suggest that assessing and evaluating risks and risk control options cannot be left to experts alone", Parviainen states.

Credit: 
University of Helsinki

Study reveals significant gaps in essential rheumatoid arthritis care across Europe and between European countries

Madrid, Spain, 14 June 2019: The results of a large pan-European survey presented today at the Annual European Congress of Rheumatology (EULAR 2019) investigated significant gaps in rheumatoid arthritis care across 16 patient-centred Standards of Care (SoC) in rheumatoid arthritis.1

Results reveal 'diagnosis within six weeks' as the most concerning SoC, with 52% (weighted means across countries) of patients and 59% of rheumatologists reporting problematic gaps. The next highest were; information about patient organisations (40% and 38%), training on aids, devices and ergonomic principles (39% and 34%), vaccination-related information (38% and 27%), receiving a schedule of regular assessment (33% and 23%), information on adequate physical exercise (35% and 20%), and availability of treatment plan (35% and 18%). The least frequent problematic SoC for both patients (8%) and rheumatologists (3%) was adequate disease-modifying anti-rheumatic drug received.1

"It is concerning to see so many problematic gaps reported across many essential aspects of rheumatoid arthritis care," said Rachelle Meisters, PhD, Care and Public Health Research Institute (CAPHRI), Maastricht University, The Netherlands. "We hope these results act as a loud wake up call to services across Europe."

Analysis of the data reveals patients with higher education and lower self-reported health report problematic gaps more frequently. Among rheumatologists, patterns in determinants across SoCs were less consistent.

Country disparities by GDP

However, for about half of the SoCs, rheumatologists from lower gross domestic product (GDP) countries identified problematic gaps more often than those from medium or high GDP countries. Additionally, large variation remained across countries for patient analyses, and most rheumatologist analyses, despite adjustment for individual characteristics.1

"At EULAR, our aim is to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases within and across countries," said Professor Thomas Dörner, Chairperson of the Scientific Programme Committee, EULAR. "These results highlight how far there is to go to translate the advantages elucidated through scientific study into the daily care of people suffering these diseases."

The survey included 1,422 patients from 27 European countries, and 1,044 rheumatologists from 33 European countries. The mean age was 57.2 and 47.7 for patients and rheumatologists respectively, with 74% and 53% being female. The 16 SoCs were those developed by Eumusc.net, a EULAR and EU supported initiative to raise and harmonise quality of care for patients across Europe. Participants were asked to rate each SoC on the level of care standard that was achieved (1-10), and on level of importance (1-10). The distance of level of care from the maximum was multiplied by the level of importance and was defined as problematic when this score was greater than 30 and the importance score was six or more.1

An additional study presented today at EULAR 2019 analysed the quality of care of patients with systemic lupus erythematosus in Germany. They also revealed significant gaps as on average only 61% of relevant care aspects were fulfilled. In a second step, the study analysed whether the quality of care was associated with disease outcomes.2

Results showed that fulfilling more quality measures in 2013 was predictive for high disease-related quality of life (p=0.004), low progress in disease-related damage (p=0.048) and low disease activity (p=0.046) in the subsequent years.2

"Our results show that consistent consideration of these care parameters, recommended in several management guidelines, yield a positive effect on outcome," said Dr. Med. Anna Kernder, Policlinic of Rheumatology & Hiller-Research Unit, Heinrich-Heine-University Düsseldorf, Germany.

Data derived from the LuLa study, collecting annual data from a representative cohort of patients with SLE in Germany. In 2013 they additionally inquired about clinical care as a main topic. From 21 clinical care parameters, 10 were evaluated in univariate analysis.
The fulfillment varied between 22.8% having fat metabolism counseling to 97.6% receiving osteoporosis protection with a glucocorticoid. The others were antimalarials, vaccination, blood pressure, yearly testing of urine and blood, treatment of fat metabolism disorder, osteoporosis, and hypertension. Linear regression was used to examine the relationship between quality measures calculated in 2013 and outcome parameters in subsequent years adjusted for age, disease duration and gender.2

Abstract number: OP0307/OP0308

Credit: 
European Alliance of Associations for Rheumatology (EULAR)

Study develops updated national birth weight reference

BOSTON, MA - A new paper provides an updated national birth weight reference for the United States using the most recent, nationally representative birth data. The study, "A 2017 US reference for singleton birth weight percentiles using obstetric estimates of gestation," led by the Harvard Pilgrim Health Care Institute, appears in the June 14 issue of Pediatrics.

Fetal growth, typically measured as birth weight-for-gestational-age is an important clinical indicator of morbidity, survival, and long-term health outcomes in children and their mothers. Previous birth weight-for-gestational-age references may not reflect the current socio-demographic composition of the U.S. and rely on less accurate estimates of gestational age. Investigators conducted this project to create an updated reference for clinicians and researchers using the most recent, nationally representative data on birth weight and more reliable obstetric estimates of gestational age.

