Researchers Identified Calcium Flares In Rods For the First Time (Neuroscience)

Thanks to refined microscopy techniques, researchers of SISSA and CNR-Iom have identified calcium flares in rods that no one had previously seen or even imagined. They raise the alarm and warn that it is necessary to carry out a replacement

Moving around in the half-light is difficult but not impossible. To help us in this undertaking we have the rods, a type of light-sensitive cells (photoreceptors) present in the retina of vertebrates, capable of detecting very low lights which allow to move about even in poorly lit cellars or caves. They are biological wonders capable of detecting even a single quantum of light, but they need continuous maintenance. They are the protagonists of the new study published in PNAS by a team of researchers of SISSA – Scuola Internazionale Superiore di Studi Avanzati and the Istituto officina dei materiali of the National research council CNR-Iom which reveals new and essential details of how the retina works and in particular photoreceptors.

©SISSA

These consist of two segments: the outer segment (OS) and the inner segment (IS). The OS of the rods is the one where the biological machine capable of capturing the light is located, while the IS is responsible for the information to be transferred to the brain. “We have understood that the outer segment is more fragile than what was thought”, comments Vincent Torre, neuroscientist of SISSA leading the team that conducted the research, adding “The OS consists of a stack of lipid discs containing the proteins responsible for phototransduction. New discs are generated at the base of the OS while used discs are removed at the tip of the OS. Traditionally, it was thought that in a stack of about 1000 discs there was almost perfect uniformity. However, our work shows that only the first 200 or 300 discs at the base of the OS are those effectively capable of detecting the single photon of light, characteristic from which comes the great sensitivity of the rods. The other discs positioned close to the tip gradually lose effectiveness and sensitivity and for this reason they must be disposed of and replaced with new discs in perfect condition”.

It was the Calcium, an ion present in large numbers in biological processes that allowed the understanding of this mechanism. Its concentration in the OS is an excellent indicator of the functionality and integrity of phototransduction, the process with which the photoreceptors convert light into nerve signals. “With new optical probes we measured the concentration and the distribution of calcium in the OS. Using advanced optical microscopy instruments, we were able to study the distribution of this metal with unprecedented resolution and accuracy.” Dan Cojoc of Cnr-Iom explains “what has emerged from the analyses is that there is greater concentration of calcium at the base of the outer segment with respect to the tip, which helps to understand the structure of the rod showing its non-homogeneity, as was thought until now.

A second and no less important result is the discovery of spontaneous calcium flares, i.e. rapid increases in calcium. These flares are not evenly distributed but located in the tips of the OS, which shows the existence of a functional gradient along the OS, a fundamental property for photoreceptor transduction of all vertebrates.” Cojoc concludes. Like a warning light, the Calcium flares indicate that the discs start to stop working at their best and need turnover. The article was also recommended to Faculty Opinions by the editor of PNAS -something reserved only for the most important contributions – for the following reasons: “This interesting article uses a new Calcium measurement method to show that light-dependent changes of Calcium in the outer segment of the rods are greater at the base than at the tip”.

Neuroscientist Gordon Fain of the University of California continues, “These differences can reflect an energy gradient that originates from the mitochondria of the inner segment. The authors of the study also make the amazing observation that Calcium increases spontaneously both at the tip and at the base (but more often at the tip), as well as more rarely in the inner segment. These increases produce sudden flares, i.e. peaks of Calcium concentration, which decrease slowly for several seconds and which remain local without propagating inside the outer segment or between the inner and outer segment.”

References: Yunzhen Li, Fabio Falleroni, Simone Mortal, Ulisse Bocchero, Dan Cojoc, Vincent Torre, “Calcium flares and compartmentalization in rod photoreceptors”, Proceedings of the National Academy of Sciences Sep 2020, 117 (35) 21701-21710; DOI: 10.1073/pnas.2004909117 link: https://www.pnas.org/content/117/35/21701/tab-article-info

Provided by SISSA

Protective Shield: Membrane-attached Protein Protects Bacteria & Chloroplasts From Stress (Chemistry)

IM30 loses its complex ring structure under stress conditions and forms a protective carpet on the membrane surface / Surface structure observed for the first time.

Stress is present everywhere, even bacteria and plant cells have to cope with it. They express various specific stress proteins, but how exactly this line of defense works is often not clear. A group of scientists headed by Professor Dirk Schneider of Johannes Gutenberg University Mainz (JGU) has now discovered a protective mechanism in cyanobacteria as well as in chloroplasts of plant cells: Complex ring structures formed by a protein attach to cell membranes and dissociate. Thereafter, the individual proteins spread out on the membrane surface and form a carpet structure. “Via formation of such a shield, bacteria and chloroplasts protect their membranes under certain stress conditions,” stated Professor Dirk Schneider, head of the Membrane Biochemistry section at the JGU Department of Chemistry.

