Culture

Researchers develop method for measuring quality of life for people on autism spectrum

image: Judith S. Miller, PhD, MS, is a psychologist in the Department of Child and Adolescent Psychiatry and Behavioral Sciences and a senior scientist and training director in the Center for Autism Research at CHOP.

Image: 
Children's Hospital of Philadelphia

Philadelphia, March 23, 2020 - A new study led by researchers at Children's Hospital of Philadelphia (CHOP) shows that a set of simple questionnaires can help clinicians and families better evaluate the quality of life of people diagnosed with autism spectrum disorder (ASD). The newly-developed tool is designed for children, adolescents, and adults on the autism spectrum, and early findings show where clinicians can learn more about how to support the needs of autistic individuals by directly asking them these critical questions. The findings were published online this month by the journal Autism Research.

While clinical researchers often focus on measuring diagnostic criteria or behavioral impairments, autistic self-advocates, family members, and community organizations have long called for a greater emphasis on measuring specific and practical areas that, if properly addressed, could then help people on the autism spectrum achieve a better quality of life. Several methods on how to accomplish this have been proposed, but they have not necessarily addressed topics covering a person's entire lifespan or had sufficient data on women and girls.

"Individual studies have examined specific quality of life measurements for people with autism, but we believed there was an opportunity to create an approach that could measure quality of life across multiple areas, in a way that can grow throughout their lifetime as needs change," said Laura Graham Holmes, PhD, a postdoctoral researcher at the A.J. Drexel Autism Institute at Drexel University who led the research while she was a postdoctoral fellow at the CHOP Center for Autism Research. "We wanted to be sure this tool encompassed a variety of domains, including physical and mental health, relationships, and subjective well-being, so we could begin to understand on a more nuanced level the struggles and successes that autistic people experience throughout their lives."

The study team developed and tested an autism-specific lifespan quality of life measurement tool, using the National Institutes of Health Parent-Reported Outcomes Measurement Information System (PROMIS®) as its foundation. The new tool is named the PROMIS Autism Battery - Lifespan (PAB-L). After reviewing each area and receiving feedback from autistic people and their families as well as autism experts, the tool was administered for autistic children ages 5-13 (reported through parent proxy), adolescents ages 14-17 (parent proxy and/or self-reported), and adults ages 18-65 (self reported) and then results were compared with the general population.

A total of 912 participants completed the tool's surveys online. The study measured feasibility, and participants reported that the survey was easy to understand, covered important topics, and may even change the way an individual or parent manages their autism support programs or clinical care based on the results.

While some individuals reported strengths, on average, people of all ages on the autism spectrum reported greater challenges and lower quality of life compared with their peers without an autism diagnosis. In particular, they reported lower life statisfaction, less social support and more social isolation, were more likely to exhibit emotional distress through symptoms like anger and anxiety, and were more likely to have sleep problems. Women and teenaged girls on the autism spectrum reported higher levels of anxiety and sleep problems than their male counterparts. As this is the first study to use this tool, more work is needed. However, these measurements give researchers an important starting point.

"This study demonstrated that assessing quality of life among patients of different ages and genders is possible, and that it's meaningful," said Judith S. Miller, PhD, a psychologist in the Department of Child and Adolescent Psychiatry and Behavioral Sciences, a senior scientist and training director in the Center for Autism Research at CHOP and senior author of the study. "We believe that these findings provide an important foundation to answer some very important questions about how to support the quality of life for people with autism, including those who have been historically under-represented in clinical research."

Credit: 
Children's Hospital of Philadelphia

Study examines association of sleep-disordered breathing with Alzheimer's disease biomarkers

What The Study Did: This study used data and brain imaging from a randomized clinical trial for older adults who are cognitively unimpaired and examined brain changes, including the presence of biomarkers for Alzheimer disease, between those with sleep-disordered breathing and those without.

Authors: Gael Chetelat, Ph.D., of the Universite de Caen in France, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaneurol.2020.0311)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Estimating breast cancer screening use, costs among women in 40s with private insurance

What The Study Did: Researchers used a large commercial claims database to estimate the percentage of U.S. women in their 40s with private insurance who were eligible and received screening mammography in 2017 and national costs for this screening.

Authors: Natalia Kunst, M.Sc., of the University of Oslo in Norway, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamainternmed.2020.0262)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Wearable strain sensor using light transmittance helps measure physical signals better

image: Schematic diagram of the sensor based on the optical transmittance changes of the CNT-embedded Ecoflex thin film.

