We Now Know Precise Value Of Total Amount Of Matter In The Universe (Astronomy)

Mohamed H. Abdullah and colleagues precisely measure the total amount of matter in the universe for the first time. They determined that matter makes up 31% of the total amount of matter and energy in the universe, with the remainder consisting of dark energy.

The team determined that matter makes up about 31% of the total amount of matter and energy in the universe. Cosmologists believe about 20% of the total matter is made of regular — or “baryonic” matter — which includes stars, galaxies, atoms, and life, while about 80% is made of dark matter, whose mysterious nature is not yet known but may consist of some as-yet-undiscovered subatomic particle. Credit: Mohamed Abdullah, UC Riverside.

They used galaxy cluster technique for determining the total amount of matter in the universe which is to compare the observed number and mass of galaxy clusters per unit volume with predictions from numerical simulations. Because present-day galaxy clusters have formed from matter that has collapsed over billions of years under its own gravity, the number of clusters observed at the present time is very sensitive to cosmological conditions and, in particular, the total amount of matter.

Like Goldilocks, the team compared the number of galaxy clusters they measured with predictions from numerical simulations to determine which answer was “just right.” Credit: Mohamed Abdullah, UC Riverside.

A higher percentage of matter would result in more clusters. The challenge for their team was to measure the number of clusters and then determine which answer was ‘just right.’ But it is difficult to measure the mass of any galaxy cluster accurately because most of the matter is dark so they can’t see it with telescopes.

To overcome this difficulty, they first developed “GalWeight”, a cosmological tool to measure the mass of a galaxy cluster using the orbits of its member galaxies. The researchers then applied their tool to observations from the Sloan Digital Sky Survey (SDSS) to create “GalWCat19,” a publicly available catalog of galaxy clusters. Finally, they compared the number of clusters in their new catalog with simulations to determine the total amount of matter in the universe.

They have succeeded in making one of the most precise measurements ever made using the galaxy cluster technique. Moreover, this is the first use of the galaxy orbit technique which has obtained a value in agreement with those obtained by teams who used noncluster techniques such as cosmic microwave background anisotropies, baryon acoustic oscillations, Type Ia supernovae, or gravitational lensing.

A huge advantage of using GalWeight galaxy orbit technique was that their team was able to determine a mass for each cluster individually rather than rely on more indirect, statistical methods.

By combining their measurement with those from the other teams that used different techniques, the UCR-led team was able to determine a best combined value, concluding that matter makes up 31.5±1.3% of the total amount of matter and energy in the universe.

References: Mohamed H. Abdullah et al, Cosmological Constraints on Ω m and σ 8 from Cluster Abundances Using the GalWCat19 Optical-spectroscopic SDSS Catalog, The Astrophysical Journal, 901(2), (2020). DOI: 10.3847/1538-4357/aba619 link: https://iopscience.iop.org/article/10.3847/1538-4357/aba619

Study Sheds Light On Abnormal Neural Function In Rare Genetic Disorder (Neuroscience)

Findings show deficits in the electrical activity of cortical cells; possible targets for treatment for 22q11.2 deletion syndrome.

A genetic study has identified neuronal abnormalities in the electrical activity of cortical cells derived from people with a rare genetic disorder called 22q11.2 deletion syndrome. The overexpression of a specific gene and exposure to several antipsychotic drugs helped restore normal cellular functioning. The study, funded by the National Institutes of Health (NIH) and published in Nature Medicine, sheds light on factors that may contribute to the development of mental illnesses in 22q11.2 deletion syndrome and may help identify possible targets for treatment development.

This stylistic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). The chromosome is X-shaped because it is dividing. Introns are regions often found in eukaryote genes that are removed in the splicing process (after the DNA is transcribed into RNA): Only the exons encode the protein. The diagram labels a region of only 55 or so bases as a gene. In reality, most genes are hundreds of times longer. Credit: Thomas Splettstoesser/Wikipedia/CC BY-SA 4.0

22q11.2 deletion syndrome is a genetic disorder caused by the deletion of a piece of genetic material at location q11.2 on chromosome 22. People with 22q11.2 deletion syndrome can experience heart abnormalities, poor immune functioning, abnormal palate development, skeletal differences, and developmental delays. In addition, this deletion confers a 20-30% risk for autism spectrum disorder (ASD) and an up to 30-fold increase in risk for psychosis. 22q11.2 deletion syndrome is the most common genetic copy number variant found in those with ASD, and up to a quarter of people with this genetic syndrome develop a schizophrenia spectrum disorder.

