Culture

The blood vasculature in the brain is a highly ramified, complex but well-organized vessel network. During development, the pathfinding of growing vessels is critical for the patterning of the brain vasculature. However, its underlying mechanism still remains elusive.

A research team led by Dr. DU Jiulin of the Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Sciences, has revealed that Ca2+ activities mediated by mechanosensitive Piezo1 channels regulate the pathfinding of growing brain vessels in larval zebrafish.

The formation of the brain vasculature is initiated by vessel invasion from the surrounding perineural vascular plexus around the ventral neural tube during early development, and then the brain vasculature is expanded by the continuous emergence and growth of newborn vessels from preexisting ones, a process known as angiogenesis.

Endothelial tip cells (ETCs) located at the forefront of growing vessels usually extend a few motile primary branches and many dynamical fine filopodia, navigate through tissue microenvironments, and steer angiogenic sprouts to their appropriate targets. This process of ETC pathfinding is critical for the proper patterning of the vasculature in the brain as well as in all other organs, but its underlying mechanism still remains largely unknown.

To investigate the cellular and molecular mechanism underlying ETC pathfinding, Dr. DU's group first monitored the entire process of ETC pathfinding during brain vascular development through in vivo long-term time-lapse simultaneous imaging of both the morphological dynamics and Ca2+ activity of ETCs in larval zebrafish.

They found that before reaching target vessels, ETCs frequently extended and retracted subcellular primary branches, leading to continuous changes in the direction of ETC migration and vessel growth.

Interestingly, branches of ETCs exhibited spontaneous local Ca2+ transients at different frequencies during pathfinding, with high- and low-frequency local Ca2+ transients associated with branch retraction and extension, respectively.

Then the researchers examined the causal relationship between local Ca2+ transients and fate determination of ETC branches via local manipulation of Ca2+ concentration at ETC branches, and found that high- and low-frequency Ca2+ transients were necessary and sufficient for the retraction and extension of ETC branches, respectively.

Furthermore, they investigated the origin of local Ca2+ activities of ETCs, and discovered that mechanosensitive Piezo1 cationic channels were preferentially expressed on ETC branches and activated by tissue stiffness-associated mechanical force. "They mediated local Ca2+ activities of ETC branches, thus regulating the retraction and extension of ETC branches," said Dr. DU.

Mutating piezo1 largely diminished local Ca2+ transients of ETC branches, impaired the pathfinding of ETCs, and therefore disrupted the patterning of the brain vasculature.

Finally, the researchers showed that the protease calpain and nitric oxide synthase mediated the effects of Piezo1-mediated Ca2+ activities on ETC branch retraction or extension, respectively.

This study reveals that Piezo1 and downstream Ca2+ signaling act as molecular bases for ETC pathfinding and highlights a novel function of Piezo1 and Ca2+ in vascular development.

STONY BROOK, NY, August 21, 2020 - China is the world's largest producer and consumer of coal. A team of international scientists led by Stony Brook University's Gang He, PhD, contend that China needs to transition away from coal to help the world achieve global decarbonization and improve the nation's environmental and human health. They outline steps that can be taken for an albeit difficult, yet just and quicker transition away from coal in a perspective paper published in One Earth.

The study proposes a political-socio-economic perspective targeting an integrated value chain to highlight a few overarching strategies and implementing policies accelerating China's transition away from coal. This is different from the conventional discussion on coal transition, which usually centers on air pollution, carbon emission and competition from renewables.

"Our paper is an effort to include in the overall discussion the employment and social justice impacts, including environmental justice, of such a transition," said Dr. He, Assistant Professor in the Department of Technology and Society in the College of Engineering and Applied Sciences at Stony Brook University.

"The benefits of China's transition away from coal is huge. We estimate that the most aggressive coal-transition pathway could reduce premature death related to coal combustion by 224,000 in 2050, compared to the business-as-usual scenario," says Dr. He. "Similarly, our maximum estimated reduction in water consumption, arguably the most vital of all resources, is about 4.3 billion m3 in 2050."

The researchers argue that for a rapid transition away from coal, China needs to take these steps: 1) Retire coal generating plants earlier and cancel newly planned coal projects. 2) Reduce the nation's coal consumption beyond the massive power sector. 3) A rapid transition presents economic and social challenges that should be met with new economic opportunities. 4) Attempt to align the motivations and incentives of key business and government stakeholders, which are often not coordinated.

Dr. He emphasizes that a successful coal transition would involve changes that must take into account the well-being and economic security of some three million people who work in coal mining-related jobs in China, as well as another 500,000 who work within the coal power industry. A just transition away from coal, the authors write, also needs to accommodate low-income groups that rely on abundant, cheap and readily available coal for basic electricity and heating service.

To start the transition, the authors propose the creation of a dedicated task force charged with facilitating action plans to be carried out and a process that serves the best interests of affected stakeholders and China's diverse population.

What The Study Did: The potential for contract tracing to reduce the spread of SARS-CoV-2 in the context of reduced physical distancing under different assumptions for case detection, tracing and quarantine efficacy is examined in this mathematical modeling study.

Authors: Joshua A. Salomon, Ph.D.,of the Stanford University School of Medicine in Stanford, California, 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/jamanetworkopen.2020.19217)

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

COLUMBUS, Ohio - An upcoming NASA mission could find that there are more rogue planets - planets that float in space without orbiting a sun - than there are stars in the Milky Way, a new study theorizes.