Image: 
Professor Inkyu Park, KAIST

KAIST researchers have developed a novel wearable strain sensor based on the modulation of optical transmittance of a carbon nanotube (CNT)-embedded elastomer. The sensor is capable of sensitive, stable, and continuous measurement of physical signals. This technology, featured in the March 4th issue of ACS Applied Materials & Interfaces as a front cover article, shows great potential for the detection of subtle human motions and the real-time monitoring of body postures for healthcare applications.

A wearable strain sensor must have high sensitivity, flexibility, and stretchability, as well as low cost. Those used especially for health monitoring should also be tied to long-term solid performance, and be environmentally stable. Various stretchable strain sensors based on piezo-resistive and capacitive principles have been developed to meet all these requirements.

Conventional piezo-resistive strain sensors using functional nanomaterials, including CNTs as the most common example, have shown high sensitivity and great sensing performance. However, they suffer from poor long-term stability and linearity, as well as considerable signal hysteresis. As an alternative, piezo-capacitive strain sensors with better stability, lower hysteresis, and higher stretchability have been suggested. But due to the fact that piezo-capacitive strain sensors exhibit limited sensitivity and strong electromagnetic interference caused by the conductive objects in the surrounding environment, these conventional stretchable strain sensors are still facing limitations that are yet to be resolved.

A KAIST research team led by Professor Inkyu Park from the Department of Mechanical Engineering suggested that an optical-type stretchable strain sensor can be a good alternative to resolve the limitations of conventional piezo-resistive and piezo-capacitive strain sensors, because they have high stability and are less affected by environmental disturbances. The team then introduced an optical wearable strain sensor based on the light transmittance changes of a CNT-embedded elastomer, which further addresses the low sensitivity problem of conventional optical stretchable strain sensors.

In order to achieve a large dynamic range for the sensor, Professor Park and his researchers chose Ecoflex as an elastomeric substrate with good mechanical durability, flexibility, and attachability on human skin, and the new optical wearable strain sensor developed by the research group actually shows a wide dynamic range of 0 to 400%.

In addition, the researchers propagated the microcracks under tensile strain within the film of multi-walled CNTs embedded in the Ecoflex substrate, changing the optical transmittance of the film. By doing so, it was possible for them to develop a wearable strain sensor having a sensitivity 10 times higher than conventional optical stretchable strain sensors.

The proposed sensor has also passed the durability test with excellent results. The sensor's response after 13,000 sets of cyclic loading was stable without any noticeable drift. This suggests that the sensor response can be used without degradation, even if the sensor is repeatedly used for a long time and in various environmental conditions.

Using the developed sensor, the research team could measure the finger bending motion and used it for robot control. They also developed a three-axes sensor array for body posture monitoring. The sensor was able to monitor human motions with small strains such as a pulse near the carotid artery and muscle movement around the mouth during pronunciation.

Professor Park said, "In this study, our group developed a new wearable strain sensor platform that overcomes many limitations of previously developed resistive, capacitive, and optical-type stretchable strain sensors. Our sensor could be widely used in a variety of fields including soft robotics, wearable electronics, electric skin, healthcare, and even entertainment."

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

Extract from seeds of the Melinjo tree may improve obesity and diabetes

image: Mechanism by which MSE promotes the expression of DsbA-L in the living body, increases the amount of activated adiponectin, and improves obesity and diabetes symptoms

Image: 
Associate Professor Tsuyoshi Shuto

In Southeast Asia, the fruit, flowers, and leaves of Indonesia's "Melinjo" tree are traditional foods. Researchers from Kumamoto University, Japan who study plants from around the world for useful medicinal properties have found that Melinjo seed extract (MSE) stimulates the production of adiponectin, a beneficial hormone that improves obesity and diabetes. They also discovered that individual genotype differences were responsible for variations in its efficacy.

Melinjo fruit have high antioxidant and antibacterial qualities and are known to contain large amounts of polyphenols. One such compound, resveratrol, has been shown to induce adiponectin and may improve lifestyle-related diseases like metabolic syndrome. Gnetin C, a type of resveratrol abundant in MSE, is known to have higher antioxidant activity and stays in the body longer than resveratrol. However, the detailed mechanism by which these compounds exert their biological activity is still unknown.

Kumamoto University's Global Center for Natural Resources Sciences conducts component isolation and identification of useful plants and natural products from around the world and evaluates their pharmacological activities. Within the center, Dr. Kentaro Oniki's research team used genetic analysis to find that differences in the type of DsbA-L (Disulfide-bond-A oxidoreductase-like protein) gene affects adiponectin activation. In other words, DsbA-L induction may promote adiponectin activation and improve lifestyle-related diseases. In their recent work, they attempted to determine 1) whether MSE enhances the function of DsbA-L, 2) whether MSE promotes adiponectin activation, and 3) whether MSE has a therapeutic effect on obesity and diabetes.

