Daily Archives: 22 Mar 2021

Planetary Science

Trinity Researchers Tackle the Spiders From Mars (Planetary Science)

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Researchers at Trinity College Dublin have been shedding light on the enigmatic “spiders from Mars”, providing the first physical evidence that these unique features on the planet’s surface can be formed by the sublimation of CO2 ice.  

Spiders, more formally referred to as araneiforms, are strange-looking negative topography radial systems of dendritic troughs; patterns that resemble branches of a tree or fork lightning. These features, which are not found on Earth, are believed to be carved into the Martian surface by dry ice changing directly from solid to gas (sublimating) in the spring.  Unlike Earth, Mars’ atmosphere comprises mainly CO2 and as temperatures decrease in winter, this deposits onto the surface as CO2 frost and ice.

The Trinity team, along with colleagues at Durham University and the Open University,  conducted a series of experiments funded by the Irish Research Council and Europlanet at the Open University Mars Simulation Chamber (pictured below), under Martian atmospheric pressure, in order to investigate whether patterns similar to Martian spiders could form by dry ice sublimation.

Its findings are detailed in a paper published today in the Nature Journal Scientific Reports: “The Formation of Araneiforms by Carbon Dioxide Venting and Vigorous Sublimation Dynamics Under Martian Atmospheric Pressure”.

Dr Lauren McKeown drilling holes in the iceblocks for the project © TCD

Dr Lauren McKeown, who led this work during her PhD at Trinity and is now at the Open University, said:  

“This research presents the first set of empirical evidence for a surface process that is thought to modify the polar landscape on Mars. Kieffer’s hypothesis [explained below] has been well-accepted for over a decade, but until now, it has been framed in a purely theoretical context. … The experiments show directly that the spider patterns we observe on Mars from orbit can be carved by the direct conversion of dry ice from solid to gas.  It is exciting because we are beginning to understand more about how the surface of Mars is changing seasonally today.” 

The research team drilled holes in the centres of CO2 ice blocks and suspended them with a claw similar to those found in arcades, above granular beds of different grain sizes. They lowered the pressure inside a vacuum chamber to Martian atmospheric pressure (6mbar) and then used a lever system to place the CO2 ice block on the surface 

They made use of an effect known as the Leidenfrost Effect, whereby if a substance comes in contact with a surface much hotter than its sublimation point, it will form a gaseous layer around itself. When the block reached the sandy surface, CO2 turned directly from solid to gas and material was seen escaping through the central hole in the form of a plume 

In each case, once the block was lifted, a spider pattern had been eroded by the escaping gas. The spider patterns were more branched when finer grain sizes were used and less branched when coarser grain sizes were used.  

This is the first set of empirical evidence for this extant surface process.

Dr Mary Bourke, of Trinity’s Department of Geography, who supervised the Ph.D research, said:

“This innovative work supports the emergent theme that the current climate and weather on Mars has an important influence not only on dynamic surface processes, but also for any future robotic and/or human exploration of the planet.” 

The main hypothesis proposed for spider formation (Kieffer’s hypothesis) suggests that in spring, sunlight penetrates this translucent ice and heats the terrain beneath it. The ice will sublimate from its base, causing pressure to build up and eventually the ice will rupture, allowing pressurised gas to escape through a crack in the ice. The paths of the escaping gas will leave behind the dendritic patterns observed on Mars today and the sandy/dusty material will be deposited on top of the ice in the form of a plume.  

However, until now, it has not been known if such a theoretical process is possible and this process has never been directly observed on Mars.  

Additionally, the researchers observed that when CO2 blocks were released and allowed to sublimate within the sand bed, sublimation was much more vigorous than expected and material was thrown all over the chamber. This observation will be useful in understanding models of other CO2 sublimation-related processes on Mars, such as the formation of lateral Recurring Diffusive Flows surrounding linear dune gullies on Mars. 

The methodology used can be refocused to study the geomorphic role of CO2 sublimation on other active Martian surface feature formation – and indeed, can pave the way for further research on sublimation processes on other planetary bodies with no/scant atmospheres like Europa or Enceladus.

Featured image: An image from NASA’s Mars Reconnaissance Orbiter, acquired May 13, 2018 during winter at the South Pole of Mars, shows a carbon dioxide ice cap covering the region and as the sun returns in the spring, “spiders” begin to emerge from the landscape. © TCD

Reference: Mc Keown, L., McElwaine, J.N., Bourke, M.C. et al. The formation of araneiforms by carbon dioxide venting and vigorous sublimation dynamics under martian atmospheric pressure. Sci Rep 11, 6445 (2021). https://doi.org/10.1038/s41598-021-82763-7

Provided by Trinity College Dublin

Astronomy

Can Dark Matter Be Lighter Than The Tremaine-Gunn Lower Bound? (Cosmology / Astronomy)

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While the astrophysical evidence for dark matter (DM) is overwhelming, its particle nature has evaded detection. It is generally held that DM cannot be lighter than ∼ 10¯22 eV below which point the de Broglie wavelength of DM becomes larger than observed DM structures. On the other end DM heavier than ∼ 1067 eV (∼ 10 M) would cause significant tidal effects on visible structures. This represents the broadest allowed range of DM mass.

In 1979, Tremaine and Gunn (TG) pointed out that fermionic DM lighter than ∼ 100 eV would not be contained within a galactic halo, immediately ruling out about 24 orders of magnitude of parameter space for fermions. Modern treatments looking at dwarf spheroidal galaxies find similar bounds on fermionic DM m ≳ 50−190 eV.

