“Scalar Field” Can Explain Expansion of Universe and The Dark Matter (Astronomy / Cosmology)

Bennai and colleagues proposed a new unified model that describes dark energy and dark matter in the context of f(R, φ) gravity using a massive scalar field in five dimensions.

Expansion of Universe © gettyimages

Recently, various models of modified gravity have been proposed in order to solve the problem of dark energy (DE) and dark matter (DM), using a function f(R) which depends essentially on the Ricci scalar “R”. Various models of f(R) modified gravity were proposed, as R² inflation, which can describe the cosmic acceleration of the universe and also inflation, the Brans-Dicke theory, depending on the coupling constant ω, which is a model with a scalar field describing the gravitation, or the 1/R gravity which can explain the acceleration of the Universe’s expansion.

There are several ways to choose the form of the function f(R). Note that, only a few models that can describe dark energy, dark matter or inflation, and conditions for the cosmological viability of dark energy models were introduced. Recall that the modified gravity theories are considered as a perturbation theories around the Ricci scalar in the context of the Jordane frame or depending on a Ricci scalar and a new scalar field φ coupling in the Einstein frame.

On the other hand, there are other more generalized modified gravity depending on a scalar field whose the coupling with the Ricci scalar is described by a certain function f(R, φ). While the other models of f(R)-brane or f(R, φ)-brane, describe modified gravity in the brane world scenario in five-dimensional space-time.

Now, Bennai and colleagues proposed a new unified model that describes dark energy and dark matter in the context of f(R, φ) gravity using a massive scalar field in five dimensions.

“We study the evolution of a scalar fields φ in modified gravity in 5-dimensional braneworld model. We have supposed that dark matter (DM) and dark energy (DE) are only the interactions of the field φ and the 3-brane. For this reason, we described the modified gravity in 4-dimensional by the braneworld models. Recall that, the scalar field density on 3-brane depends on the curvature of space-time.”, said Bousder.

They have studied the evolution of the scalar field φ on the 3-brane and in the bulk, through a passage that transforms all parameters of 4-dimensional model to 5-dimensional one. The 5-dimensional theory depends on the field φ. They have shown that the description of dark energy, dark matter and ordinary matter is obtained by the evolution equation of the scalar field φ. They found a relation between the density of dark matter (DM) and the speed of the universe’s expansion and showed that expansion speed on the 3-brane depends on the expansion speed of bulk.

They also note that the mass of field φ creates dark matter, which changes over time. This is called chameleonic dark matter. On the other hand, they have shown that, the kinetic energy of scalar field, is responsible for the bulk’s expansion, which means that, the bulk generates an the accelerating expansion of the Universe. The decrease of the scalar field mass with the acceleration of Universe expansion, showed that the mass of the field φ is transformed to an energy (dark energy).

“We showed that the field φ describes both the accelerating expansion of the Universe and the dark matter. However, for the some reasons, we have shown that the bulk is also expanding. Thus, the expansion of the Universe depends on bulk expansion. The dark energy is then defined as the variation of a large values of the scalar field φ and the dark matter is described as a minimal values of the field φ.”, said Bennai.

References: M. Bousder, Z. Sakhi, M. Benna, “A new unified model of dark matter and dark energy in 5-dimensional f(R, φ) gravity”, International Journal of Geometric Methods in Modern Physics, Vol. 17, No. 13, 2050183 (2020). https://www.worldscientific.com/doi/10.1142/S0219887820501832 https://doi.org/10.1142/S0219887820501832

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New Research Highlights The Importance Of The Thymus in Successful Pregnancies (Medicine)

How the immune system adapts to pregnancies has puzzled scientists for decades. Now, findings from an international group of researchers, led by experts at Karolinska Institutet in Sweden, reveal important changes that occur in the thymus to prevent miscarriages and gestational diabetes. The study was published today (23 December 2020) in Nature.