In their first study (double-blind, placebo-controlled, randomized controlled), 42 healthy adult men took MSE supplements orally for 14 days. They found that taking 300 mg of MSE per day activated adiponectin in human males. They also found that effects varied depending on the differences in the type of DsbA-L gene (G/G, G/T, T/T) possessed by the individual. MSE effects were large in G/T or T/T genotype carriers whose gene expression level was presumed to be low.

Following the results of the clinical trials, another of the center's researchers, Dr. Tsuyoshi Shuto, and his research team tested the compound in a high fat diet mouse model with obesity-induced diabetes. By measuring the effects of MSE on DsbA-L expression and blood adiponectin concentration in various tissues, they found that daily oral administration of MSE over a period of four weeks increased the expression of DsbA-L and the amount of activated adiponectin in the body. Diabetic pathologies, in muscle tissue also improved. Symptoms such as increased fat accumulation and fasting blood sugar levels significantly improved.

These research results show that MSE promotes DsbA-L expression, increases the amount of activated adiponectin, and may improve obesity and diabetic symptoms in living organisms, especially in mice.

"We believe that our findings can benefit human health through the treatment of obesity and diabetes by focusing on the induction of the DsbA-L gene using MSE," said Associate Professor Shuto. "We hope that this work contributes to a healthier society through the creation of innovative medicines and products from plants and other natural resources. It is important to provide solid scientific evidence that supports the use of natural resources in emerging countries and using them for beneficial drug discovery and health."

Credit: 
Kumamoto University

Taking a break helps drosophila germline cells reach their destination

Tsukuba, Japan - In most cases, taking a break isn't the most efficient way of getting a job done. But in a study published this week in iScience, researchers from Japan's University of Tsukuba have uncovered the regulatory pathway governing the first of two breaks that are essential for proper germline cell development in model species Drosophila melanogaster.

Germ cells go on to form the mature cells (gametes) needed for sexual reproduction--sperm and eggs. During germ cell cycling in Drosophila, primordial germ cells, called pole cells, migrate through the developing embryo to the gonads, where they mature into gametes. Interestingly, cell cycling is arrested during this migration period.

Previous studies have shown that there are actually two rest, or quiescence, periods in Drosophila germ cell cycling that appear to be essential for pole cell maturation and, ultimately, fertility. However, while the pathway regulating the second of these rest cycles has been characterized, the first pathway appears to be independently regulated via an as yet unknown mechanism.

"Research has shown that newly-formed pole cells lack nucleoli, while nucleoli are prominent in somatic cells at the same time point," says lead author of the study Dr Shumpei Morita. "This led us to investigate factors that influence nucleolus formation, specifically the Pgc peptide, encoded by pgc."

Sure enough, the researchers found that Pgc repressed nucleolus formation in pole cells and inhibited the expression of a microRNA, miR-10404, which is encoded within the nucleolus organizer region of the chromosome. microRNAs degrade specific target messenger RNA, preventing protein expression. By examining messenger RNA levels in pgc mutant versus normal pole cells, the researchers were able to pinpoint the target of miR-10404.

"Our results showed that miR-10404 degrades dap messenger RNA in pole cells," explains senior author Professor Satoru Kobayashi. "Dap is a Cdk inhibitor that blocks cell cycle progression. Thus, in normal pole cells, Pgc-dependent suppression of miR-10404 expression prevents the degradation of dap messenger RNA, resulting in Dap accumulation and inhibition of cell cycle progression."

When the researchers artificially increased cellular levels of miR-10404 and CycB, which inhibits the first and second germline quiescence, pole cells failed to migrate to the gonads and were eliminated in the resulting embryos. This observation confirmed that the two rest periods are essential for Drosophila germline development.

Says Professor Kobayashi, "Given the widespread occurrence of cell cycle quiescence in animals, our findings will help us to better understand the mechanism and significance of these rest periods during germline development."

Credit: 
University of Tsukuba

New material developed could help clean energy revolution

Fuel cells and water electrolyzers that are cheap and efficient will form the cornerstone of a hydrogen fuel based economy, which is one of the most promising clean and sustainable alternatives to fossil fuels. These devices rely on materials called electrocatalysts to work, so the development of efficient and low-cost catalysts is essential to make hydrogen fuel a viable alternative. Researchers at Aalto university have developed a new catalyst material to improve these technologies.

