Culture

Risk of coronavirus importation in Africa

image: The map shows the global distribution of importation risk over human population density.

Image: 
Vittoria Colizza and colleagues

The COVID-19 coronavirus continues to spread in China and cases have been reported in more than 25 countries. The African continent was spared for a long time until a first case was recently reported in Egypt. Vittoria Colizza, research director at Inserm (French Institute for Health and Medical Research), and her team from Unit 1136 Pierre Louis Institute of Epidemiology and Public Health (Inserm / Sorbonne University), in collaboration with the Université libre de Bruxelles, the Oxford Martin Programme on Pandemic Genomics and the University of California Los Angeles, assessed the risk of importing the virus into Africa, country by country, and the capacities of each of them to detect and deal with it.

The researchers evaluated the risk of the virus importation according to the number of cases declared by each chinese province and according to air traffic between the three
main airports of each of these provinces (except Hubei due to flights suspension) and each African country. Moreover, they analyzed the potential of each country to face
the risk of the spread of a contagious disease using WHO data and official data.

Each country makes a mandatory annual declaration to the WHO of its resources to deal with an epidemic (State Parties self-assessment Annual Reporting SPAR). It includes twenty-four items weighted into an overall score between 0 and 100, 100 showing a strong preparedness to face an epidemic.

These indicators are legislation, adherence to WHO standards, laboratory skills, medical staff, emergency organization, food safety, level of equipment in healthcare centers and public communication.

The researchers also took into account the IDVI score (for Infectious Disease Vulnerability Index), also noted out of 100, 0 corresponding to an extreme vulnerability and 100 to the lowest vulnerability. The IDVI takes into account factors not directly linked to the health system but which can influence the response to an epidemic: the size of the population, the socio-economic level or even political stability. Thus, high
IDVI and SPAR scores are predictive to an efficient response in case of virus importation.

The results show that Egypt, Algeria and Republic of South Africa are the countries most at risk of importing the virus to Africa due to high trade exchanges with China.
On the other hand, their SPAR and IDVI scores are among the best on the continent, letting expect effective detection and containment of the virus. Other countries as
Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana and Kenya, are at lower risk of virus importation but their SPAR and IDVI scores are lower, raising fears of the nondetection
of possible imported cases and of local or even national spread.

Finally, the researchers clustered the African countries at risk into three groups according to the influence of the Chinese provinces in these countries. Thus, a first group including 18 countries will be more vulnerable in the event of a major epidemic in the province of Beijing, a second comprising 7 countries will be more exposed in the event of a strong growth of the epidemic in the province of Guangdong and a third group of two countries is risking virus importation only from Fujian province.

"This work will allow the international community to make projections and plans according to the evolution in China. It also alerts the countries most exposed to the need of being prepared for the possible introduction of the virus. We can see how hard it is to quickly detect imported cases, as even well prepared developed countries missed some of them. For several poorly equipped African countries, the risks are
significant of not having sufficient organization and infrastructure for detection, containment and urgent care, raising fears of a risk of epidemic on the continent",
concludes Vittoria Colizza.

Credit: 
INSERM (Institut national de la santé et de la recherche médicale)

Hate speech dominates social media platform when users want answers on terrorism

People often resort to using hate speech when searching about terrorism on a community social media platform, a study has found.
Community question answering sites (CQAs) are social media platforms where users ask questions, answer those submitted by others, and have the option to evaluate responses.

Previous studies have mainly looked at terrorism-related data drawn from Facebook and Twitter, this was the first to examine trends on the CQA site, Yahoo! Answers.

The University of York study explored the use of Yahoo! Answers on the topic of terrorism and looked at a dataset of 300 questions that attracted more than 2,000 answers.

The questions reflected the community's information needs, ranging from the life of extremists to counter-terrorism policies. Sensitive questions outnumbered innocuous ones.

A typical innocuous question was: Who exactly created ISIS?, while a more sensitive question was: Do you agree with Donald Trump that we should ban Muslims coming from countries seized by ISIS, Al Qaeda and other terrorists?

Author, Dr Snehasish Banerjee, lecturer at the York Management School, University of York, said: "It seems that people are really curious to know about terrorists, what terrorists think, their ideas etc.

"While portrayed as a threat to society and human civilization by mainstream media, terrorists sell terrorism as freedom fighting via social networking sites and private messaging platforms

However, the actual workings of terrorism are largely shrouded in secrecy. For the curious, a convenient avenue to turn to is the community question answering sites."

Sensitive questions were significantly more likely to be submitted anonymously than innocuous ones, the study found.

While no significant difference arose with respect to answers, the paper found that identities were seldom recognisable. Using names non-traceable to themselves, CQA users become embolden to use provocative, inflammatory or uncivil language.

Dr Banerjee added: "We found that answers were laden with negative emotions reflecting hate speech and Islamophobia, making claims that were rarely verifiable.

"Users who posted sensitive questions and answers generally tended to remain anonymous.

"This paper calls for governments and law enforcement agencies to collaborate with major social media companies, including CQAs, to develop a process for cross-platform blacklisting of users and content, as well as identifying those who are vulnerable."

Credit: 
University of York

New results on the function of the tumor suppressor HERC protein

image: Studies by experts from the Faculty of Medicine and Health Sciences of the UB and IDIBELL under direction of Professor José Luis Rosa confirm the decisive role of HERC proteins -ubiquitin ligase- in the suppressor molecular mechanisms of carcinogenesis and tumor progression..

Image: 
UNIVERSITY OF BARCELONA

The RAF protein could be a therapeutical target to treat the tumor growth in regulated pathways by the p38 protein, according to a new study published in the journal Scientific Reports by a team of experts of the Faculty of Medicine and Health Sciences of the University of Barcelona and the Bellvitge Institute for Biomedical Research (IDIBELL).

