K. Rubinur and colleagues presented radio observations of the galaxy merger remnant Mrk 212 with the Karl G. Jansky Very Large Array (VLA) and the upgraded Giant Meter Radio Telescope (uGMRT). Their objective was to confirm the object’s dual AGN nature and to provide more insights into the properties of this source.
The SDSS color composite image of Mrk 212. The slit position of the HCT observations is indicated by the dashed line. Mrk 212 is referred to as Source 1 (S1) and the companion as Source 2 (S2). Credit: Rubinur et al., 2020.
Galaxy mergers play an essential role in the evolution of galaxies. Major mergers even have the ability to change the shape of the parent galaxies and form an object with a completely new morphology.
Their observations showed that gas inflow during galaxy mergers can trigger mass accretion onto the supermassive black holes (SMBHs), turning them into active galactic nuclei (AGN). When both SMBHs are ignited at the same time, it may form AGN pairs. If the separation between the two AGN is less than 326 light years, they are known as binary AGN. In the case that the separation is bigger, astronomers call them dual AGN.
At a luminosity distance of about 322 million light years, Mrk 212 is a galaxy merger remnant with two known radio sources associated with two optical nuclei, designated S1 and S2. The projected separation between the two nuclei is estimated to be around 18,250 light years, making it a dual AGN candidate.
VLA observations revealed a double radio source associated with S1 and a compact radio structure associated with S2. The VLA images also show an extended radio structure at 8.5 GHz that, located one arcsecond away from the S2 optical nuclei, which has a relatively flat spectral index and is assumed to be a compact core.
The researchers found that the total extent of S1 is about 2,445 light years and its average 1.4−8.5 GHz spectral index is at a level of approximately −0.81. These properties mean that S1 resembles a compact symmetric object (CSO).
According to the study, the presence of the compact radio core and the presence of AGN emission lines in the optical spectrum of S2 suggest the presence of another AGN in S2. Moreover, the optical observations show that S1 and S2 both fall in the AGN+SF (star formation) region in the BPT (Baldwin, Philips and Terlevich) diagram. All in all, the astronomers concluded that the obtained results strongly support the dual AGN nature of Mrk 212.
References: Rubinur et al., “A Multi-wavelength Study of the Dual Nuclei in Mrk 212”, ArXiv, pp. 1-14, 2020 arXiv:2010.14914 [astro-ph.GA] arxiv.org/abs/2010.14914 https://arxiv.org/abs/2010.14914
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Pancreatic cancer is highly lethal: according to the National Cancer Institute, only about 10 percent of patients remain alive five years after diagnosis. Now, a preclinical study from the lab of Marsha Moses, PhD at Boston Children’s Hospital, reports marked and lasting tumor regression in a mouse model, using a highly selective, potent, engineered antibody-drug combination.
At left, fluorescence imaging shows six different pancreatic tumors, treated with PBS (a sham treatment), gemcitabine, DM1 conjugated to a non-targeting antibody (IgG), and DM1 conjugated to the targeting ICAM1 antibody. Tumor diameters are quantified at right. Credit: Jing Huang PhD, Boston Children’s Hospital.
The findings, published November 3 in the journal Advanced Science, provide the basis for further pre-clinical studies to advance this approach to the clinic, the researchers say.
Pancreatic cancer has proven very difficult to treat with drugs. Not only do the tumors have a limited blood supply, making it hard to deliver drugs, they are also surrounded by stroma (a dense connective tissue) and tumor cells are protected by an extracellular matrix (a meshwork of proteins and carbohydrates).
“It can be difficult to get drugs into these tumors,” says Moses, who directs the Vascular Biology Program at Boston Children’s. “We developed a novel chemo-immunotherapy agent that selectively recognizes and penetrates pancreatic tumors better than other therapeutics.”
Led by Jing Huang, PhD, the Moses lab developed an antibody-drug conjugate, or ADC, consisting of two parts: an antibody that selectively homes to a molecule on the surface of pancreatic cancer cells, known as ICAM1, and a drug toxic to cancer cells. Cells bearing ICAM1 on their surface are killed by the drug, while normal cells are spared.