Now, Davoudiasl and colleagues in their recent paper note that this bound can be significantly weakened if there are many, N_F, distinct species of fermionic dark matter whose masses are nearly degenerate. For very large number of species the momentum of the matter stored within any one of the fermionic species will not exceed the escape velocity from galactic structures and the mass scale of the fermions can be brought down to well below O(eV), often considered the ultralight regime. They thus referred to this possibility as ultralight fermionic dark matter (UlFDM).

“If one allows for the dark matter population to comprise a large number NF of fermions, the phase space restrictions which depend on spin statistics of identical fermions i.e. Pauli’s exclusion principle, are avoided and the mass lower bound can be relaxed with NF ^ (–1/4). “

— wrote authors of the study

Their ultralight fermion dark matter scenario has a number of striking phenomenological consequences. Due to the enormous number of species one could expect gravitational effects that are normally completely negligible. These include detectable effects from graviton exchange at the TeV scale, such as in collider experiments or via high energy cosmic rays, as well as accelerated evaporation of solar-mass black holes on astronomical time scales.

We find that the LHC constrains the number of distinct species, bosons or fermions lighter than ∼ 500 GeV, to be N ≲ 1062. This, in particular, implies that roughly degenerate fermionic dark matter must be heavier than ∼ 10¯13 eV, which thus relaxes the Tremaine-Gunn bound by ∼ 16 orders of magnitude.

— told Davoudiasl, first author of the study

They considered these and other effects, and found that they roughly yield the constraint N ≲ 1062, for which one could accommodate fermionic dark matter as light as 10¯13 eV. Depending on the assumptions of the underlying model, stronger bounds could apply, for example originating from the possibility of gravity-mediated fast proton decay or non-standard neutrino oscillations, as well as possible modifications of Newton’s constant.

A summary of several constraints relevant for any new physics model assuming a large number of species with no SM interactions; shaded regions are ruled out. All constraints apply regardless of spin, unless specified. © Davoudiasl et al.

Their work illustrated that departure from a monolithic picture of fermionic dark matter, by allowing a large number of species, could open novel and exciting phenomenological possibilities that deserve attention, as the decades-long search for clues to the identity of dark matter continues.

Reference: Hooman Davoudiasl, Peter B. Denton, David A. McGady, “Ultralight Fermionic Dark Matter”, Phys. Rev. D 103, 055014 – Published 19 March 2021. https://journals.aps.org/prd/abstract/10.1103/PhysRevD.103.055014

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Medicine

Detonating Fuse for Breast Cancer Discovered (Medicine)

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Targeted treatment of basal-like breast cancer could be facilitated by YAP inhibitors in the future. As reported by an MDC team headed by Walter Birchmeier in the scientific journal Cancer Research, this type of cancer requires the support of the YAP protein to stimulate the growth of cancer stem cells.

Breast cancer is the most common type of tumour found in women. 69,000 new cases are diagnosed each year in Germany alone. Around 80 percent of tumours originate in the luminal cells, the milk-producing cells of the mammary gland. 10 percent of the cells resemble those of the underlying (basal) cell layer. These are muscle-like epithelial cells that contract when the mammary gland produces milk in order to push it out.

“We do not see any breast tumours in the absence of YAP. YAP is therefore required for the development and spread of the tumour.”

— Hazel Quinn, First author of the study

“While luminal breast tumours are usually sensitive to hormones, 80 percent of basal-like tumours are triple-negative. They have no receptors for estrogen (ER), progesterone (PR) or the growth factor receptor HER2”, says Professor Walter Birchmeier. He heads the Signal Transduction in Development and Cancer Lab at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC). As there are currently no targeted treatments for this very aggressive form of cancer, the prognosis for affected patients is poor. These tumours rarely respond to conventional chemotherapeutic agents, which are intended to inhibit cell division.

The tumours did not grow in the mice in the absence of YAP

In previous studies, Birchmeier’s team was able to demonstrate that the Wnt/b-catenin pathway plays a key role in the development of basal-like breast cancer. This signalling cascade normally regulates cell proliferation and differentiation during embryonic development. Wnt is essential for the b-catenin protein to signal to the nucleus. Once the cells are mature and ‘the job has been done’, this reaction chain is disabled and b-catenin is degraded. However, the signalling pathway can be reactivated in some types of cancer. In the case of basal-like breast cancer, it is activated and b-catenin accumulates in the tumour cells. It was also known that the YAP oncogene is upregulated in cancer stem cells. The YAP protein stimulates cell growth and is also active in the nucleus.

Immunofluorescence image of the postpartum mouse mammary gland with membrane-bound B-catenin (white) and cell nuclei (blue). © AG W. Birchmeier, MDC

The aim of the current study was to investigate the connection between Wnt signalling and YAP. PhD student Hazel Quinn, lead author of the study, deactivated the YAP gene at the onset of tumour growth in mice in which the Wnt signalling pathway was activated and basal-like breast cancer was induced. It was found that while mice in the control group developed massive tumours within weeks, this did not occur in the YAP knockout mice.

Section through breast tissue: the top row shows a proliferating carcinoma. On the right, the YAP is stained brown. The alveoli, where milk is formed and stored, are displaced by the cancer cells. In the mammary glands at the bottom, the YAP gene has been deactivated. The alveoli are very well visible and free of tumors. © Birchmeier Lab, MDC

“We do not see any breast tumours in the absence of YAP. YAP is therefore required for the development and spread of the tumour,” says Hazel Quinn The scientist used dyes and specific antibodies to make YAP in the nuclei visible in tissue sections. The alveoli – small sack-like structures in which the milk is formed and stored – are easily recognisable and free of tumours when the YAP gene is deactivated. They are almost invisible in the tissue of the control group because the proliferating carcinoma displaces them.