The study analyzes the mechanisms that regulate some molecular signaling pathways related to carcinogenesis and tumor progression and opens new perspectives to the fight against human cancer.

Among the participants in the new study, led by Professor José Luis Rosa, are the researchers Leonardo Pedrazza, Taiane Schneider, Ramon Bartrons and Francesc Ventura, from the Department of Physiological Sciences of the UB and IDIBELL.

How does HERC1 ligase regulate the activation of ERK and p38 kinase?

The p38 protein, which belongs to the family of mitogen-activated kinase (MAP or MAPK kinase), is a factor with a distinguished role in the response to cellular stress signals and the control of proliferation and progress of tumor cells.

MAPK proteins and the regulator kinases -MAPKK and MAPKKK- take part in intracellular signaling cascades such as the RAF/MEK/ERK pathway, which controls the essential cell processes (growth, proliferation, differentiation, survival and cell migration). Dysfunctions in the regulation of these molecular signaling pathways can alter the physiological cycle of the cell and therefore generate the tumor proliferation and growth.

The published study in the journal Scientific Reports describes for the first time how the HERC1 enzyme -ubiquitin ligase- is able to regulate the process of cell migration through the MKK·/p38 signaling pathway, regulated by the C-RAF factor.

The new study expands the knowledge on the tumor-suppressor role of HERC proteins (ubiquitin ligase); enzymes that regulate the function of some proteins involved in processes such as cell growth and proliferation through its molecular marking with ubiquitin molecules (ubiquitination). In particular, the new study reveals HERC1 ligase i sable to regulate the activation of ERK and p38 kinase through the union of ubiquitin molecules with the C-RAF factor.

According to the authors, the discovery of an unexpected communication between RAF proteins and MKK3/p38 pathway opens new perspectives regarding future therapeutical targets in the fight against human cancers.

Moreover, the research group has a distinguished experience in the study of HERC proteins and their link to several pathologies (cancer, ataxia, etc.). In previous studies, the team contributed to the functional characterization of two ubiquitin kinases -HERC1 and HERC2 (Frontiers in Oncology, 2019)-- and the description of the role of HERC1 ligase in the regulation of the cell proliferation through the activation of the ERK signaling pathway through a mechanism that affects ubiquitination and degradation of C-RAF (Oncotarget, 2018).

HERC2 ligase and regulation of p5 protein, tumor suppressor

In another study, which was published in the journal Molecular Oncology, the experts of the UB and IDIBELL stated that Mdm2 protein -the main regulator of the p53 protein, tumor suppressor-, is part of the ternary complex known as p53-HERC2-NEURL4. The authors of this study are the experts Jesús García Cano, Susana Sánchez Tena, Joan Sala Gaston, Agnès Figueras, Francesc Viñals, Ramon Bartrons and Francesc Ventura, under the supervision of Professor José Luis Rosa.

In tumor processes, tumor cells do not respond to molecular signals that can inhibit its proliferative growth. The protein p53, which is coded by the TP53 gene, is a transcription factor that regulates the expression of genes related to the DNA reparation, genomic stability, inhibition of cell cycle progression, senescence and apoptosis (cell death).

In more than 50% of human cancers, the TP53 gene is mutated and generates a non-functional protein p53 that induces proliferation and growth of tumor cells. The active form of p53 is constituted by a tetrameter of four identical sub-units, and the levels of the protein are strictly regulated by the Mdm2 ubiquitin ligase. In a negative retro-alimentation circuit, the genic expression of Mdm2 is transcriptionally regulated by p53.

According to the new study, the Mdm2 enzyme is also part of the complex p53-HERC2-NEURL4, so a decrease of HERC2 levels also reduces the expression of the Mdm2-carrier ARN and therefore, its transcription. When the DNA is damaged by the effect of the bleomycin chemical-therapeutical agent, the Mdm2 protein disassociates from the complex p53-HERC2-NEURL4 and increases the phosphorylation and acetylation of the protein p53 bound to HERC2 and NEURL4.

The study also states that the Mdm2 promoter -which contains response elements to p53- competes against HERC2 for the union of p53, a feature that could explain the role of HERC2 in the regulation of the p53-Mdm2 circuit, and therefore, its function in the molecular mechanisms of tumor suppression.

Credit: 
University of Barcelona

A scaffold at the center of our cellular skeleton

image: Schematic view of the nano-cylinder (fuchsia) which is in the center of the cell skeleton (in black on the image).

Image: 
© UNIGE

All animal cells have an organelle called a centrosome, which is essential to the organization of their cell skeleton. The centrosome plays fundamental roles, especially during cell division, where it allows equal sharing of genetic information between two daughter cells. When the cells stop dividing, the centrioles, cylindrical structures composed of microtubules at the base of the centrosome, migrate to the plasma membrane and allow the formation of primary and mobile cilia, which are used respectively for the transfer of information and the genesis of movement. While performing these crucial biological functions, centrioles are therefore subjected to many physical forces, which they must resist. Scientists from the University of Geneva (UNIGE) have discovered an internal structure at the center of these nano-cylinders, a real cellular scaffolding that maintains the physical integrity of this organelle. This study, published in the journal Science Advances, will provide a better understanding of the functions of the centriole and the pathologies associated with its dysfunction.

The centrioles, cylindrical nano-structures, form the centrosome, the main microtubule organizing center of the cell skeleton, and the cilia, real cellular antennas. Defects in the assembly or functioning of the centriole can lead to pathologies in humans, such as ciliopathies, retinal disorders that can cause loss of vision.

