Patient Education Program With Mental Health Component Reduces Cardiovascular Disease Risks (Medicine)

People who participated in a health education program that included both mental health and physical health information significantly reduced their risks of cardiovascular disease and other chronic diseases by the end of the 12-month intervention – and sustained most of those improvements six months later, researchers found.

People who participated in the integrated mental and physical health program maintained significant improvements on seven of nine health measures six months after the program’s conclusion. These included, on average, a 21% decrease in fasting blood sugar, a 17% decrease in low-density lipoprotein cholesterol and a 12% decrease in their body mass index.

However, patients in the group that focused only on physical health information maintained their improvements on just two risk factors – BMI and systolic blood pressure.

Data collected at the conclusion of the 12-month intervention indicated that patients in the program with the mental health component improved on eight of nine health measures, while their peers in the traditional program improved on just three.

“The gains achieved by patients in the integrated program were greater than those of their counterparts in the other group and had greater lasting effects,” said University of Illinois Urbana-Champaign social work professor Tara M. Powell, the first author of a study on the project, published in the journal Preventive Medicine Reports.

Social work professor Tara Powell found that people at risk of cardiovascular disease achieved significant improvements in their weight, blood pressure and other metrics that lasted six months after completing an informational program that included both physical health and mental health information. Photo by L. Brian Stauffer

Study participants were 213 Syrian refugees and 382 Jordanians who were patients of three health clinics in Irbid, Jordan, a border community that has experienced a large influx of people fleeing the civil war in Syria.

Powell conducted the research in partnership with the health-focused relief and development nonprofit organization Americares and the Royal Health Awareness Society, Jordan.

Powell’s group explored the efficacy of a health education intervention called the Healthy Community Clinic, delivered in clinics throughout Jordan to improve patients’ management of chronic conditions such as cardiovascular disease and diabetes, and reduce their risks of complications. Trained health educators or nurses led 20 interactive educational sessions that patients attended twice a month for one year.

Patients’ outcomes in the traditional HCC program were compared with those of peers who received routine health care only and with a group who participated in an expanded HCC program that integrated four additional sessions focused on mental health.

The mental health sessions included discussions of topics such as grief and physical and emotional traumatic stress reactions. Participants also learned tangible coping skills for reducing emotional distress such as deep-breathing exercises and walking.

“This study is among the first to illustrate how an integrated physical and mental health educational intervention can improve health outcomes and ultimately help reduce cardiovascular disease risk in refugees and low-income populations,” said co-principal investigator Dr. Shang-Ju Li, Americares’ senior director of monitoring and evaluation. “We are thrilled to share this groundbreaking research and look forward to making even more progress as we continue to look for ways to improve health outcomes for people affected by poverty or disaster.”

Additional co-authors of the study were Michelle Thompson, an associate director of emergency response, Americares; sociology graduate student Yuan Hsiao of the University of Washington; Aseel Farraj, a program manager of the Royal Health Awareness Society; Mariam Abdoh, a senior population and health advisor/project management specialist, USAID; and Dr. Rami Farraj, of the King Hussein Medical Center.

Based upon the findings of this research, the Royal Health Awareness Society has since deployed the HCC with the mental health component to public health centers across Jordan, Powell said.

In a prior study with the same participants that examined the impact of social support on mental and physical health, Powell and her colleagues found that more than half of the participants had experienced at least one traumatic event. Among Syrians, the most frequently reported traumatic experience was living in a war zone (73%), while among Jordanians it was witnessing a violent death (18%).

That study, published in PLOS ONE, was co-written by Li, Hsiao and U. of I. graduate student Oe Jin Shin.

“Because mental health conditions such as depression and anxiety often co-occur with chronic physical problems and with poverty, patient education programs that integrate mental and physical health information are critical for countries such as Jordan,” Powell said. “Making these integrated programs widely available can reduce the burden of noncommunicable diseases on marginalized populations and increase their access to care.”

Featured image: A mother and daughter participated in the patient education program at a clinic in Irbid, Jordan. Photo by Kathy Kukula, Americares


Reference: (1) The paper “An integrated physical and mental health awareness education intervention to reduce non-communicable diseases among Syrian refugees  and Jordanians in host communities: A natural experiment study” is available online DOI: 10.1016/j.pmedr.2021.101310  (2) The paper “Post-traumatic stress, social and physical health: A mediation and moderation analysis of Syrian refugees and Jordanians in a border community” is available online DOI: 10.1371/journal.pone.0241036


Provided by Illinois News Bureau

A Plant’s Nutrient-Sensing Abilities Can Modulate Its Response To Environmental Stress (Botany)

Understanding how plants respond to stressful environmental conditions is crucial to developing effective strategies for protecting important agricultural crops from a changing climate. New research led by Carnegie’s Zhiyong Wang, Shouling, Xu, and Yang Bi reveals an important process by which plants switch between amplified and dampened stress responses. Their work is published by Nature Communications.

To survive in a changing environment, plants must choose between different response strategies, which are based on both external environmental factors and internal nutritional and energy demands. For example, a plant might either delay or accelerate its lifecycle, depending on the availability of the stored sugars that make up its energy supply.  