Multiple IM30 proteins form large, oligomeric ring structures. IM30 rings bind to stressed membrane surfaces, disassemble, and individual proteins partially unfold. Multiple IM30 proteins form a protective carpet structure on the membrane surface. ©: Dirk Schneider and Benedikt Junglas, JGU.

The biochemist and his team have examined the protein IM30, i.e., the inner membrane-associated protein having a mass of approximately 30 kilodaltons. Previous studies have already shown that the IM30 protein is involved in the formation and preservation of membranes in photosynthetic cells. Without IM30, the amount of thylakoid membranes, in which the photosynthetic light reaction occurs, decreases, ultimately resulting in cell death. The hitherto unknown molecular mechanism of membrane stabilization has now been observed and revealed in detail. The results of this collaborative research project have recently been published in the Nature journal Communications Biology.

Atomic Force Microscopy (AFM) reveals ring disassembly and carpet formation

“For quite some time now, we were well aware that IM30 is somehow related to stress. However, we did not know how exactly these proteins manage to protect the cells on a molecular level”, explained Schneider. Employing biochemical and biophysical methods in cooperation especially with Professor Stefan Weber of the Max Planck Institute of Polymer Research in Mainz and Professor Eva Wolf of the Institute of Molecular Biology (IMB), the mystery was finally solved. Using atomic force microscopy, the scientists were able to observe how the ring structures disassemble and form carpets on membrane surfaces. “For the very first time we were able to visualize the neat IM30 structure on the surface of membranes,” said Schneider.

Intrinsically disordered proteins have important functions

IM30 belongs to the group of intrinsically disordered proteins, which have shifted into the focus of science in recent years. When IM30 binds to the membrane, it unfolds in half – which makes it particularly complicated to study. The traditional understanding of proteins has been based on the assumption that their function is associated with its structure and that disordered structures more or less take over no function. “It is now becoming increasingly clear that disordered protein regions can be involved in defined interactions”, stated Schneider as to the classification of the results in a large-scale context.

The study defines the thus far enigmatic structural basis for the physiological function of IM30 and related proteins, including the phage shock protein A (PspA), the main representative of the protein family to which IM30 belongs. It also “highlights a hitherto unrecognized concept of membrane stabilization by intrinsically disordered proteins,” stated the authors in the Communications Biology paper. In fact, self-organization of proteins on membrane surfaces, resulting in membrane-covering protein structures, has already been observed before, for example in Alzheimer’s or Parkinson’s disease. In these cases, however, the result is membrane destabilization. In contrast, the protective protein carpet formed by IM30 results in membrane stabilization.

“Our discovery now answers the long-standing question as to how exactly the protein protects the membrane. This, however, raises new questions, for example how the individual proteins exactly interact on the membrane surface and form the carpet,” said Schneider about the research now planned.

References: Junglas, B., Orru, R., Axt, A. et al. IM30 IDPs form a membrane-protective carpet upon super-complex disassembly. Commun Biol 3, 595 (2020). https://doi.org/10.1038/s42003-020-01314-4 link: http://dx.doi.org/10.1038/s42003-020-01314-4

Provided by Johannes Gutenberg University Mainz (MPGC)

Fish Exposed To Even Small Amounts Of Estrogen Produce Fewer Males (Biology)

Water tainted with even a small concentration of human hormones can have profound effects on fish, according to a University of Cincinnati biologist.

UC is using least killifish as a model organism to study the effects of hormones in drinking water. They are among the smallest vertebrates on Earth. ©Andrew Higley/UC Creative.

UC assistant professor Latonya Jackson conducted experiments with North American freshwater fish called least killifish. She found that fish exposed to estrogen in concentrations of 5 nanograms per liter in controlled lab conditions had fewer males and produced fewer offspring.

Scientists have found estrogen at as much as 16 times that concentration in streams adjacent to sewage treatment plants.

The study suggests that even this small dose of estrogen could have significant consequences for wild fish populations living downstream from sewage treatment plants.

The study was published this week in the journal Aquatic Toxicology.

What’s special about least killifish is they have a placenta and give birth to live young, Jackson said. It’s uncommon among fish, who more typically lay eggs.

Jackson studied a synthetic estrogen called 17α-ethinylestradiol, an active ingredient in oral contraceptives also used in hormone replacement therapy. Estrogen been found in streams adjacent to sewage treatment plants in concentrations of as high as 60 nanograms or more per liter.