“This is the largest study of its type in terms of the number of patients who donated cells, and it is significant for its focus on a key genetic risk factor for mental illnesses,” said David Panchision, Ph.D., chief of the Developmental Neurobiology Program at the NIH’s National Institute of Mental Health. “Importantly, this study shows consistent, specific patient-control differences in neuronal function and a potential mechanistic target for developing new therapies for treating this disorder.”

While some effects of this genetic syndrome, such as cardiovascular and immune concerns, can be successfully managed, the associated psychiatric effects have been more challenging to address. This is partly because the underlying cellular deficits in the central nervous system that contribute to mental illnesses in this syndrome are not well understood. While recent studies of 22q11.2 deletion syndrome in rodent models have provided some important insights into possible brain circuit-level abnormalities associated with the syndrome, more needs to be understood about the neuronal pathways in humans.

To investigate the neural pathways associated with mental illnesses in those with 22q11.2 deletion syndrome, Sergiu Pasca, M.D.(link is external), associate professor of psychiatry and behavioral sciences at Stanford University, Stanford, California, along with a team of researchers from several other universities and institutes, created induced pluripotent stems cells — cells derived from adult skin cells reprogramed into an immature stem-cell-like state — from 15 people with 22q11.2 deletion and 15 people without the syndrome. The researchers used these cells to create, in a dish, three-dimensional brain organoids that recapitulate key features of the developing human cerebral cortex.

“What is exciting is that these 3D cellular models of the brain self-organize and, if guided to resemble the cerebral cortex, for instance, contain functional glutamatergic neurons of deep and superficial layers and non-reactive astrocytes and can be maintained for years in culture. So, there is a lot of excitement about the potential of these patient-derived models to study neuropsychiatric disease,” said Dr. Pasca.

The researchers analyzed gene expression in the organoids across 100 days of development. They found changes in the expression of genes linked to neuronal excitability in the organoids that were created using cells from individuals with 22q11.2 deletion syndrome. These changes prompted the researchers to take a closer look at the properties associated with electrical signaling and communication in these neurons. One way neurons communicate is electrically, through controlled changes in the positive or negative charge of the cell membrane. This electrical charge is created when ions, such as calcium, move into or out of the cell through small channels in the cell’s membrane. The researchers imaged thousands of cells and recorded the electrical activity of hundreds of neurons derived from individuals with 22q11.2 deletion syndrome and found abnormalities in the way calcium was moved into and out of the cells that were related to a defect in the resting electrical potential of the cell membrane.

A gene called DGCR8 is part of the genetic material deleted in 22q11.2 deletion syndrome, and it has been previously associated with neuronal abnormalities in rodent models of this syndrome. The researchers found that heterozygous loss of this gene was sufficient to induce the changes in excitability they had observed in 22q11.2-derived neurons and that overexpression of DGCR8 led to partial restoration of normal cellular functioning. In addition, treating 22q11.2 deletion syndrome neurons with one of three antipsychotic drugs (raclopride, sulpiride, or olanzapine) restored the observed deficits in resting membrane potential of the neurons within minutes.

“We were surprised to see that loss in control neurons and restoration in patient neurons of the DGCR8 gene can induce and, respectively, restore the excitability, membrane potential, and calcium defects,” said Pasca. “Moving forward, this gene or the downstream microRNA(s) or the ion channel/transporter they regulate may represent novel therapeutic avenues in 22q11.2 deletion syndrome.”

References: Khan, T.A., Revah, O., Gordon, A. et al. Neuronal defects in a human cellular model of 22q11.2 deletion syndrome. Nat Med (2020). https://doi.org/10.1038/s41591-020-1043-9 link: http://www.nature.com/articles/s41591-020-1043-9

Provided by NIH

Fine-Tuning Stem Cell Metabolism Prevents Hair Loss (Medicine)

A team of researchers from Cologne and Helsinki has discovered a mechanism that prevents hair loss: hair follicle stem cells, essential for hair to regrow, can prolong their life by switching their metabolic state in response to low oxygen concentration in the tissue. The team was led by Associate Professor Sara Wickström (University of Helsinki and Max Planck Institute for the Biology of Ageing) and the dermatologist Professor Sabine Eming (University of Cologne), and included researchers from the University of Cologne’s Cluster of Excellence in Aging Research CECAD, the Max Planck Institute for the Biology of Ageing, Collaborative Research Centre 829 ‘Molecular Mechanisms Regulating Skin Homeostasis’, the Center for Molecular Medicine (CMMC) (all in Cologne), and the University of Helsinki. The paper ‘Glutamine Metabolism Controls Stem Cell Fate Reversibility and Long-Term Maintenance in the Hair Follicle’ has been published in Cell Metabolism.