The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are the most important electrochemical reactions that limit the efficiencies of hydrogen fuel cells (for powering vehicles and power generation), water electrolyzers (for clean hydrogen production), and high-capacity metal-air batteries. Physicists and chemists at Aalto collaborating with researchers at CNRS France, and Vienna in Austria have developed a new catalyst that drive these reactions more efficiently than other bifunctional catalysts currently available. The researchers also found that the electrocatalytic activity of their new catalyst can be significantly altered depending on choice of the material on which the catalyst was deposited.

"We want to replace traditional expesive and scarce catalysts based on precious metals like platinum and iridium with highly active and stable alternatives composed of cheap and earth-abundant elements such as transition metals, carbon and nitrogen." says Dr Mohammad Tavakkoli, the researcher at Aalto who led the work and wrote the paper.

In collaboration with CNRS the team produced a highly porous graphene-carbon nanotube hybrid and doped it with single atoms of other elements known to make good catalysts. Graphene and carbon nanotube (CNT) are the one?atom?thick two- and one?dimensional allotropes of carbon, respectively, which have attracted tremendous interest in both academia and industry due to their outstanding properties compared more traditional materials. They developed an easy and scalable method to grow these nanomaterials at the same time, combining their properties in a single product. "We are one of the leading teams in the world for the scalable synthesis of double-walled carbon nanotubes. The innovation here was to modify our fabrication process to prepare these unique samples," said Dr Emmanuel Flahut, research director at CNRS.

In this one-step process, they could also dope the graphene with nitrogen and/or metallic (Cobalt and Molybdenum) single-atoms as a promising strategy to produce single-atom catalysts (SACs). In catalysis science, the new field of SACs with isolated metal atoms dispersed on solid supports has attracted wide research attention because of the maximum atom-utilization efficiency and the unique properties of SACs. Compared with rival strategies for making SACs, the method used by the Aalto & CNRS team provides an easy method which takes place in one step, keeping costs down.

Catalysts are usually deposited on an underlying substrate. The role this substrate plays on the final reactivity of the catalyst is usually neglected by researchers, however for this new catalyst, the researchers spotted the substrate played an important part in its efficiency. The team found porous structure of their material allows to access more active catalyst sites formed at its interface with the substrate, so they developed a new microscopy analysis method to measure how this interface could be altered to produce the most effective catalyst. They hope their study of substrate effects on the catalytic activity of porous materials establishes a basis for the rational design of high-performance electrodes for the electrochemical energy devices and provides guidelines for future studies.

Credit: 
Aalto University

Ultrafast and broadband perovskite photodetectors for large-dynamic-range imaging

image: OIHP photodetectors for Visible and NIR (with an 830-nm long-pass filter) imaging, as well as imaging of SITP (an abbreviation of Shanghai Institute of Technology and Physics) letter graphics under LED illumination. The white and blue lines in the figure represent the normalized photocurrent signal intensity.

Image: 
by Chenglong Li, Hailu Wang, Fang Wang, Tengfei Li, Mengjian Xu, Hao Wang, Zhen Wang, Xiaowei Zhan, Weida Hu, Liang Shen

Photodetectors, a key optoelectrical component for the translation of optical signals into electrical signals, are of great interest to a wide range of industrial production, military affairs, biochemical detection, optical communication. Organic-inorganic hybrid perovskites (OIHPs), owing to their excellent optical and electrical properties including tunable direct bandgap, preeminent optical absorption, high carrier mobility, and low trap density, have attracted immense research interest for thin-film solar cells, LEDs, and photodetectors. In recent years, the fabrication and characterizations of OIHPs have been advanced and photodetectors thereof with high sensitivity, fast response, and large linear dynamic range have been reported. However, to circumvent existing limitation to the detection band of visible light resulting from the bandgap of the perovskite material, new device architectures and material systems are needed which offer high performance over a wide spectral range up to NIR.

In the new paper published in Light Science & Application, scientists from the State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, China, State Key Laboratory of Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences and University of Chinese Academy of Sciences, China, and co-workers have designed new OIHP photodetectors combined with organic bulk heterojunction (BHJ) ofsuitable band structure, achieving a high external quantum efficiency (EQE) of higher than ~54% in the NIR region. Benefitting from low trap density in the light absorption layer and high carrier mobility in the transport layer, the OIHP/BHJ photodetectors have ultra-fast response times of just 5.6 nanoseconds by the transient photocurrent method (TPC) that can mitigate the issue of the resistance-capacitance time constant. To further verify the broadband detection capability and large linear dynamic range (LDR), they adopted the OIHP/BHJ photodetectors to construct a single-pixel scanning optical imaging system. High-quality imaging of complex letter graphics and visible/NIR imaging of the heat coil are obtained through the imaging system based on the OIHP/BHJ photodetectors with large LDR, ultra-fast response speed, and room temperature stability. We believe that state-of-the-art OIHP photodetectors can accelerate the translation of solution-processed photodetector applications from the laboratory to the imaging market.