“We know plants are able to modulate their response to environmental stresses based on whether or not nutrients are available,” Wang explained. “But the molecular mechanisms by which they accomplish this fine tuning are poorly understood.”  

For years, Carnegie plant biologists have been building a treasure trove of research on a system by which plants sense available nutrients. It is a sugar molecule that gets tacked onto proteins and alters their activities. Called O-linked N-Acetylglucosamine, or O-GlcNAc, this sugar tag is associated with changes in gene expression, cellular growth, and cell differentiation in both animals and plants.

The functions of O-GlcNAc are well studied in the context of human diseases, such as obesity, cancer, and neurodegeneration, but are much less understood in plants. In 2017, the Carnegie-led team identified for the first time hundreds of plant proteins modified by O-GlcNAc, providing a framework for fully parsing the nutrient-sensing network it controls.

In this most recent report, researchers from Wang’s lab—lead author Bi, Zhiping Deng, Dasha Savage, Thomas Hartwig, and Sunita Patil—and Xu’s lab—Ruben Shrestha and Su Hyun Hong—revealed that one of the proteins modified by an O-GlcNAc tag provides a cellular physiological link between sugar availability and stress response. It is an evolutionarily conserved protein named Apoptotic Chromatin Condensation Inducer in the Nucleus, or Acinus, which is known in mammals to play numerous roles in the storage and processing of a cell’s genetic material.

Through a comprehensive set of genetic, genomic, and proteomic experiments, the Carnegie team demonstrated that in plants Acinus forms a similar protein complex as its mammalian counterpart and plays a unique role in regulating stress responses and key developmental transitions, such as seed germination and flowering. The work further demonstrates that sugar modification of the Acinus protein allows nutrient availability to modulate a plant’s sensitivity to environmental stresses and to control seed germination and flowering time.

“Our research illustrates how plants use the sugar sensing mechanisms to fine tune stress responses,” Xu explained. “Our findings suggest that plants choose different stress response strategies based on nutrient availability to maximize their survival in different stress conditions.”

Looking forward, the researchers want to study more proteins that are tagged by O-GlcNAc and better understand how this important system could be harnessed to fight hunger.

“Understanding how plants make cellular decisions by integrating environmental and internal information is important for improving plant resilience and productivity in a changing climate,” Wang concluded. “Considering that many parts of the molecular circuit are conserved in plant and human cells, our research findings can lead to improvement of not only agriculture and ecosystems, but also of human health.”        

This work was supported by the U.S. National Institutes of Health and the Carnegie Institution for Science endowment.

Featured image: Photo of flowering Arabidopsis Thaliana © Shutterstock


Reference: Bi, Y., Deng, Z., Ni, W. et al. Arabidopsis ACINUS is O-glycosylated and regulates transcription and alternative splicing of regulators of reproductive transitions. Nat Commun 12, 945 (2021). https://doi.org/10.1038/s41467-021-20929-7


Provided by Carnegie Science

Scent Detection Dogs Can Identify Individuals Infected with COVID-19 (Medicine)

The use of trained scent detection dogs to detect volatile organic compounds associated with the COVID virus shows promise in early studies

In a recent article in the Journal of Osteopathic Medicine, authors gathered previously published research to summarize current thinking on the feasibility and efficacy of using scent detection dogs to screen for the COVID-19 virus. The researchers report that sensitivity, specificity, and overall success rates reported by the canine scent detection studies are comparable or better than the standard RT-PCR and antigen testing procedures.

These findings indicate scent detection dogs can likely be used to effectively screen and identify individuals infected with the COVID-19 virus in hospitals, senior care facilities, schools, universities, airports, and even large public gatherings for sporting events and concerts.

“Accurate and rapid screening of individuals who may be carriers, symptomatic or asymptotic, of the COVID-19 virus will remain important for slowing and limiting the spread of infection,” said Tommy Dickey, PhD, professor, University of California, Santa Barbara. “These preliminary studies suggest the use of medical scent detection dogs offers a promising approach.”

Documented success detecting disease

Dogs can sense a broad range of molecules with extremely small concentrations: 1 part in a quadrillion compared with 1 part in 1 billion for humans. This capability is used for search and for identification of diseases with their individual chemistries and odors.

Using inhaled air molecules and particulates, dogs can detect odorous human molecules (volatile organic compounds, or VOCs) that originate from flaked off skin or hair cells, blood, breath, saliva, sweat, tears, nasal mucous, urine, semen, or feces. Since smells linger, dogs can maintain a historical library of the smells of complex molecules.

“The science behind and efficacy of using dogs in detecting medical conditions and diseases such as cancers, diabetes, malaria, Parkinson’s disease, and more has been documented,” said Heather Junqueira. “These new studies provide support for additional research to determine their ability to detect COVID-19 at scale.”

The qualified studies

For their review, the authors assessed four recent studies analyzing the success of scent detecting dogs at identifying VOCs associated with COVID-19. First, they described the work of a team of collaborating researchers from France and Lebanon, who tested with 8 dogs that had previously been trained to detect both explosives and colon cancer.