Cross-section of a skin biopsy showing hair follicles extending downwards from the skin surface. Low oxygen around the hair follicle stem cells activates Rictor signaling (phosphorylated Akt; in magenta) locally at this site. Cell nuclei are labeled in blue. Credit: Sara Wickström

Every day, tissues such as the skin and its hair follicles are exposed to environmental damage like ultraviolet radiation. Damaged material is continuously removed and renewed. On average, 500 million cells and 100 hairs are shed every day, amounting to 1.5 gram of material. The dead material is replaced by stem cells, which are specialized, highly proliferative and long-lived. Tissue function relies on the activity and health of these stem cells; compromised function or reduced number leads to aging. ‘Although the critical role of stem cells in aging is established, little is known about the mechanisms that regulate the long-term maintenance of these important cells. The hair follicle with its well understood functions and clearly identifiable stem cells was a perfect model system to study this important question’, said Sara Wickström.

To understand what made stem cells functionally distinct from their differentiated daughter cells, the team investigated the transcriptional and metabolic profiles of the two cell populations. ‘Intriguingly, these studies showed that stem cells and daughter cells have distinct metabolic characteristics’, said Dr. Christine Kim, co-leading scientist of the study. ‘Our analyses further predicted that Rictor, an important but relatively poorly understood molecular component of the metabolic master regulator mTOR pathway, would be involved.’ The mTOR signal transduction regulates processes like growth, energy, and oxygen consumption of cells.

In more detailed analyses, the team showed that stem cell depletion was due to the loss of metabolic flexibility. At the end of each regenerative cycle, during which a new hair is made, the stem cells will return to their specific location and resume a quiescent state. Dr. Xiaolei Ding, the other co-leading scientist, explained: ‘The key finding of this study is that this so called “fate reversibility” requires a shift from glutamine metabolism and cellular respiration to glycolysis. The stem cells reside in an environment with low oxygen availability and thus use glucose rather than glutamine as a carbon source for energy and protein synthesis. This shift is triggered by the low oxygen concentration and Rictor signaling. The removal of Rictor impaired the ability of this stem cell fate reversal, triggering slow, age-dependent exhaustion of the stem cells and age-induced hair loss.’ Ding and Eming had recently generated a genetic mouse model to study Rictor function and observed that mice lacking Rictor had significantly delayed hair follicle regeneration and cycling, which indicated impaired stem cell regulation. ‘Interestingly, with aging these mice showed hair loss and reduction in stem cell numbers’, said Ding.

‘A major future goal will be to understand how these preclinical findings might translate into stem cell biology in humans and potentially could be pharmaceutically harnessed to protect from hair follicle aging’, said Eming. ‘We are particularly excited about the observation that the application of a glutaminase inhibitor was able to restore stem cell function in the Rictor-deficient mice, proving the principle that modifying metabolic pathways could be a powerful way to boost the regenerative capacity of our tissues.’

References: Christine S.Kim, Sara A.Wickström, “Glutamine Metabolism Controls Stem Cell Fate Reversibility and Long-Term Maintenance in the Hair Follicle”, Cell Metabolism, 2020, DOI: 10.1016/j.cmet.2020.08.011


How Genetic Differences In Fat Tissue Shape Men And Women’s Health Risks? (Genetics / Biology)

Sex differences in adipose tissue distribution and function are associated with sex differences in cardiometabolic disease. While many studies have revealed sex differences in adipocyte cell signaling and physiology, there is a relative dearth of information regarding sex differences in transcript abundance and regulation. Now, Warren Anderson and colleagues investigated sex differences in subcutaneous adipose tissue transcriptional regulation using omic-scale data from ∼3000 geographically and ethnically diverse human samples.