Credit: 
Light Publishing Center, Changchun Institute of Optics, Fine Mechanics And Physics, CAS

'Thermometer' protein regulates blooming

image: Left: Evening Complex (EC) attached to DNA.
Right: LUX protein bound to DNA double helix.
EC acts like a temperature sensor. At low temperatures, it prevents the expression of growth genes by binding to the DNA. When temperatures are high enough, it separates from the DNA, permitting gene expression and subsequent plant flowering.

Image: 
© Silva et al. / PNAS

As average temperatures rise every year, it is no longer rare to see plants flower as early as February. Behind this phenomenon is a complex of proteins whose activity is controlled by temperature changes, as has just been demonstrated by researchers from the Cell and Plant Physiology Laboratory (CNRS / CEA / INRAE / Université Grenoble Alpes) and their partners.* Composed of three proteins (LUX, ELF3, and ELF4), the Evening Complex regulates the expression of genes involved in plant growth and flowering, as a function of exterior temperatures. The research team has shown, in vitro, that while all three proteins are needed for the complex to function correctly, ELF3 is the only one whose activity directly depends on temperature. When the temperature increases, ELF3 prevents the complex from binding to DNA and repressing plant growth genes. Consequently, growth proceeds. A study of the structure of LUX nonetheless demonstrated that certain mutations could alter plant sensitivity to temperature. These findings are published in PNAS (12 March 2020).

Credit: 
CNRS

Can soap really 'kill' the coronavirus? (video)

image: Constantly being told to wash your hands? Us too. So we're diving into the chemistry behind why soap is so effective against viruses like the coronavirus that causes COVID-19: https://youtu.be/K2pMVimI2bw.

Image: 
The American Chemical Society

WASHINGTON, March 23, 2020 -- Constantly being told to wash your hands? Us, too. So we're diving into the chemistry behind why soap is so effective against viruses like the coronavirus that causes COVID-19: https://youtu.be/K2pMVimI2bw.

Credit: 
American Chemical Society

Microbiome search engine can increase efficiency in disease detection and diagnosis

image: Multiple disease detection and classification via microbiome search

Image: 
SU Xiaoquan

Big data makes big promises when it comes to providing insights into human behavior and health. The problem is how to harness the information it provides in an efficient manner. An international team of researchers has proposed a microbiome search-based method, via Microbiome Search Engine (MSE), to analyze the wealth of available health data to detect and diagnose human diseases.  

They published their method on March 17, 2020 in mSystems, a peer-reviewed open access journal of the American Society for Microbiology.  
"Microbiome-based disease classification depends on well-validated, disease-specific models or markers," said Dr. SU Xiaoquan, from Single-Cell Center at Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS). "However, current models are lacking that information for many diseases." 

In addition, SU said, multiple diseases can share the same biomarkers - the microorganisms that indicate something out of the ordinary, such as a mutated protein found in cancer cells, making it harder for researchers to correctly classify each one.  

To combat these issues for disease detection and classification, SU and his joint software team from Single-Cell Center, QIBEBT and Center for Microbiome Innovation (CMI), University of California at San Diego (UCSD), developed a new search approach based on the whole microbial community a human body contains, collectively called the microbiome. Every person has a microbiome, even if they do not have a disease.  

Traditional models compare samples from healthy subjects to those from people known to have specific diseases. With the new method, by searching based on the specific outlier, rather than known biomarkers that can code for several diseases, the researchers can identify the microbiome state associated with the disease across different cohorts or sequencing platforms.  

In this new approach, the research team employs a two-step process to identify disease. First, they search a baseline database of healthy individuals to detect any specific microbiome outlier novelty - or any known anomaly that differentiates the microbiome from a healthy state. They then search for that outlier in a database of disease-specific examples.  

"Our strategy's precision, sensitivity and speed outperform model-based approaches," SU said.  

The results of the search can provide quick predictions to help clinicians diagnose and treat diseases.  

"This search-based strategy shows promise as an important first step in microbiome big data-based diagnosis," according to Rob Knight, Director of CMI and UCSD. "In light of the general shift of microbiome-sequencing focus from healthy to diseased hosts, the findings here advocate for adding more baseline samples from across different geographic locations."