These dogs were independently presented with cotton or wool gauze samples that had been soaked with sweat from one of 198 human armpits of patients in different hospitals. While the COVID-19 virus does not itself have a smell, researchers hypothesized that the resulting infection generates metabolic changes, which cause the release of a distinctive type of sweat odor that can be detected by a dog.

The dogs were trained to only sit in front of a COVID-19-positive sample contained in a box with a sample canister. After four days of training using COVID-19 samples, the success rate for the dogs ranged between 83 and 100%.

Saliva or tracheobronchial secretions

In another study described by the authors, a research team in Germany conducted a randomized, double-blinded, controlled pilot study to determine whether previously trained scent dogs could successfully detect the presence of the COVID-19 virus. Dogs were trained over 1 week to detect the COVID-19 virus in samples of saliva or tracheobronchial secretions collected from infected patients.

Each dog, its handler, and the person observing the study were blindfolded. The number and duration of each dogs’ “nose dips” into the scent holes, along with the location of the positive and negative samples, were automatically recorded and verified using time-stamped video analysis, which automated the process and reduced trainer interference.

The results, derived from 1,012 automated sample presentations, showed an overall average detection rate of 94%: 157 correct indications of positive, 792 correct rejections of negative, 33 false positives, and 30 false negative indications. Interestingly, the team reported no notable difference in detection ability between the use of sample saliva and sample tracheal secretion.

While that pilot study had limitations—in particular, the positive samples came only from severely affected, hospitalized COVID-19 patients and the negative samples were from healthy individuals with no indications of respiratory infections—the authors of the present study found those results encouraging.

Support for additional research

A third study done by a team in Colombia tested 6 trained scent dogs of various and mixed breeds to develop a screening method for detecting COVID-19 in individuals who may be asymptomatic, pre-symptomatic, or symptomatic.

The researchers developed a device to safely expose the scent-trained dogs to VOC samples collected from respiratory secretions of COVID-19-positive patients, and their detailed study was conducted in 3 phases, with the third phase ongoing.

“Of the 6,000 samples, the dogs’ performances [in that study] resulted in a sensitivity of 95.5% and a selectivity of 99.6%,” said Dickey. “The high success rates among different types of dogs suggests a range of breeds or mixed breeds may be trained to effectively screen for COVID-19.”

Challenges remain

“The results of recently reported and ongoing research are encouraging; however, there remain challenges to be considered before broad-scale implementation of scent detecting dogs to identify and screen for COVID-19,” said Junqueira. “Nonetheless, the research supports the use of scent detection dogs for pilot COVID-19 screening studies in venues such as airports and sporting events.”

The authors hope that their research review, which presented recent information and perspectives on the potential for broad application of trained scent dogs for screening of COVID-19-infected individuals, can be used to assist in the development of future studies and implementation of screening programs to benefit preventative medical research.

Featured image: Author Tommy Dickey, PhD, demonstrates how he conducts simple canine scent detection training with his own dogs. These dogs were not part of the reviewed research. © Tommy Dickey, PhD


Reference: Dickey T, Junqueira H. Toward the use of medical scent detection dogs for COVID-19 screening. J Am Osteopath Assoc 2021;121(2):141–148. doi: https://doi.org/10.1515/jom-2020-0222.


Provided by American Osteopathic Association

Hope For Children With Bow Hunter Syndrome (Medicine)

New protocol for managing this rare condition can identify its cause and prevent repeat strokes

Fusing the neck’s top two vertebrae can prevent repeat strokes in children with bow hunter syndrome, a rare condition that affects a handful of U.S. pediatric patients each year, UT Southwestern researchers suggest in a recent study. The finding, published online in Child’s Nervous System, offers a new way to treat these children and protect them from potentially lifelong neurological consequences.

Bow hunter syndrome – so named because of the head’s position when a person is shooting an arrow – is a condition affecting children and adults in which turning the head compresses blood vessels supplying the back of the brain from the vertebral artery. In adults, this condition is usually caused by a bone spur on the neck and presents with temporary symptoms of fainting, dizziness, headache, or tinnitus that resolve when the head turns back to a neutral position.

But for children with bow hunter syndrome, the cause is often unclear, and they have a far different and more serious presentation, explains study leader Bruno P. Braga, M.D., assistant professor of neurological surgery and pediatrics at UTSW and an attending physician at Children’s Health. This condition is only discovered when these young patients suffer a tear in the vertebral artery, which spills out blood clots that subsequently cause a stroke. Even after this tear heals, it leaves a weak spot that is vulnerable to re-tearing and potentially causing additional strokes.

Bruno P. Braga, M.D. © UTSWMC

“Strokes in children are exceedingly rare, and those caused by bow hunter syndrome are even rarer,” says Braga, also a member of the Peter O’Donnell Jr. Brain Institute. “Because this condition is so uncommon, it is often underdiagnosed. In addition, the best way to treat it and prevent subsequent strokes has been unknown.”