They identified 162 genes in fat tissue, which are strongly affected by differences in fat storage and formation in men and women. Further, 13 of the genes come in variants that have different effects in men and women.

They further determined that sex differences in gene expression levels could be related to sex differences in the genetics of gene expression regulation. Their analyses revealed sex-specific genetic associations, and the finding was replicated in a study of 98 inbred mouse strains. The genes under genetic regulation in human and mouse were enriched for oxidative phosphorylation and adipogenesis.

Enrichment analysis showed that the associated genetic loci resided within binding motifs for adipogenic transcription factors (e.g., PPARG and EGR1). They demonstrated that sex differences in gene expression could be influenced by sex differences in genetic regulation for six genes (e.g., FADS1 and MAP1B). These genes exhibited dynamic expression patterns during adipogenesis and robust expression in mature human adipocytes.

Their results support a role for adipogenesis-related genes in subcutaneous adipose tissue sex differences in the genetic and environmental regulation of gene expression. While, their findings help explain the differing health risks men and women face, and they set the stage for better, more targeted treatments.

References: Warren D. Anderson et al. Sex differences in human adipose tissue gene expression and genetic regulation involve adipogenesis, Genome Research (2020). DOI: 10.1101/gr.264614.120 link: http://m.genome.cshlp.org/content/early/2020/09/23/gr.264614.120

How The Brain Balances Emotions And Reasoning? (Neuroscience)

“Area 32” balances activity from cognitive and emotional brain areas in primates

Navigating through life requires balancing emotion and reason, a feat accomplished by the brain region “area 32” of the anterior singulate cortex. The area maintains emotional equilibrium by relaying information between cognitive and emotional brain regions, according to new research in monkeys published in JNeurosci.

Superficial layer neurons from the DLPFC send feedforward projections to the deep layers of A32. A32 sends projections to A25 originating in superficial and deep layers of A32. By predominantly targeting disinhibitory neurons in the superficial layers, pathways from A32 to the superficial layers of A25 may allow excitatory signals to propagate through the local circuitry. By predominantly targeting PV neurons in the deep layers, A32 engages a stronger inhibitory system and likely has a stronger ability to dampen activity in the local circuitry. Credit: Joyce et al., JNeurosci 2020

Emotional balance goes haywire in mood disorders like depression, leading to unchecked negative emotions and an inability to break out of rumination. In fact, people with depression often have an overactive area 25, a region involved in emotional expression. Healthy emotional regulation requires communication between cognitive regions, like the dorsolateral prefrontal cortex (DLPFC), and emotion regions, like area 25, also known as the subgenual cortex. But because these two areas are weakly connected, there must be a middleman involved.

Joyce et al. used bidirectional neuron tracers to visualize the connections between the DLPFC, area 25, and area 32, a potential middleman, in rhesus monkeys. The DLPFC connects to the deepest layers of area 32, where the strongest inhibitory neurons reside. Area 32 connects to every layer of area 25, positioning it as a powerful regulator of area 25 activity. In healthy brains, the DLPFC signals to area 32 to balance area 25 activity, allowing emotional equilibrium. But in depression, silence from the DLPFC results in too much area 25 activity and out-of-control emotional processing.

References: Joyce et al., “Serial Prefrontal Pathways Are Positioned To Balance Cognition and Emotion in Primates”, Journal Of Neuroscience, 2020 doi: http://dx.doi.org/10.1523/JNEUROSCI.0860-20.2020

Provided by Society for Neuroscience

Scientists Kill Cancer Cells By “Shutting The Door” To The Nucleus (Oncology / Medicine)

Scientists at Sanford Burnham Prebys Medical Discovery Institute have shown that blocking the construction of nuclear pores complexes—large channels that control the flow of materials in and out of the cell nucleus—shrank aggressive tumors in mice while leaving healthy cells unharmed. The study, published in Cancer Discovery, a journal of the American Association for Cancer Research, reveals a new Achilles heel for cancer that may lead to better treatments for deadly tumors such as melanoma, leukemia and colorectal cancer.