Conclusions regarding survival

YAP is a key regulator in the Hippo signalling pathway, which was only discovered a few years ago. It plays an important role in cell regeneration and differentiation for stem cells. If it does not function correctly, cancer can develop. “It is also likely to be the reason why the YAP gene is highly expressed in basal-like breast cancer but not in luminal breast cancer. The cells of basal-like tumours are similar to stem cells, whereas luminal tumours are much more differentiated,” explains Hazel Quinn.

Head of proteomics platform © David Ausserhofer / MDC

Quinn’s co-author Dr. Philipp Mertins, expert in proteomic analysis and group leader at MDC and the Berlin Institute of Health (BIH), carried out gene expression analyses on tissue samples from human breast tumours and was able to confirm this hypothesis. While basal-like tumours generally exhibit high expression levels of the YAP gene, these are significantly lower in luminal breast cancer. How much YAP is present in the tumour is also directly correlated with the survival time of patients. “The higher the YAP level in triple-negative breast cancer, the earlier women died. In the case of luminal breast cancer, the reverse is true,” explains Hazel Quinn.

Approach to targeted therapy

Cancer stem cells are usually the reason why small tumour clusters remain in the tissue despite chemotherapy, and the cancer returns at a later stage and forms metastases.  Unlike in mice, genes in humans cannot simply be deactivated. However, the good news is that YAP can be inhibited with medication. “As we now know how important YAP is for these cells, the combination of YAP inhibitors that do not produce any non-specific side effects and conventional therapeutic strategies could improve patients’ chance of survival without recurrence,” says Hazel Quinn.

“Combination treatments with different inhibitors that work at different points of signalling pathways are currently being favoured.”

— Professor Walter Birchmeier, Head of Signal Transduction in Development and Cancer

Quinn demonstrated that this could be done in mice by inhibiting YAP activity with the substances Simvastatin or Verteporfin, which are approved for treating other diseases. Both inhibitors significantly reduced the tumour volume. “A German pharmaceutical company is currently researching molecules that can specifically inhibit YAP,” adds Walter Birchmeier. It may be some time before a highly effective and well-tolerated new active ingredient is discovered and can be used in the clinic. “Combination treatments with different inhibitors that work at different points of signalling pathways are currently being favoured,” says Birchmeier.

Featured image: Immunofluorescene image of a basal breast cancer © AG W. Birchmeier, MDC

Reference: Hazel M. Quinn, Regina Vogel, Oliver Popp, Philipp Mertins, Linxiang Lan, Clemens Messerschmidt, Alexandro Landshammer, Kamil Lisek, Sophie Chateau-Joubert, Elisabetta Marangoni, Elle Koren, Yaron Fuchs and Walter Birchmeier, “YAP and β-catenin cooperate to drive oncogenesis in basal breast cancer”, Cancer Research, 2021. DOI: 10.1158/0008-5472.CAN-20-2801

Provided by MDC Berlin

Material science

Study Could Help Develop Biosensors For Non-invasive Diagnosis of Diseases (Material Science)

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Brazilian researchers tested the capacity of different materials to produce sensors for the detection of PCA3, a gene that is overexpressed in prostate cancer. The technique can also be used to diagnose infectious diseases, including COVID-19.

The efficacy of biosensors used in clinical tests depends critically on the surface of the device on which the biorecognition molecules are immobilized. This surface can be adjusted and sometimes controlled using self-assembled molecular monolayers as matrices. The monolayers are films made up of organic molecules that under the right conditions assemble spontaneously on metal surfaces via chemical bonds between the sulfur atoms and the metal. 

A study conducted at the University of São Paulo’s São Carlos Physics Institute (IFSC-USP) in Brazil compared the performances of two types of self-assembled monolayers, one consisting of mercaptoacetic acid (MAA) in water and ethanol, and another of 11-mercaptoundecanoic acid (11-MUA) in ethanol. The respective films were evaluated in terms of their capacity to produce sensors for detection of the gene PCA3, which is specific to prostate cancer cells.

“We showed that efficient immobilization of a simple DNA strip to detect the gene PCA3 can be achieved even in less organized monolayers, provided the terminal groups are ionized,” Paulo Augusto Raymundo Pereira, lead author of the study, told Agência FAPESP.

An article reporting the findings is published in The Journal of Physical Chemistry C.

The study was supported by FAPESP via a postdoctoral fellowship awarded to Raymundo-Pereira, and a scholarship and a Regular Research Grant awarded to other participants. Another source of funding was the Thematic Project “Toward a convergence of technologies: from sensing and biosensing to information visualization and machine learning for data analysis in clinical diagnosis”, led by Osvaldo Novais de Oliveira Junior, Raymundo-Pereira’s research advisor.

“The study showed that the differences in performance between biosensors made with MAA film and 11-MUA film are not due solely to monolayer organization. Carboxylate group ionization is important. For this reason, it’s necessary to know the right conditions for formation of the film with these characteristics,” Raymundo-Pereira said.

Because MAA has proved promising for biosensor matrices, the comparison of the different preparation conditions investigated in the study can contribute to the production of high-quality films. “This knowledge can help construct other types of matrix prepared with monolayers,” Raymundo-Pereira said. “It’s now available to any researcher. As a side-effect, our own group has created another biosensor to detect the novel coronavirus.”