The study team used data on over 3 million live births from the 2017 U.S. Natality files, a database of U.S. birth certificates publicly available from the National Vital Statistics System of the National Center for Health Statistics. Investigators used their analyses to provide a simple, easy to use online tool for both researchers and clinicians to calculate measures of birth size.

"Given the concerns regarding the validity of previous birth weight references based on maternal reports of last menstrual period, the need for an obstetric estimate-based reference has become increasingly appreciated. This updated reference will allow researchers and clinicians to weigh its appropriateness against their specific needs," said lead author Izzuddin Aris, PhD, Research Fellow in the Department of Population Medicine at the Harvard Pilgrim Health Care Institute and Harvard Medical School. "We expect clinicians to be able to use the percentile thresholds from this updated reference to identify at-risk infants who may have had restricted or excessive fetal growth. Researchers may also use this reference to derive continuous measures of birth size for studies examining predictors of fetal growth or associations of fetal growth with later health outcomes."

Credit: 
Harvard Pilgrim Health Care Institute

Higher coronary artery calcium levels in middle-age may indicate higher risk for future heart problems

DALLAS, June 14, 2019 -- Higher coronary artery calcium levels in middle-age were associated with structural heart abnormalities linked to future heart failure, particularly among blacks, according to new research in Circulation: Cardiovascular Imaging, an American Heart Association journal.

Coronary artery calcium (CAC) is the buildup of calcified plaque made up of fat, calcium and cholesterol. The calcium found in this type of plaque is not related to dietary calcium. Elevated cholesterol levels in the blood can contribute to plaque buildup, known as atherosclerosis, which narrows the channel within an artery and reduces blood flow.

CAC is a risk marker for heart health problems, and CAC screening was added to the American Heart Association's 2018 cholesterol management guidelines to further improve early detection of heart health abnormalities, especially among people who might be at a higher risk. A CAC score of zero indicates there is low risk in the absence of other high-risk conditions, while a score above zero indicates increasing risk.

In this study, researchers tracked 2,449 people (52% white, 57% women) from young adulthood to middle-age. Non-invasive computed tomography imaging tests were used to gauge the participants' vascular health, with participants' imaging tests and CAC scores compared at years 15 and 25 of the study period.

By year 25, participants' average age was about 50. Seventy-two percent of the group had a CAC score of zero compared with 77% a decade earlier.

"We looked at early adulthood to middle-age because this is a window in which we can see abnormalities that might not be causing symptoms, but could later increase the risk of heart problems," said Henrique Turin Moreira, M.D., Ph.D., study co-author and an attending physician at Hospital das Clínicas de Ribeirão Preto at the University of São Paulo in Brazil. "Prevention and control of these abnormalities are key, so early identification of risks can be crucial."

Moreira and team found that increases in CAC scores were independently related to increasing age, male sex, black race, higher systolic blood pressure, higher total cholesterol, diabetes mellitus and current smoking, as well as the use of medications to lower blood pressure and cholesterol. Additionally, they found:

Compared with patients who had CAC scores of zero, those who had higher CAC scores at middle-age had a 12% increase in left ventricular mass and a 9% increase in left ventricular volume, independent of other risk factors including demographic information and cardiovascular risks. Abnormalities in the left ventricle means the heart had to work harder to effectively pump blood, and as a result, became enlarged and thickened, a risk factor for heart failure.

These findings were even more significant among blacks. For every one-unit change in a CAC score, blacks had four times higher increase in left ventricular mass compared with whites.

While progression in CAC over the follow-up was strongly related to higher left ventricular mass in blacks, this relationship was not significant in whites.

Blacks already face a greater risk and burden of heart disease and stroke: 60% of adult black men and 57% of adult black women have some form of cardiovascular disease, compared with 50% of white men and 43% of white women.

"Racial differences in our findings may be due to genetic factors or perhaps greater exposure to cardiovascular risk factors that usually appear earlier in blacks," Moreira said. "We need more research to examine the link between coronary artery calcium and heart health."

"Prior studies have shown that presence of CAC and higher CAC scores are associated with atherosclerotic cardiovascular disease in young to middle aged adults. The results of this study are important as they highlight that presence of CAC and higher CAC scores may also be associated with echocardiographic markers of subclinical LV systolic and diastolic dysfunction," said Salim Virani, M.D., a member of the writing committee for the American Heart Association's 2018 cholesterol guidelines and director of the Cardiology Fellowship Training Program at Baylor College of Medicine in Houston. "Given the burden of morbidity and mortality associated with heart failure, these are important findings. Prior studies from this cohort have also shown that a better risk factors profile in young adulthood is associated with much lower CAC and therefore, these results further highlight the importance of primordial prevention and risk factor modification in early adulthood."