Melanoma cells create more nuclear pores (green) than normal cells. The scientists showed that blocking the formation of nuclear pores selectively killed cancer cells, revealing a new Achilles heel for cancer that may lead to better treatments for aggressive tumors such as melanoma, leukemia and colorectal cancer. Credit: Sanford Burnham Prebys Medical Discovery Institute

“Nuclear pore complexes are the ‘doors’ that all materials pass through to gain entry to the cell’s nucleus. Because cancer cells are rapidly growing and dividing they need and create more nuclear pore complexes than normal cells,” says Maximiliano D’Angelo, Ph.D., associate professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys. “Our study is the first to demonstrate that by blocking the formation of these nuclear ‘doors’ we can selectively kill cancer cells.”

A promising new way to treat cancer

Because cancer cells are highly dependent on the nuclear transport process—the movement of molecules through nuclear pores—targeting the nuclear transport machinery is a promising strategy for cancer therapies. D’Angelo is hopeful that targeting the formation of nuclear pore complexes, which only impacts dividing cells and thus would likely only kill cancer cells, may offer a safe way to treat many cancer types. However, until now this hypothesis had not yet been tested.

In the study, D’Angelo and his team tested this hypothesis by transplanting human tumor cells that are unable to form nuclear pore complexes into mice. Three different tumor cell types were tested—melanoma, leukemia and colorectal cancer—which are known to be especially reliant on nuclear pore complexes. The scientists found that all of these mice had smaller tumors and slower tumor growth.

“We showed that the inability to build nuclear pore channels is devastating for rapidly-growing cancer cells, but doesn’t seem to have an impact on healthy cells—which simply halt their growth, and then recover,” says Stephen Sakuma, a graduate student in the D’Angelo lab and first author of the study. “Our findings provide an important proof of concept that this approach could lead to a new type of cancer treatment, which might be especially beneficial for aggressive or metastatic cancers that are difficult to treat.”

From discovery to drug

Now that the scientists have demonstrated that their approach works, they are working to find a drug that can block the formation of nuclear pore complexes. This work is ongoing at the Conrad Prebys Center for Chemical Genomics at Sanford Burnham Prebys, one of the most advanced drug discovery centers in the nonprofit world.

“In addition to one day helping people with tough-to-treat cancers, we envision this drug candidate might be used to prevent drug resistance, which happens when tumors adopt properties to resist therapy,” says D’Angelo. “Tumors would have a hard time adopting to an environment where their ‘doors’ are removed, so this drug might help certain treatments, such as targeted therapies, remain effective for longer periods of time.”

Provided by Stanford Burnham Prebys Medical Research Institute

References: Stephen Sakuma, Marcela Raices, Joana Borlido, Valeria Guglielmi, Ethan Y.S. Zhu and Maximiliano A D’Angelo, “Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death”, Cancer Discovery, 2020 DOI: 10.1158/2159-8290.CD-20-0581

First Study With CHEOPS Data Describes One Of The Most Extreme Planets In The Universe (Planetary Science)

Eight months after the space telescope CHEOPS started its journey into space, the first scientific publication using data from CHEOPS has been issued. CHEOPS is the first ESA mission dedicated to characterising known exoplanets. Exoplanets, i.e. planets outside the Solar system, were first found in 1995 by two Swiss astronomers, Michel Mayor and Didier Queloz, who were last year awarded the Nobel Prize for this discovery. CHEOPS was developed as part of a partnership between ESA and Switzerland. Under the leadership of the University of Bern and ESA, a consortium of more than a hundred scientists and engineers from eleven European states was involved in constructing the satellite over five years. The Science Operations Center of CHEOPS is located at the observatory of the University of Geneva.

When a planet passes in front of its star as seen from Earth, the star seems fainter for a short time. This phenomenon is called a transit. When the planet passes behind the star, the light emitted and/or reflected by the planet is obscured by the star for a short time. This phenomenon is called occultation. ©ESA

Using data from CHEOPS, scientists have recently carried out a detailed study of the exoplanet WASP-189b. The results have just been accepted for publication in the journal Astronomy & Astrophysics. Willy Benz, professor of astrophysics at the University of Bern and head of the CHEOPS consortium, was delighted about the findings: “These observations demonstrate that CHEOPS fully meets the high expectations regarding its performance.”

One of the most extreme planets in the universe

WASP-189b, the target of the CHEOPS observations, is an exoplanet orbiting the star HD 133112, one of the hottest stars known to have a planetary system. “The WASP-189 system is 322 light years away and located in the constellation Libra (the weighing scales),” explains Monika Lendl, lead author of the study from the University of Geneva, and member of the National Centre of Competence in Research PlanetS.