He stressed the importance of constructing non-invasive biosensors, especially in light of the growing use of telemedicine during the pandemic because of social distancing. “In the diagnosis and monitoring of prostate cancer, which was our proof of concept, the standard procedure is to quantify the level of prostate-specific antigen or PSA,” he said. “This entails taking a blood sample from the patient, which is an invasive procedure. Moreover, the result isn’t always conclusive as a large proportion of false-positives result from high levels of PSA associated with inflammation of the prostate, for example. In this case, the medical recommendation is biopsy, which is even more invasive. The antigen expressed by the gene PCA3 can be detected in urine by users of a biosensor that could be sold by drugstores.”

“Both contributions of the study relate to more accurate diagnosis of prostate cancer and the possibility of replacing such detection methods as PCR (polymerase chain reaction), which is essential to diagnose not just cancer but also other diseases, including COVID-19,” Oliveira Junior said.

Besides the IFSC-USP group, the study involved researchers at the Brazilian National Nanotechnology Laboratory (LNNano), run by the Brazilian Center for Research in Energy and Materials (CNPEM) in Campinas, in the state of São Paulo; Hospital de Amor in Barretos, also in São Paulo; and Instituto de Pesquisa Pelé Pequeno Príncipe in Curitiba, Paraná state.

The article “Influence of the molecular orientation and ionization of self-assembled monolayers in biosensors: application to genosensors of prostate cancer antigen 3” is at: pubs.acs.org/doi/10.1021/acs.jpcc.0c09055.

Featured image: Brazilian researchers tested the capacity of different materials to produce sensors for the detection of PCA3, a gene that is overexpressed in prostate cancer. The technique can also be used to diagnose infectious diseases, including COVID-19 (prototype of the biosensor produced at the University of São Paulo: the device can be used to detect biomarkers non-invasively / Paulo A. Raymundo-Pereira, IFSC-USP)

Provided by FAPESP

Medicine

New Treatment Proves More Effective and Less Toxic for Neuroendocrine Tumor Patients (Medicine)

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A new treatment for late-stage neuroendocrine tumors (NETs) has been found to be more effective and have fewer side effects than the current standard of care, according to research published in the March issue of The Journal of Nuclear Medicine. The novel peptide receptor radionuclide therapy holds promise to reduce mortality among NET patients and decrease the financial burden of their continual treatment.

NETs are a diverse group of tumors that originate from the neuroendocrine system, which is responsible for regulating hormones throughout the body. The number of people who are diagnosed with NETs is growing; the incidence of NETs increased 6.4-fold from 1973 to 2012. However, because they are rare, varied, and slow growing, the diagnosis of a NET can be delayed up to seven years. As a result, more than 50 percent of NET cases are at an advanced stage at the time of diagnosis.

The current standard of care for late-stage NET patients is peptide receptor radionuclide therapy with 177Lu-DOTATATE, which is flushed from a patient’s system rapidly after administration. Preclinical studies found that if a special dye (Evans blue) is added to the 177Lu-DOTATATE, the treatment can last longer in the body and be more effective. In this study, researchers sought to determine what dose of the modified therapy, known as 177Lu-DOTA-EB-TATE, is safest and produces the best tumor response.

Study participants were divided into three groups, and each group was given a different dose of 177Lu-DOTA-EB-TATE. All the groups tolerated the therapy well, with almost no side effects regardless of the dose. Ultimately, researchers found that a 177Lu-DOTA-EB-TATE dose of 1.89 GBq/cycle was the most effective for tumor control in the NET patients. They also noted that with careful patient selection and monitoring, a 3.97 GBq/cycle dose could achieve an even better response.

“In terms of NETs, the more effectively we can use 177Lu for treatment, the more we will be able to reduce the financial strain on patients,” said Xiaoyuan (Shawn) Chen, PhD, Nazarat Muzayyin Chair professor at the National University of Singapore in Singapore. “Overall, this new treatment has the potential to significantly impact mortality and morbidity for neuroendocrine tumor patients.”

He continued, “Now that we understand the efficacy of Evans blue dye in NET treatment, we hope that it can be utilized in the future to create various novel therapeutic radiopharmaceuticals not just for NET patients, but for other types of cancer patients as well.”


The authors of “Peptide Receptor Radionuclide Therapy of Late-Stage Neuroendocrine Tumor Patients with Multiple Cycles of 177Lu-DOTA-EB-TATE” include Qingxing Liu, Jie Zang, Huimin Sui, Jiakun, Ren, Hua Guo, Hao Wang, Rongxi Wang and Zhaohui Zhu, Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China, and Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China; Orit Jacobson and Xiaoyuan Chen, Departments of Diagnostic Radiology, Chemical and Biomolecular Engineering, Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, Singapore; Jingjing Zhang, Theranostics Center for Molecular Radiotherapy and Precision Oncology, Zentralklinik Bad Berka, Bad Berka, Germany; and Yuejuan Cheng, Division of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Featured image: Representative images of partial remission in group A (A), group B (B), and group C (C). © SNMMI

Provided by SNMMI

Medicine

Cholesterol Accumulation Contributes to Movement Disorder in Patients with NUS1 mutation (Medicine)

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SC Family Finds Hope in Research Breakthrough for Rare Disorder

Chloe Murphy’s parents had been concerned about her balance from the time she started walking. Then came strong hand and eye tremors. Through the years, Chloe, now 15, has also experienced seizures and learning delays.

The Murphys of Bluffton, SC have looked to multiple medical specialists and Chloe has undergone numerous EEGs, blood tests, and genetic testing.