"This gives us a window into these worlds that we would otherwise not have," said Samson Johnson, an astronomy graduate student at The Ohio State University and lead author of the study. "Imagine our little rocky planet just floating freely in space - that's what this mission will help us find."

The study was published today in he Astronomical Journal.

The study calculated that NASA's upcoming Nancy Grace Roman Space Telescope could find hundreds of rogue planets in the Milky Way. Identifying those planets, Johnson said, will help scientists infer the total number of rogue planets in our galaxy. Rogue, or free-floating, planets are isolated objects that have masses similar to that of planets. The origin of such objects is unknown, but one possibility is they were previously bound to a host star.

"The universe could be teeming with rogue planets and we wouldn't even know it," said Scott Gaudi, a professor of astronomy and distinguished university scholar at Ohio State and a co-author of the paper. "We would never find out without undertaking a thorough, space-based microlensing survey like Roman is going to do."

The Roman telescope, named for NASA's first chief astronomer who was also known as the "mother" of the Hubble telescope, will attempt to build the first census of rogue planets, which could, Johnson said, help scientists understand how those planets form. Roman will also have other objectives, including searching for planets that do orbit stars in our galaxy.

That process is not well-understood, though astronomers know that it is messy. Rogue planets could form in the gaseous disks around young stars, similar to those planets still bound to their host stars. After formation, they could later be ejected through interactions with other planets in the system, or even fly-by events by other stars.

Or they could form when dust and gas swirl together, similar to the way stars form.

The Roman telescope, Johnson said, is designed not only to locate free-floating planets in the Milky Way, but to test the theories and models that predict how these planets formed.

Johnson's study found that this mission is likely to be 10 times more sensitive to these objects than existing efforts, which for now are based on telescopes tethered to the Earth's surface. It will focus on planets in the Milky Way, between our sun and the center of our galaxy, covering some 24,000 light years.

"There have been several rogue planets discovered, but to actually get a complete picture, our best bet is something like Roman," he said. "This is a totally new frontier."

Rogue planets have historically been difficult to detect. Astronomers discovered planets outside Earth's solar system in the 1990s. Those planets, called exoplanets, range from extremely hot balls of gas to rocky, dusty worlds. Many of them circle their own stars, the way Earth circles the sun.

But it is likely that a number of them do not. And though astronomers have theories about how rogue planets form, no mission has studied those worlds in the detail that Roman will.

The mission, which is scheduled to launch in the next five years, will search for rogue planets using a technique called gravitational microlensing. That technique relies on the gravity of stars and planets to bend and magnify the light coming from stars that pass behind them from the telescope's viewpoint.

This microlensing effect is connected to Albert Einstein's Theory of General Relativity and allows a telescope to find planets thousands of light-years away from Earth--much farther than other planet-detecting techniques.

But because microlensing works only when the gravity of a planet or star bends and magnifies the light from another star, the effect from any given planet or star is only visible for a short time once every few million years. And because rogue planets are situated in space on their own, without a nearby star, the telescope must be highly sensitive in order to detect that magnification.

The study published today estimates that this mission will be able to identify rogue planets that are the mass of Mars or larger. Mars is the second-smallest planet in our solar system and is just a little bigger than half the size of Earth.

Johnson said these planets are not likely to support life. "They would probably be extremely cold, because they have no star," he said. (Other research missions involving Ohio State astronomers will search for exoplanets that could host life.)

But studying them will help scientists understand more about how all planets form, he said.

"If we find a lot of low-mass rogue planets, we'll know that as stars form planets, they're probably ejecting a bunch of other stuff out into the galaxy," he said. "This helps us get a handle on the formation pathway of planets in general."

Prof. MENG Wenxiang's group from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences recently reported a new mechanism by which microtubule networks instruct neuronal polarity.

The study, published in PNAS, deepens the understanding of the fundamental question of neuroscience, "What microtubular factor is decisive in the establishment of neuronal polarity?"

A typical mature neuron has one axon and multiple dendrites, forming the physical basis of neuronal function. In neurons, the establishment of axon/dendrite polarity is regulated by a variety of factors, including the polarization of signaling regulators and cytoskeletons. Microtubules are the final performer in this process. However, how microtubules instruct axon/dendrite differentiation has been unclear.

In this study, the researchers found that CAMSAP1, a microtubule minus-end binding protein, is an indispensable factor in neuronal multipolar-bipolar transition and radial migration.

Collaborating with WANG Yingchun's group, the researchers demonstrated that the polarity regulatory factor MARK2 kinase phosphorylated the serine at amino acid 1485 of CAMSAP1 and thereby regulated the ability of CAMSAP1 to bind and protect microtubule minus-ends.

This finding shows that the asymmetric distribution of microtubule-associated CAMSAP1 is a trigger in neurons and controls neuronal polarization by creating an unbalanced distribution of microtubules among neuronal processes.

"In fact, in the early stage of neuronal polarization, it was the unbalanced stability of the noncentrosomal microtubule minus-ends that caused the asymmetric distribution of microtubules, which in turn promoted the changes of stability or modification of microtubules," said Dr. ZHOU Zhengrong, the first author of the study. "Our research answers a question that has long plagued neuroscientists, that is, whether the stability and acetylated modification of microtubules are the decisive factors in establishing neuronal polarity."