Researchers found that during pregnancy, the female sex hormones instruct the thymus to produce Tregs specialised in dealing with physiological changes during pregnancy. © University of Birmigham

The thymus is a central organ of the immune system where specialised immune cells called T lymphocytes mature. These cells, commonly referred to as T cells, then migrate into the blood stream and tissues to help combat pathogens and cancer. An important T cell subset, known as a regulatory T cell or Treg, is also produced in the thymus. The main function of a Treg is to help regulate other immune cells.

Researchers found that during pregnancy, the female sex hormones instruct the thymus to produce Tregs specialised in dealing with physiological changes during pregnancy. The study—which involved researchers at Karolinska Institutet, the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) in Vienna, University of British Columbia in Vancouver, further reveals that RANK, a receptor expressed in the thymus epithelia, is the key molecule behind this mechanism.

The study builds on work by a team at the University of Birmingham as researcher and collaborator Professor Graham Anderson from the Institute of Immunology and Immunotherapy explains: “In 2007, our lab provided the first evidence that RANK plays a critical role in controlling thymus function in the steady state immune system. Now, this new research shows how RANK in the thymus regulates the immune system in pregnancy, which is an exciting new direction.”

“We knew RANK was expressed in the thymus, but its role in pregnancy was unknown”, says first and co-corresponding author Dr. Magdalena Paolino, assistant professor at the Department of Medicine, Solna, Karolinska Institutet.

To get a better understanding, the authors studied mice where RANK had been deleted from the thymus.

“The absence of RANK prevented the production of Tregs in the thymus during pregnancy. This resulted in less Tregs in the placentas, leading to miscarriages,” continues Magdalena Paolino.

This latest study further shows that in normal pregnancies, the produced Tregs also migrate to the mother’s fat tissue to prevent inflammation and help control glucose levels in the body. Pregnant mice lacking RANK had high levels of glucose and insulin in their blood and many other indicators of gestational diabetes, including fetal macrosomia.

“Similar to babies of women with gestational diabetes, the newborn pups were much heavier than average,” explains Magdalena Paolino.

In addition, the deficiency of Tregs during pregnancy was proven to result in long-lasting transgenerational effects on the offspring, which remained prone to diabetes and overweight throughout their life spans. Giving the RANK deficient mice thymus-derived Tregs that had been isolated from normal pregnancies, reversed all issues including fetal loss and maternal glucose levels and the body weights of the pups.

The researchers also analysed women with gestational diabetes, revealing a reduced number of Tregs in their placentas, much similar to the study on mice.

“This research changes our view of the thymus, as an active and dynamic organ required to safeguard pregnancies,” Magdalena Paolino says. “It also provides new molecular insight for gestational diabetes, a disease that affects many women and which we still know little about. It emphasises the importance of clinics detecting and managing glucose metabolism in pregnant women to avert its long-term effects.”

Co-corresponding author Dr. Josef Penninger notes that how rewiring of the thymus contributes to a healthy pregnancy was one of the remaining mysteries of immunology – until now.

“Our work over many years has now not only solved this puzzle – pregnancy hormones rewire the thymus via RANK – but uncovered a new paradigmatic function: the thymus not only changes the immune system of the mother to allow the fetus, but it also controls metabolic health of the mother,” Josef Penninger says.

The study was possible thanks to a close collaboration between the laboratory of Magdalena Paolino at Karolinska Institutet and the laboratories of Josef Penninger at IMBA and UBC. Researchers from the CeMM Institute and the Medical University of Vienna, as well as from the Universities of Birmingham and Oxford also participated.