“Anything you flush down the toilet or put in the sink will get in the water supply,” she said.

This includes not only medicine people flush (never do that) but also unmetabolized chemicals that get flushed when people use the bathroom.

“Our wastewater treatment systems are good at removing a lot of things, but they weren’t designed to remove pharmaceuticals,” Jackson said. “So when women on birth control or hormone therapy go to the bathroom, it gets flushed into wastewater treatment plants.”

Chronic exposure of fish to estrogen led to smaller populations and a gender ratio imbalance with more females than males.

Now Jackson wants to know how the exposure to hormones such as estrogen and androgen in a female fish affects her offspring. She is collaborating with the U.S. Environmental Protection Agency to examine local waters in southwestern Ohio.

Jackson said the impacts on streams are not limited to fish. Hormones and other chemicals that are not removed during treatment can bioaccumulate in the food chain or end up in our drinking water.

“Our drinking water is not a renewable resource. When we run out of clean drinking water, it’s gone,” Jackson said. “It’s very important that we keep this resource clean.”

References: Latonya Jackson, Paul Klerks, “Effects of the Synthetic Estrogen 17α-ethinylestradiol on Heterandria Formosa Populations: Does matrotrophy circumvent population collapse?”, Aquatic Toxicology, 2020, 105659, ISSN 0166-445X,
https://doi.org/10.1016/j.aquatox.2020.105659.
(http://www.sciencedirect.com/science/article/pii/S0166445X20304094)

Provided by University Of Cincinnati

Bone Density Is Associated With Regular Use, Study Finds (Biology)

Researchers at the University of Illinois Urbana-Champaign have studied a population of women in rural Poland for the past four years to understand how their lifestyle affects their bone density. The age group and lifestyle of these women are often overlooked in such studies.

The study “Bone density and frame size in adult women: effects of body size, habitual use, and life history” was published in the American Journal of Human Biology.

“My work focuses on understanding how our activities shape our skeleton and what it means for the modern population,” said Katharine Lee, a recent graduate of the Clancy group, which is affiliated with the Beckman Institute for Advanced Science and Technology.

The study focused on a population of farmers whose lifestyles involve substantial farm and domestic labor, such as growing fruits and vegetables, churning butter, beating rugs, washing windows, and caring for children. “We made some basic body measurements and looked at the physical activity patterns of these women,” Lee said. “We also used a bone sonometer, which was provided through Beckman’s Biomedical Imaging Center. It is a portable device that can be conveniently used to carry out bone density measurements.”

Previous studies in the field have looked at bone density measurements in menopausal women. The researchers wanted to focus on women between the ages of 18 and 46, an age group that is not often looked at in bone density studies. “We wondered why there was so little research on premenopausal women, since presumably their bone density and activity predicts postmenopausal osteoporosis,” said Kathryn Clancy, an associate professor of anthropology at Illinois and a part-time Beckman faculty member.

“We saw that measures such as grip strength and lean mass are associated with the bone density and frame size of these premenopausal women. We also saw that the bone density of the radius, which is the bone at the base of your thumb, is very high compared to an average white woman of European descent,” Lee said. “Interestingly, we don’t see this increased bone density in Polish American women. We don’t fully understand what factors are causing it.”

The researchers believe that this study sheds light on the specific contexts of this lifestyle. “A lot of these measures have looked at large populations and averaged, so they have missed many of these details,” Lee said. “It is also important to think about which populations are not represented in the literature and look at lifestyles that are different to the modern, sedentary lifestyle that most people in the U.S. have.”

Moving forward, the researchers are interested in understanding whether the childhood environment has helped shape the bone health of the women. “We have interviewed them about the different types of work they did when they were growing up. We asked whether they grew up on a farm, whether they had farm animals, or whether they tended a garden. Those activities, rather than the ones they are doing now, might be associated with the bone health measures,” Lee said.

References: Lee, KMN, Rogers‐LaVanne, MP, Galbarczyk, A, Jasienska, G, Clancy, KBH. Bone density and frame size in adult women: Effects of body size, habitual use, and life history. Am J Hum Biol. 2020;e23502. https://doi.org/10.1002/ajhb.23502 https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajhb.23502.

Provided by Beckman Institute

Texas A&M Expert: New Clues Revealed About Clovis People (Archeology)

A study by professor Michael Waters shows that tools made by some of North America’s earliest inhabitants were made only during a 300-year period.