Balanophora have some of the smallest fruits among angiosperms, leading researchers to question how the seeds of these plants are dispersed. However, very little is currently known about their seed dispersal system. Associate Professor SUETSUGU Kenji (Kobe University Graduate School of Science) documents an unrecognized seed dispersal mutualism between the peculiar, mushroom-like non-photosynthetic plant Balanophora yakushimensis and its avian visitors. The birds obtain nutrients, not from the tiny undernourished fruits, but from the larger fleshy bracts, while B. yakushimensis plants benefit from the seed dispersal. In contrast to well-studied fleshy-fruited plants, the dry-fruited Balanophora species has adopted an avian seed dispersal mutualism through its fleshy bracts, which act as both visual attractants and nutritional rewards. These findings were published on 19 August, 2020 in 'Ecology'.

The color green is a defining feature of the plant kingdom, and plants are mostly assumed to be autotrophs that can make their own food from simple inorganic substances such as carbon dioxide. Therefore, the biological oddities of non-photosynthetic plants have long attracted the attention of naturalists. The genus Balanophora comprises partially or entirely subterranean non-photosynthetic plants with extremely reduced morphological features. Just like the most famous parasitic plant Rafflesia, Balanophora mooch water and nutrients off the host plants they are attached to. Consisting of highly specialized root parasites, Balanophora is definitely one of the most unusual plant genera (Figure 1).

Recent studies have suggested that the evolutionary transition to full heterotrophy is a complex process, although, superficially, it may seem like a loss of photosynthetic ability. One of the most significant characteristics is the extreme reduction in the size and complexity of their seeds. In fact, Balanophora infructescences contain 100,000 to 1,000,000 tiny dry fruits situated at the base of a fleshy, club-shaped transformed bracts (Figure 2). As Balanophora fruits are some of the smallest among angiosperms, the fundamental question arises as to what mode of seed dispersal occurs in these plants.

Yet surprisingly, almost nothing is known about the seed dispersal system of Balanophora, despite this being one of the most important aspects of plant biology. Due to Balanophora infructescences being morphologically similar to mushrooms, it had been assumed that mycophagous rodents were its main seed dispersers. However, the lack of information about the animals that actually feed on Balanophora fruits has prevented the elucidation of the seed dispersal system employed by the group.

Suetsugu studied the B. yakushimensis seed dispersal system in the understory of the temperate forests on Yakushima Island, Kagoshima Prefecture, Japan. Consequently, he documented a previously unnoticed seed dispersal mutualism between the dry-fruited B. yakushimensis and its avian visitors (Figure 3; Video). Even though plants have evolved various mechanisms to mediate seed dispersal by animals, the predominant strategy is the production of fleshy fruits with embedded seeds. However, B. yakushimensis have adopted alternative approaches; not tiny undernourished fruits but larger fleshy bracts act as a tool to elicit seed dispersal. Since the bright red transformed bracts are much larger than their minute fruits, they should function as the primary visual attractants and edible rewards for birds. Overall, the study documents a previously unrecorded seed dispersal mutualism; avian visitors obtain nutrients from transformed bracts, while B. yakushimensis plants benefit from seed dispersal. Further studies on the seed dispersal systems of other Balanophora members will provide greater insights into ecology of these bizarre plants.

The human body is home to trillions of microbes. Through its natural functioning, much of the time, this ecosystem regulates our health. But like the environment of the world at large, this bodily ecosystem is delicate, and any change in the composition of the microbial community, also called the "microbiome," can cause an overall imbalance in their collective functioning, resulting in disease.

Now, advances in research in this field have yielded a technique called next-generation DNA sequencing, which allows for very accurate identification of the members of this microbial community, thereby offering insights into microbial community composition. For several diseases, knowing which microbes densely populate the organ/tissue in question or become absent from it during disease can help develop effective treatments. Such is the case for dental caries, a type of tooth decay in which acid-producing bacteria eat away at the out layer of teeth and cause cavities.

A type of bacteria called the mutans streptococci are the most commonly implicated microbes in dental caries. Their increase causes dental decay. But, could other microbes be responsible as well?

Scientists globally have looked into this question. However, focus on the younger demographic has been low. Meanwhile, in Japan, the number of young adults developing dental caries is increasing.

Spurred by this increase and this insufficient literature, a team of researchers from Japan, led by Dr. Uchida-Fukuhara from Okayama University, called for Japanese university student volunteers for oral examinations at the Health Service Center in Okayama University.

The students answered a survey about their dental health at the beginning of the study and during a follow-up after three years. This told the researchers which students had significantly increased dental caries after this time and who didn't. The researchers grouped the students accordingly during the follow-up (let's say, Groups A and B respectively). They then collected saliva samples of randomly selected students from these groups, which they analyzed via next-generation DNA sequencing to obtain microbial profiles.

It turned out that very similar oral microbial diversities existed in both groups. But in Group A, the abundances of the bacterial families Prevotellaceae and Veillonellaceae, and genera Alloprevotella and Dialister, were greater than those in Group B. These two families are known to comprise species that produce acid as well. This finding, therefore, suggests new prevention possibilities for dental caries that does not focus on keeping mutans streptococci populations in check.

Interestingly, both groups had low levels of mutans streptococci. Should the focus of research on what causes dental caries change?

The striking results of the study, published in the International Journal of Environmental Research and Public Health, underscore the necessity of updating current knowledge on the oral microbial community and its role in the development of dental caries. But Dr. Uchida highlights limitations in the study's applicability and advises taking these findings with a pinch of salt. "Among other things, all our participants were from Okayama University, so our results may not be generalizable to the wider population," she says.

Yet, Dr. Uchida is hopeful, "For many years our group has been conducting population studies to reduce oral diseases. We believe that the results of this new study will help us develop novel strategies to prevent dental caries and our students will achieve greater life satisfaction because of better teeth and oral health."