XU Jian, Director of Single-Cell Center, QIBEBT, agrees. Next, the joint Sino-USA team is working towards encouraging their colleagues to join a coordinated effort to continue expanding the microbiome database, to include every population and every ecosystem on the globe. 

"With Microbiome Search Engine, performing a search can become as standard and enabling for new microbiome studies as performing a BLAST against your new DNA sequence is today." XU said. 

Credit: 
Chinese Academy of Sciences Headquarters

Supermassive black holes shortly after the Big Bang: How to seed them

image: According to classical theories, these space giants would not have had the time to develop in the young Universe. Yet, observations say they were already present. A new study by SISSA proposes a response to the fascinating question

Image: 
NASA/JPL-Caltech

They are billions of times larger than our Sun: how is it possible that, as recently observed, supermassive black holes were already present when the Universe, now 14 billion years old, was "just" 800 million years old? For astrophysicists, the formation of these cosmic monsters in such a short time is a real scientific headache, which raises important questions on the current knowledge of the development of these celestial bodies. A recent article published in The Astrophysical Journal, by the SISSA Ph.D. student Lumen Boco and his supervisor Andrea Lapi, offers a possible explanation to the thorny issue. Thanks to an original model theorized by the scientists from Trieste, the study proposes a very fast formation process in the initial phases of the development of the supermassive black holes, those up to now considered slower. Proving, mathematically, that their existence was possible in the young Universe, the results of the research reconcile the timing required for their growth with the limits imposed by the age of the Cosmos. The validity of the theory can be fully validated thanks to future gravitational wave detectors namely Einstein Telescope and LISA, but tested in several basic aspects also with the current Advanced LIGO/Virgo system.

The cosmic monster that grows at the centre of galaxies

The scientists started their study with a piece of well-known observational evidence: the growth of supermassive black holes occurs in the central regions of galaxies, progenitors of the current elliptical galaxies, which had a very high gas content and in which the stellar formation was extremely intense. "The biggest stars live a short time and very quickly evolve into stellar black holes, as large as several scores of solar masses; they are small, but many form in these galaxies". The dense gas that surrounds them, explain Boco and Lapi, has a very powerful definitive effect of dynamic friction and causes them to migrate very quickly to the centre of the galaxy. The majority of the numerous black holes that reach the central regions merge, creating the supermassive black hole seed. Boco and Lapi continue: "According to classical theories, a supermassive black hole grows at the centre of a galaxy capturing the surrounding matter, principally gas, "growing it" on itself and finally devouring it at a rhythm which is proportional to its mass. For this reason, during the initial phases of its development, when the mass of the black hole is small, the growth is very slow. To the extent that, according to the calculations, to reach the mass observed, billions of times that of the Sun, a very long time would be required, even greater than the age of the young Universe". Their study, however, showed that things could go much faster than that.

The crazy dash of black holes: what the scientists have discovered

"Our numerical calculations show that the process of dynamic migration and fusion of stellar black holes can make the supermassive black hole seed reach a mass of between 10,000 and 100,000 times that of the Sun in just 50-100 million years". At this point, the researchers say, "the growth of the central black hole according to the aforementioned direct accretion of gas, envisaged by the standard theory, will become very fast, because the quantity of gas it will succeed in attracting and absorbing will become immense, and predominant on the process we propose. Nevertheless, precisely the fact of starting from such a big seed as envisaged by our mechanism speeds up the global growth of the supermassive black hole and allows its formation, also in the Young Universe. In short, in light of this theory, we can state that 800 million years after the Big Bang the supermassive black holes could already populate the Cosmos".

"Looking" at the supermassive black hole seeds grow

The article, besides illustrating the model and demonstrating its efficacy, also proposes a method for testing it: "The fusion of numerous stellar black holes with the seed of the supermassive black hole at the centre will produce gravitational waves which we expect to see and study with current and future detectors", explain the researchers. In particular, the gravitational waves emitted in the initial phases, when the central black hole seed is still small, will be identifiable by the current detectors like Advanced LIGO/Virgo and fully characterisable by the future Einstein Telescope. The subsequent development phases of the supermassive black hole could be investigated thanks to the future detector LISA, which will be launched in space around 2034. In this way, explain Boco and Lapi, "the process we propose can be validated in its different phases, in a complementary way, by future gravitational wave detectors.