Super-powered microscopes

Centrioles, formed by microtubules, are components of the cell skeleton. "They have a canonical organization defined by nine triplets of microtubules that must be maintained as a structural unit in order to resist the various forces they face during their cellular functions,» explains Paul Guichard, Professor in the Department of Cell Biology of the Faculty of Science at UNIGE. The group of Paul Guichard and Virginie Hamel, a researcher at the Department of Cell Biology and co-leader of the study, discovered an internal scaffolding for this organelle using high-powered electron microscopes, in collaboration with researchers at the University of Basel and the Helmholtz Campus in Neuherberg, Germany. "This study allowed to analyze centrioles of four different species and to demonstrate that this inner scaffold is present systematically", reports Maeva Le Guennec, a UNIGE researcher and first author of the study.

"We then investigated which centriolar proteins were located in this new structure", says Virginie Hamel. To do this, the UNIGE researchers used an innovative super-resolution method, called expansion microscopy, which makes it possible to inflate cells without deforming them in order to observe their internal organization. Thus, they were able to identify four proteins that are located at the level of this inner scaffold.

Towards a better understanding of retinal degeneration

"We realized that the four proteins we identified are associated with pathologies related to retinal degeneration", notes Virginie Hamel. The loss of retinal photoreceptors is possibly due to a failure to maintain the microtubule doublets present in these specialized cells. "We now intend to discover the possible link between such a structural maintenance defect and retinal disorders, in order to pave the way for a better understanding of this pathology", concludes Paul Guichard.

Credit: 
Université de Genève

New therapy stops seizures in mouse model of rare childhood epilepsy

Seizure disorders in babies are frightening and heartbreaking. A new basic science breakthrough offers hope for a potential treatment for rare developmental and epileptic encephalopathies resulting from a single genetic mutation. The gene in question, called SCN8A, controls a sodium channel that allows neurons to transmit an electric signal. When this gene is mutated, these channels can become hyperactive, resulting in recurrent seizures. The average age of onset of SCN8A-related encephalopathy is just four months old.

"Approximately half of patients are severely impaired and cannot walk or talk," says Miriam Meisler, Ph.D. Meisler is the Myron Levine Distinguished University Professor of Human Genetics and a Professor of Neurology at U-M Medical School. She and her team have studied this disease and its genetic mechanisms for many years, painstakingly developing mouse models that would allow for testing new therapies.

Within the past few years, a new therapy called antisense oligonucleotide (ASOs) has entered the scene, enabling researchers to control gene expression. ASOs are short DNA or RNA molecules designed to block messenger RNA molecules and their encoded proteins. This allows them to control the amount of RNA expressed by mutated genes, dampening their effects on the body.

The team realized the potential of ASOs for this seizure disorder. Their first achievement was developing a mouse model that accurately and predictably mimicked the disease in people. They generated a mouse with the same SCN8A mutation found in several patients but with the mutation turned off long enough to test the therapy.

Developing mice with an "on switch", they were able to administer the ASO, and then turn on the mutation. "The effect was dramatic and unambiguous," says Meisler. "We had a four-fold increase in lifespan, with added effects of repeated treatments." There was no evidence of low-level seizure activity in the treated mice.

The amount of mRNA expressed was reduced by half after ASO treatment, which was well tolerated. The treatment was also effective against other types of epilepsy, including Dravet syndrome. They're currently testing other mouse models of seizure disorders to see how widespread the effectiveness might be, "This has the potential to go beyond sodium channel disorders," says Meisler.

She notes that ASOs are already FDA approved for several disorders, including spinal muscular atrophy. "I think this will be a breakthrough for these devastating neurological conditions; they are now amenable to a truly personalized treatment." The work is described in a recent publication in the Annals of Neurology.

Credit: 
Michigan Medicine - University of Michigan

Outreach effective for opioid use disorder long-term treatment

Proactive outreach, including knocking on the doors of individuals who recently overdosed on opioids, can be an effective way to engage more people who have opioid use disorder with long-term care, according to researchers at The University of Texas Health Science Center at Houston (UTHealth).

In a pilot study, the UTHealth research team measured results of a clinical research program, HEROES, that they created to curb opioid use disorder (OUD) in Houston. Findings were recently published in the Journal of Substance Abuse Treatment. HEROES is one of only a handful of programs in the country engaged in large-scale, door-to-door outreach and tracking results.

According to data from the Harris County Institute of Forensic Sciences, there were 325 opioid-related deaths from January through November of 2019 in Houston, up from 295 in all of 2018. The risk of overdose deaths is rising due to the increased availability of fentanyl and synthetic opioids. Federal data shows nearly 90% of people who have substance use disorder in the U.S. are not currently in treatment.

"People with OUD don't always voluntarily seek treatment like you would with any other disease," said James Langabeer, PhD, EdD, MBA, a professor at UTHealth who leads the HEROES program. "Even if they recognize they need help, there are few places for them to turn, especially if they don't have insurance. We want to remove all those barriers and bring help directly to them at a time when they are more likely to accept it."

Theories suggest that people have greater readiness for behavioral change during critical periods or life events, and surviving an overdose could represent such an event, said Langabeer, who was the lead author on the study.

Langabeer and his team at HEROES designed an intervention strategy to identify survivors of overdose through secured data from Memorial Hermann-Texas Medical Center and the Houston Fire Department Emergency Medical Services. Using a motivational interview guide, a trained recovery support coach and a paramedic knock on their doors. If the survivors are home and willing to talk, the team uses motivational interviewing techniques to encourage them to enroll in the HEROES program at no cost to them.

"This type of engagement is important because it helps to emphasize compassion and collaboration with each patient. We use it to have the person feel autonomy in their own decisions and not to be led or forced to a conclusion, but to reach a choice on their own and to feel accountable for it. We find that if they are engaged, they are more likely to follow through in the long run," Langabeer said.

The peer recovery coaches are people who are in long-term recovery from opioid use disorder themselves.

"We've been through the fire and came out with buckets of water to fight this disease," said Jessica Yeager, a coach with HEROES. "Now people can look at me and say 'You're just like me - you can help me!' If someone had knocked on my door when I was at my worst, my life would be different today."