There is much debate surrounding the age of the Clovis — a prehistoric culture named for stone tools found near Clovis, New Mexico in the early 1930s — who once occupied North America during the end of the last Ice Age. New testing of bones and artifacts show that Clovis tools were made only during a brief, 300-year period from 13,050 to 12,750 years ago.

Clovis spear points from the Gault site in Texas. ©Center for the Study of the First Americans, Texas A&M University.

Michael Waters, distinguished professor of anthropology and director of the Center for the Study of the First Americans, along with Texas A&M anthropologist David Carlson and Thomas Stafford of Stafford Research in Colorado, have had their new work published in the current issue of Science Advances.

The team used the radiocarbon method to date bone, charcoal and carbonized plant remains from 10 known Clovis sites in South Dakota, Colorado, Pennsylvania, Ohio, Virginia, Montana and two sites in Oklahoma and Wyoming. An analysis of the dates showed that people made and used the iconic Clovis spear-point and other distinctive tools for only 300 years.

“We still do not know how or why Clovis technology emerged and why it disappeared so quickly,” Waters said.

“It is intriguing to note that Clovis people first appears 300 years before the demise of the last of the megafauna that once roamed North America during a time of great climatic and environmental change,” he said. “The disappearance of Clovis from the archaeological record at 12,750 years ago is coincident with the extinction of mammoth and mastodon, the last of the megafauna. Perhaps Clovis weaponry was developed to hunt the last of these large beasts.”

Waters said that until recently, Clovis was thought to represent the initial group of indigenous people to enter the Americas and that people carrying Clovis weapons and tools spread quickly across the continent and then moved swiftly all the way to the southern tip of South America. However, a short age range for Clovis does not provide sufficient time for people to colonize both North and South America. Furthermore, strong archaeological evidence “amassed over the last few decades shows that people were in the Americas thousands of years before Clovis, but Clovis still remains important because it is so distinctive and widespread across North America,” he said.

Waters said the revised age for Clovis tools reveals that, “Clovis with its distinctive fluted lanceolate spear point, typically found in the Plains and eastern United States, is contemporaneous with stemmed point-making people in the Western United States and the earliest spear points, called Fishtail points, in South America.

“Having an accurate age for Clovis shows that people using different toolkits were well settled into multiple areas of North and South America by 13,000 years ago and had developed their own adaptation to these various environments.”

Waters noted that a new accurate and precise age for Clovis and their tools provides a baseline to try to understand the mystery surrounding the origin and demise of these people.

References: Michael R. Waters, Thomas W. Stafford Jr., and David L. Carlson, “The age of Clovis—13,050 to 12,750 cal yr B.P.”,Science Advances 21 Oct 2020:
Vol. 6, no. 43, eaaz0455 DOI: 10.1126/sciadv.aaz0455 link: https://advances.sciencemag.org/content/6/43/eaaz0455/tab-article-info

Provided by Texas A&M University

Response To Adjuvant Bevacizumab Among Patients With Resected Melanoma May Vary By Age (Medicine / Oncology)

sFRP2, but not VEGF, may promote angiogenesis in older patients with melanoma.

Bottom Line: Younger patients with resected melanoma had some benefit from adjuvant treatment with the anti-VEGF therapeutic bevacizumab (Avastin) while older patients with resected melanoma did not.

Preclinical data showed that VEGF, a protein that promotes angiogenesis and is the target of bevacizumab, decreased with age, and was superseded by the protein sFRP2 in promoting angiogenesis.

Journal in Which the Study was Published: Clinical Cancer Research, a journal of the American Association for Cancer Research

Author: Ashani Weeraratna, PhD, a Bloomberg Distinguished Professor of Cancer Biology and an E.V. McCollum professor and chair in the Department of Biochemistry and Molecular Biology at the Johns Hopkins School of Public Health and professor in the Department of Oncology at Johns Hopkins School of Medicine in Baltimore

Background: “Over the years, it has become increasingly clear that we cannot rely on a one-size-fits-all approach when selecting treatments for patients with cancer,” said Weeraratna. “Our work highlights the fact that younger patients can have very different responses to a given therapy compared with older patients. Understanding that the age of a patient can affect response to treatment is critical to providing the best care for all patients.”

How the Study was Conducted & Results: Weeraratna and colleagues analyzed data from the phase III AVAST-M clinical trial, which evaluated bevacizumab as an adjuvant treatment among 1,343 patients with resected melanoma. Previous studies demonstrated that treatment with bevacizumab resulted in a slight improvement in disease-free survival compared with those who did not receive bevacizumab. However, these prior analyses did not consider age as a variable, Weeraratna noted.