In the study, Braga and his colleagues outline a new method that they developed at UTSW and Children’s Health that they used to prevent repeat strokes in 11 children with bow hunter syndrome. These patients, ranging in age from 18 months to 15 years, were all diagnosed with a stroke after showing a combination of neurological symptoms, such as vomiting, headache, impaired coordination, and dizziness.

After tracing the cause of their strokes to a tear in the vertebral artery at the top of the neck, doctors prescribed the standard treatment: placing these patients in a neck brace and giving them anti-clotting drugs, which help the artery to heal. Most children with this type of stroke are not investigated further and its cause is never discovered; consequently, many can have recurrent strokes. To see if the tear was caused by bow hunter syndrome, Braga and his colleagues tested the children after three months using a dynamic angiogram, a special type of X-ray that provides a map of the blood’s circulation during head rotation. When these patients’ heads turned gently from side to side, the researchers saw compression in one or both of their vertebral arteries at the site of the previous tear – a hallmark of bow hunter syndrome. Most importantly, their study identified one specific segment and configuration of the vertebral artery that is highly suggestive of the disease.

To alleviate this compression and help prevent a subsequent stroke, Braga and his colleagues fused the top two vertebrae using surgical screws. Although spinal fusion is often performed for other conditions in children, such as scoliosis, it had rarely been used for bow hunter syndrome, Braga says.

Possible risks and complications from the procedure include injury to the vertebral artery or spinal cord, leading to stroke or spinal cord injury, infection, abnormal growth of the spine, inability to fully rotate the neck, or need for revision surgery.

The fusions were successful in each of the children, with minimal blood loss and just one post-surgical complication – a superficial wound infection treated with antibiotics. None of the children had blood vessel or neurological injuries. Although each child was on anti-clotting therapy after their stroke and leading up to surgery, they all discontinued this therapy just before surgery and never used it again. Interestingly, the researchers note, patients younger than 10 had no apparent restrictions in head rotation after surgery.

Over up to five years of follow-up, none of these patients has had a repeat stroke, Braga says – suggesting that spinal fusion could offer a permanent solution to protect young patients with bow hunter syndrome from future strokes.

“Avoiding a second stroke is infinitely better than treating a second stroke,” Braga says. “Our new protocol could offer a lasting way to prevent pediatric bow hunter syndrome patients from a further devastating neurological event.”

Other researchers who contributed to this study include Rafael Sillero, Rosalina M. Pereira, Dale M. Swift, Nancy K. Rollins, Amy J. Hogge, and Michael M. Dowling, all of UTSW/Children’s Health; and Kamran Urgun of University of California, Irvine.


Reference: Braga, B.P., Sillero, R., Pereira, R.M. et al. Dynamic compression in vertebral artery dissection in children: apropos of a new protocol. Childs Nerv Syst (2020). https://doi.org/10.1007/s00381-020-04956-1


Provided by UT Southwestern Medical Center

Wafer-scale Production Of Graphene-based Photonic Devices (Material Science)

Graphene Flagship researchers have devised a wafer-scale fabrication method that paves the way to the next generation of telecom and datacom devices.

The crystal seeding, growth and transfer technique adopted in this work ensures wafer-scale high-mobility graphene exactly where is needed: a great advantage for the scalable fabrication of photonic devices like modulators.

Camilla Coletti, Coordinator of the ‘Graphene Labs’ at Graphene Flagship partner IIT, Italy

Our world needs reliable telecommunications more than ever before. However, classic devices have limitations in terms of size and cost and, especially, power consumption – which is directly related to greenhouse emissions. Graphene could change this and transform the future of broadband. Now, Graphene Flagship researchers have devised a wafer-scale fabrication technology that, thanks to predetermined graphene single-crystal templates, allows for integration into silicon wafers, enabling automation and paving the way to large scale production.

This work, published in the prestigious journal ACS Nano, is a great example of a collaboration fostered by the Graphene Flagship ecosystem. It counted on the participation of several Graphene Flagship partner institutions like CNIT and the Istituto Italiano di Tecnologia (IIT), in Italy, the Cambridge Graphene Centre at the University of Cambridge, UK, and Graphene Flagship Associated Member and spin-off CamGraphIC. Furthermore, Graphene Flagship-linked third party INPHOTEC and researchers at the Tecip Institute in Italy provided the graphene photonics integrated circuits fabrication. Through the Wafer-scale Integration Work Package and Spearhead Projects such as Metrograph, the Graphene Flagship fosters collaboration between academia and leading industries to develop high-technology readiness level prototypes and products, until they can reach market exploitation.

The new fabrication technique is enabled by the adoption of single-crystal graphene arrays. “Traditionally, when aiming at wafer-scale integration, one grows a wafer-sized layer of graphene and then transfer it onto silicon,” explains Camilla Coletti, coordinator of IIT’s Graphene Labs, who co-led the study. “Transferring an atom-thick layer of graphene over wafers while maintaining its integrity and quality is challenging” she adds. “The crystal seeding, growth and transfer technique adopted in this work ensures wafer-scale high-mobility graphene exactly where is needed: a great advantage for the scalable fabrication of photonic devices like modulators,” continues Coletti.