Perhaps, in the future, students' teeth will be clean as a hound's tooth.

Joint research, led by Kumamoto University in Japan, has successfully reproduced the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) from human iPS cells in vitro. ADPKD is a disease that causes multiple cysts in both kidneys and is the most common hereditary kidney disease. Although cysts derived from renal tubules have been previously documented, this is the first induction of cysts from collecting ducts, which is more closely related to the pathogenesis of the disease. The researchers expect that this will lead to a better understanding of disease states and the development of new treatment methods.

ADPKD is estimated to affect 1 in every 400-1,000 people. Although half of ADPKD patients progress to renal failure by the age of 60, the underlying mechanisms of the disease are not clear and a treatment has yet to be found. ADPKD is caused by mutations in the PKD genes, and will develop if one or both copies of the PKD genes, inherited from the father and mother each, have mutations (heterozygous or homozygous mutations). The PKD genes consist of PKD1 and PKD2 and about 85% of all ADPKD patients have a heterozygous mutation of the PKD1 gene. The remaining 15% have a heterozygous mutation of the PKD2 gene. Those with heterozygous mutations of the PKD1 gene have a more severe prognosis, with approximately half developing renal failure by the age 60 due to the progression of renal cysts. The mechanism of ADPKD has been mainly studied in mice. However, mice with a heterozygous mutation in the PKD1 gene develop few renal cysts, even in adults, and human symptoms are not reproduced.

Kidneys develop through the interactions between the two different precursors; nephron progenitors and ureteric buds. Nephron progenitors differentiate into the renal tubules that reabsorb salt and water in the urine, and ureteric buds differentiate into the collecting ducts that collect urine and reabsorb water. ADPKD cysts can originate from both the renal tubules and the collecting ducts, but the collecting ducts appear to be their predominate origin. In 2014, Nishinakamura et al. reported on a method of inducing renal tubules from human iPS cells via nephron progenitor cells. Since then, several research groups have successfully produced renal tubule-derived cysts from iPS cells that had a homozygous mutation of the PKD1 gene, but cysts derived from collecting ducts have not yet been produced. Because renal tubule-cysts have also been formed from normal iPS cells without gene mutation, it was not possible to reproduce the disease state from iPS cells derived from ADPKD patients who had the heterozygous mutation of the PKD1 gene. However, Professor Nishinakamura's research group induced collecting ducts from human iPS cells via ureteric buds in 2017, and have since been attempting to reproduce cysts derived from collecting duct by building on their own methods.

To reproduce the ADPKD cysts, the researchers used the gene editing technology CRISPR-Cas9 to create both homozygous and heterozygous mutant iPS cells with the PKD1 gene and induced them into renal tubules. After administration of a drug called forskolin, which activates a factor that exacerbates ADPKD cysts, tubular cysts were reproduced as in previous reports. However, mild cysts also formed from the renal tubules that had not been genetically mutated.

When these iPS cells were induced into collecting ducts and treated with forskolin, cysts formed from the collecting duct that had the PKD1 homozygous mutation. On the other hand, cysts did not form from collecting ducts that had no gene mutations, indicating that their response to forskolin was different from that of renal tubules. When researchers checked the expression of the receptor for the antidiuretic hormone vasopressin, which acts on the collecting duct, they found that it was only expressed in the collecting duct. Vasopressin is known to exacerbate ADPKD cysts from collecting ducts, and when it was administered to the induced collecting ducts and renal tubules, cysts formed, albeit at a low frequency, only in collecting ducts with PKD1 homozygous mutation. Furthermore, cysts partially formed in collecting ducts with the PKD1 heterozygous mutation after administration of forskolin. When iPS cells from an ADPKD patient with the PKD1 heterozygous mutation were used to induce collecting ducts, cysts formed in the same way. According to the researchers, this is the first successful reproduction of ADPKD disease pathology from patient-derived iPS cells.

"This study shows that the method of inducing collecting ducts from iPS cells can be a new disease model for ADPKD," said study leader, Professor Nishinakamura. "By analyzing these collecting duct cysts--which are similar to actual clinical conditions--we may find mechanisms and develop new therapeutic methods that have been difficult to identify until now. We also expect that the replication of cysts from patient-derived iPS cells will lead to research and treatments for individual cases."

Overview:

A research group composed of Professor Takayuki Shibata and his colleagues at the Department of Mechanical Engineering, Toyohashi University of Technology has applied a microfluidic chip technology to develop a multiplex genetic diagnostic device for the early detection and prevention of crop diseases. The group conducted a gene amplification experiment using four kinds of cucumber viruses on the palm-size diagnostic device, and successfully demonstrated that the rapid multiplex diagnosis can be performed within 1 hour of testing. This diagnostic device is a highly versatile technology that can be used for genetic diagnosis not only in viral diseases of crops, but also in various areas including human infections (e.g., the agriculture/livestock/fisheries industries, the food industry, and health/medical care).

Details:

With increased food demand due to world population growth and decreased production due to abnormal weather as a backdrop, the "steady supply of safe and high quality agricultural, forest, and fishery products and food" has become a pressing issue common to all humankind in order to actualize a sustainable world (Sustainable Development Goals, SDGs). This research aims at developing a diagnostic technology to support the effective and stable production of high quality crops. By utilizing this technology, even regular agricultural producers without special knowledge or skills can easily and rapidly test for plant diseases and insect pests at their farms at the genetic level.