In their post-hoc trial analysis, Weeraratna and colleagues aimed to determine if there was an interaction between age and response to adjuvant bevacizumab. They found that among younger patients with resected melanoma (those under the age of 45), those who received bevacizumab had significantly longer disease-free survival with a 29 percent decreased risk in disease progression compared with those who did not receive bevacizumab. There was also a 25 percent decreased risk in overall mortality, but this finding was not statistically significant. However, among older patients with resected melanoma (those over the age of 45), there was no significant impact of bevacizumab therapy on disease-free survival or overall survival.

Bevacizumab inhibits the protein VEGF, a cytokine that promotes angiogenesis (the development of new blood vessels), which is a process that facilitates tumor growth. To understand how age impacts angiogenesis, Weeraratna and colleagues analyzed whole tumor samples from young and aged melanoma patients. They found that blood vessel density was significantly increased in patients over the age of 65 compared with those under the age of 65, indicating that aging increases angiogenesis among patients with melanoma. However, when the researchers analyzed age-stratified melanoma samples from The Cancer Genome Atlas (TCGA) database, they found that the expression of both VEGF and its associated receptors were significantly decreased among aged patients.

“This finding was really surprising to us, as we assumed that an increase in angiogenesis would correspond with an increase in VEGF expression among aged melanoma patients,” said Weeraratna.

Because the increase in age-related angiogenesis was not accompanied by increased expression of VEGF, and because older patients with melanoma did not appear to benefit from treatment with adjuvant bevacizumab, the researchers hypothesized that other factors were driving angiogenesis in this patient population. Weeraratna and colleagues performed extensive preclinical analyses and found that the proangiogenic factor sFRP2 (for secreted frizzle-related protein 2) superseded VEGF as the predominant angiogenic factor during aging.

“While sFRP2 levels increase in the aged tumor microenvironment, accounting for the increase in angiogenesis, VEGF levels decrease, which explains why anti-VEGF treatment is no longer effective in older patients with melanoma,” said Mitchell Fane, PhD, a postdoctoral fellow in the Weeraratna lab and one of the three lead authors of this study, along with Brett Ecker, MD, and Amanpreet Kaur, PhD.

Author’s Comments: “Our results underscore the importance of considering age in designing preclinical studies, in clinical trial enrollment, and when interpreting trial results,” Weeraratna added.

Study Limitations: Because the AVAST-M trial was not designed to assess the impact of age on the effectiveness of adjuvant bevacizumab and therefore was not adjusted for patient age in the randomization process, these post-hoc data must be interpreted with caution, Weeraratna said. She also noted that much of their preclinical findings have yet to be corroborated in patient samples, representing another limitation of the study.

Funding & Disclosures: This study was sponsored by the National Institutes of Health, a Melanoma Research Alliance/L’Oréal Paris-USA Women in Science Team Science Award, and the Wistar Science Discovery Fund.

Weeraratna declares no conflicts of interest.

References: Mitchell E. Fane, Brett L. Ecker, Amanpreet Kaur, Gloria E. Marino, Gretchen M. Alicea, Stephen M. Douglass, Yash Chhabra, Marie R. Webster, Andrea Marshall, Richard Colling, Olivia Espinosa, Nicholas Coupe, Neera Maroo, Leticia Campo, Mark R. Middleton, Pippa Corrie, Xiaowei Xu, Giorgos C. Karakousis and Ashani T. Weeraratna, “sFRP2 Supersedes VEGF as an Age-related Driver of Angiogenesis in Melanoma, Affecting Response to Anti-VEGF Therapy in Older Patients”, Clin Cancer Res October 23 2020 DOI: 10.1158/1078-0432.CCR-20-0446 link: https://clincancerres.aacrjournals.org/content/early/2020/10/08/1078-0432.CCR-20-0446

Provided by American Association for Cancer Research

Happiness And The Evolution Of Brain Size (Neuroscience)

Serotonin can act as a growth factor for the stem cells in the fetal human brain that determine brain size.

During human evolution, the size of the brain increased, especially in a particular part called the neocortex. The neocortex enables us to speak, dream and think. In search of the causes underlying neocortex expansion, researchers at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, together with colleagues at the University Hospital Carl Gustav Carus Dresden, previously identified a number of molecular players. These players typically act cell-intrinsically in the so-called basal progenitors, the stem cells in the developing neocortex with a pivotal role in its expansion. The researchers now report an additional, novel role of the happiness neurotransmitter serotonin which is known to function in the brain to mediate satisfaction, self-confidence and optimism – to act cell-extrinsically as a growth factor for basal progenitors in the developing human, but not mouse, neocortex. Due to this new function, placenta-derived serotonin likely contributed to the evolutionary expansion of the human neocortex.