Full paper: “RANK links thymic Tregs to fetal loss and gestational diabetes in pregnancy”, Magdalena Paolino*, Rubina Koglgruber, Shane J. F. Cronin, Iris Uribesalgo, Esther Rauscher, Juergen Harreiter, Michael Schuster, Dagmar Bancher-Todesca, Blanka Pranjic, Maria Novatchkova, Andrea White, Verena Sigl, Sabine Dekan, Juan P. Fededa, Thomas Penz, Christoph Bock, Lukas Kenner, Georg A. Holländer, Graham Anderson, Alexandra Kautzky-Willer, and Josef M. Penninger*, Nature, in press 23/12/2020 DOI: 10.1038/s41586-020-03071-0. 

Provided by University of Birmingham

Study Reveals “Seeds of Skin Cancer” – Gene Mutations Associated with Early Stages of Skin Cancer (Medicine)

Penn experts identify specific mutations and biomarkers associated with squamous cell carcinoma and other skin cancers.

Specific DNA mutations are correlated with the beginnings of squamous cell carcinoma (SCC) and other cancers, according to researchers in the Perelman School of Medicine at the University of Pennsylvania. After using an innovative approach to analyze skin samples and compare them to healthy skin on the same individuals, the team sequenced DNA and found mutations in NOTCH 1-3 – signaling pathways at the cellular level. The researchers also found no cancer-causing mutations in RAS genes, mutations which are common in other forms of cancer and in more progressed SCC, suggesting it’s not a factor in the early development of SCC. The research may illuminate potential ways clinicians can prevent and treat SCC and other skin cancers. The findings were published in the Journal of Investigative Dermatology.

©WebMD

For decades, medical experts have known that UV radiation causes mutations in skin cells that lead to cancers including SCC, which are known to contain more cell mutations than almost all other forms of cancer. Nevertheless, many mutations that have been identified in SCCs are “passenger” mutations, meaning that, while they are present, they don’t appear to cause the cancer. This situation makes it difficult to identify which mutations present in SCCs are important for driving the early stages of UV-induced skin cancer called squamous cell carcinoma in situ (SCCIS).

To identify the mutations associated with SCCIS, a team researchers led by John T. Seykora, MD, PhD, a professor of Dermatology at Penn, analyzed samples using laser-capture microdissection, a way to dissect the skin using a microscope and lasers to make the cut. With this equipment, the investigators were able to precisely identify and isolate SCCIS cells and cut them out of the tissue samples to collect them. Concurrently, the investigators also dissected skin cells from adjacent, healthy-looking skin to serve as a control sample. Following sequencing, the investigators saw NOTCH1, NOTCH2, and NOTCH3 cellular pathways had mutations. Those mutations were then followed by mutations of the TP53 gene.

“Our findings suggest that the NOTCH mutations may be like seeds, encouraged to “grow” into cancer by the later mutation of the TP53 gene,” Seykora said.

Another major finding of this study was that cancer-causing mutations in RAS genes are not found in the early stages of SCC development.

“The fact that they’re not found in those initial growth stages suggests that they’re not the culprits and are not responsible for the formation of squamous cell carcinoma,” Seykora said. “That mutation is likely just a byproduct of the other mutations.”

Knowing what precipitates SCC and other skin cancers and what the skin looks like early on at the cellular level is vital to those researching treatments and prevention. Seykora and his colleagues plan to investigate treatments that could either specifically manipulate or specifically block the effects of the mutated cells or that could prevent the cells from mutating in the first place.

The research team included first author Qi Zheng, PhD, a senior bioinformatician in Dermatology and Brian Capell, MD, PhD, an assistant Professor of Dermatology. Additional Penn authors of the study include Vishwa Parekh, Conor O’Day, Cem Attilasoy, Hasan Bashir, Christopher Yeh, Eun-Hee Shim, Stephen Prouty, Tzevete Dentchev, Vivian Lee, Lily Wushanley, Yerin Kweon, Yoko Suzuki-Horiuchi, Warren Pear and Elizabeth Grice.

The work was supported by the National Institutes of Health (R01 CA165836, P30-CA016520, P30 AR06958901, R01 CA163566, RO1 ES013508 and P30CA016520, K08 EY025742).