It is estimated that, by 2023, the world will see over 28 billion connected devices, most of which will require 5G. These challenging requirements will demand new technologies. “Silicon and germanium alone have limitations; however, graphene provides many advantages,” says Marco Romagnoli from Graphene Flagship partner CNIT, linked third party INPHOTEC, and associated member CamGraphiC, who co-led the study. “This methodology allows us to obtain over 12.000 graphene crystals in one wafer, matching the exact configuration and disposition we need for graphene-enabled photonic devices,” he adds. Furthermore, the process is compatible with existing automated fabrication systems, which will accelerate its industrial uptake and implementation.

In another publication in Nature Communications, researchers from Graphene Flagship partners CNIT, Istituto Italiano di Tecnologia (IIT), in Italy, Nokia – including their teams in Italy and Germany, Graphene Flagship-linked third party INPHOTEC and researchers at Tecip, used this approach to demonstrate a practical implementation: “We used our technique to design high-speed graphene photodetectors,” says Coletti. “Together, these advances will accelerate the commercial implementation of graphene-based photonic devices,” she adds.

Graphene-enabled photonic devices offer several advantages. They absorb light from ultraviolet to the far-infrared – this allows for ultra-broadband communications. Graphene devices can have ultra-high mobility of carriers – electrons and holes – enabling data transmission that exceeds the best performing ethernet networks, breaking the barrier of 100 gigabits per second.

Reducing the energetic demands of telecom and datacom is fundamental to provide more sustainable solutions. At present, Information and communication technologies are already responsible for almost 4% of all greenhouse emissions, comparable to the carbon footprint of the airline industry, projected to increase to around 14% by 2040. “In graphene, almost all the energy of light can be converted into electric signals, which massively reduces power consumption and maximises efficiency,” adds Romagnoli.

Frank Koppens, Graphene Flagship Leader for Photonics and Optoelectronics, says: “This is the first time that high-quality graphene has been integrated on the wafer-scale. The work shows direct relevance by revealing high-yield and high-speed absorption modulators. These impressive achievements bring commercialisation of graphene devices into 5G communications very close.”

Andrea C. Ferrari, Science and Technology Officer of the Graphene Flagship and Chair of its Management Panel added: “This work is a major milestone for the Graphene Flagship. A close collaboration between academic and industrial partners has finally developed a wafer-scale process for graphene integration. The Graphene Foundry is no more a distant goal, but it starts today.”

Featured image credit: Unsplash


References

(1) “Wafer-scale integration of graphene-based photonic devices.” M.A. Giambra, V. Mišeikis, S. Pezzini, S. Marconi, A. Montanaro, F. Fabbri, V. Sorianello, A.C. Ferrari, C. Coletti, M. Romagnoli. ACS Nano, 2021, DOI: 10.1021/acsnano.0c09758. (2) “Photo thermal effect graphene detector featuring 105 Gbit/s NRX and 120 Gbit/s PAM direct detection.” S. Marconi, M.A. Giambra, A. Montanaro, V. Mišeikis, S. Soresi, S. Tirelli, P. Galli, F. Buchali, W. Templ, C. Coletti, V. Sorianello, M. Romagnoli. Nature Communications, 2021, DOI: 10.1038/s41467-021-21137-z.


Provided by Graphene Flagship

Hubble Uncovers Concentration of Small Black Holes (Astronomy)

Scientists were expecting to find an intermediate-mass black hole at the heart of the globular cluster NGC 6397, but instead they found evidence of a concentration of smaller black holes lurking there. New data from the NASA/ESA Hubble Space Telescope have led to the first measurement of the extent of a collection of black holes in a core-collapsed globular cluster.

Globular clusters are extremely dense stellar systems, in which stars are  packed closely together. They are also typically very old — the globular cluster that is the focus of this study, NGC 6397, is almost as old as the Universe itself. It resides 7800 light-years away, making it one of the closest globular clusters to Earth. Because of its very dense nucleus, it is known as a core-collapsed cluster.

When Eduardo Vitral and Gary A. Mamon of the Institut d’Astrophysique de Paris set out to study the core of NGC 6397, they expected to find evidence for an “intermediate-mass” black hole (IMBH). These are smaller than the supermassive black holes that lie at the cores of large galaxies, but larger than stellar-mass black holes formed by the collapse of massive stars. IMBH  are the long-sought “missing link” in black hole evolution and their mere existence is hotly debated, although a few candidates have been found (see [1], for example). 

To look for the IMBH, Vitral and Mamon analysed the positions and velocities of the cluster’s stars. They did this using previous estimates of the stars’ proper motions [2] from Hubble images of the cluster spanning several years [3], in addition to proper motions provided by ESA’s Gaia space observatory, which precisely measures the positions, distances and motions of stars. Knowing the distance to the cluster allowed the astronomers to translate the proper motions of these stars into velocities. 