The placenta in the soil, which supplies the tree of brain with serotonin, helping the brain to grow. ©Lei Xing et al., Neuron 2020 / MPI-CBG.

The research team of Wieland Huttner at the Max Planck Institute of Molecular Cell Biology and Genetics, who is one of the institute’s founding directors, has investigated the cause of the evolutionary expansion of the human neocortex in many studies. A new study from his lab focuses on the role of the neurotransmitter serotonin in this process. Serotonin is often called the happiness neurotransmitter because it transmits messages between nerve cells that contribute to well-being and happiness. However, a potential role of such neurotransmitters during brain development has not yet been explored in detail. In the developing embryo, the placenta produces serotonin, which then reaches the brain via the blood circulation. This is true for humans as well as mice. Yet, the function of this placenta-derived serotonin in the developing brain has been unknown.

The postdoctoral researcher Lei Xing in the Huttner group had studied neurotransmitters during his doctoral work in Canada. When he started his research project in Dresden after that, he was curious to investigate their role in the developing brain. Lei Xing says: “I exploited datasets generated by the group in the past and found that the serotonin receptor HTR2A was expressed in fetal human, but not embryonic mouse, neocortex. Serotonin needs to bind to this receptor in order to activate downstream signaling. I asked myself if this receptor could be one of the keys to the question of why humans have a bigger brain.” To explore this, the researchers induced the production of the HTR2A receptor in embryonic mouse neocortex. “Indeed, we found that serotonin, by activating this receptor, caused a chain of reactions that resulted in the production of more basal progenitors in the developing brain. More basal progenitors can then increase the production of cortical neurons, which paves the way to a bigger brain”, continues Lei Xing.

Significance for brain development and evolution

“In conclusion, our study uncovers a novel role of serotonin as a growth factor for basal progenitors in highly developed brains, notably human. Our data implicate serotonin in the expansion of the neocortex during development and human evolution”, summarizes Wieland Huttner, who supervised the study. He continues: “Abnormal signaling of serotonin and a disturbed expression or mutation of its receptor HTR2A have been observed in various neurodevelopmental and psychiatric disorders, such as Down syndrome, attention deficit hyperactivity disorder and autism. Our findings may help explain how malfunctions of serotonin and its receptor during fetal brain development can lead to congenital disorders and may suggest novel approaches for therapeutic avenues.”

References: Lei Xing, Nereo Kalebic, Takashi Namba, Samir Vaid, Pauline Wimberger and Wieland B. Huttner “Serotonin receptor 2A activation promotes evolutionarily relevant basal progenitor proliferation in the developing neocortex” Neuron, 19 October 2020. https://www.cell.com/neuron/fulltext/S0896-6273(20)30758-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627320307583%3Fshowall%3Dtrue

Provided by Max Planck Gesellschaft

New Study Details Atmosphere On ‘Hot Neptune’ 260 light years Away That ‘Shouldn’t Exist’ (Planetary Science)

A team led by an astronomer from the University of Kansas has crunched data from NASA’s TESS and Spitzer space telescopes to portray for the first time the atmosphere of a highly unusual kind of exoplanet dubbed a “hot Neptune.”

This artist’s impression shows the LTT9779 system approximately to scale, with the hot Neptune-sized planet at left and its bright, nearby star at right. The trail of material streaming off of the planet is hypothetical but likely, based on the intense irradiation of this planet. ©Ethen Schmidt | University of Kansas.

The findings concerning the recently found planet LTT 9779b were published today in Astrophysical Journal Letters. The paper details the very first spectral atmospheric characterization of any planet discovered by TESS, the first global temperature map of any TESS planet with an atmosphere and a hot Neptune whose emission spectrum is fundamentally different from the many larger “hot Jupiters” previously studied.

“For the first time, we measured the light coming from this planet that shouldn’t exist,” said Ian Crossfield, assistant professor of physics & astronomy at KU and lead author of the paper. “This planet is so intensely irradiated by its star that its temperature is over 3,000 degrees Fahrenheit and its atmosphere could have evaporated entirely. Yet, our Spitzer observations show us its atmosphere via the infrared light the planet emits.”

While LTT 9779b is extraordinary, one thing is certain: People probably wouldn’t like it there very much.

“This planet doesn’t have a solid surface, and it’s much hotter even than Mercury in our solar system — not only would lead melt in the atmosphere of this planet, but so would platinum, chromium and stainless steel,” Crossfield said. “A year on this planet is less than 24 hours — that’s how quickly it’s whipping around its star. It’s a pretty extreme system.”