Provided by Penn Medicine

How Can Fathers Shape Their Daughters’ Body Image? (Psychology)

Study analyzes fathers’ communication with young daughters about their body image.

The holidays are coming up, and when tables become overflowed with plates and bowls of delicious foods, be thoughtful with the way you talk about the food with your children. It can be common for children to feel pressure and insecurities about their bodies, and it turns out, parents can play a large role in children’s perception of their bodies.

Though she is the Director of the Center for Body Image Research at the University of Missouri, even Virginia Ramseyer Winter still often worries if her family is doing everything they can to make sure her daughter has a positive relationship with her body.

“I have a daughter that falls in this age range, between 5 and 10, so certainly it’s something that I’m always navigating at home, and my spouse— her dad— is also navigating,” Ramseyer Winter said. “You know, I work in this field and its still really tricky. How do you talk about food in a way that helps kids develop a healthy relationship with it and prevent eating disorders, and focus on their character as opposed to the way they look?”

While much of the previous research around the role parents take in their children’s body image focuses on the mother, there is little research about fathers’ role. So, in a recent study, Ramseyer Winter, in collaboration with Jaclyn Siegel at Western University and Mackenzie Cook at the University of Missouri, analyzed fathers’ strengths and barriers when it comes to communicating with their young daughters about their body image.

The researchers found through interviews that fathers tend to understand the importance of a healthy self-body image among their children. However, they often felt uncomfortable discussing body image and health with their daughters.

“Unsurprisingly, all of the dads we talked to really are interested in addressing this with their daughters. They know it’s important and they place a lot of value on it,” Ramseyer Winter said. “However, we found that there are some common barriers. They are struggling to have these conversations, and many of them are conflating health with body size.”

The 30 fathers interviewed identified several common barriers when attempting to discuss bodily health with their daughters, including a lack of confidence in uncomfortable conversations, gender differences with their daughters, and a recognition of their daughter’s discomfort with discussing their bodies. The study also found that the fathers noticed that their daughters can take negative statements about their own bodies and positive statements about other people’s body to heart.

There has been little prior research stating that fathers can have a positive impact on their daughter’s self-body image. In this study, researchers found the fathers attempted to have positive impacts by praising their daughters’ skills, strengths and talents instead of their body and accepting the way their daughters choose to present themselves. Ramseyer Winter said that understanding these conversations can help fathers learn what resources may be necessary to prevent some of the issues that can cause negative perceptions of body image at a young age.

“Dads obviously influence their children, so we need to understand what fathers are doing, and what is and isn’t working. There wasn’t much discussion on that topic before this study,” Ramseyer Winter said. “My hope is that this research can help to ultimately develop interventions that are easily accessible for fathers and their children to positively impact body image development. If we can prevent negative body image perceptions early on in children’s life, we can impact health and mental health outcomes long-term.”

Ramseyer Winter also said that if parents are looking for advice on how to help their children grow with a healthy perception of their body, there are currently a few resources they can utilize, including books on intuitive eating and Health at Every Size.

References: Jaclyn A. Siegel, Virginia Ramseyer Winter, Mackenzie Cook, “It really presents a struggle for females, especially my little girl”: Exploring father’s experiences discussing body image with their young daughters”, Body Image, Volume 36, 2021, Pages 84-94, ISSN 1740-1445, https://doi.org/10.1016/j.bodyim.2020.11.001.
http://www.sciencedirect.com/science/article/pii/S1740144520304228

Provided by University of Missouri

Artificial Intelligence Predicts Gestational Diabetes in Chinese women (Medicine)

Machine learning, a form of artificial intelligence, can predict which women are at high risk of developing gestational diabetes and lead to earlier intervention, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Gestational diabetes is a common complication during pregnancy that affects up to 15 percent of pregnant women. High blood sugar in the mother can be dangerous for the baby and lead to complications like stillbirth and premature delivery. Most women are diagnosed with gestational diabetes during the second trimester, but some women are at high risk and could benefit from earlier intervention.