Credit: 
American Heart Association

It's not easy being green

image: Seedlings (a) grown in dark, (b) in light, (c) blind phytochrome mutant, and (d) albino rcb-10 mutant found by Chen's lab.

Image: 
Chan Yul Yoo / UC Riverside

Despite how essential plants are for life on Earth, little is known about how parts of plant cells orchestrate growth and greening. By creating mutant plants, UC Riverside researchers have uncovered a cellular communication pathway sought by scientists for decades.

Both plants and humans have specialized light-sensitive proteins. In humans these proteins reside in the retina, allowing us to see. In plants, they are called phytochromes and are housed mainly in the nucleus, which serves as master control for the cell's activities.

The process of photosynthesis, which converts carbon dioxide into sugar and fuels plant growth, begins when light hits the phytochromes in the nucleus. The nucleus then has to send a command to a sub-organ called a plastid to transform itself into a chloroplast, which manufactures the green pigment chlorophyll.

"The nucleus is like the federal government of the cell, while a sub-organ called the plastid functions more like the state," said UCR's Meng Chen, an associate professor of cell biology whose lab is one of few in the world focused on phytochrome communications. "Until now, we did not know how the nucleus sent the 'turn green' command to the plastids, telling them to activate their photosynthesis genes."

The way Chen's team arrived at the answer is detailed in two new papers published today in the journal Nature Communications.

Historically, part of the challenge has been identifying which of the 25,000 nuclear genes is responsible for regulating the cell's greening process. To find the regulators, Chen and his team reasoned that the same genes must control not only plant greening, but other processes as well, such as height.

"The regulator we were looking for would control both qualities, height and color," Chen said.

They took a small flowering plant and chemically created versions of it unable to manufacture chloroplasts, even when exposed to light. Next, they looked for mutants that are both albino and tall. As luck would have it, Chen's team found they'd created some mutants with both qualities.

Comparing the wild plant DNA with the mutated plant DNA allowed the team to identify two genes responsible for regulating greening.

"Plants without either of these genes fail to respond to light, becoming tall and albino seedlings," said study co-author Chan Yul Yoo, a UCR molecular biologist and first author of both papers.

Understanding the master control of chloroplast development could have profound implications for new technologies to improve crop yields and help plants cope with climate change. But the benefits of this discovery are not limited to plants. Chen's laboratory is funded by the National Institutes of Health because of the implications of this work on cancer research.

Mitochondria, the power generators of plant and animal cells, play a role in cancer because they are involved in programmed cell death. Communications between a cell's nucleus and mitochondria are analogous to communications between a plant cell nucleus and chloroplasts.

"Uncovering the nucleus-chloroplast communication pathway in plants could yield new insights into gene expression in human cells and its misregulation in cancers," Chen said.

Credit: 
University of California - Riverside

Exciting plant vacuoles

image: The activity of the TPC1 ion channel in the vacuole membrane (yellow) is essential for the excitability of the vacuole. On the left is a plant cell, in the middle the vacuole with chloroplasts (red) and a 3D reconstruction of the TPC1 crystal structure.

Image: 
Dawid Jaslan / University of Würzburg

Many plant processes are not different from humans: Cells and tissues in grain plants, including maize also communicate through electrical signals. The shape and frequency of these signals tell a plant different things. For example, it allows them to respond to heat and cold, excessive light intensities or insect pests.

If, for instance, a caterpillar starts to nibble on the leaves of a wild plant, an electrical signal is sent to the leaves that haven't been harmed yet, triggering a response mechanism: Bitter agents or toxic substances are subsequently produced throughout the plant, causing the caterpillar to stop eating or killing it after a while. But the ability to produce bitter substances has been bred out of modern crops for reasons of taste. Therefore, chemical pesticides are sprayed on field crops to rid them of caterpillar pests.

Researchers from the Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, have now shed new light on plant communication via electrical signals. They found out that the TPC1 ion channel contributes to plant excitability. The function of this channel had been previously unknown. This discovery may pave the way to breed plants that are more resistant to pests, heat or drought in the long run - properties that are crucial in the face of climate change.

Publication in Nature Communications

The JMU scientists led by biophysicist Professor Rainer Hedrich have now presented their findings in the renowned journal "Nature Communications". It was Hedrich who had discovered the TPC1 ion channel in the mid-1980s, when he was a postdoc with Nobel Laureate Erwin Neher in Göttingen. Over the years, he has thoroughly studied the channel and described almost all of its properties.

Hedrich's new paper fills another knowledge gap. The cell membranes of plants were already known to be excitable; the scientists have now proved that this also applies to the membrane which encloses the central vacuole of the plant cells - and TPC1 plays a key role here as well. The vacuole is an enclosed compartment filled with an aqueous solution that can take up as much as 90 percent of the volume of a plant cell. Its main purpose is that of a pantry for storing nutrients.