“WASP-189b is especially interesting because it is a gas giant that orbits very close to its host star. It takes less than 3 days for it to circle its star, and it is 20 times closer to it than Earth is to the Sun,” Monika Lendl describes the planet, which is more than one and a half times as large as Jupiter, the largest planet of the Solar system.

Monika Lendl further explains that planetary objects like WASP-189b are very exotic: “They have a permanent day side, which is always exposed to the light of the star, and, accordingly, a permanent night side.” This means that its climate is completely different from that of the gas giants Jupiter and Saturn in our solar system. “Based on the observations using CHEOPS, we estimate the temperature of WASP-189b to be 3,200 degrees Celsius. Planets like WASP-189b are called “ultra-hot Jupiters”. Iron melts at such a high temperature, and even becomes gaseous. This object is one of the most extreme planets we know so far,” says Lendl.

Highly precise brightness measurements

“We cannot see the planet itself as it is too far away and too close to its host star, so we have to rely on indirect methods,” explains Lendl. For this, CHEOPS uses highly precise brightness measurements: When a planet passes in front of its star as seen from Earth, the star seems fainter for a short time. This phenomenon is called a transit. Monika Lendl explains: “Because the exoplanet WASP-189b is so close to its star, its dayside is so bright that we can even measure the ‘missing’ light when the planet passes behind its star; this is called an occultation. We have observed several such occultations of WASP-189b with CHEOPS,” says Lendl. “It appears that the planet does not reflect a lot of starlight. Instead, most of the starlight gets absorbed by the planet, heating it up and making it shine.” The researchers believe that the planet is not very reflective because there are no clouds present on its dayside: “This is not surprising, as theoretical models tell us that clouds cannot form at such high temperatures.”

And the star is special too

“We also found that the transit of the gas giant in front of its star is asymmetrical. This happens when the star possesses brighter and darker zones on its surface,” adds Willy Benz. “Thanks to CHEOPS data, we can conclude that the star itself rotates so quickly that its shape is no longer spherical; but ellipsoidal. The star is being pulled outwards at its equator.” continues Benz.

The star around which WASP-189b orbits is very different from the sun. Monika Lendl says: “The star is considerably larger and more than two thousand degrees Celsius hotter than our sun. Because it is so hot, the star appears blue and not yellow-white like the sun.” Willy Benz adds: “Only a handful of planets are known to orbit such hot stars, and this system is the brightest by far.” As a consequence, it forms a benchmark for further studies.

In conclusion, Willy Benz explains: “We are expecting further spectacular findings on exoplanets thanks to observations with CHEOPS. The next papers are already in preparation.”

Provided by University of Bern.

References: M. Lendl, Sz. Csizmadia, A. Deline, L. Fossati, D. Kitzmann, K. Heng, S. Hoyer, S. Salmon, W. Benz, C. Broeg. The hot dayside and asymmetric transit of WASP-189 b seen by CHEOPS. Astronomy & Astrophysics, 2020; DOI: 10.1051/0004-6361/202038677 link: https://www.aanda.org/component/article?access=doi&doi=10.1051/0004-6361/202038677

Lipids, Lysosomes, And Autophagy Are The Keys To Preventing Kidney Injury (Biology)

A team of researchers led by Osaka University unravel a tangle of pathways involving calcium, lipids, and the degradation of damaged lysosomes that is essential for preventing crystal-induced kidney injury.

TFEB is localized to the nucleus upon lysosomal damage in WT cells, while ATG7 KO cells, in which LC3 lipidation is defective, show impaired TFEB nuclear localization. Credit: Osaka University

Human cells need to work like well-oiled machines to keep our bodies running as they should. Waste products such as misfolded proteins, damaged cellular components, and carbohydrates get in the way and must be quickly disposed of. Dealing with this cellular “trash” are spherical, membrane-bound organelles called lysosomes filled with a mixture of potent enzymes. In a process called autophagy, waste products are contained within a double-membraned vesicle, called an autophagosome, that fuses with a lysosome. The lysosomal enzymes then get to work breaking down the waste into components that can be recycled.

The problem with lysosomes is that if they are ruptured, their contents can leak out and cause serious damage to the cell. Calcium oxalate crystal-induced kidney injury, which is linked to the progression of chronic kidney disease, is actually the result of lysosomal damage caused by the crystals. It is not surprising then that cells have several pathways to repair or quickly eliminate damaged lysosomes. Yet the exact steps in these pathways and how they interact during the lysosomal damage response are not entirely clear.