“Our study leveraged artificial intelligence to predict gestational diabetes in the first trimester using electronic health record data from a Chinese hospital,” said study author He-Feng Huang Ph.D. of the Shanghai Jiao Tong University School of Medicine and the International Peace Maternity and Child Health Hospital in Shanghai, China. “These findings can help clinicians identify women at high risk of diabetes in early pregnancy and start interventions such as diet changes sooner. The artificial intelligence technology will continue to improve over time and help us better understand the risk factors for gestational diabetes.”

The researchers analyzed nearly 17,000 electronic health records from a hospital in China in 2017 with machine learning models to predict women at high risk for gestational diabetes. They compared their predictions with 2018 electronic health record data and found they were successful at identifying who would develop gestational diabetes. The prediction models also found an association between low body mass and gestational diabetes.

Other authors of the study include: Yan-Ting Wu, Chen-Jie Zhang, Cheng Li, Yu Wang, Jian-Xia Fan, and Lei Chen of the Shanghai Jiao Tong University School of Medicine and the International Peace Maternity and Child Health Hospital; Ben Willem Mol and Andrew Kawai of Monash University in Melbourne, Australia; Jian-Zhong Sheng of the Zhejiang University in Zhejiang, China; and Yi Shi of the Shanghai Jiao Tong University.

The manuscript received funding from the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Foundation of Shanghai Municipal Commission of Health and Family Planning, the Clinical Skills Improvement Foundation of Shanghai Jiaotong University School of Medicine, the Natural Science Foundation of Shanghai, the Shanghai Shenkang Hospital Development Center, Clinical Technology Innovation Project, the Program of Shanghai Academic Research Leader, the CAMS Innovation Fund for Medical Sciences, and the Outstanding Youth Medical Talents of Shanghai Rising Stars of Medical Talent Youth Development Program.

The manuscript, “Early Prediction of Gestational Diabetes Mellitus in the Chinese Population Via Advanced Machine Learning,” was published online, ahead of print.

Reference: Yan-Ting Wu, PhD, Chen-Jie Zhang, MD, Ben Willem Mol, PhD, Andrew Kawai, Cheng Li, PhD, Lei Chen, Yu Wang, MD, Jian-Zhong Sheng, PhD, Jian-Xia Fan, PhD, Yi Shi, PhD, He-Feng Huang, PhD, Early prediction of gestational diabetes mellitus in the Chinese population via advanced machine learning, The Journal of Clinical Endocrinology & Metabolism, , dgaa899, https://doi.org/10.1210/clinem/dgaa899

Provided by Endocrine Society

Shapeshifting Crystals-varying Stability in Different Forms of Gallium Selenide Monolayers (Material Science)

Researchers investigate the structure and properties of a recently identified polymorph of gallium selenide crystal layer.

The gallium selenide monolayer has been recently discovered to have an alternative crystal structure and has diverse potential applications in electronics. Understanding its properties is crucial to understand its functions. Now, scientists from the Japan Advanced Institute of Science and Technology and the University of Tokyo have explored its structural stability, electronic states, and transformation of crystal phases.

The P and AP phases of a GaSe monolayer © Hirokazu Nitta from Japan Advanced Institute of Science and Technology

Solid materials comprise a symmetric arrangement of atoms that confer properties like conductivity, strength, and durability. Changes in size can change this arrangement, thereby changing the overall properties of the material. For instance, the electrical, chemical, optical and mechanical properties of certain materials can change as we move towards the “nano” scale. Science now lets us study the differences in properties across various dimensions right from monolayer (atomic) level.