Electrical signal concurrent with calcium wave

How do electrical signals in the membrane of the vacuole develop? When a leaf is wounded, a calcium wave is triggered in the injured leaf in addition to the electrical signal. "The two signals are mutually reinforcing, allowing the signal to propagate throughout the plant," explains Ingo Dreyer, a professor at the University of Talca in Chile and a collaborator of Hedrich.

In plants with a defective TPC1, the calcium wave travels more slowly or not at all. "This finding led us to study the properties of the vacuole using the patch clamp technique," Hedrich says. It turned out that vacuoles lacking TPC1 cannot be excited, neither by an electric charge nor by a calcium boost. In a hyperactive mutant of TPC1, however, the excitation was sustained. "This technique and other analyses have enabled us to mathematically model vacuolar behaviour and predict yet unknown properties of the vacuole channels," Dreyer says.

Investigating the structure and functioning of the ion channel

"Our discovery is also of interest for medical research," Hedrich says. This is because relatives of the TPC1 channel have also been identified in humans. But it is not fully known yet which role the channel plays in the tiny membrane vesicles, the endosomes of our cells. Therefore, medical researchers are also looking for common features in the structure and function of TPC1 in plants and humans.

"To provide answers, US scientists conducted X-ray structural analyses for our patch clamp measurements to determine the molecular blueprint underlying the channel function. This makes TPC1 one of the best understood, voltage-dependent ion channels," the JMU professor says.

TPC1 consists of two identical subunits. When they assemble to form a pair, a complex is created that has an ion channel at its centre which responds to voltage and calcium ions. There is a calcium receptor in the cytoplasmic end of TPC1 to activate the channel and another receptor on the inside of the vacuole. If the internal calcium concentration becomes too high, the channel is blocked and the vacuole loses its excitability.

TPC1 in evolution and climate change

"We also asked ourselves when the calcium-dependent TPC1 functions occurred in plants for the first time," Hedrich says. Mosses were evidently the first to do so. "Now we aim to find out whether TPC1 is also responsible for the excitability in early ancestors of our crops and whether implanting alga or moss TPC1 is capable of healing the functional failure in mutants of modern crop plants."

Moreover, the researchers discovered that there are plant families whose members exhibit significant differences in the development of the individual channel functions. They now want to understand the reason for these differences at the molecular level. Moreover, they intend to check whether the minor differences facilitate plant stress adaptation.

Credit: 
University of Würzburg

Phantom sensations: When the sense of touch deceives

image: When one's hands and feet are crossed, a touch on the right hand can be felt to have been on the right foot.

Image: 
Bielefeld University

Without being aware of it, people sometimes wrongly perceive tactile sensations. A new study in the scientific journal Current Biology shows how healthy people can sometimes misattribute touch to the wrong side of their body, or even to a completely wrong part of the body. The study was conducted by researchers at Bielefeld University's Cluster of Excellence CITEC, the University of Hamburg, and New York University.

"The limitations of the previous explanations for how and where our brain processes touch become apparent when it comes to individuals who have had parts of their bodies amputated or suffer from neurological diseases," says Professor Dr. Tobias Heed, one of the authors of the study. His research group "Biopsychology and Cognitive Neuroscience" is part of CITEC and the Department of Psychology at Bielefeld University. "People who have had a hand or a leg amputated often report phantom sensations in these limbs. But where exactly does this false perception come from?"

To begin answering this question, Heed, working together with Dr. Stephanie Badde (New York University, USA) and Professor Dr. Brigitte Röder (University of Hamburg), studied whether phantom sensations could also be found in healthy people. "In doing so, we showed that healthy adults actually did systematically misattribute touch on the hands to the feet, and vice versa," says Heed.

The Starting Point

In the brain, neighboring neurons respond to corresponding parts of the skin. "Previously, scientists thought that our conscious perception of where a touch occurred stems from a topographical map in the brain. Following this assumption, parts of the body such as the hands, feet, or the face are represented on this map. Our new findings, however, demonstrate that other characteristics of touch are also used to attribute a touch to parts of the body," says Heed. He refers to the presumed "map" as an anatomical system of reference. Previously, it was also believed that spatial perception had an influence on the processing of touch, meaning where a touch takes place in spatial terms, such as to the left, in front of, or below, as Heed explains. Many previous findings were interpreted such that the brain was probably using this other map, which is referred to as an external reference system.

"When parts of the body are positioned on the other side of the body than they usually are - for example, when crossing your legs - the two coordinate systems come into conflict." The external coordinate system then locates, for instance, the left leg as being on the right side - and this does not conform what is stored in the brain about the side of the body that the leg belongs to. "In our study, our initial goal was to sort out the role of the brain's anatomical perception as well as the impact of spatial perception," says Heed.