Loop-mediated isothermal amplification (LAMP) 1) is one of methods for detecting target nucleic acids (DNA or RAN). This approach can amplify the targeted gene at a constant temperature (60-65ºC for 30 minutes to 1 hour) without expensive instrumentation for high-precision temperature control in PCR assays, which is the most commonly used genetic diagnosis technique. Therefore, the LAMP method has considerable potential for providing an easy-to-use diagnostic tool and enabling on-site diagnoses. However, the conventional LAMP assay is troublesome in that it is necessary to prepare and test as many sample (the DNA or RNA targets)/reagent mixtures individually for each targeted virus. This process also requires specialized knowledge and skills.

Here, our research team has solved this problem by employing microfluidic chip technology. We have developed a polydimethylsiloxane (PDMS)-based microfluidic device for the multiplex genetic diagnosis of plant diseases by using semiconductor manufacturing technology. The fabricated multiplex genetic diagnostic device consists of an array of five reaction chambers (3 μL in volume) and a microchannel (200 μm in width and 80 μm in height) forming a network connecting them. The device was approximately 45 mm×25 mm in size (less than 1/3 of name card). As a sample, total RNA containing viral RNA target extracted from diseased cucumber leaves collected at a farm was used. In the operating procedure for the multiplex LAMP assay, a mixture of sample and reagents were autonomously dispensed into the multiple reaction chambers, with just one operation for introducing the mixture into the inlet port of the device. Then, the device was heated in hot water (63ºC for 40 minutes to 1 hour), resulting in the specific amplification of targeted nucleic acids. As shown in the figure, two kinds of RNA viruses were successfully detected simultaneously on our diagnostic device. It should be noted that the device has the ability to simultaneously diagnose up to four different kinds of plant viral diseases.

1) LAMP is an isothermal gene amplification method developed by Eiken Chemical Co., Ltd.. This is a technique to amplify a target DNA at a constant temperature (60 - 65ºC) by using a set of four to six primers specially designed to recognize six to eight distinct regions on the target gene based on strand displacement reaction.

Future Outlook:

We will develop a diagnostic device for enabling the simultaneous detection of a total of eight items, including four kinds of cucumber viral diseases and four kinds of insect pests, with the aim of putting the device to practical use. In principle, it is possible to freely customize the types of target viruses to meet individuals' specific needs on our diagnostic device. Therefore, looking ahead to the "life with corona" era, we will provide a platform for the rapid multiplex diagnosis of human infectious diseases (such as the novel coronavirus and the influenza viruses). We will also realize the rapid multiplex allergen testing in food production (seven specified raw material items: wheat, buckwheat, peanut, egg, milk, shrimp, and crab) as food safety technology.

Tokyo, Japan - Intestinal stem cells keep a fine balance between two potential forms: remaining as stem cells, or developing into intestinal epithelial cells. In a new study, researchers from Tokyo Medical and Dental University (TMDU) discovered a novel molecular mechanism that regulates this balance and preserves the stemness of intestinal stem cells--that is, their ability to develop into any intestinal epithelial cell type.

The inner lining of intestines, the intestinal epithelium, ensures adequate digestion and adsorption of nutrients. It is made up of several different cell types, all of which fulfill a specific function. Intestinal stem cells ensure proper functioning of the intestines, which requires constantly replacing old and damaged cells with young cells, by developing, or differentiating, into one of the different intestinal epithelial cell types when needed. Because there is a constant demand for new cells, intestinal stem cells have the ability to self-renew, thereby providing a constant supply of stem cells as well. However, little is known about the mechanisms that regulate this balance between self-renewal and differentiation.

"Just like any other type of stem cell, intestinal stem cells have the ability to differentiate into any cell within their lineage," says corresponding author of the study Professor Toshiaki Ohteki. "But they have to do it in a regulated manner, only differentiating when needed. The goal of our study was to understand the regulatory mechanism that preserves the stemness of intestinal stem cells."

To achieve their goal, Taku Sato, a main contributor of this project, and collaborators focused on a molecular signaling pathway that they had previously shown to preserve the stemness of hematopoietic stem cells (HSCs) that give rise to blood cells. Interferons are molecules that are produced especially during viral and bacterial infections, but more recently it was also shown that they are present even in the absence of infections to regulate various biological processes. In either case, interferons induce the expression of certain genes, a process that is regulated by the protein interferon regulatory factor-2 (IRF2) to ensure that the actions of interferons are balanced. In the case of HSCs, IRF2 turned out to be a critical factor for their stemness.

In the current study, the researchers found that IRF2 is produced throughout the intestinal epithelium and that IRF2-deficient mice had normal anatomical structure during homeostasis (the absence of an infection or any other damaging factor). However, in the presence of 5-fluorouracil, which is known to damage the intestinal epithelium, normal mice were able to regenerate completely, but IRF2-deficient mice showed a blunted regenerative response (Figure 1), indicating that intestinal stem cells were not able to function properly in the absence of IRF2. Interestingly, immature Paneth cells, which are specialized secretory cells, were highly abundant in IRF2-deficient mice. The researchers had the same finding in normal mice exposed to lymphocytic choriomeningitis virus (LCMV), which causes chronic infection.

"These are striking results that show how excess interferon signaling in the absence of IRF2 impairs the ability to self-renew and directs intestinal stem cells towards the secretory cell lineage (Figure 2). Our findings provide new insight into the biology of intestinal stem cells and show that regulated interferon signaling is a means to preserve the stemness of intestinal stem cells," says Professor Ohteki.