Our analysis indicated that the orbits of the stars are close to random throughout the globular cluster, rather than systematically circular or very elongated,” explained Mamon.

We found very strong evidence for invisible mass in the dense central regions of the cluster, but we were surprised to find that this extra mass is not point-like but extended to a few percent of the size of the cluster,” added Vitral.

This invisible component could only be made up of the remnants (white dwarfsneutron stars, and black holes) of massive stars whose inner regions collapsed under their own gravity once their nuclear fuel was exhausted. The stars progressively sank to the cluster’s centre after gravitational interactions with nearby less massive stars, leading to the small extent of the invisible mass concentration. Using the theory of stellar evolution, the scientists concluded that the bulk of the unseen concentration is made of stellar-mass black holes, rather than white dwarfs or neutron stars that are too faint to observe.

Two recent studies had also proposed that stellar remnants and in particular, stellar-mass black holes, could populate the inner regions of globular clusters.

Our study is the first finding to provide both the mass and the extent of what appears to be a collection of mostly black holes in a core-collapsed globular cluster,” said Vitral. 

Our analysis would not have been possible without having both the Hubble data to constrain the inner regions of the cluster and the Gaia data to constrain the orbital shapes of the outer stars, which in turn indirectly constrain the velocities of foreground and background stars in the inner regions,” added Mamon, attesting to an exemplary international collaboration.

The astronomers also note that this discovery raises the question of whether mergers of these tightly packed black holes in core-collapsed globular clusters may be an important source of gravitational waves recently detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO) experiment.

Notes

[1] In 2020, new data from the NASA/ESA Hubble Space Telescope provided the strongest evidence to date for a mid-sized black hole. Read the full press release on this result here.

[2] Proper motion describes how fast objects move in the sky.

[3] The Hubble data for this study were provided by A. Bellini, who measured the proper motions for over 1.3 million stars in 22 globular clusters, including NGC 6397.

More information

The Hubble Space Telescope is a project of international cooperation between ESA and NASA.

The team of astronomers in this study consists of E. Vitral and G. A. Mamon. The results have been published today in Astronomy & Astrophysics.

Featured image: Artist’s Impression of the Black Hole Concentration in NGC 6397: Scientists were expecting to find an intermediate-mass black hole at the heart of the globular cluster NGC 6397, but instead they found evidence of a concentration of smaller black holes lurking there. New data from the NASA/ESA Hubble Space Telescope have led to the first measurement of the extent of a collection of black holes in a core-collapsed globular cluster. This is an artist’s impression created to visualize the concentration of black holes at the center of NGC 6397. In reality, the small black holes here are far too small for the direct observing capacities of any existing or planned future telescope, including Hubble. It is predicted that this core-collapsed globular cluster could be host to more than 20 black holes. © ESA/Hubble, N. Bartmann


Reference: Eduardo Vitral and Gary A. Mamon, “Does NGC 6397 contain an intermediate-mass black hole or a more diffuse inner subcluster?”, A&A 646, A63 (2021). https://www.aanda.org/articles/aa/full_html/2021/02/aa39650-20/aa39650-20.html


Provided by ESA/Hubble

Insights Into the Role of DNA Repair & Huntington’s Disease Gene Mutation Open New Avenues For Drug Discovery (Medicine)

A special issue of the Journal of Huntington’s Disease focusing on recent genetic advances in the disease synthesizes the latest research and has the potential to serve as a catalyst to improve patient care and outcomes

Recent genetic data from patients with Huntington’s disease (HD) show that DNA repair is an important factor that determines how early or late the disease occurs in individuals who carry the expanded CAG repeat in the HTT gene that causes HD. The processes of DNA repair further expand the CAG repeats in HTT in the brain implicated in pathogenesis and disease progression. This special issue of the Journal of Huntington’s Disease (JHD) is a compendium of new reviews on topics ranging from the discovery of somatic CAG repeat expansion in HD, to our current understanding of the molecular mechanisms involved and the development of potential new therapies targeting these mechanisms.

The CAG expansion varies from 6 to 35 repeats in HTT on chromosomes of unaffected individuals and from more than 36 to greater than 180 repeats in HD patients.

“The CAG repeat mutation in the HTT gene that causes HD was discovered in 1993. Although our understanding of the underlying biology and our ability to model many aspects of the disease have improved substantially, no treatment that alters the course of this devastating disorder has been found,” explain Guest Editors Lesley Jones, PhD (Cardiff University, UK), Vanessa Wheeler, PhD (Massachusetts General Hospital, USA), and Christopher E. Pearson, PhD (The Hospital for Sick Children, University of Toronto, Canada).

Recent advances in genetics have now transformed our understanding of the factors that are critical in the pathogenesis of HD and are beginning to provide similar insight into other repeat expansion disorders such as Friedreich’s ataxia, myotonic dystrophy and many of the repeat-expansion spinocerebellar ataxias. This special issue of JHD provides an important and novel synthesis of the wealth of HD research information and the knowledge of DNA repair and somatic repeat expansion in HD. This has the potential to help drive discovery forward, leading to new treatments and improved quality of life and outcomes for individuals with HD.