The Study

For the experiments, tactile stimulators were affixed to each of the study participants' hands and feet. These stimulators could generate a sensation on the skin. Using this impulse generator, the researchers then quickly touched the test subjects successively on two different parts of the body, such as on the left foot and the left hand. In the next step, the participants said or showed where they felt the first touch. This process was then repeated several hundred times on each test subject. In some instances, the study participants had to cross their feet or their hands, while at other times their limbs remained in their normal positions. "Remarkably, in 8% of all cases, subjects attributed the first touch to a part of the body that had not even been touched - this is a kind of phantom sensation," explains Stephanie Badde, the study's lead author.

The Reasons Why

The previous conception - that the attributed location of touch on the body depends on "maps" of the body - cannot explain these new findings. We show that phantom sensations depend on three characteristics," says Tobias Heed. "The most important is the identity of the limb - whether we're dealing with a hand or a foot. This is why a touch on one hand is often perceived on the other hand."

The second most-important factor is the side of the body where the touched limb belongs to, which explains why a touch on the left foot can sometimes erroneously be felt on the left hand.

Another factor is the canonical anatomical position of the part of the body in question - where in space the hands or the feet are usually located. This was demonstrated by the researchers in their experiment with crossed body parts: the left hand was positioned on the right side in the experiment. If the left hand were to be touched, the brain sometimes misattributes this touch to the right foot - to another part of the body that belongs neither to the same side of the body nor the same external spatial position as the part of the body that was actually touched. "Decisive is the normal position of the part of the body that was touched: here, the left hand results in a response from a part of the body that is now positioned where the hand that was touched would normally be located," says Stephanie Badde.

The findings from this study shed new light on the way in which the brain represents our own body. "The findings could be used, for instance, to drive forward new research on the genesis of phantom pain," says Tobias Heed. "Developments using touch in artificial systems are currently based on the firm assumption that the issue of touch should be able to be solved by using one or multiple maps. But it might be that other processing principles are more efficient for some types of behavior."

Credit: 
Bielefeld University

International experts call for action for world's 450 million scabies sufferers

image: Feet infested with scabies

Image: 
Dr Millicent Osti, MCRI

An alignment of researchers, health ministries and the World Health Organization has outlined the key steps to develop a global program to control scabies - the parasitic disease that affects 450 million people each year in mainly low-income countries.

The research paper, 'The public health control of scabies: priorities for research and action' published in The Lancet journal was led by Australia's Murdoch Children's Research Institute, in collaboration with the International Alliance for the Control of Scabies, the World Health Organization, international researchers and the Ministries of Health of Ethiopia, Solomon Islands and Fiji.

Lead author, MCRI's Daniel Engelman, said global scabies control was dependent on developing key operational procedures, including methods for identifying scabies prevalence in all impacted countries.

"Scabies is a disease of poverty, and people in low-income, crowded, and warm environments are most vulnerable to infestation caused by the microscopic Sarcoptes scabiei mite," Dr Engelman said.

"Scabies causes skin rash and severe itch that can be unbearable, but there is no blood-test, and not even a standardised approach to diagnosis. We don't know how prevalent scabies is in most countries. "

Dr Engelman said that a major priority was mapping the global scabies problem using simple skin examinations, which can be conducted by nurses and community health workers.

Dr Mike Kama, public health expert and scabies focal person at the Fiji Ministry of Health, said scabies infection rates could now be radically decreased by treating whole populations with an antiparasitic medication called ivermectin, after previous successful trials of the drug in Fiji.

"Scientific advances over the past five years suggest that the number of people with scabies in a community can be reduced by more than 90 per cent with a single mass treatment" he said. "This is one of the most effective public health interventions we have."

Dr Paul Cantey, Medical Officer for Scabies from the World Health Organization in Geneva, said more work is required to identify when mass treatments for scabies are needed, how best to implement them, and how to engage communities to ensure scabies control initiatives are sustainable.

"During studies of mass treatment for scabies, young children were not given ivermectin but treated with topical medicines, which can make treatment of affected communities more complicated. This paper highlights the need to determine if oral scabies medicines can be safely given to young children," Dr Cantey said.

The research found scabies infection rates were high in many Pacific nations, parts of South America and Africa, and in Australian, New Zealand and Canadian indigenous communities, where up to 50 per cent of children may have scabies.

Senior author, MCRI's Professor Andrew Steer, said the scabies mite causes 'traumatic itching' when the surface of the skin is broken, allowing bacteria to enter.

"This can lead to impetigo (school sores), and if the wound becomes infected with the Strep A or Staph bacteria, the sufferer can develop severe, life-threatening infections, as well as chronic health issues such as rheumatic heart disease or chronic kidney disease," Prof Steer said.