Between April and December 2018, the team visited 103 people, and 33% chose to engage in the treatment program. After 30 days, 88% of those participants were still active in the program, and 56% were still active after 90 days.

"Having one third of people we reached out to agree to a major step in their recovery while we are in their doorway is a huge accomplishment and much better than we expected, since other studies have shown far lower results," Langabeer said. "Recognizing that major life decisions require time, we are extremely satisfied with the results. Also, we've seen people choose to come into treatment weeks or even months later, so the information we provide during outreach can also help shape future choices."

Treatment through the HEROES program includes access to opioid overdose reversal medication, a recovery coach available 24/7, behavioral counseling with an addiction therapist, weekly support group meetings, and help connecting to county resources.

Another study Langabeer's team just published, which appeared in Substance Abuse Treatment, Prevention, and Policy, found evidence that engaging individuals through nontraditional routes such as community outreach, the criminal justice system, and emergency departments can be effective in engaging more people in medication-assisted treatment.

"We have to find more proactive ways to identify and locate these individuals in order to offer choices and paths for recovery that fit their unique situation," said Langabeer, who was the senior author of the study.

Credit: 
University of Texas Health Science Center at Houston

New discovery has important implications for treating common eye disease

image: The honeycomb structure of human retinal pigment epithelial (RPE) cells with oxidative stress induced complement (C5b-C9) in red.

Image: 
Dr Sarah Doyle, Trinity College Dublin.

Scientists from Trinity College Dublin have made an important discovery with implications for those living with a common, debilitating eye disease (age-related macular degeneration, AMD) that can cause blindness.

They have discovered that the molecule TLR2, which recognises chemical patterns associated with infection in the body, also seems to play an important role in the development of retinal degeneration.

AMD is the most common form of central visual blindness in adults, with approximately 70,000 Irish people living with the condition. People with AMD may have difficulty recognising faces, reading, watching television and driving as their central retina degenerates.

Aging is the greatest risk factor for development of AMD, with one in four people over the age of 75 living with the condition. To date, no pharmaceutical interventions are available to prevent the progression of disease. Patients living with dry AMD are generally advised to make lifestyle changes such as stopping smoking and improving diet and exercise regimes.

Dr Sarah Doyle, assistant professor of immunology at Trinity, who led the study which has just been published in leading journal Cell Reports, said:

"The lack of approved therapies for AMD is mainly because the factors involved in triggering the disease are not very well understood. Understanding and identifying early molecular events that may trigger dry AMD will allow us to develop a more targeted approach to therapy. In this case, we believe that regulating the activity of TLR2 may, over time, help to prevent the progression of dry AMD."

Two biological processes involved in AMD are the uncontrolled "oxidative stress" that results in the formation of bleach-like chemicals in the retina, and the laying down of a protein called complement, that "tags" whatever it touches for elimination.

In this study the scientists implicated TLR2 as a critical bridge between oxidative damage and complement-mediated retinal degeneration. TLR2, which is found on the surface of cells, is part of the immune system because it is known to sense infection through recognising chemical danger signals that are found on microorganisms like bacteria and yeast.

Once TLR2 is activated by a danger signal it triggers a signal cascade, which is a bit like a cellular assembly line, with information about the cells immediate environment passed to our genes, which then respond with an inflammatory response.

"In the case of the eye, TLR2 appears to act as a sensor of oxidative-stress, recognising a chemical pattern that is generated during oxidation, rather than infection, and triggering a signal cascade that ends in promoting the laying down of complement," said first author on the paper, Dr Kelly Mulfaul, from Trinity.

Dr Sarah Doyle added:

"A function for TLR2 has not previously been reported in retinal neurodegenerative disease pathology but it is likely to play an important role, because when we remove TLR2 from our experimental model systems we reduce the level of complement and this has the effect of protecting cells that are essential for vision from dying.

"With the continual increase in life expectancy outpacing the rate at which drugs for age-related conditions are developed new avenues of therapy are badly needed, so the fact that blocking this single protein can have such a protective effect in the eye is a particularly exciting discovery."

Credit: 
Trinity College Dublin

Sub-Neptune sized planet validated with the habitable-zone planet finder

image: A candidate planet outside our solar system was validated using data from the Habitable-zone Planet Finder Spectrograph, a Penn State-led near-infrared spectrograph recently installed on the 10m Hobby-Eberly Telescope at McDonald Observatory in Texas .

Image: 
Gudmundur Stefansson (left) and Ethan Tweedie Photography (right)

A signal originally detected by the Kepler spacecraft has been validated as an exoplanet using the Habitable-zone Planet Finder (HPF), an astronomical spectrograph built by a Penn State team and recently installed on the 10m Hobby-Eberly Telescope at McDonald Observatory in Texas. The HPF provides the highest precision measurements to date of infrared signals from nearby low-mass stars, and astronomers used it to validate the candidate planet by excluding all possibilities of contaminating signals to very high level of probability. The details of the findings appear in the Astronomical Journal.

The planet, called G 9-40b, is about twice the size of the Earth, but likely closer in size to Neptune, and orbits its low mass host star, an M dwarf star, only 100 light years from Earth. Kepler detected the planet by observing a dip in the host star's light as the planet crossed in front of--or transited--the star during its orbit, a trip completed every six Earth days. This signal was then validated using precision spectroscopic observations from the HPF, ruling out the possibility of a close stellar or substellar binary companion. Observations from other telescopes, including the 3.5m telescope at Apache Point Observatory and the 3m Shane Telescope at Lick Observatory, helped to confirm the identification.

"G 9-40b is amongst the top twenty closest transiting planets known, which makes this discovery really exciting," said Guðmundur Stefánsson, lead author of the paper, and a former PhD student at Penn State who is currently a postdoctoral fellow at Princeton University. "Further, due to its large transit depth, G 9-40b is an excellent candidate exoplanet to study its atmospheric composition with future space telescopes."