Hot Neptune LTT 9779b was discovered just last year, becoming one of the first Neptune-sized planets discovered by NASA’s all-sky TESS planet-hunting mission. Crossfield and his co-authors used a technique called “phase curve” analysis to parse the exoplanet’s atmospheric makeup.

“We measure how much infrared light was being emitted by the planet as it rotates 360 degrees on its axis,” he said. “Infrared light tells you the temperature of something and where the hotter and cooler parts of this planet are — on Earth, it’s not hottest at noon; it’s hottest a couple of hours into the afternoon. But on this planet, it’s actually hottest just about at noon. We see most of the infrared light coming from the part of the planet when its star is straight overhead and a lot less from other parts of the planet.”

This artist’s impression shows LTT9779b near the star it orbits, and highlights the planet’s ultra-hot (2000 Kelvin) day-side and its quite-toasty night-side (around 1000 K). ©Ethen Schmidt | University of Kansas.

Readings of the the planet’s temperature is seen as a way to characterize its atmosphere.

“The planet is much cooler than we expected, which suggests that it is reflecting away much of the incident starlight that hits it, presumably due to dayside clouds,” said co-author Nicolas Cowan of the Institute for Research on Exoplanets (iREx) and McGill University in Montreal, who helped in the analysis and interpretation of the thermal phase curve measurements. “The planet also doesn’t transport much heat to its nightside, but we think we understand that: The starlight that is absorbed is likely absorbed high in the atmosphere, from whence the energy is quickly radiated back to space.”

According to Crossfield, the results are just a first step into a new phase of exoplanetary exploration as the study of exoplanet atmospheres steadily moves toward smaller and smaller planets.

“I wouldn’t say we understand everything about this planet now, but we’ve measured enough to know this is going to be a really fruitful object for future study,” he said. “It’s already being targeted for observations with the James Webb Space Telescope, which is NASA’s next big multibillion-dollar flagship space telescope that’s going up in a couple of years. What our measurements so far show us are what we call the spectral absorption features — and its spectrum indicates carbon monoxide and or carbon dioxide in the atmosphere. We’re starting to get a handle on what molecules make up its atmosphere. Because we see this, and because of how this global temperature map looks, it also tells us something about how the winds are circulating energy and material around through the atmosphere of this mini gas planet.”

Crossfield explained the extreme rarity of Neptune-like worlds found close to their host stars, a region typically so devoid of planets astronomers call it the “hot Neptune desert.”

“We think this is because hot Neptunes aren’t massive enough to avoid substantial atmospheric evaporation and mass loss,” he said. “So, most close-in hot exoplanets are either the massive hot Jupiters or rocky planets that have long ago lost most of their atmospheres.”

A companion paper to this research led by Diana Dragomir, University of New Mexico physics and astronomy assistant professor, investigates the expoplanet’s atmospheric composition via secondary eclipse observations with the Spitzer Infrared Array Camera (IRAC) of the hot Neptune.

Although LTT 9779b isn’t suitable for colonization by human beings or any other known life form, Crossfield said evaluating its atmosphere would hone techniques that someday could be used to find more welcoming planets for life.

“If anyone is going to believe what astronomers say about finding signs of life or oxygen on other worlds, we’re going to have to show we can actually do it right on the easy stuff first,” he said. “In that sense these bigger, hotter planets like LTT 9779b act like training wheels and show that we actually know what we’re doing and can get everything right.”

Crossfield said his peek into the atmosphere of such a strange and distant planet also was valuable on its own merits.

“As someone who studies these, there’s just a lot of interesting planetary science we can do in measuring the properties of these planets — just like people study the atmospheres of Jupiter, Saturn and Venus — even though we don’t think those will host life,” he said. “They’re still interesting, and we can learn about how these planets formed and the broader context of planetary systems.”

Crossfield said much work is left to do in order to better understand LTT 9779b and similar hot Neptunes not yet discovered. (A companion paper concerning LTT 9779b’s atmospheric composition via analysis of its secondary eclipse “spectrum” is being published concurrently, which Crossfield co-wrote.)

“We want to continue observing it with other telescopes so that we can answer more questions,” he said. “How is this planet able to retain its atmosphere? How did it form in the first place? Was it initially larger but has lost part of its original atmosphere? If so, then why is its atmosphere not just a scaled-down version of the atmospheres of ultra-hot larger exoplanets? And what else might be lurking in its atmosphere?”

Some of the KU researcher’s co-authors on the paper also plan to continue study of the improbable exoplanet.