More than 300,000 people die from rheumatic heart disease around the world every year. Prof Steer said that there was the potential to reduce the burden of rheumatic heart disease by controlling scabies and maintaining healthy skin.

The 24 authors of the paper called for a global strategy to tackle scabies and outlined five key steps:

Develop a global strategy for the public health control of scabies

Map the global population affected by scabies.

Facilitate affordable and reliable access to effective treatments

Scale-up mass drug administration strategies in highly-affected countries.

Work together with affected communities and health programs

Credit: 
Murdoch Childrens Research Institute

Part of the immune strategy of the strawberry plant is characterized

image: This is a model used in the study.

Image: 
University of Cordoba

Seven years have gone by since the first publication of the strawberry plant's complete genoma (Fragaria vesca), and all the information necessary to understand the thousands of biological processes going on within these plants, became available to the international scientific community. It is not such a long time for the Plant Biotechnology and Pharmacognosy research group at the University of Cordoba, a group that has spent over 20 years working on understanding strawberry defense strategies.

What José Luis Caballero, José Garrido, José Higuera and Juan Muñoz have done is characterize, for the first time, a specific gene family, VQ genes, and explain their direct relationship to protein transcription factors that either activate or block the expression of certain genes related to the stress response that pathogens cause. Thus, they were able to identify part of the strawberry's defense system headquarters, specifying some of the response strategies when under enemy attack.

This characterization performed at a basic level, as in at a molecular level, was published in the journal Scientific Reports, and carries with it an immediate effect on applied research, because it lays out information especially valuable in order to continue progressing in the genetic improvement of such an important plant for the Spanish economy. Not for nothing is Spain the largest producer of strawberries in the E.U. and the sixth worldwide.

The thorough study of this gene family, its classification and the characterization of its behavior in situations of biotic stress -as in stress caused by pathogenic organisms- opens up the possibility of choosing certain genes in order to perform a more in-depth study of their behavior. This could clarify what kind of mechanisms strawberry plants put into action and why on many occasions strawberry plants are not effective in their fight. In order to carry out this study, the research team receives financial support from Excellence Funds by the Andalusian Regional Government and the PRIMA Foundation via the MED-BERRY project entitled "Developing new strategies to protect strawberry crop in Mediterranean countries."

Credit: 
University of Córdoba

Overweight men are inhibiting childbirth

image: Doctoral Thesis.

Image: 
University of Tartu

About 15% of couples in fertile age have experienced fertility problems. Men contribute to 50% of the cases when a couple cannot achieve the desired pregnancy. The proportion of overweight men has tripled in parallel with the increase in fertility problems worldwide. The doctoral thesis conducted at the University of Tartu Institute of Clinical Medicine confirmed that central obesity affects fertility parameters negatively. To alleviate their fertility problems, men should pay attention to their lifestyle.

According to Kristel Ehala-Aleksejev, a doctoral student at the UT Institute of Clinical Medicine and a physician at Tartu University Hospital Men's Clinic, men's semen quality has dropped dramatically over the last century. "Possible reasons for the decline of fertility parameters can be the rapidly changed lifestyle, altered physical activity and eating habits along with other factors. A western lifestyle is conducive to weight gain, which is also a problem among Estonian men."

She noted that there are studies associating obesity with reduced fertility, but there are other studies denying this. Conflicting results also characterise the relationship between central obesity-related metabolic syndrome and sperm quality. There is, however, an almost unanimous agreement that increased weight has a negative correlation with testosterone levels.

"At an andrology appointment, we often see links between weight and fertility. An important factor with men is the accumulation of fat in the waist region. However, central obesity is a great health risk. In addition, obesity as a change in the hormonal balance promotes the development of erection problems, which in turn reduces fertility," said Ehala-Aleksejev.

Male fertility is mainly assessed based on semen analysis, but one of the easiest methods for determining fertility potential is the measurement of testicular volume.

In her doctoral thesis "The Associations Between Body Composition, Obesity and Obesity-Related Health and Lifestyle Conditions with Male Reproductive Function," Aleksejev looked at provenly fertile men and the male partners of infertile couples. Comparing the groups showed that a significantly higher prevalence of adiposity and metabolic syndrome was found among the male partners of infertile couples. Central obesity was associated with a decline in fertility parameters in both groups. According to the doctoral student, the analysis importantly revealed that men with smaller testicles were more affected by an increase in body weight and central obesity.

Kristel Ehala-Aleksejev, who is also a nutritional therapist, confirmed that men could do a lot for their health. "They should try to keep physically active, move, and if possible, do sports. They should include more fruit and vegetables and whole-grain products in their diet. Smoking and excessive alcohol consumption are notable risk factors of infertility. However, mental health or ability to alleviate stress and finding time for themselves and their loved ones is no less important."