Black holes are at the center of almost all galaxies that have been studied so far. They have an unimaginably large mass and therefore attract matter, gas and even light. But they can also emit matter in the form of plasma jets - a kind of plasma beam that is ejected from the centre of the galaxy with tremendous energy. A plasma jet can extend several hundred thousand light years far into space.

When this intense radiation is emitted, the black hole remains hidden because the light rays near it are strongly bent leading to the appearance of a shadow. This was recently reported by researchers of the Event Horizon Telescope (EHT) collaboration for the massive black hole in the giant ellipse galaxy M87.

In quasar 3C279 - also a black hole - the EHT team found another phenomenon: At a distance of more than a thousand times the shadow of the black hole, the core of a plasma jet suddenly lit up. How the energy for this jet could get there as if through an invisible chimney was not yet known.

Extremely flickering gamma radiation detected

This quasar has now been observed with the NASA space telescope Fermi-LAT by the astrophysicist Amit Shukla, who until 2018 did research at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany. He now is working at the Indian Institute of Technology in Indore. Shukla discovered that the core of the jet, which was found in the millimeter wavelength range, also emits high-energy gamma radiation, but with an extremely flickering brightness. This brightness can double within a few minutes, as reported in the journal Nature Communications.

The special pattern of the sequence of brightness changes is characteristic of a universal process called magnetic reconnection, which occurs in many astrophysical objects with strong magnetic fields. Solar activity also has to do with the dynamics of magnetic fields and reconnection. This was recently demonstrated by observing "campfires" in the solar atmosphere with the "Solar Orbiter" mission of the European Space Agency ESA.

Invisibly stored energy is suddenly released

But back to the quasar 3C279: "I saw how the analysis of the data revealed the special pattern of magnetic reconnection in the light curve. It felt as if I had suddenly deciphered a hieroglyph in the black hole alphabet," says Amit Shukla happily.

During reconnection, energy that is initially stored invisibly in the magnetic field is suddenly released in numerous "mini-jets". In these jets, particles are accelerated, which then produce the observed gamma radiation. Magnetic reconnection would explain how the energy reaches the jet's core from the black hole and where it ultimately comes from.

Energy from the spinning black hole

Professor Karl Mannheim, head of the JMU Chair of Astronomy and co-author of the publication, explains: "Spacetime near the black hole in the quasar 3C279 is forced to swirl around in corotation. Magnetic fields anchored to the plasma around the black hole expel the jet slowing down the black hole's rotation and converting part of its rotational energy into radiation".

Using a simple 'thermometer scale survey' to measure public attitudes towards people with autism could help improve public understanding and acceptance, say researchers.

In a new study, published in the journal Experimental Results, psychologists from the universities of Bath and Essex, propose a simplification in the way in which attitudes are measured - replacing existing, complex surveys with just one question that would gauge public attitudes and acceptance.

They say that changing the way we measure attitudes towards people with autism and mental health conditions would increase the usefulness of such measures and improve public understanding of such conditions.

Public attitudes about autism can feed into government and NGO policies when, for example, they decide on levels of funding and other support directed towards autistic people, they add.

In a new study, Dr Punit Shah, an autism expert from the University of Bath, and Dr Paul Hanel, an attitude expert from the University of Essex, analysed data from the only survey for measuring attitudes towards autism.

Their results suggest that this outdated scale, which includes questions such as - 'people with autism should not have children' - was confusing attitudes, intentions, and behaviours towards autistic people. They concluded that it is not fit for purpose.

In its place they created a simple 'thermometer' scale, where members of the public were simply asked, 'please provide a number between 0 and 100 to indicate your overall evaluation of an autistic person'. They found that this sliding scale was as accurate as time-consuming surveys at predicting how much people said they wanted to interact with autistic people.

Dr Punit Shah from the University of Bath's Department of Psychology explained: "Autism is the 'costliest health condition' in the UK, more so than the cancer, stroke, and heart disease, combined. This is because it is a lifelong condition, meaning that autistic people are impacted by societal attitudes which influence behaviours towards them from non-autistic people.

"Despite the impact that non-autistic people have on the lives of those with autism, overall public attitudes towards autistic people are very poorly understood. This is because there has been no scientifically-robust way to measure public attitudes and therefore no robust way at devising interventions to improve acceptance and cohesion."

The researchers found that, on average, non-autistic students rated autistic people relatively favourably - 71/100; they have since found this to be around 62/100 more generally in the UK. The researchers say that it is good to see that public attitudes towards autistic people are generally more favourable than unfavourable, but that there is a long way to go in understanding and changing negative attitudes to autism and mental health conditions.

Dr Shah, adds: "Our research is a critical step towards improving the science of attitudes towards people with autism and mental health conditions. Our scale, which is freely available for use by researchers and policymakers, will enable us to better understand the many reasons for negative and positive attitudes towards autistic people and other neurodevelopmental conditions. Using this scale, researchers in my group are now looking into how people's autism knowledge and level of contact with autistic people are linked to their attitudes towards people with the conditions."

Dr Paul Hanel, a Lecturer at the University of Essex and researcher at Bath, added: "Our scale is an important step towards a better of understanding and ultimately improving attitudes towards people with autism. Because it is so simple it can also be translated and used in other countries and cultures, whereas old measures could not. While attitudes towards people with autism are on average favourable in the UK, and also in India and the USA, we are currently discussing ways how those attitudes can be further enhanced.

"For example, many people still have some misconceptions about autism and might believe that people with autism are more different to them than they actually are on various attributes such as their personality or beliefs. We want to test whether correcting misconceptions improves intergroup attitudes. To test for attitude change it is crucial to have a reliable and valid measure of attitudes towards people with autism, as we have developed in this study."