Initial genetic tests were normal, until at 12 years of age, her geneticist, Dr. Mike Lyons of the Greenwood Genetic Center’s (GGC’s) Charleston SC office, suggested whole exome sequencing, which analyzes all 20,000 human genes. In Chloe, this test identified a variant in a gene called NUS1. NUS1 has previously been associated with a condition of intellectual disability and seizures and is a potential contributor to Parkinson’s Disease.

“Chloe’s test results identified a variant in this NUS1 gene, but it was a variant that no one had seen before, so we weren’t sure that it was the answer,” said Lyons. “We reached out to the research team at GGC to help clarify its meaning.”

“This was a gene that we were very interested in studying,” said Rich Steet, PhD, Director of Research at GGC. “We ran experiments on skin cells from Chloe and were also able to find two other patients with NUS1 variants and similar symptoms.”

Studies in skin cells showed that the amount of the typical protein produced by the NUS1 gene was reduced in all three patients. Their skin cells also accumulated excess cholesterol in lysosomes.

The research team also developed zebrafish models that mimicked the NUS1 variants seen in these patients.

“Zebrafish and humans share approximately 70% of the same genes, so we can study the effects of human genetic variants in an animal model,” said Heather Flanagan-Steet, PhD, Director of Functional Studies and Director of the Hazel and Bill Allin Aquaculture Facility at GGC. “Studying how NUS1 variants affected the zebrafish provided powerful information, confirming that these variants in our patients were indeed the cause of their symptoms and allowing us to better understand how these variants cause disease.”

GGC’s zebrafish studies showed that the fish also accumulated cholesterol in their cells and, through a tool called a Zebrabox, scientists were able to analyze behavioral swimming patterns in the fish, akin to the movement symptoms exhibited by the patients.

“When we compared the wild type fish to those with the NUS1 mutations, we found that those with the mutations displayed abnormal swimming behaviors including slower swimming and staying near the edges of the swimming area,” said Flanagan-Steet.

Flanagan-Steet shared that in some cases, they can also identify drugs that may rescue the abnormal features in the fish. They can test these drugs on the fish before considering them for human trials.

Chloe Murphy’s parents had been concerned about her balance from the time she started walking. Then came strong hand and eye tremors. Through the years, Chloe, now 15, has also experienced seizures and learning delays.

The Murphys of Bluffton, SC have looked to multiple medical specialists and Chloe has undergone numerous EEGs, blood tests, and genetic testing.

Initial genetic tests were normal, until at 12 years of age, her geneticist, Dr. Mike Lyons of the Greenwood Genetic Center’s (GGC’s) Charleston SC office, suggested whole exome sequencing, which analyzes all 20,000 human genes. In Chloe, this test identified a variant in a gene called NUS1. NUS1 has previously been associated with a condition of intellectual disability and seizures and is a potential contributor to Parkinson’s Disease.

“Chloe’s test results identified a variant in this NUS1 gene, but it was a variant that no one had seen before, so we weren’t sure that it was the answer,” said Lyons. “We reached out to the research team at GGC to help clarify its meaning.”

“This was a gene that we were very interested in studying,” said Rich Steet, PhD, Director of Research at GGC. “We ran experiments on skin cells from Chloe and were also able to find two other patients with NUS1 variants and similar symptoms.”

Studies in skin cells showed that the amount of the typical protein produced by the NUS1 gene was reduced in all three patients. Their skin cells also accumulated excess cholesterol in lysosomes.

The research team also developed zebrafish models that mimicked the NUS1 variants seen in these patients.

“Zebrafish and humans share approximately 70% of the same genes, so we can study the effects of human genetic variants in an animal model,” said Heather Flanagan-Steet, PhD, Director of Functional Studies and Director of the Hazel and Bill Allin Aquaculture Facility at GGC. “Studying how NUS1 variants affected the zebrafish provided powerful information, confirming that these variants in our patients were indeed the cause of their symptoms and allowing us to better understand how these variants cause disease.”

GGC’s zebrafish studies showed that the fish also accumulated cholesterol in their cells and, through a tool called a Zebrabox, scientists were able to analyze behavioral swimming patterns in the fish, akin to the movement symptoms exhibited by the patients.

“When we compared the wild type fish to those with the NUS1 mutations, we found that those with the mutations displayed abnormal swimming behaviors including slower swimming and staying near the edges of the swimming area,” said Flanagan-Steet.

Flanagan-Steet shared that in some cases, they can also identify drugs that may rescue the abnormal features in the fish. They can test these drugs on the fish before considering them for human trials.

Lower photo: Confocal images of the zebrafish hindbrain and tail comparing cholesterol accumulation in wild type zebrafish (top), and zebrafish with the NUS1 mutation before (center) and after treatment (bottom). Zebrafish displayed reduced cholesterol accumulation after treatment. ©GGC

“The cholesterol storage in both the patient and zebrafish cells suggested that treatments targeting cholesterol accumulation could be therapeutic,” said Steet. “When we treated the affected zebrafish with the drug, 2-hydroxypropyl-beta-cyclodextrin, the fish showed reduced cholesterol accumulation and significant improvement in swimming behaviors.”

“These studies not only confirmed that this variant was indeed the cause of Chloe’s symptoms, providing a long-awaited answer for her family, but they also gave us the opportunity to better understand this rare diagnosis and consider potential treatments,” said Lyons.

The Murphy family has found hope through their research participation.

“Our journey so far has been to find the ‘why.’ We felt like once we could determine this, we could better understand what could help Chloe,” said her mother, Jessica. “Our hope now is that these breakthroughs with NUS1 will lead to a solution to improve her health.”