Credit: 
Estonian Research Council

Sweden was not always destined to become a welfare state

In a new study, Lund University economic historian Erik Bengtsson debunks the myth that Sweden was destined to become a social democratic country. Instead, he argues that it was actually against all odds, as Sweden in the early 1900s was one of the western world's most unequal countries - and the least democratic in western Europe.

Has Sweden always flown the flag for equality and welfare? No, that is a misleading, romanticized picture, according to Erik Bengtsson from the School of Economics and Management at Lund University in Sweden.

"Sweden is romanticised internationally as the small country in the north that took the lead in equality because of a tradition of independent farmers and a lack of nobility. The only problem is that this is a complete fabrication. There is a wish to believe that Sweden was a unique, idyllic land, but that's wrong."

Instead, Bengtsson shows, among other things, how the temperance movement's strong organisational culture and the free churches formed the basis for the Swedish welfare state in the late 1800s. This helped to educate the future social democrats, whose party, formed in 1889, grew strong rapidly and gained many members who defined themselves as working class.

"It was a method for organising people that proved to be successful and was the reason that Sweden became the world's strongest social democracy. It was very simple: If there is a strong organisation that wants to have an equality model, you get an equality model", says Erik Bengtsson.

Ethnologists usually describe Swedish stories of Swedishness as an echo chamber. The assertions are repeated again and again, but they actually originate from the same questionable sources.

"The story of Swedish democracy stemming from the farmers is a good one and perhaps we would prefer to see ourselves linked to happy people in folk costumes, rather than impoverished peasants. However, it's our job as historians to slow things down a little, shift the debate and show how this narrative is deficient", says Erik Bengtsson.

In the essay "The Swedish Sonderweg in question: Democratization and inequality in comparative perspective", recently published in the journal Past and Present, Erik Bengtsson also highlights another aspect as to why Sweden from the 1930s until the early 1980s became the model for a social democratic country.

"Sweden was the least democratic country in Western Europe in the early 1900s. Almost no one could be involved in politics, and very few could vote. This meant that a large proportion of the population could reach a consensus that another type of order was possible. We had a political world in which nearly the entire population was posited against a small elite, and when the people gained power it created a political dynamic with a strong popular alliance for democracy and equality", says Erik Bengtsson.

Today, Sweden is the eleventh most equal OECD country, overtaken by all the Nordic countries as well as Slovenia, Belgium and Austria. The welfare state's redistribution of wealth policy has diminished so much that researchers now question whether Sweden is still a "social democratic model".

"There is no continuity in Swedish history - equality is not based on our culture. This research shows that it is a fragile construction that we can lose or is subject to change, and not eternal and unconnected with history", concludes Erik Bengtsson.

Credit: 
Lund University

Heritable behavioral differences between cat breeds

image: The research group studied the heritability of behavior traits in three different breeds: Maine Coon, Ragdoll and Turkish Van.

Image: 
Heikki Siltala

Cat breeds differ from each other in behaviour with regard to activity, aggressiveness, shyness, sociability and stereotypical behaviour. A study conducted at the University of Helsinki discovered that behavioural traits are highly heritable. Heritability of behaviour explains differences between breeds.

Cats are our most popular pets but few studies have been conducted on their behaviour.

"Dozens of international studies have been conducted on dog breeds' behaviour traits and heritability, whereas ours is the first study on behaviour trait heritability in cats," says Milla Salonen (formerly Ahola), doctoral student at the University of Helsinki.

All studied traits manifested differences in behaviour between various breeds: activity level, sociability with humans, shyness, aggressiveness and stereotypical behaviour. The largest differences in behaviour were observed in activity and the smallest in stereotypical behaviour.

"Since the age of about two weeks, activity is a reasonably permanent trait, whereas stereotypical behaviour is affected by many environmental factors early on in the cat's life as well as later. This may explain the differences observed," says Professor Hannes Lohi, the principal investigator of the feline genetic research group.

The research group studied the heritability of behaviour traits in three different breeds: Maine Coon, Ragdoll and Turkish Van. These breeds were chosen because there was a sufficient number of questionnaire responses on them and there was also enough information on the parents of the cats.

"Furthermore, these breeds are genetically diverse. Based on prior research, the Maine Coon is related to Nordic cat breeds and landrace cats, while the Ragdoll is related to Western European and American cat breeds. The Turkish Van and Angora seem to have separated from other breeds," says Lohi.

Approximately half of behaviour traits are inherited

The study discovered that the heritability estimate of behaviour traits varied from 0.40 to 0.50 on average. This means that little under half of the variation in behaviour traits is explained by hereditary variation. Heritability estimates are fairly similar between cat breeds regardless of genetic differences between the breeds.

There are a number of alternative explanations for behavioural differences. It is possible that behaviour has been subject to selection in the breeding of cats. It is possible that the aim has been to make some cats active and some docile. Behaviour traits can also 'hitchhike' with some other selected gene, such as the gene for fur or eye colour.