War atrocities are sometimes committed by 'normal' people obeying orders. Researchers from the Netherlands Institute for Neuroscience measured brain activity while participants inflicted pain and found that obeying orders reduced empathy and guilt related brain activity for the inflicted pain. This may explain why people are able to commit immoral acts under coercion.

Many examples in the history of mankind have shown that when people obey orders from an authority, they are able to perform atrocious acts towards others. All the genocides that mankind has known, generally referred to as crimes of obedience, have shown that having a part of the population complying with orders to exterminate other human beings led to the loss of countless lives, cultures and civilizations. "We wanted to understand why obeying orders impacts moral behavior so much. Why people's willingness to perform moral transgressions is altered in coerced situations", says Dr Emilie Caspar, co-first author of the present study.

When humans witness another person experiencing pain, be it emotional or physical, they have an empathic reaction, and this is thought to be what makes us averse to harming others. "We can measure that empathy in the brain, because we see that regions normally involved in feeling our own pain, including the anterior insula and the rostral cingulate cortex, become active when we witness the pain of others, and the stronger that activity, the more empathy we experience, and the more we do to prevent harm to others", explains Dr Valeria Gazzola, co-senior author of the paper. This process is deeply ingrained in our biology and shared by other mammals, such as rodents or apes. "We evaluated in this study if obeying orders to inflict pain to someone else would reduce the empathic response compared to freely deciding to inflict - or not to inflict - the same pain", reports prof. Christian Keysers, the other co-senior author of the present study.

In the study published in NeuroImage, the authors used pairs of participants, with one being assigned the role of 'agent' and the other the role of 'victim'. Agents were placed in an MRI scanner to record their brain activity during the task. They were told that they had two buttons; one triggering the administration of a real, mildly painful, shock on the victim's hand in exchange for +0.05€, and another triggering no shock and no money. Over the course of 60 rounds, agents were either free to choose to administer - or not - this shock to the victim, or they received orders from the experimenter to inflict - or not - the same shock. This task was designed to involve a difficult moral decision for agents: increasing one's own monetary gain by causing pain to another person or not.

The authors observed that agents sent more shocks to victims when they were coercively instructed than when they freely decided. "Neuroimaging results showed that empathy-related regions were less active when obeying orders compared to acting freely. We also observed that obeying orders reduced activations in brain regions associated with the feeling of guilt", explains Kalliopi Ioumpa, co-first author of the present study.

The observation that obeying an order to inflict pain reduced activation in empathy and guilt related brain regions explains, at least partly, why people can commit highly immoral acts towards others under coercion. These results have huge implications in terms of understanding the power that obedience has over human behavior and offer new insights into the possibility of preventing mass-atrocities committed because of a lack of empathy for victims. "The next step will be to understand why so few people resist immoral orders. Is it because their empathy weakens when they are following orders? A better understanding of how the brain processes empathy and instructions may lead to ways to help us resist calls to commit violence in the future", says Dr Emilie Caspar.

Sending a "selfie" to the doctor could be a cheap and simple way of detecting heart disease, according to the authors of a new study published today (Friday) in the European Heart Journal [1].

The study is the first to show that it's possible to use a deep learning computer algorithm to detect coronary artery disease (CAD) by analysing four photographs of a person's face.

Although the algorithm needs to be developed further and tested in larger groups of people from different ethnic backgrounds, the researchers say it has the potential to be used as a screening tool that could identify possible heart disease in people in the general population or in high-risk groups, who could be referred for further clinical investigations.

"To our knowledge, this is the first work demonstrating that artificial intelligence can be used to analyse faces to detect heart disease. It is a step towards the development of a deep learning-based tool that could be used to assess the risk of heart disease, either in outpatient clinics or by means of patients taking 'selfies' to perform their own screening. This could guide further diagnostic testing or a clinical visit," said Professor Zhe Zheng, who led the research and is vice director of the National Center for Cardiovascular Diseases and vice president of Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

He continued: "Our ultimate goal is to develop a self-reported application for high risk communities to assess heart disease risk in advance of visiting a clinic. This could be a cheap, simple and effective of identifying patients who need further investigation. However, the algorithm requires further refinement and external validation in other populations and ethnicities."

It is known already that certain facial features are associated with an increased risk of heart disease. These include thinning or grey hair, wrinkles, ear lobe crease, xanthelasmata (small, yellow deposits of cholesterol underneath the skin, usually around the eyelids) and arcus corneae (fat and cholesterol deposits that appear as a hazy white, grey or blue opaque ring in the outer edges of the cornea). However, they are difficult for humans to use successfully to predict and quantify heart disease risk.

Prof. Zheng, Professor Xiang-Yang Ji, who is director of the Brain and Cognition Institute in the Department of Automation at Tsinghua University, Beijing, and other colleagues enrolled 5,796 patients from eight hospitals in China to the study between July 2017 and March 2019. The patients were undergoing imaging procedures to investigate their blood vessels, such as coronary angiography or coronary computed tomography angiography (CCTA). They were divided randomly into training (5,216 patients, 90%) or validation (580, 10%) groups.

Trained research nurses took four facial photos with digital cameras: one frontal, two profiles and one view of the top of the head. They also interviewed the patients to collect data on socioeconomic status, lifestyle and medical history. Radiologists reviewed the patients' angiograms and assessed the degree of heart disease depending on how many blood vessels were narrowed by 50% or more (? 50% stenosis), and their location. This information was used to create, train and validate the deep learning algorithm.