“We detected carbon monoxide in its atmosphere and that the permanent dayside is very hot, while very little heat is transported to the night side,” said Björn Benneke of iREx and the Université de Montréal. “Both findings make LTT 9779b say that there is a very strong signal to be observed making the planet a very intriguing target for future detailed characterization with JWST. We’re now also planning much more detailed phase curve observations with NIRISS on JWST.”

Provided by University Of Kansas

Research Team Discovers Molecular Processes In Kidney Cells That Attract And Feed COVID-19 (Medicine)

Although the lungs are a common target for COVID-19’s cytokine storm, so are the kidneys, making the 1 in 4 U.S. adults with diabetes resulting in diabetic kidney disease at increased risk for virus mortality.

©University Of Michigan.

But why are the kidneys so attractive to the coronavirus?

Recently published in Kidney International, a national research team made up of kidney clinicians, bioinformaticians, a molecular biologist, pathologist and virologist found that a protein on the surface of some kidney cells, called angiotensin-converting enzyme 2 (ACE2), is the primary COVID-19 entry receptor and aids in the activation of its uncontrolled immune response.

It also is responsible for the virus’ duplication, leaving patients sicker, longer.

Since higher levels of ACE2 expression on cells correlates with higher risk of serious COVID-19 illness, Matthias Kretzler, M.D., a study author and nephrologist at Michigan Medicine, sought out to learn more about which kidney cells create elevated levels of this protein and why, as well as if the molecular process of the vulnerable cells is similar to those in patients with COVID-19.

Using machine learning technology developed by study author Olga Troyanskaya, Ph.D., from Princeton University, the researchers were able to identify and categorize groups of genes that produced higher ACE2 expression levels in three different subject groups: healthy, living kidney donors (18 participants), those with diabetic kidney disease (44 participants) and those hospitalized with COVID-19 (13 participants.)

After analyzing more than 110,000 different cells in the three groups, Kretzler and the team identified networks of molecules that result in higher levels of ACE2.

“Being able to characterize these molecular processes may help scientists quickly identify and develop therapies to lessen the risk of serious illness for patients, or even prevent COVID-19 infection from damaging the kidney,” Kretzler says.

The groups shared a few molecular similarities, but one would become the focus of the researchers: ACE2 was predominantly expressed in cells that also expressed markers of specialized transport epithelial cells in the proximal tubules.

This area of the kidney is responsible for reabsorbing nutrients during the kidney’s filtration process.

Using machine learning technology

Using kidney biopsies from the healthy kidneys and those with diabetic kidney disease, and kidney cells retrieved from the urine samples of COVID-19 patients, the machine learning technology allowed the research team to pinpoint in what kidney cells ACE2 is found and what characteristics these cells have.

Cells that express the virus receptor, ACE2, were found to be “locked and loaded” for the virus, meaning many other proteins are found with ACE2 which interact with viruses during infection.

This wasn’t only true in the COVID-19 infected patients, but also in kidneys from patients with diabetes. When comparing the kidney cells of COVID-19 patients with those with diabetic kidney disease, similar molecular processes were activated in both that would trigger severe COVID-19 illness.

“Diabetic kidney disease, by nature, primes kidney cells in a way that can make them vulnerable to COVID-19,” Kretzler says. “In conjunction with COVID-19 and its inflammatory nature, serious kidney damage can occur.”

What we know and don’t know

Discovering the importance of the proximal tubules epithelial cells in its relation to the severity of COVID-19 illness opens a door for novel therapeutics to address COVID-19 and its related kidney injury.

“We weren’t sure before this study if medications commonly used to treat hypertension and diabetic kidney disease increase the risk of COVID-19 infection. There was a serious concern from colleagues and my patients about how these medications affect ACE2 in the kidney,” Kretzler says.

Now, the team can confidently conclude these medications won’t harm those with diabetic kidney disease, providing reassurance for patients to continue to take these live saving medicines.

However, further studies need to look at a population that has both diabetic kidney disease and COVID-19. Kretzler confirms these are underway.

“To help in the global research response to COVID-19, we made our data available to scientists around the world so that they can use the information from our patients to help identify novel ways to treat patients in the pandemic,” Kretzler says. “Our team is focused now on learning how treatments given to COVID-19 patients affect kidney cells, so we can offer the best medications to patients with COVID-19 and kidney disease in the ongoing pandemic.”

References: Menon, Rajasree et al., “SARS-CoV-2 receptor networks in diabetic and COVID-19 associated kidney disease”, Kidney International, 2020. DOI:https://doi.org/10.1016/j.kint.2020.09.015 link: https://www.kidney-international.org/article/S0085-2538(20)31113-3/fulltext#main-menu

Provided by University Of Michigan