"The spectroscopic observations from HPF allowed us to place an upper bound of 12 Earth masses on the mass of the planet," said Caleb Cañas, a graduate student at Penn State and an author of the paper. "This demonstrates that a planet is causing the dips in light from the host star, rather than another astrophysical object such as a background star. We hope to obtain more observations with HPF to precisely measure its mass, which will allow us to constrain its bulk composition and differentiate between a predominantly rocky or gas-rich composition."

HPF was delivered to the 10m Hobby-Eberly Telescope at McDonald Observatory in late 2017 and started full science operations in late 2018. The instrument is designed to detect and characterize planets in the habitable-zone--the region around the star where a planet could sustain liquid water on its surface--around nearby low-mass stars. A unique feature of HPF is its precise spectral calibration with a laser frequency comb built by collaborators at the National Institute of Standards and Technology and the University of Colorado Boulder.

"Using HPF, we are currently surveying the nearest low-mass stars--also called M-dwarfs, which are the most common stars in the galaxy--with the goal of discovering exoplanets in our stellar neighborhood," said Suvrath Mahadevan, professor of astronomy and astrophysics at Penn State and principal investigator of the HPF spectrograph.

In addition to the data obtained with HPF, the scientists obtained another observation of the transiting planet using the 3.5m telescope at Apache Point Observatory in New Mexico using a photometric technique and instrumentation developed as part of Stefánsson's doctoral thesis. These transit observations helped further resolve the "transit shape"--the curve that represents how much of the host planet's light is blocked--resulting in more precise planetary parameters. In addition, high-contrast imaging observations using the 3m Shane Telescope at Lick Observatory showed that the host star was the true source of the transits.

"It is exciting to see this first result of the HPF survey coming out. HPF was built from the ground up to enable precision measurements to discover and confirm planets," said Larry Ramsey, emeritus professor of astronomy and astrophysics at Penn State.

Credit: 
Penn State

How newborn stars prepare for the birth of planets

image: This image shows the Orion Molecular Clouds, the target of the VANDAM survey. Yellow dots are the locations of the observed protostars on a blue background image made by Herschel. Side panels show nine young protostars imaged by ALMA (blue) and the VLA (orange).

Image: 
ALMA (ESO/NAOJ/NRAO), J. Tobin; NRAO/AUI/NSF, S. Dagnello; Herschel/ESA

An international team of astronomers used two of the most powerful radio telescopes in the world to create more than three hundred images of planet-forming disks around very young stars in the Orion Clouds. These images reveal new details about the birthplaces of planets and the earliest stages of star formation.

Most of the stars in the universe are accompanied by planets. These planets are born in rings of dust and gas, called protoplanetary disks. Even very young stars are surrounded by these disks. Astronomers want to know exactly when these disks start to form, and what they look like. But young stars are very faint, and there are dense clouds of dust and gas surrounding them in stellar nurseries. Only highly sensitive radio telescope arrays can spot the tiny disks around these infant stars amidst the densely packed material in these clouds.

For this new research, astronomers pointed both the National Science Foundation's Karl G. Jansky Very Large Array (VLA) and the Atacama Large Millimeter/submillimeter Array (ALMA) to a region in space where many stars are born: the Orion Molecular Clouds. This survey, called VLA/ALMA Nascent Disk and Multiplicity (VANDAM), is the largest survey of young stars and their disks to date.

Very young stars, also called protostars, form in clouds of gas and dust in space. The first step in the formation of a star is when these dense clouds collapse due to gravity. As the cloud collapses, it begins to spin - forming a flattened disk around the protostar. Material from the disk continues to feed the star and make it grow. Eventually, the left-over material in the disk is expected to form planets.

Many aspects about these first stages of star formation, and how the disk forms, are still unclear. But this new survey provides some missing clues as the VLA and ALMA peered through the dense clouds and observed hundreds of protostars and their disks in various stages of their formation.

Young planet-forming disks

"This survey revealed the average mass and size of these very young protoplanetary disks," said John Tobin of the National Radio Astronomy Observatory (NRAO) in Charlottesville, Virginia, and leader of the survey team. "We can now compare them to older disks that have been studied intensively with ALMA as well."

What Tobin and his team found, is that very young disks can be similar in size, but are on average much more massive than older disks. "When a star grows, it eats away more and more material from the disk. This means that younger disks have a lot more raw material from which planets could form. Possibly bigger planets already start to form around very young stars."

Four special protostars

Among hundreds of survey images, four protostars looked different than the rest and caught the scientists' attention. "These newborn stars looked very irregular and blobby," said team member Nicole Karnath of the University of Toledo, Ohio (now at SOFIA Science Center). "We think that they are in one of the earliest stages of star formation and some may not even have formed into protostars yet."

It is special that the scientists found four of these objects. "We rarely find more than one such irregular object in one observation," added Karnath, who used these four infant stars to propose a schematic pathway for the earliest stages of star formation. "We are not entirely sure how old they are, but they are probably younger than ten thousand years."

To be defined as a typical (class 0) protostar, stars should not only have a flattened rotating disk surrounding them, but also an outflow - spewing away material in opposite directions - that clears the dense cloud surrounding the stars and makes them optically visible. This outflow is important, because it prevents stars from spinning out of control while they grow. But when exactly these outflows start to happen, is an open question in astronomy.

One of the infant stars in this study, called HOPS 404, has an outflow of only two kilometers (1.2 miles) per second (a typical protostar-outflow of 10-100 km/s or 6-62 miles/s). "It is a big puffy sun that is still gathering a lot of mass, but just started its outflow to lose angular momentum to be able to keep growing," explained Karnath. "This is one of the smallest outflows that we have seen and it supports our theory of what the first step in forming a protostar looks like."