"This research" concludes Andrea Lapi, coordinator of the Astrophysics and Cosmology group of SISSA, "shows how the students and researchers of our group are fully approaching the new frontier of gravitational waves and multi-messenger astronomy. In particular, our main goal will be to develop theoretical models, like that devised in this case, which serve to capitalise on the information originating from the experiments of current and future gravitational waves, thereby hopefully providing solutions for unresolved issues connected with astrophysics, cosmology and fundamental physics".

Credit: 
Scuola Internazionale Superiore di Studi Avanzati

Stem cells and nerves interact in tissue regeneration and cancer progression

image: Cancer cells (green) are innervated with nerve cells (red). The cell nuclei (blue) are also visible.

Image: 
Institute of Oral Biology, University of Zurich

Stem cells can generate a variety of specific tissues and are increasingly used for clinical applications such as the replacement of bone or cartilage. However, stem cells are also present in cancerous tissues and are involved in cancer progression and metastasis. Nerves are fundamental for regulating the physiological and regenerative processes involving stem cells. However, little is known about the interactions between stem cells and neurons in regenerating tissues and in cancers.

Comparing stem cell types in tissue regeneration

A team of researchers led by Thimios Mitsiadis, professor at the Institute of Oral Biology of the University of Zurich, has now published two studies that elucidate how stem cells promote neuronal growth in tissue regeneration and in cancer progression. The first study compared the interaction of neurons with two different human stem cell populations, namely dental pulp stem cells and bone marrow stem cells. Both can differentiate into various cell types such as bone, cartilage and fat cells. Human bone marrow stem cells are isolated from skeletal bones and are the gold standard for bone regenerative approaches. Extracted teeth are the source of dental pulp stem cells, which represent a promising alternative.

Dental stem cells are highly innervated

Using the "organ-on-a-chip" technology, which relies on small three-dimensional devices mimicking the basic functions of human organs and tissues, the researchers demonstrated that both types of stem cells promoted neuronal growth. The dental pulp stem cells, however, yielded better results compared to bone marrow stem cells: They induced more elongated neurons, formed dense neuronal networks and established close contacts with nerves.

"Dental stem cells produce specific molecules that are fundamental for the growth and attraction of neurons. Therefore, stem cells are abundantly innervated," says Mitsiadis. The formation of such extended networks and the establishment of numerous contacts suggest that dental stem cells create functional connections with nerves of the face. "Therefore, these cells could represent an attractive choice for the regeneration of functional, properly innervated facial tissues," adds co-author and junior group leader Pierfrancesco Pagella.

Cancer stem cells also recruit neurons

In the second study, the researchers examined the interaction between nerves and cancer stem cells found in ameloblastoma, an aggressive tumour of the mouth. They first demonstrated that ameloblastomas have stem cell properties and are innervated by facial neurons. When ameloblastoma cells were isolated and placed in the "organ-on-a-chip" devices, they retained not only their stem cell properties but also attracted nerves and established contact with them.

"It appears that nerves are fundamental for the survival and function of cancer stem cells," explains Pagella. "These results create new possibilities for cancer treatment using drugs that modify the communication between neurons and cancer stem cells. We hope this opens unforeseen paths towards effective therapies against cancer," adds Mitsiadis. "The combination of advanced molecular and imaging tools and "organ-on-a-chip" technology offers an exciting opportunity to reveal the hidden functions of neurons and their interactions with various stem cell types, in both healthy and pathological conditions."

Credit: 
University of Zurich

New device quickly detects harmful bacteria in blood

image: This image shows bacterial cells trapped in a 3D microbead matrix.

Image: 
Wenrong He/Rochester Institute of Technology.

Engineers have created a tiny device that can rapidly detect harmful bacteria in blood, allowing health care professionals to pinpoint the cause of potentially deadly infections and fight them with drugs.

The Rutgers coauthored study, led by researchers at Rochester Institute of Technology, is published in the journal ACS Applied Materials & Interfaces.

"The rapid identification of drug-resistant bacteria allows health care providers to prescribe the right drugs, boosting the chances of survival," said coauthor Ruo-Qian (Roger) Wang, an assistant professor in the Department of Civil and Environmental Engineering in the School of Engineering at Rutgers University-New Brunswick.

Drug-resistant bacteria, or super-bugs, are a major public health concern. Globally, at least 700,000 people die each year as a result of drug-resistant infections, including 230,000 deaths from multidrug-resistant tuberculosis. That number could soar to 10 million deaths a year by 2050 if no action is taken, according to a 2019 report.

Based on a new approach, the tiny new device rapidly isolates, retrieves and concentrates target bacteria from bodily fluids. It efficiently filters particles and bacteria, capturing about 86 percent of them. The nano-device has magnetic beads of different sizes that are designed to trap, concentrate and retrieve Escherichia coli (E. coli) bacteria. The small spaces between the beads are used to isolate bacteria in the device.