This work was supported by the Greenwood Genetic Center and grants from the National Institutes of Health. It was published in Genetics in Medicine, the official Journal of the American College of Medical Genetics and Genomics.

Top photo: Chloe Murphy with her parents, Jessica and Patrick. © GGC

Reference: Yu, SH., Wang, T., Wiggins, K. et al. Lysosomal cholesterol accumulation contributes to the movement phenotypes associated with NUS1 haploinsufficiency. Genet Med (2021). https://www.nature.com/articles/s41436-021-01137-6 https://doi.org/10.1038/s41436-021-01137-6

Provided by Greenwood Genetic center

Astronomy

Five Myths About the Big Bang (Cosmology / Astronomy)

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Where did the Big Bang happen, and what was going on around it? Two physicists take us through the most common misunderstandings of what the theory is about.

The whole universe was packed together in an infinitely small point, then it exploded, and the entire mass that made up the universe was sent out into space.

An astrophysicist would tell you that everything about that statement is wrong.

“That’s not at all how we should think about the Big Bang,” says Torsten Bringmann.

Bringmann is a professor and works with cosmology and astroparticle physics at the University of Oslo (UiO).

Are Raklev, a professor of theoretical physics at UiO, has noticed that a lot of descriptions give a misleading picture of what the Big Bang theory actually states.

Raklev and Bringmann take us through the most common misunderstandings.

Warm and dense

First of all, what does “Big Bang” really mean?

‘The Big Bang theory is that about 14 billion years ago the universe was in a state that was much warmer and much denser, and that it expanded. That’s it, it’s not much more than that,” says Raklev.

Since then space has continued to expand and has become colder.

Are Raklev is a professor in the Department of Physics at the University of Oslo. (Photo: UiO)

Based on the theory, scientists have gained a clearer overview of the history of the universe, such as when elementary particles were formed and when atoms, stars and galaxies formed.

They have a good idea of what happened back when the universe was about 10^-32 seconds old. That’s 0.0000000000000000000000000000000001 seconds, according to an article written by astrophysicist Jostein Riiser Kristiansen.

Now on to the myths.

1. “It was an explosion.”

The Big Bang phrase itself makes it sound like it was an explosion, says Are Raklev. But that isn’t actually that accurate a description. You’ll find out why soon.

In the early 1920s, mathematician Alexander Friedmann discovered that Einstein’s general theory of relativity provides for an expanding universe. The Belgian priest Georges Lemaître came to the same conclusion.

Shortly afterwards, Edwin Hubble showed that galaxies are actually moving apart.

The galaxies are moving away from us. The light from them is red-shifted, meaning the waves have become longer and shifted towards the red end of the light spectrum. Not only that, galaxies are disappearing from us faster and faster.

Someday, almost all the galaxies we can currently observe in telescopes will be out of view. Eventually the stars will go out and observers will look out into an eternally dark and lonely sky.

Fortunately, that’s an extremely long way off.

We can also play the story the opposite way. The galaxies are moving apart and they have been closer before.

“If you take the entire observable universe and rewind all the way back, everything fit into a very, very small area,” Raklev says.

Then we come to the point in time of the Big Bang. What happened?

It’s easy to think that the Big Bang was an explosion, in which substances were thrown out, like pieces of wood flying off after a hand grenade goes off.

“But when it comes to the Big Bang, it’s not the substance that travels out,” says Raklev.

“The universe itself expands, space itself expands.”

An explosion where the mass explodes in all directions is not an accurate picture of the Big Bang.

2. “The universe is expanding into something.”

So it isn’t the galaxies that are moving apart, but space that’s expanding.

We can think of it as a ball of dough with raisins. The dough represents space and the raisins are the galaxies. Set the dough to rise, and the raisins will end up further apart, without actually having moved.

Bringmann uses the surface of a balloon as an example. Draw dots on the uninflated balloon and see how the distance between points increases as it inflates.

“At the same time, it’s true that galaxies also move due to mutual gravitational attraction – that’s an additional effect,” says Raklev.

A few galaxies are blue-shifting, meaning they’re moving towards us. This applies to some nearby galaxies. But over large distances, this effect is eclipsed by Hubble-Lemaître’s law, which states how fast galaxies are moving away in proportion to distance. In fact, the distance increases faster than light between points that are extremely far apart.

A ball of dough in the oven expands within the existing space inside the oven. What about the universe? What’s outside?

The universe doesn’t expand into anything. Scientists don’t believe that the universe has an edge.

That which we call the observable universe is a bubble surrounding us that is 93 billion light-years in diameter. The more distant something is that we look at, the farther back in time we’re seeing. We can’t observe or measure anything farther away than the distance light has managed to travel towards us since the Big Bang.

Since the universe has been expanding, the observable universe is counterintuitively larger than 14 billion light-years.

An illustration of the observable universe. Starting from the centre we see the solar system, the Kuiper belt, Orts cloud, the nearest solar systems and galaxies, then the cosmic web, the microwave background radiation and invisible plasma at the end. (Illustration: Pablo Carlos Budassi, wikimedia commons, CC BY-SA 3.0)

But scientists calculate that the universe outside our bubble is much, much larger than that, perhaps infinite.

The universe can be “flat,” it appears. That would mean that two light rays would remain parallel and never meet. If you tried to travel to the end of the universe, you would never reach it. The universe goes on infinitely.

If the universe has positive curvature, it could in theory be finite. But then it would be like a kind of strange sphere. If you travelled to the “end” you would end up in the same place you started, no matter which direction you took. It’s a bit like being able to travel around the world and ending up back where you started.

In either case, the universe can expand without having to expand into anything.