Gallium selenide (GaSe) is a “layered metal-chalcogenide,” which is known to have polytypes, which differ in their stacking sequence of layers, but not a polymorph, which has a different atomic arrangement inside the layer. GaSe has sparked a great deal of interest in areas of physical and chemical research, owing to its potential usage in photoconduction, far-infrared conversion, and optical applications. Conventionally, a GaSe monolayer is composed of gallium (Ga) and selenium (Se) atoms bonded covalently, with the Se atoms projecting outwards, forming a trigonal prism-like structure named “P phase.” Part of the same research group had earlier reported a novel crystal phase of GaSe using transmission electron microscopy in Surface and Interface Analysis, wherein the Se atoms are arranged in a trigonal antiprismatic manner to the Ga atoms referred to as “AP phase” with a symmetry different from the conventional P phase (see Picture 1). Because of the novelty of this monolayer structure, very little is known about how it does its “shapeshifting.” Moreover, how do variations in the intralayer structure of such compounds affect stability?

To answer this, Mr. Hirokazu Nitta and Prof. Yukiko Yamada-Takamura from the Japan Advanced Institute of Science and Technology (JAIST) explored the structural stability and electronic states of phases of GaSe monolayer using first-principles calculations, in their latest study in Physical Review B.

Hirokazu Nitta explains their study, stating, “We have found out through first-principles calculations that this new phase is metastable, and stability against the ground-state conventional phase reverses upon applying tensile strain, which we think is strongly related to the fact that we saw this phase formed only at the film-substrate interface.” The published study is also trending as a #PRBTopDownload on the official Physical Review B handle on Twitter: https://twitter.com/PhysRevB/status/1338837972003811331

To compare the structural stability of the P and AP phases of GaSe, the researchers first calculated the total energy at different in-plane lattice constants, which represent the size of a unit cell in the crystal, given that its structure comprises a “lattice” or organized meshwork of atoms. The lowest energy that corresponds to the most stable state was computed and at this state, the P phase was found to be more stable than the AP phase.

Then, to investigate if the AP and P phases can transform into each other, they determined the “energy barriers” that the material needs to cross to change, and additionally performed molecular dynamics calculations using a supercomputer (see Picture 2). They found the energy barrier for phase transition of P-phase and AP-phase GaSe monolayers is large likely due to the need of breaking and making new bonds, which prohibits direct transition from P to AP phase. The calculations also revealed that the relative stability of P-phase and AP-phase GaSe monolayers can be reversed by applying “tensile strain,” or a stretching-type force.

Highlighting the importance and future prospects of their study, Prof. Yamada-Takamura remarks, “Layered chalcogenides are interesting 2D materials after graphene, having wide variety and especially bandgap. We have just found out a new polymorph (not polytype) of a layered monochalcogenide. Its physical as well as chemical properties are yet to be discovered.”

Together, the findings of this study describe the electronic structure of a less-known structure of GaSe that can provide insights into the behavior of similar epitaxially grown monolayers, revealing yet another secret about the unknown family members of GaSe and related monochalcogenides.

Provided by JAIST

Discovery of Aging Mechanism For Hematopoietic Stem Cells (Biology)

Limited rejuvenation of aged hematopoietic stem cells in young bone marrow niche.

By transferring mouse aged hematopoietic stem cells (aged HSCs, *1) to the environment of young mice (bone marrow niche, *2), it was demonstrated that the pattern of stem cell gene expression was rejuvenated to that of young hematopoietic stem cells. On the other hand, the function of aged HSCs did not recover in the young bone marrow niche. The epigenome (DNA methylation, *3) of aged HSCs did not change significantly even in the young bone marrow niche, and DNA methylation profiles were found to be a better index than the gene expression pattern of aged HSCs.

A research group led by Professor Atsushi Iwama at the Division of Stem Cell and Molecular Medicine, The Institute of Medical Science, The University of Tokyo (IMSUT) announced these world-first results and was published in the Journal of Experimental Medicine (online) on November 24th.

“The results will contribute to the development of treatments for age-related blood diseases,” states lead scientist, Professor Iwama at IMSUT.