The researchers then tested the algorithm on a further 1,013 patients from nine hospitals in China, enrolled between April 2019 and July 2019. The majority of patients in all the groups were of Han Chinese ethnicity.

They found that the algorithm out-performed existing methods of predicting heart disease risk (Diamond-Forrester model and the CAD consortium clinical score). In the validation group of patients, the algorithm correctly detected heart disease in 80% of cases (the true positive rate or 'sensitivity') and correctly detected heart disease was not present in 61% of cases (the true negative rate or 'specificity'). In the test group, the sensitivity was 80% and specificity was 54%.

Prof. Ji said: "The algorithm had a moderate performance, and additional clinical information did not improve its performance, which means it could be used easily to predict potential heart disease based on facial photos alone. The cheek, forehead and nose contributed more information to the algorithm than other facial areas. However, we need to improve the specificity as a false positive rate of as much as 46% may cause anxiety and inconvenience to patients, as well as potentially overloading clinics with patients requiring unnecessary tests."

As well as requiring testing in other ethnic groups, limitations of the study include the fact that only one centre in the test group was different to those centres which provided patients for developing the algorithm, which may further limit its generalisabilty to other populations.

In an accompanying editorial [2], Charalambos Antoniades, Professor of Cardiovascular Medicine at the University of Oxford, UK, and Dr Christos Kotanidis, a DPhil student working under Prof. Antoniades at Oxford, write: "Overall, the study by Lin et al. highlights a new potential in medical diagnostics......The robustness of the approach of Lin et al. lies in the fact that their deep learning algorithm requires simply a facial image as the sole data input, rendering it highly and easily applicable at large scale."

They continue: "Using selfies as a screening method can enable a simple yet efficient way to filter the general population towards more comprehensive clinical evaluation. Such an approach can also be highly relevant to regions of the globe that are underfunded and have weak screening programmes for cardiovascular disease. A selection process that can be done as easily as taking a selfie will allow for a stratified flow of people that are fed into healthcare systems for first-line diagnostic testing with CCTA. Indeed, the 'high risk' individuals could have a CCTA, which would allow reliable risk stratification with the use of the new, AI-powered methodologies for CCTA image analysis."

They highlight some of the limitations that Prof. Zheng and Prof. Ji also include in their paper. These include the low specificity of the test, that the test needs to be improved and validated in larger populations, and that it raises ethical questions about "misuse of information for discriminatory purposes. Unwanted dissemination of sensitive health record data, that can easily be extracted from a facial photo, renders technologies such as that discussed here a significant threat to personal data protection, potentially affecting insurance options. Such fears have already been expressed over misuse of genetic data, and should be extensively revisited regarding the use of AI in medicine".

The authors of the research paper agree on this point. Prof. Zheng said: "Ethical issues in developing and applying these novel technologies is of key importance. We believe that future research on clinical tools should pay attention to the privacy, insurance and other social implications to ensure that the tool is used only for medical purposes."

Prof. Antoniades and Dr. Kotanidis also write in their editorial that defining CAD as ? 50% stenosis in one major coronary artery "may be a simplistic and rather crude classification as it pools in the non-CAD group individuals that are truly healthy, but also people who have already developed the disease but are still at early stages (which might explain the low specificity observed)".

Chess requires playing ability and strategic thinking; in roulette, chance determines victory or defeat, gain or loss. But what about skat and poker? Are they games of chance or games of skill in game theory? This classification also determines whether play may involve money. Prof. Dr Jörg Oechssler and his team of economists at Heidelberg University studied this question, developing a rating system similar to the Elo system used for chess. According to their study, both skat and poker involve more than 50 per cent luck, yet over the long term, skill prevails.

"Whether a game is one of skill or luck also determines whether it can be played for money. But assigning a game to these categories is difficult owing to the many shades of gradation between extremes like roulette and chess," states Prof. Oechssler. Courts in Germany legally classify poker as a game of chance that can be played only in government-sanctioned casinos, whereas skat is considered a game of skill. This classification stems from a court decision taken in 1906. One frequently used assessment criterion is whether the outcome for one player depends more than 50 per cent on luck. But how can this be measured objectively?

It is this question the Heidelberg researchers investigated in their game theoretic study. Using data from more than four million online games of chess, poker, and skat, they developed a rating system for poker and skat based on the Elo method for chess, which calculates the relative skill levels of individual players. "Because chess is purely a game of skill, the rating distribution is very wide, ranging from 1.000 for a novice to over 2.800 for the current world champion. So the wider the distribution, the more important skill is," explains Dr Peter Dürsch. In a game involving more luck and chance, the numbers are therefore not likely to be so far apart.

The Heidelberg research confirms exactly that: the distribution is much narrower in poker and skat. Whereas the standard deviation - the average deviation from the mean - for chess is over 170, the other two games did not exceed 30. To create a standard of comparison for a game involving more than 50 per cent luck, the researchers replaced every other game in their chess data set with a coin toss. This produced a deviation of 45, which is still much higher than poker and skat. "Both games fall below the 50 per cent skill level, and therefore depend mainly on luck," states Marco Lambrecht. "Skill, however, does prevail in the long run. Our analyses show that after about one hundred games, a poker player who is one standard deviation better than his opponent is 75 per cent more likely to have won more games than his opponent."

In principle, the method can be applied to all games where winners are determined, report the researchers. The percentage of skill in the popular card game Mau-Mau, for example, is far less than poker, whereas the Chinese board game Go involves even more skill than chess.