Combining ALMA and VLA

The exquisite resolution and sensitivity provided by both ALMA and the VLA were crucial to understand both the outer and inner regions of protostars and their disks in this survey. While ALMA can examine the dense dusty material around protostars in great detail, the images from the VLA made at longer wavelengths were essential to understand the inner structures of the youngest protostars at scales smaller than our solar system.

"The combined use of ALMA and the VLA has given us the best of both worlds," said Tobin. "Thanks to these telescopes, we start to understand how planet formation begins."

Credit: 
National Radio Astronomy Observatory

The climate and increased extreme weather affect our energy systems

image: This is Deliang Chen.

Image: 
University of Gothenburg

Climate change, with more and more storms and heat waves, also has consequences for our energy supply. An international research team has now developed a new method for calculating how extreme weather affects energy systems.

Climate change is often described in terms of average temperature changes. But it is mainly extreme weather events, like cold snaps, autumn storms and summer heat waves, that have the greatest impact on the economy and society.

And our energy systems - especially systems that include renewable energy sources - are highly dependent on the weather and climate. But to date, there have been no suitable methods for calculating how future extreme weather events will affect these energy systems.

Weather changes affect renewable energy sources

Renewable energy, such as solar and wind power, play a crucial role for reducing climate change by partially replacing fossil-fuel-based energy sources.

"But their capacity is highly dependent on weather conditions, which makes their share in the existing energy system something of a challenge when it comes to reliability and stability," says Deliang Chen, professor of physical meteorology at the University of Gothenburg and one of the five researchers on the international research team.

Designed a new method

The researchers have now developed a new method for predicting how energy systems that contain renewable energy technology may be affected in the future by a changing climate with a focus on extreme weather. Researchers have used the method to analyse 30 Swedish cities, including Gothenburg, Stockholm and Malmö.

The results show that future extreme climate events can have a considerable impact on energy systems.

"When we used the method in 30 Swedish cities and considered 13 scenarios for climate change, we saw uncertainty in the potential for renewable energy and energy demand."

The gap between access to and energy demand may, with certain future climate variations, be as much as 34 per cent.

"That means a reduction in power supply reliability of up to 16 per cent due to extreme weather events."

Collaboration necessary

Faced with upcoming climate changes, shaping and optimising an energy system that can coordinate renewable energy sources in the energy supply requires close collaboration between energy system experts and climate researchers, according to Deliang Chen.

"We need this kind of collaboration to handle the complexity of climate and energy systems and to be able to predict the multidimensional effects that await."

Credit: 
University of Gothenburg

Pill-sized 'heater' could increase accessibility in diagnosing infectious disease

image: The technology significantly reduces the footprint of heating. Left: typical plate heater used in the laboratory. Right: Miniature heater.

Image: 
Qin Dai / University of Toronto Engineering

Researchers at the University of Toronto Engineering have developed a tiny "heater" - about the size of a pill - that could allow resource-limited regions around the world to test for infectious diseases without the need for specialized training or costly lab equipment.

The technology regulates the temperature of biological samples through different stages of diagnostic testing, which is crucial to the accuracy of test results.

"The precision and flexibility of our heater opens the door to a future of do-it-yourself diagnostic kits," says PhD candidate Pranav Kadhiresan, who developed the device alongside PhD candidate Buddhisha Udugama, under the supervision of Professor Warren Chan.

"We could combine the simplicity of a high school chemistry set with the precision of cutting-edge lab instruments," adds Kadhiresan. The technology behind the team's miniaturized heater invention is describe in a paper published in the journal of Proceedings of the National Academy of Sciences (PNAS).

In a typical diagnostic test for infectious pathogens, multiple temperature-regulation steps are involved. The ability to control temperature is especially important in areas where access to large research facilities are limited.

"The lack of electricity adds a layer of complexity," says Udugama. "Our miniature heater addresses that. It can be used in various settings to detect viruses without the need for electricity. If we were to summarize the benefits of our technology, it would be accessibility, portability and precision."

The outside of the heater tablet is composed of a non-reactive acrylic mould that encapsulates lithium, a reactive element that is commonly found in battery cells. When dissolved in water, the reactive lithium interacts with the solution to release heat and hydrogen gas. This results in an increase of temperature for an extended period of time.

The researchers observed that the reproducibility of the temperature profile is controlled by constant gas release, which is dictated by the shape of the lithium mould. After testing multiple shapes of the lithium mould - from circles to triangles - they found the star shape, measuring just 8 millimetres in diameter, to be the most ideal for precise heating.

Consolidating multiple steps into a single tablet also means specialized training is not required to operate any diagnostic testing, reducing the chance of human error and making the device accessible to the public.

"Tablets are conventionally used for medications such as aspirins. But we have now developed a series of tablets and pills that can diagnose diseases," says Chan.

"Combined with smartphone technology, everyone would have a portable system that can track, monitor and diagnose infections. This is critical for preventing the spread of diseases."

Credit: 
University of Toronto Faculty of Applied Science & Engineering

Study highlights potential need to standardize quality measurement for cardiovascular care

In a new study published today in JAMA Cardiology, a team of researchers led by Rishi Wadhera, MD, MPP, MPhil, an investigator in the Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center (BIDMC), found that hospitals that received awards from the American Heart Association (AHA) and American College of Cardiology (ACC) for the delivery of high-quality care for acute myocardial infarction (AMI) and heart failure (HF) were more likely to be financially penalized under value-based programs than other hospitals.

"Our findings highlight that evaluations of hospital quality for acute myocardial infarction and heart failure care differ between the American Heart Association/American College of Cardiology national quality improvement initiatives and federal value-based programs," said Wadhera. "Hospitals recognized by the AHA/ACC for high quality care were more likely to be financially penalized by federal value-based programs than other hospitals, despite achieving similar and/or better outcomes."