"On the other hand, cat breeds have been bred from local landrace populations, which they continue to genetically resemble. Consequently, the behaviour of breeds descended from cats in the same region may resemble each other due to their common history," says Salonen.

Based on the current research, differences can be explained partly by genetic similarity and partly by preference for certain features, such as long hair.

"However, discovering the evolutionary background of differences in behaviour traits requires further studies," says Lohi.

The study utilised feline behaviour questionnaire material on 6,000 cats collected earlier. The material consists of questionnaire responses on 40 different cat breeds. It is the world's second largest body of material on feline behaviour.

"In March, we published a new and improved feline behaviour and personality questionnaire on the Petsofi platform with the aim of collecting responses on more than 20,000 cats. A sample size this large would allow us to conduct unique research as well as to confirm our current results, and I wish to take this opportunity to thank those cat owners who have already responded to the questionnaire," says Lohi.

Credit: 
University of Helsinki

Patient organization challenges government to bring vital support to people with rheumatic diseases in Cyprus

Madrid, Spain, 14 June 2019: The campaign presented today at the Annual European Congress of Rheumatology (EULAR 2019) reports how the Cyprus League Against Rheumatism (CYPLAR) successfully took on the Ministry of Health after authorisation was denied to introduce specialised rheumatology nurses due to a perceived lack of interest in rheumatology education.1

In many countries, rheumatology has developed into a recognised nursing specialty where nurses undertake advanced and extended roles. While some countries have accepted that interventions undertaken by nurses are essential to effectively tackle the challenges of chronic illness in an integrated fashion, this concept has not been widely adopted across Europe.2

"We are determined to challenge the government in Cyprus to implement a rheumatology nurse service into the health system," said Ms Andri Phoka Charalambous, Patient Expert General Secretary of the Cyprus League Against Rheumatism, Cyprus. "We're proud to have achieved a significant step towards our goal with the successful implementation of the first rheumatology nurse educational program in Cyprus."

After many meetings with the Government Nursing Services demonstrating the value of rheumatology nurses, the officers became very excited about the development of a new "Patient Care with Rheumatic Diseases" educational programme. CYPLAR were instrumental stakeholders in both the design and delivery of the program which was provided to 27 nurses at the end of 2018. Following the training a survey of the participants demonstrated very encouraging results. When asked, "after training will you be interested in working as a rheumatology nurse in a rheumatology clinic?", they were delighted to announce that 100% answered yes!

"We highly commend the work of the Cyprus League Against Rheumatism to bring the vital support of rheumatology nurses to people living with rheumatic and musculoskeletal diseases," said Professor Thomas Dörner, Chairperson of the Scientific Programme Committee, EULAR. "We hope this project acts as an inspiration to others involved in supporting the work of nurses specialising in rheumatology to make a difference in patients' lives."

The "Patient Care with Rheumatic Diseases" educational programme was conducted one day per week over three months, with several lectures being delivered by CYPLAR. There were three days of clinical experience in an outpatient Rheumatology Clinic and one day in the Care Department gaining experience in the preparation and delivery of biological and biosimilar therapeutics. Examination consisted of a final written evaluation (60%) and a case study presentation.

The significance of this campaign is supported by the results of a randomised controlled trial, also presented today at EULAR 2019, which demonstrates that nurse-led patient education can significantly improve essential safety skills in patients with inflammatory arthritis.3

Results of the study show that, at six months, the 'intervention group' had significantly higher acquisition of safety skills compared to the 'usual care' group with a Biosecure score of 81.2+13.1 versus 75.6+13.0 respectively (p=0.016).3

"Safety is an important issue in the management of inflammatory arthritis treated with biologic disease-modifying antirheumatic drugs," said Catherine Beauvais MD, University Hospital Saint Antoine, Paris, France. "We hope our results provide evidence to support the implementation of nurse-led patient education programs in centres across Europe."

The study included 120 patients with rheumatoid arthritis, axial spondyloarthritis or peripheral spondyloarthritis at the time of their first introduction of a biologic disease-modifying antirheumatic drug (bDMARD). Patients were randomised to receive 'usual care' or 'intervention care' which was a face-to-face nurse-led patient education session at baseline and then at three months. The mean duration of the intervention was 65.5+17.9 minutes at baseline and 43.7±18.7 at three months.3 At six months, the acquisition of safety skills was measured using the Biosecure score (0-100 scale), a 55-item validated questionnaire assessing competences to deal with fever, infections, vaccination, and other daily life situations. Patients in the intervention group also had a significantly better capacity to cope with their arthritis.

Abstract numbers: OP0289-PARE/SAT0679

Credit: 
European Alliance of Associations for Rheumatology (EULAR)