An infinite universe that’s getting bigger is still infinite. A “spherical universe” has no edge.

3. “The Big Bang had a centre.”

If we imagine the Big Bang as an explosion, it’s easy to think that it exploded outwards, from a centre. That’s how explosions work.

But that wasn’t the case with the Big Bang. Almost all galaxies are moving away from us, in all directions. It seems like the Earth was the centre of the beginning of the universe. But it wasn’t.

All other observers would see the same thing from their home galaxy, Bringmann explains.

The universe is expanding everywhere at the same time. The Big Bang didn’t happen in any particular place.

“It happened everywhere,” says Raklev.

A galaxy cluster consisting of thousands of individual galaxies, 2.1 billion light-years from Earth. The universe we can see is unbelievably large and might even continue forever.
 (Photo: NASA, ESA, and Johan Richard (Caltech, USA)

4. “The whole universe was gathered in a tiny little point.”

It’s true that our entire observable universe was gathered incredibly tightly together in very little space at the beginning of the Big Bang.

But how can the universe be infinite, and at the same time have been so small?

You might read that the universe was smaller than an atom at first and then the size of a football. But that analogy insinuates that space had boundaries in the beginning, and an edge.

“There’s nothing that says that the universe wasn’t already infinite at the Big Bang,” says Raklev.

“It was just smaller in the sense that what was then a metre, has now expanded into enormous distances of many billions of light years.”

When you talk about how big the universe was at certain times, it refers to our observable universe.

“The whole observable universe comes from a tiny little area that you can call a point. But the point next to it has also expanded, and the next point as well. It’s just that it’s so far away from us that we can’t observe it,” says Raklev.

5. “The universe was infinitely small, hot and dense.”

Maybe you’ve heard that the universe began as a singularity. Or that it was infinitely small, hot and so on. That might be true, but a lot of physicists don’t think it’s a correct understanding.

Singularities are an expression for mathematics that breaks down and can’t be described with ordinary physics, according to cosmologist Steen H. Hansen.

Torsten Bringmann is a professor of theoretical physics at the University of Oslo. (Photo: UiO)

Bringmann sums up what this all means when it comes to the Big Bang.

“The universe today is a little bigger than it was yesterday. And it’s even a little bigger still than it was a million years ago. The Big Bang theory involves extrapolating this back in time. Then you need a theory for that: and that’s the general theory of relativity.”

“If I extrapolate all the way back, the universe gets smaller and smaller, it gets denser and denser, and warmer and warmer. Finally you get to a point where it’s really small, really hot and dense. That’s actually the Big Bang theory: that the universe started in such a condition. That’s where you really have to stop,” says Bringmann.

If you run the general relativity theory all the way back you reach a point of infinitely high density and heat, where the size is zero.

“That’s pure mathematical extrapolation beyond what the theory actually allows,” Bringmann says.

“You then come to a point where the energy density and temperatures are so high that we no longer have physical theories to describe them.”

He says that physicists need a different theory. And there are people who are researching just that.

“What do we need in order to describe such an extreme condition? That’s where we enter an area where you need a theory that combines gravity and quantum theory. No one has been able to formulate it yet. The expectation is precisely that a quantum gravity theory wouldn’t lead to the conclusion that everything goes back to one point,” Bringmann says.

So what happened at this time, the earliest point in the history of the universe, is still hidden from us, at least so far.

Featured image: An illustration of an explosion showing the substance of the mass shooting out in all directions is not an accurate picture of the Big Bang. (Image: Johan Swanepoel / Shutterstock / NTB scanpix)

Provided by Sciencenorway

Astronomy

Hubble Captures Re-energized Planetary Nebula (Astronomy)

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Located around 5,000 light-years away in the constellation of Cygnus (the Swan), Abell 78 is an unusual type of planetary nebula. 

After exhausting the nuclear fuel in their cores, stars with a mass of around 0.8 to eight times the mass of our Sun collapse to form dense and hot white dwarf stars. As this process occurs, the dying star will throw off its outer layers of material, forming an elaborate cloud of gas and dust known as a planetary nebula. This phenomenon is not uncommon, and planetary nebulae are a popular focus for astrophotographers because of their often beautiful and complex shapes. However, a few like Abell 78 are the result of a so-called “born again” star. 

Although the core of the star has stopped burning hydrogen and helium, a thermonuclear runaway at its surface ejects material at high speeds. This ejecta shocks and sweeps up the material of the old nebula, producing the filaments and irregular shell around the central star seen in this image, which features data from Hubble’s Wide Field Camera 3 and the Panoramic Survey Telescope and Rapid Response System.

Provided by NASA Goddard

Planetary Science

Mars Water Loss Shaped by Seasons And Storms (Planetary Science)

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Mars has lost most of its once plentiful water, with small amounts remaining in the planet’s atmosphere. ESA’s Mars Express now reveals more about where this water has gone, showing that its escape to space is accelerated by dust storms and the planet’s proximity to the Sun, and suggesting that some water may have retreated underground.

Although arid today, Mars was likely once a water-covered world like our own. Evidence of this is seen in images of vast, flood-formed outflow channels, river valleys and deltas carved into the planet’s surface, as well as in radar observations of liquid water reservoirs locked up beneath the ice and dust of Mars’ south pole.

Water can now only exist on Mars in the form of ice or gas due to the low atmospheric pressure on the planet, which is less than 1% that of Earth. Mars has lost much of its former water to space over the past few billion years, and is still leaking water from its atmosphere today.