Since the passage of the Affordable Care Act, the Centers for Medicare and Medicaid Services (CMS) have implemented national value-based programs that aim to incentivize the delivery of higher value care. The Hospital Readmissions Reduction Program (HRRP) imposes financial penalties on hospitals with higher-than-expected 30-day readmission rates. In addition, the Hospital Value-Based Purchasing Program (VBP) - a pay-for-performance initiative - rewards or penalizes hospitals based on their performance on multiple domains of care, including 30-day mortality. Both programs have focused on heart failure and acute myocardial infarction, in part due to their clinical and financial burden.

In this study of hospitals that received awards for high quality cardiovascular care from AHA/ACC national quality improvement initiatives, the researchers observed several findings about those hospitals' performance in national value-based programs:

1. Hospitals recognized for high quality care by the AHA/ACC ("award hospitals") were more likely to be penalized by the HRRP and VBP compared with other hospitals.

2. Award hospitals were less likely to receive financial rewards (payment increases) by the VBP.

3. Median payment reductions were higher for award hospitals than other hospitals under the VBP, and median payment increases were lower.

The team of researchers concluded that one potential explanation for the difference in evaluations of hospital quality may be that AHA/ACC award hospitals are disproportionately penalized by value-based programs for factors unrelated to the quality care they deliver. Award hospitals tended to be larger, urban, teaching hospitals - sites that often care for medically and socially complex populations. Because risk-adjustment models used for value-based programs do not include important clinical and social risk factors (e.g. poverty), award hospitals may be penalized for the patient populations and communities they serve rather than for poor quality of care.

"As the shift to value-based care continues in the United States and as multiple bodies simultaneously assess hospital systems, we need to prioritize efforts to promote fair, equitable and standardized measurement of cardiovascular care quality," said Wadhera, who is also an Instructor in Medicine at Harvard Medical School.

Credit: 
Beth Israel Deaconess Medical Center

Exploring a genome's 3D organization through a social network lens

image: Much as groups of sailors work together with ropes to accomplish tasks aboard ship, collections of transcription factor proteins work with sections of chromosomes as a community in the nucleus of a cell to carry out cell functions. Computational biologists at Carnegie Mellon University have developed algorithms for identifying these communities in cell nuclei.

Image: 
Ella Marushchenko

PITTSBURGH--Computational biologists at Carnegie Mellon University have taken an algorithm used to study social networks, such as Facebook communities, and adapted it to identify how DNA and proteins are interconnected into communities within the cell nucleus.

Jian Ma, associate professor in CMU's Computational Biology Department, said scientists have come to appreciate that DNA, proteins and other components within the nucleus appear to form structurally and functionally important communities. The behavior of these communities may prove key to understanding basic cellular processes and disease mechanisms, such as aging and cancer development.

Figuring out how to identify these communities among the tens of thousands of genes, proteins and other components of the cell is daunting, however. An important factor is proximity - both in terms of genes being controlled by the same regulatory proteins called transcription factors and in terms of spatial arrangement, with the complex folding and packing of DNA putting certain genes close to each other.

In many cases, the relationships are similar to many Facebook communities, with some members located near each other, while others who may be far apart are nevertheless drawn together through shared interests.

In a paper featured on the cover of the February issue of the journal Genome Research, lead authors Dechao Tian, a post-doctoral researcher, and Ruochi Zhang, a Ph.D. student in computational biology, explain how they developed a new algorithm, MOCHI, to subdivide the interwoven nuclear components into communities.

MOCHI was inspired by an algorithm originally developed by the laboratory of computer scientist Jure Leskovec. Beginning as a Ph.D. student at CMU and continuing as a faculty member at Stanford University, Leskovec has specialized in the analysis of large social and information networks.

The MOCHI algorithm looks at the spatial arrangement of all the genes and transcription factor proteins in a nucleus based on genome-wide chromosome interactions and global gene regulatory networks. Viewing this information as a 3D graph, the algorithm looks for certain subgraphs or "motifs," within it. A motif might be, say, a triangular shape, as is typical in social network analysis, or a four-node subgraph, which MOCHI uses for analyzing complex networks in the cell nucleus. The algorithm then clusters, or subdivides, the graph in a way that minimizes disruption of these motifs.

They tested MOCHI by applying it to five different cell types. Just as the original algorithm has proved adept at identifying communities within a large mass of social network data, MOCHI identified what appear to be hundreds of communities within the nuclei of these cell types.

As of yet, the researchers don't know what each community might do, but they say they have reason to believe the subdivisions made by MOCHI are valid. For instance, Ma said that the algorithm identified communities that seem to be common to all of the cell types used in this study. It also identified some communities that appear to be unique to a particular cell type. In addition, Ma said they found "enrichment" of disease related genes within the communities.

Much more work will be necessary to identify the function and behavior of each of these communities, Ma said, but the MOCHI algorithm gives researchers a starting point for study.

"There's a reason why these communities are formed in the nucleus," he said. "We just don't know the formation mechanisms of these communities yet." Understanding them might help researchers delineate fundamental cellular processes and suggest possible ways to better understand disease development.

The researchers also plan to include additional cell nucleus components, such as RNAs and other types of proteins, into their analysis.

In addition to Ma, Tian and Zhang, authors of the paper include Yang Zhang and Xiaopeng Zhu, a research associate and a project scientist, respectively, in the Computational Biology Department. The National Institutes of Health, including its 4D Nucleome Program, and the National Science Foundation supported this research.

Credit: 
Carnegie Mellon University

Active droplets

image: Prof. Job Boekhoven and Caren Wanzke at the Technical University of Munich discovered a new material system that can release drugs with a constant release rate over a tunable period of time. The microscopic image (right screen) shows droplets of the hydrolyzable oil embedded in a hydrogel.

Image: 
Andreas Heddergott / TUM

Using a mixture of oil droplets and hydrogel, medical active agents can be not only precisely dosed, but also continuously administered over periods of up to several days. The active agents inside the droplets are released at a constant rate, decreasing the risk of over- or underdosage.