Focus on changes in aged HSCs in the bone marrow niche

The research group investigated whether rejuvenating aged HSCs in a young bone marrow niche environment would rejuvenate.

Tens of thousands of aged hematopoietic stem/progenitor cells collected from 20-month-old mice were transplanted into 8-week-old young mice without pretreatment such as irradiation. After two months of follow-up, they collected bone marrow cells and performed flow cytometric analysis.

The research team also transplanted 10-week-old young mouse HSCs for comparison. In addition, engrafted aged HSCs were fractionated and RNA sequence analysis and DNA methylation analysis were performed.

They found that engrafted aged HSCs were less capable of producing hematopoietic cells than younger HSCs. They also showed that differentiation of aged HSCs into multipotent progenitor cells was persistently impaired even in the young bone marrow niche and that the direction of differentiation was biased. It was found that the transfer of aged HSCs to the young bone marrow niche does not improve their stem cell function. © Tohoku University

A more detailed analysis may reveal mechanisms that irreversibly affect aged HSC function

Aging studies focusing on HSCs have been actively pursued in mice using a bone marrow transfer model. However, the effect of aging on HSCs remains to be clarified.

Professor Iwama states as follows.“This study has a significant impact because it clarified the effect of aging on HSCs. Our results are expected to contribute to further elucidation of the mechanism of aging in HSCs and understanding of the pathogenic mechanism of age-related blood diseases.”

Research Notes

(*1) Aged hematopoietic stem cells (aged HSCs)
The functions and characteristics of hematopoietic stem cells change with age. The ability to produce blood cells is reduced and differentiation is biased, increasing the risk of developing myeloid tumors.

(*2) Bone marrow niche
The microenvironment in the bone marrow that is essential for maintaining hematopoietic stem cells.

(*3) Epigenome (DNA methylation)
Chemical modification of genomic DNA and histone proteins. The epigenome is acquired and changes according to cell conditions. DNA methylation acts to suppress gene expression (transcription).

Reference: Wakako Kuribayashi, Motohiko Oshima, Naoki Itokawa, Shuhei Koide, Yaeko Nakajima-Takagi, Masayuki Yamashita, Satoshi Yamazaki, Bahityar Rahmutulla, Fumihito Miura, Takashi Ito, Atsushi Kaneda, Atsushi Iwama, “Limited rejuvenation of aged hematopoietic stem cells in young bone marrow niche” Journal of Experimental Medicine. 2020. DOI: 10.1084/jem.20192283
Article URL: https://www.rupress.org/jem/article-lookup/doi/10.1084/jem.20192283

Provided by Institute of Medical Science– the University of Tokyo

Protein Tells Developing Cells to Stick Together (Biology)

Tohoku University scientists have, for the first time, provided experimental evidence that cell stickiness helps them stay sorted within correct compartments during development. How tightly cells clump together, known as cell adhesion, appears to be enabled by a protein better known for its role in the immune system. The findings were detailed in the journal Nature Communications.

Compartments in adult tissues. Fluorescent protein expression shows posterior compartments in the wing and the abdomen. Please notice that boundaries between compartments are amazingly straight. © Tohoku University

Scientists have long observed that not-yet-specialized cells move in a way that ensures that cell groups destined for a specific tissue stay together. In 1964, American biologist Malcolm Steinberg proposed that cells with similar adhesiveness move to come in contact with each other to minimize energy use, producing a thermodynamically stable structure. This is known as the differential adhesion hypothesis.

“Many other theoretical works have emphasized the importance of differences in cell-to-cell adhesion for separating cell populations and maintaining the boundaries between them, but this had not yet been demonstrated in living animal epithelial tissues,” says Erina Kuranaga of Tohoku University’s Laboratory for Histogenetic Dynamics, who led the investigations. “Our study showed, for the first time, that cell sorting is regulated by changes in adhesion.”