In a study published in Nature Cell Biology, a team of researchers led by Osaka University have finally unraveled the interactions among the lysosomal damage response pathways and determined how they prevent oxalate-induced kidney injury.

“A protein called TFEB turns on genes necessary for autophagy and the production of new lysosomes in response to lysosomal damage,” explains lead author Shuhei Nakamura. “By inhibiting TFEB function in HeLa cells and then inducing lysosome damage, we confirmed that TFEB is activated upon lysosomal damage and is necessary for the removal of damaged lysosomes.”

In the crystal nephropathy mouse model, TFEB-deficient mice showed increased severity of kidney injury and lysosomal damage compared with control mice. Credit: Osaka University

Attachment of lipids to a protein called LC3 is an essential step in the formation of the autophagosome. To their surprise, the researchers also found that lipidated LC3 was necessary for the activation of TFEB during the lysosomal damage response, but there was no clear link between the systems.

“Calcium is a known activator of TFEB,” says senior author Tamotsu Yoshimori. “To identify how the TFEB and LC3 systems overlapped, we investigated lysosomal calcium channel TRPML1. We found that lipidated LC3 was recruited by lysosomes in response to damage, and that the lipidated protein interacted with TRPML1, causing increased calcium efflux from the lysosome, which activated TFEB.”

The physiological importance of this interaction was then confirmed using a mouse model of oxalate crystal-induced kidney damage. Mice lacking TFEB had more severe kidney damage compared with control animals. Understanding how these pathways interact is the first step in preventing lysosomal damage-associated diseases.

This article is provided by Osaka University..

References: Nakamura, S., Shigeyama, S., Minami, S. et al. LC3 lipidation is essential for TFEB activation during the lysosomal damage response to kidney injury. Nat Cell Biol (2020). https://doi.org/10.1038/s41556-020-00583-9 link: http://www.nature.com/articles/s41556-020-00583-9

Many-Body Dephasing Is The Main Culprit Behind Quasiparticles Death (Quantum)

Quasiparticle, in physics, a disturbance, in a medium, are a group of particles, that may conveniently be regarded as one. Understanding the properties of quasiparticles may be key to comprehending, and eventually controlling, technologically important quantum effects like superconductivity and superfluidity. But, they live for a very short time and another thing is, they are only useful while they are alive. Now, Haydn S. Adlong and colleagues in their study investigated why do quasiparticle decay into lower energy states and they identified a main culprit behind: “many-body dephasing”.

Over time, many-body dephasing kills the quasiparticle’s resemblance to a single particle. Credit: FLEET

Many-body dephasing is the disordering of the constituent particles in the quasiparticle that occurs naturally over time.

As the disorder increases, the quasiparticle’s resemblance to a single particle fades. Eventually, the inescapable effect of many-body dephasing kills the quasiparticle.

Far from a negligible effect, the authors demonstrate that many-body dephasing can even dominate over other forms of quasiparticle death.

This is shown through investigations of a particularly ‘clean’ quasiparticle—an impurity in an ultracold atomic gas—where the authors find strong evidence of many-body dephasing in past experimental results.

Two spin states (red and green) of an impurity embedded in a Fermi sea (blue) are coupled together and undergo Rabi oscillations with an effective frequency ? and damping rate ΓR. The damping rate is dominated by many-body dephasing. Credit: FLEET

The authors focus on the case where the ultracold atomic gas is a Fermi sea. An impurity in a Fermi sea gives rise to a quasiparticle known as the repulsive Fermi polaron.

The repulsive Fermi polaron is a highly complicated quasiparticle and has a history of eluding both experimental and theoretical studies.

Through extensive simulations and new theory, the authors show that an established experimental protocol—Rabi oscillations between impurity spin states—exhibits the effects of many-body dephasing in the repulsive Fermi polaron.

These previously unrecognized results provide strong evidence that many-body dephasing is fundamental to the nature of quasiparticles.

References: Haydn S. Adlong et al, Quasiparticle Lifetime of the Repulsive Fermi Polaron, Physical Review Letters (2020). DOI: 10.1103/PhysRevLett.125.133401 link: https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.125.133401