Two new studies, led by Anna Fedorova of the Space Research Institute of the Russian Academy of Sciences and Jean-Yves Chaufray of the Laboratoire Atmospheres Observations Spatiales, France, now clarify how water moves through and leaves Mars’ atmosphere. They reveal that this process is affected by the planet’s distance from the Sun and changes in its climate and weather, including the massive global dust storms often seen on the planet.

© ESA

Both studies used extensive, multi-year datasets obtained by the orbiter’s SPICAM instrument (Spectroscopy for the Investigation of the Characteristics of the Atmosphere of Mars).

“The atmosphere is the link between surface and space, and so has much to tell us about how Mars has lost its water,” says Anna. “We studied the water vapour in the atmosphere from the ground up to 100 km in altitude, a region that had yet to be explored, over eight martian years.”

Anna and colleagues found that water vapour remained confined to below 60 km when Mars was far from the Sun but extended up to 90 km in altitude when Mars was closest to the Sun. Across a full orbit, the distance between the Sun and the Red Planet ranges from 207 million to 249 million km.

Near the Sun, the warmer temperatures and more intensive circulation in the atmosphere prevented water from freezing out at a certain altitude. “Then, the upper atmosphere becomes moistened and saturated with water, explaining why water escape rates speed up during this season – water is carried higher, aiding its escape to space,” adds Anna.

In years when Mars experienced a global dust storm the upper atmosphere became even wetter, accumulating water in excess at altitudes of over 80 km.

“This confirms that dust storms, which are known to warm and disrupt Mars’ atmosphere, also deliver water to high altitudes,” says Anna. “Thanks to Mars Express’ continuous monitoring, we were able to analyse the last two global dust storms, in 2007 and 2018, and compare what we found to storm-free years to identify how the storms affected water escape from Mars.”

The high resolution stereo camera on board ESA’s Mars Express captured this impressive upwelling front of dust clouds – visible in the right half of the frame – near the north polar ice cap of Mars in April this year. It was one of several local small-scale dust storms that have been observed in recent months at the Red Planet, which is currently enduring a particularly intense dust storm season. A much larger storm emerged further southwest at the end of May and developed into a global, planet-encircling dust storm within several weeks. The intensity of this major event means very little light from the Sun reaches the martian surface, a situation extreme enough that NASA’s 15-year old Opportunity rover has been unable to recharge its batteries and call home: it has been in hibernation mode since mid-June. Credit: ESA/DLR/FU Berlin, CC BY-SA 3.0 IGO

This finding is supported by research led by Jean-Yves, which modelled the density of hydrogen atoms in Mars’ upper atmosphere over two years and explored how this related to water escape.

“We compared our results to SPICAM data and found good agreement – except during the dusty season, when our model underestimated just how much hydrogen was present,” says Jean-Yves. “Far more water escapes through the atmosphere during disturbed conditions than the model predicted.”

Across two martian years, one of which experienced a dust storm, Jean-Yves and colleagues estimated that the rate of water loss varied by a factor of about 100, highlighting the significant effect that dust storms can have on Mars’ rates of water loss.

The findings show that Mars loses the equivalent of a global two-metre-deep layer of water every billion years. However, even accumulated over Mars’ four-billion-year history, this amount is insufficient to explain where all of Mars’ water has gone.

“A significant amount must have once existed on the planet to explain the water-created features we see,” says Jean-Yves. “As it hasn’t all been lost to space, our results suggest that either this water has moved underground, or that water escape rates were far higher in the past.”

The results from Anna, Jean-Yves and colleagues complement recent findings by the ESA-Roscosmos ExoMars Trace Gas Orbiter (TGO), which, since 2018 and alongside Mars Express, has monitored the distribution of water by altitude in Mars’ atmosphere. These findings suggested that Mars’ rate of water loss may be linked to seasonal changes.

Mars Express’ work to determine Mars’ water loss is also supported by NASA’s MAVEN (Mars Atmosphere and Volatile Evolution) mission, which is systematically measuring the chemical composition of the martian atmosphere (specifically, the levels of atomic hydrogen and deuterium, a heavy isotope of hydrogen). Such multi-mission data will help constrain not only how water is currently behaving but also the cumulative water loss over martian history – vital to figure out whether Mars’ water has gone underground or to space.

“Two key themes in our ongoing exploration of Mars are the planet’s evolution and water loss, and the role of dust storms in shaping the martian climate and atmosphere,” says Dmitrij Titov, ESA’s Mars Express project scientist.

“These findings help us understand the longer-term processes behind Mars’ water loss and paint a picture of not only its present-day climatology, but how its climate has changed throughout history. For such studies we need the kind of high-quality datasets provided by SPICAM and also the instruments aboard ExoMars’ TGO. Together, these and other advanced missions will continue to unveil the mysteries of Mars.”

Mars Express launched on 2 June 2003, and has spent over 17 years in orbit at Mars carefully monitoring the properties of the planet’s atmosphere.

Featured image: Artist’s impression of Mars Express. The background is based on an actual image of Mars taken by the spacecraft’s high resolution stereo camera. Credit: Spacecraft image credit: ESA/ATG medialab; Mars: ESA/DLR/FU Berlin, CC BY-SA 3.0 IGO

Notes for Editors

“Multi-Annual Monitoring of the Water Vapor Vertical Distribution on Mars by SPICAM on Mars Express” by Fedorova et al. is published in the Journal of Geophysical Research: Planets.

“Study of the hydrogen escape rate at Mars during Martian years 28 and 29 from comparisons between SPICAM/Mars express observations and GCM-LMD simulations” by J.-Y. Chaufray et al. appears in the journal Icarus.

Provided by ESA