The genetic findings presented in this issue examine data in HD, HD models and other diseases and make sense of many previous findings with respect to how DNA repair genes altered the disease in mice. This has highlighted HD biology that can be used to generate new targets for development of drugs to treat the disease. It may eventually allow a better prediction of the clinical course of HD in specific individuals and improve the power of clinical trials enabling shorter trials or trials with fewer participants.

The findings presented in this issue imply that the expanded CAG repeat in HD causes disease through a two-part process. A review entitled “Huntington’s Disease Pathogenesis: Two Sequential Components” outlines how the compelling genetic data that highlight DNA repair and somatic expansion are critically important in the manifestation of HD. It also explores the implications of these data for mechanisms underlying disease pathophysiology. The authors propose that two steps are required for pathogenesis in HD: first an expansion of the HTT CAG repeat in somatic cells, followed by downstream pathogenic events occurring in response to those CAG repeats in cells that are expanded from the inherited length. The authors share access to their website allowing other investigators to explore recent genetic data interactively to support their own research

“The identification of the HD gene has not yet led to an effective treatment, but continued human genetic analysis of genotype-phenotype relationships in large HD subject populations, first at the HTT locus and subsequently genome-wide, has provided insights into pathogenesis that divide the course of the disease into two sequential, mechanistically distinct components,” comments author James F. Gusella, PhD, Massachusetts General Hospital and Harvard Medical School.

Although linking the genetic findings in HD to functional biological systems and then to their actual effect on disease onset or course has been challenging, many pharmaceutical companies, large and small, are now working on the new targets identified by these findings. “Drugging DNA Damage Repair Pathways for Trinucleotide Repeat Expansion Diseases” highlights and addresses the multiple challenges that will need to be overcome to generate new therapeutics or repurposing existing therapeutics that can tackle DNA repair and somatic expansion of the CAG repeat. It illustrates the gaps in our knowledge that we really need to fill to use these findings to generate novel and effective drugs for somatic expansion in HD and potentially other repeat disorders.

“The development of novel DNA damage response (DDR) drugs for neurodegeneration is also facilitated by understanding of challenges with DDR drugs for oncology and key liabilities associated with specific targets,” notes lead author Caroline L. Benn, PhD, LoQus23 Therapeutics. “We need to maintain a watching brief, continue to address the gaps in our understanding, and ensure we continue to work to realize the potential to increase therapeutic benefit and reduce risk. Taken together, we believe success is possible with close collaboration between patients, academic investigators, preclinical drug discoverers, clinicians, diagnostic developers and regulatory bodies.”

“We hope that our colleagues in the global HD research community find this special issue educational and stimulating and that it serves to speed discovery and treatments. We learned a lot – we hope our readers do likewise!” add the Guest Editors.

Co-Editors-in-Chief Blair R. Leavitt, MD (The University of British Columbia) and Leslie M. Thompson, PhD (University of California Irvine) have dedicated this special issue in memory of Professor Sir Peter Harper (1939-2021). A visionary geneticist, he was instrumental in the discovery of the repeat mutations causing HD and myotonic dystrophy. “Prof. Harper continued to influence the HD field though his perceptive anticipation of what these genetic discoveries would mean for patients, their families and the direction of HD research. He was a generous and engaged mentor to a whole generation of clinical and non-clinical researchers in HD and other repeat disorders, and his legacy will continue to inspire future generations,” adds Prof. Jones, a long-time colleague and protégé.

Featured image: Timeline of some of the key events establishing anticipation as a genuine biological phenomenon and somatic expansion as contributing toward Huntington’s disease pathology. © Darren G. Monckton


Reference: (1) Hong, Eun Pyo et al. ‘Huntington’s Disease Pathogenesis: Two Sequential Components’. 1 Jan. 2021 : 35 – 51. https://content.iospress.com/articles/journal-of-huntingtons-disease/jhd200427 (2) Benn, Caroline L., Gibson, Karl R., and Reynolds, David S. ‘Drugging DNA Damage Repair Pathways for Trinucleotide Repeat Expansion Diseases’. 1 Jan. 2021 : 203 – 220. https://content.iospress.com/articles/journal-of-huntingtons-disease/jhd200421


Provided by IOS Press

New Research Identifies Biological Causes Of Muscle Weakness in Later Life (Medicine)

A new largescale genetic analysis has found biological mechanisms that contribute to making people more susceptible to muscle weakness in later life, finding that diseases such as osteoarthritis and diabetes may play a large role in susceptibility.

As we get older we lose muscle strength, and in some people this severe weakness impacts their ability to live everyday lives, a condition called sarcopenia. Around 10 per cent of people over 50 experience sarcopenia. Many causes thought to impact likelihood of developing this weakness, which is linked to higher death rates.

In a genetic analysis of over 250,000 people aged over 60 from UK Biobank and 21 other cohorts, an international team led by researchers at the University of Exeter looked at handgrip strength, using thresholds of loss of muscle function derived from international definitions of sarcopenia.