Actually, Prof. Job Boekhoven was studying the origins of life: Together with his team at the Technical University of Munich (TUM), the chemist wanted to understand how molecules in the primordial ocean had managed to combine and form the precursors of the first living cells.

"In our research work we experimented with oil droplets, among other things. We were especially interested in mechanisms that protect molecules from degradation. We found that unstable molecules that form oil droplets would survive much longer than molecules that cannot form droplets. In a sense, the droplets protect the molecules inside."

However, the oily shield is not entirely impermeable: Some of the oil molecules react with the surrounding water. This hydrolysis causes the droplets to slowly but continuously lose mass and shrink until they eventually disappear. "The constant decay of these 'active droplets', led us to the idea of using them to dose drugs," recalls Boekhoven.

Safe from over- or underdosing

Pharmacologists have long sought methods for administering active agents at a constant rate. The ingredients in ointments or tablets are usually released quickly, increasing the risk of an overdose. Moreover, the fast rate of release shortens the duration of the intended effect. Methods for releasing drugs over extended periods of time at a constant rate are rare and often complicated to fabricate.

"We found that the droplets continuously release the drug while they get smaller and smaller. The consequence is that over the entire release period, the drug release rate remains constant", explains Boekhoven. "The power of this approach lies in its simplicity. You need only three components: droplets made of a hydrolyzable oil, a drug that partitions in the oil, and a hydrogel that stabilizes the position of the droplets."

Many fields of application

The new oil-hydrogel mix allows active agents to be administered not only continuously but also at a predetermined rate. The droplets can be loaded with larger or smaller doses of active substances. These are released as soon as the oil droplets come into contact with the water in blood or tissue. The hydrolysis proceeds at a constant rate until the droplets have dissipated completely.

These "active droplets" have many potential fields of application. They could, for example, be deployed in disinfectant or healing-promoting sore pads to treat poorly healing wounds. A patent application has already been filed for the oil-hydrogel material.

Credit: 
Technical University of Munich (TUM)

E-cigarette users are exposed to potentially harmful levels of metal linked to DNA damage

image: Prue Talbot (left), Shane Sakamaki-Ching (center) and Monique Williams.

Image: 
Talbot lab, UC Riverside.

RIVERSIDE, Calif. -- Researchers at the University of California, Riverside, have completed a cross-sectional human study that compares biomarkers and metal concentrations in the urine of e-cigarette users, nonsmokers, and cigarette smokers.

They found that the biomarkers, which reflect exposure, effect, and potential harm, are both elevated in e-cigarette users compared to the other groups and linked to metal exposure and oxidative DNA damage.

"Our study found e-cigarette users are exposed to increased concentrations of potentially harmful levels of metals -- especially zinc -- that are correlated to elevated oxidative DNA damage," said Prue Talbot, a professor of cell biology, who led the research team.

Zinc, a dietary nutrient, plays key roles in growth, immune function, and wound healing. Too little of this essential trace element can cause death; too much of it can cause disease. Its deficiency, as well as its excess, cause cellular oxidative stress, which, if unchecked, can lead to diseases such as atherosclerosis, coronary heart disease, pulmonary fibrosis, acute lymphoblastic leukemia, and lung cancer.

Electronic cigarettes consist of a battery, atomizing unit, and refill fluid. Metals in e-cigarette aerosols come mainly from the metal components in the atomizer-- nichrome wire, tin solder joints, brass clamps, insulating sheaths, and wicks -- as well as the e-fluids that the atomizers heat.

The study, which appears in BMJ Open Respiratory Research, marks the first time researchers have examined and quantified urinary biomarkers of effect and potential harm in relation to metals in e-cigarette users.

A biomarker is a quantifiable characteristic of a biological process. Biomarkers allow researchers and physicians to measure a biological or chemical substance that is indicative of a person's physiological state. Previous e-cigarette studies with humans have examined biomarkers of exposure -- for example, nicotine or nicotine metabolites -- but none have studied biomarkers of potential harm or shown how this harm correlates with metal exposure.

The biomarkers studied by the UC Riverside researchers were 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage; 8-isoprostane, an indicator of the oxidative degradation of lipids; and metallothionein, a metal response protein. All three biomarkers were significantly elevated in e-cigarette users compared to the concentrations in cigarette smokers.

"Our findings reaffirm that e-cigarette use is not harm free," said Shane Sakamaki-Ching, a graduate student in the Cell, Molecular and Developmental Biology Graduate Program and the research paper's first author. "Indeed, prolonged use may lead to disease progression."

The researchers advise physicians to exercise caution when recommending e-cigarettes to their patients. Electronic cigarette aerosols contain potentially harmful chemicals, cytotoxic flavor chemicals, metals, ultrafine particles, and reaction products. E-cigarette use has been linked to adverse health effects such as respiratory diseases, increased risk for cardiovascular disease, and impaired wound healing following surgery.

"Pregnant women, especially, should not be encouraged to use e-cigarettes," Talbot said. "Excess of zinc in their bodies can lead to nausea and diarrhea. Given the recent deaths and pulmonary illnesses related to e-cigarette usage, everyone should be made aware of the potential health risks linked to e-cigarette usage."

The study involved 53 participants from the Buffalo, New York, area. Talbot and Sakamaki-Ching were joined in the study by Monique Williams, My Hua, Jun Li, Steve M. Bates, Andrew N. Robinson, and Timothy W. Lyons of UCR; and Maciej L. Goniewicz of the Roswell Park Comprehensive Cancer Center, Buffalo, New York.

The study was supported by grants from the National Institutes of Health.

The University of California, Riverside (http://www.ucr.edu) is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment is more than 24,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual statewide economic impact of almost $2 billion. To learn more, email news@ucr.edu.

Credit: 
University of California - Riverside