The inexpensive, transparent device is easy to fabricate and operate, making it ideal for detecting disease-causing organisms in laboratory and health care settings, according to the study. The research team is working to perfect the device and plans to add multiple devices onto a small chip and explore scaling up testing in the field.

Credit: 
Rutgers University

Immunotherapy using 'young cells' offers promising option against cancer

image: Pictured is a natural killer (NK) cell that researchers developed in the lab from human pluripotent stem cells. These NK cells mimic the properties of those found in the yolk sac during the earliest stages of development. Such NK cells may be more effective as immunotherapy for cancer treatment than adult NK cells that come from bone marrow, according to a new study from Washington University School of Medicine in St. Louis. White arrows point out granules that contain potent anti-cancer enzymes. Adult NK cells have very few of these granules.

Image: 
Sturgeon Lab

Immunotherapy that involves treating cancer with the body's own immune cells, or those of a matched donor, shows promise in clinical trials for some patients, but not all.

A new study from Washington University School of Medicine in St. Louis suggests that the age of certain immune cells used in such therapy plays a role in how effective the immunotherapy is. These cells -- natural killer (NK) cells -- appear to be more effective the earlier they are in development, opening the door to the possibility of an immunotherapy that would not utilize cells from the patient or a matched donor. Instead, they could be developed from existing supplies of what are called human pluripotent stem cells.

"We are trying to improve the effectiveness of immunotherapy for more patients," said senior author Christopher M. Sturgeon, PhD, an assistant professor of medicine. "This special source of natural killer cells has the potential to fill some of the gaps remaining with adult NK cell therapy. There is early evidence that they are more consistent in their effectiveness, and we would not need to process cells from a donor or the patient. They could be manufactured from existing cell supplies following the strict federal guidelines for good manufacturing practices. The characteristics of these cells let us envision a supply of them ready to pull off the shelf whenever a patient needs them."

Unlike the adult versions of NK cells used in most investigational therapies, earlier versions of such cells do not originate from bone marrow. Rather, these NK cells are a special type of short-lived immune cell that forms in the yolk sac of the early mammalian embryo. But for therapeutic purposes, such cells do not need to originate from embryos -- they can be developed from human pluripotent stem cells, which have the ability to give rise to many different cell types, including these specialized natural killer cells. Manufacturing such cells -- which many academic medical centers already have the ability to do -- would make them available quickly, eliminating the time needed to process the patient's or donor's cells, which can take weeks.

The study appears March 19 in the journal Developmental Cell.

"Before a certain time point in early development, there is no such thing as bone marrow, but there is still blood being made in the embryo," Sturgeon said. "It's a transient wave of blood that the yolk sac makes to keep the embryo going until bone marrow starts to form. And that's the blood cell generation that's making these unique natural killer cells. This early blood appears to be capable of things that adult blood simply can't do."

Studying mouse and human induced pluripotent stem cells that have been coaxed into forming these unique NK cells, the researchers showed that the NK cells are better at releasing specific anti-tumor chemicals -- a process called degranulation -- than their adult counterparts. Even NK cells derived from umbilical cord blood do not respond as robustly. NK cells of adult origin also release different chemicals that trigger harmful inflammation, but this response is not necessarily effective against cancer.

Past work by other groups suggested NK cells from earlier development might be more effective, but how and why this was the case remained unknown. The specific origin of these cells was also a mystery.

"Now we know where these special natural killer cells come from and that we can never get them from an adult donor, only a pluripotent stem cell," Sturgeon said. "Based on their unique behavior alone, there is one small clinical trial of these cells that is ongoing. Now that we know how to manufacture them and how they work, it opens the door for more trials and for improving upon their function."

According to Sturgeon, such cells could be produced from existing lines of pluripotent stem cells that would not need to come from a matched donor because, in general, NK cells do not heavily attack the body's healthy tissues, as many T cell therapies can. T cells are another type of immune cell often used to treat blood cancer as part of a stem cell transplant, commonly called a bone marrow transplant. Even when NK cells do cause harm, they do not stay in the body for long periods of time.

From a basic science standpoint, Sturgeon also is interested in understanding why these cells are present in the early embryo in the first place and where they go in later development and after birth.

"We can only speculate at this point, but it's possible that during early embryonic development, when there is so much rapid cell division, these cells are there as a surveillance mechanism to protect against pediatric cancers or infection," he said.

Credit: 
Washington University School of Medicine