The team, including collaborators from the USA and the Netherlands, then conducted a genetic analysis, and found specific biological mechanisms push some people towards sarcopenia, whilst protecting others. The study, published in Nature Communications identified 15 areas of the genome, or loci, associated with muscle weakness, including 12 loci not implicated in previous analyses of continuous measures of grip strength.

Biomarkers in the blood including red blood cells and inflammation may also share causal pathways with sarcopenia. Together, these results highlight specific areas for intervention or for identifying those at most risk.

Lead author Garan Jones said: “The strongest associations we found were close to regions of the genome regulating the immune system, and growth and development of the musclo-skeletal system. However we also discovered associations with regions not previously known to be linked to musclo-skeletal traits.

“We found that our analysis of muscle weakness in older people shared common genetic pathways with metabolic diseases such as type-2 diabetes, and auto-immune conditions such as osteoarthritis and rheumatoid arthritis. In subgroups of people with increased risk of these conditions, sarcopenia may be a key outcome to look out for and prevent.

“We hope that by understanding the genetic contributions to muscle weakness with age, we will be able to highlight possible therapeutic interventions earlier in life, which would lead to a happier and healthier old age.”


Reference: Jones, G., Trajanoska, K., Santanasto, A.J. et al. Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women. Nat Commun 12, 654 (2021). https://doi.org/10.1038/s41467-021-20918-w


Provided by University of Exeter

A New Way of Forming Planets (Planetary Science)

In the last 25 years, scientists have discovered over 4000 planets beyond the borders of our solar system. From relatively small rock and water worlds to blisteringly hot gas giants, the planets display a remarkable variety. This variety is not unexpected. The sophisticated computer models, with which scientists study the formation of planets, also spawn very different planets. What the models have more difficulty to explain is the observed mass distribution of the planets discovered around other stars. The majority have fallen into the intermediate mass category – planets with masses of several Earth masses to around that of Neptune. Even in the context of the solar system, the formation of Uranus and Neptune remains a mystery. Scientists of the Universities of Zurich and Cambridge, associated with the Swiss NCCR PlanetS, have now proposed an alternative explanation backed up by comprehensive simulations. Their results were published in the scientific journal Nature Astronomy.

Two contrasting forces…

“When planets form from the so-called protoplanetary disk of gas and dust, gravitational instabilities could be the driving mechanism”, Lucio Mayer, study co-author and Professor of Computational Astrophysics at the University of Zurich, and member of the NCCR PlanetS, explains. In this process, dust and gas in the disk clump together due to gravity and form dense spiral structures. These then grow into planetary building blocks and eventually planets.

The scale on which this process occurs is very large – spanning the scale of the protoplanetary disk. “But over shorter distances – the scale of single planets – another force dominates: That of magnetic fields developing alongside the planets”, Mayer elaborates. These magnetic fields stir up the gas and dust of the disk and thus influence the formation of the planets. “To get a complete picture of the planetary formation process, it is therefore important to not only simulate the large scale spiral structure in the disk. The small scale magnetic fields around the growing planetary building blocks also have to be included”, says lead-author of the study, former doctoral student of Mayer and now Research Fellow at the University of Cambridge, Hongping Deng.

…that are difficult to grasp simultaneously

However, the differences in scale and nature of gravity and magnetism make the two forces very challenging to integrate into the same planetary formation model. So far, computer simulations that captured the effects of one of the forces well, usually did poorly with the other. To succeed, the team developed a new modelling technique. That required expertise in a number of different areas: First, they needed a deep theoretical understanding of both gravity and magnetism. Then, the researchers had to find a way to translate the understanding into a code that could efficiently compute these contrasting forces in unison. Finally, due to the immense number of necessary calculations, a powerful computer was required – like the “Piz Daint” at the Swiss National Supercomputing Centre (CSCS). “Apart from the theoretical insights and the technical tools that we developed, we were therefore also dependent on the advancement of computing power”, Lucio Mayer says.

A decades old puzzle solved?

Against the odds, everything came together at the right time and enabled a breakthrough. “With our model, we were able to show for the first time that the magnetic fields make it difficult for the growing planets to continue accumulating mass beyond a certain point. As a result, giant planets become rarer and intermediate-mass planets much more frequent – similar to what we observe in reality”, Hongping Deng explains.

“These results are only a first step, but they clearly show the importance of accounting for more physical processes in planet formation simulations. Our study helps to understand potential pathways to the formation of intermediate-mass planets that are very common in our galaxy. It also helps us understand the protoplanetary disks in general”, Ravit Helled, study co-author and Professor of Theoretical Astrophysics at the University of Zurich and member of the NCCR PlanetS, concludes.

Featured image: Artist’s impression of the protoplanetary disk with magnetic field lines. © Image: Jean Favre CSCS.


Reference: Hongping Deng, Lucio Mayer and Ravit Helled, “Formation of intermediate-mass planets via magnetically controlled disk fragmentation”, Nature, 2021.
https://www.nature.com/articles/s41550-020-01297-6


Provided by University of Zurich