Kuranaga and her team conducted experiments in fruit fly pupae, finding that a gene, called Toll-1, played a major role in this adhesion process.

As fruit flies develop from the immature larval stage into the mature adult, epithelial tissue-forming cells, called histoblasts, cluster together into several ‘nests’ in the abdomen. Each nest contains an anterior and a posterior compartment. Histoblasts are destined to replace larval cells to form the adult epidermis, the outermost layer that covers the flies. The cells in each compartment form discrete cell populations, so they need to stick together, with a distinct boundary forming between them.

The anterior and posterior compartments are separated by a straight boundary in normal flies (left) and a distorted one in mutant flies lacking the Toll-1 gene (right). © Tohoku University

Using fluorescent tags, Kuranaga and her team observed the Toll-1 protein is expressed mainly in the posterior compartment. Its fluorescence also showed a sharp boundary between the two compartments.

Further investigations showed Toll-1 performs the function of an adhesion molecule, encouraging similar cells to stick together. This process keeps the boundary between the two compartments straight, correcting distortions that arise as the cells divide to increase the number.

Interestingly, Toll proteins are best known for recognizing invading pathogens, and little is known about their work beyond the immune system. “Our work improves understanding of the non-immune roles of Toll proteins,” says Kuranaga. She and her team next plan to study the function of other Toll genes in fruit fly epithelial cells.

Reference: Norihiro Iijima, Katsuhiko Sato, Erina Kuranaga,and Daiki Umetsu, “Differential cell adhesion implemented by Drosophila Toll corrects local distortions of the anterior-posterior compartment boundary”, Nature Communications, 2020. https://www.nature.com/articles/s41467-020-20118-y

Provided by Tohoku University

Fighting Rhinoviruses Effectively (Medicine)

New pathways for immune response in bronchial asthma.

Autumn marks the high season for rhinoviruses in our latitudes, because they feel most comfortable in cold, wet weather. Rhinoviruses cause cold symptoms that are not dangerous for most people. However, they remain harmful in some cases, for example in children suffering from bronchial asthma. If children with bronchial asthma are infected by a rhinovirus, their state of health can deteriorate considerably. Scientists at Universitätsklinikum Erlangen (UKER) have been working as part of an international team to find a way of preventing this from happening. Their findings have been published in the European Respiratory Journal.

© Bild: Colourbox

Their research investigated processes at the molecular level as certain receptors on the cell surface play a major role in successfully combating the viruses through the body’s own immune system. Prof. Susetta Neurath-Finotto, Professor of Molecular Pneumology and Head of the Department of Molecular Pneumology at UKER, explains: ‘Normally, the immune system eliminates rhinoviruses. However, it needs to be stimulated to an immune response first.’ The immune response is triggered by the signalling protein interferon-alpha, which in turn reaches the cells infected by the virus via corresponding receptors. This process does not work as it should in asthmatic children. Interferon alpha does not pass sufficiently into the cells and the virus spreads further.

However, the receptors for interferon lambda can be activated with the molecule R848 investigated at UKER. The research group has demonstrated this on the basis of in vitro tests with blood cells of children with and without asthma. ‘Treatment with R848 paves the way for interferon lambda to enter the cells, enabling an antiviral immune response,’ says Prof. Neurath-Finotto.

Reference: Jasmin Krug, Alexander Kiefer, Julia Koelle, Tytti Vuorinen, Paraskevi Xepapadaki, Barbara Stanic, Mircea Chiriac, Mübeccel Akdis, Theodor Zimmermann, Nikolaos G. Papadopoulos, Susetta Finotto, “TLR 7/8 regulates Type I and Type III Interferon Signalling in RV1b induced Allergic Asthma”, European Respiratory Journal 2020; DOI: 10.1183/13993003.01562-2020 https://erj.ersjournals.com/content/early/2020/11/11/13993003.01562-2020

Provided by FAU