“The size of the ADC is similar to the size of a single antibody: less than 10 nanometers,” says Peng Guo, PhD, of the Moses Lab, co-corresponding author on the paper with Moses. “Because of this ultra-small diameter, it can penetrate the stroma and reach pancreatic tumor cells better than other novel treatments such as T-cell immunotherapy or nanomedicines.”
Rational selection of antibody and drug
The team chose ICAM1 as a target for the ADC antibodies after screening the tumor surface for dozens of different proteins. In 2014, the Moses lab showed high levels of ICAM1 on triple-negative breast cancers, and it is abundant on melanoma and thyroid cancers as well.
At left, the red staining shows high levels of ICAM1 antibody accumulation in human pancreatic tumors with adjacent normal pancreas tissues. The blue staining shows low accumulation of non-targeting IgG antibodies in the tumors. At right, quantification of antibody accumulation. Credit: Jing Huang, PhD, Boston Children’s Hospital.
The team performed similarly unbiased screening to select the best drug to include in the ADC. from a pool of drugs already used clinically. They tested four candidate ADCs in two human pancreatic cancer cell lines as well as in normal pancreatic cells. ADCs combining ICAM1 antibodies with the cytotoxic drug DM1 (mertansine), used clinically in HER2-positive breast cancer, were the most effective in killing tumor cells, working better than other ADC drugs. The DM1-ICAM1 antibody combination did not harm non-cancerous pancreatic cells which do not produce ICAM-1.
Shrinking pancreatic tumors
The team next randomized mice with pancreatic tumors to receive one of four treatments, given as systemic injections: the DM1-ICAM1 antibody conjugate, DM1 bound to a non-targeting antibody (IgG), gemcitabine (a first-line chemotherapy drug used in pancreatic cancer), or a sham treatment.
Compared with the other groups, mice receiving the DM1-ICAM1 antibody conjugate had a significant reduction in tumor size that persisted during the 14-week study, even after just two doses. The treatment also effectively inhibited metastasis to normal organs including lung, liver, and spleen. There was no observed toxicity, assessed by weighing the animals and through pathology analysis of their organs.
Noninvasive tumor monitoring
Finally, Huang developed an MRI-based molecular tumor imaging technique to complement ICAM1 ADC therapy, confirming the presence of ICAM1 on the tumor without the need for an invasive biopsy. This could potentially help to predict the treatment’s effect and monitor changes over time. Eventually, Moses hopes to be able to monitor the treatment effect using two non-invasive urinary biomarkers previously reported by the team.
While other ADCs have been tested in pancreatic cancer, none have shown sufficient efficacy in the clinic and have also resulted in off-target toxicity, says Moses. “The precision of our approach comes from both the specific targeting and the ability to monitor that targeting with MRI,” she says.
The ICAM1-DM1 ADC is part of a portfolio of targeted, patented cancer drug delivery systems being developed in the Moses lab; others include nanolipogels, liposomes, and exosomes.
Earth’s most arid desert may hold a key to finding life on Mars.
Diverse microbes discovered in the clay-rich, shallow soil layers in Chile’s dry Atacama Desert suggest that similar deposits below the Martian surface may contain microorganisms, which could be easily found by future rover missions or landing craft.
Led by Cornell University and Spain’s Centro de Astrobiología, scientists now offer a planetary primer to identifying microbial markers on shallow rover digs in Martian clay, in their work published Nov. 5 in Nature Scientific Reports.
In that dry environment at Atacama, the scientists found layers of wet clay about a foot below the surface.
“The clays are inhabited by microorganisms,” said corresponding author Alberto G. Fairén, a visiting scientist in the Department of Astronomy at Cornell University. “Our discovery suggests that something similar may have occurred billions of years ago – or it still may be occurring – on Mars.”
If microbes existed on Mars in the past, their biomarkers likely would be preserved there, Fairén said. “If microbes still exist today,” he said, “the latest possible Martian life still may be resting there.”
The red planet will see rovers cruising across the surface there in the next few years. NASA’s rover Perseverance will land on Mars in February 2021; Europe’s Rosalind Franklin rover will arrive in 2023. Both of those missions will seek microbial biomarkers in the clay below the planet’s surface.
“This paper helps guide the search,” Fairén said, “to inform where we should look and which instruments to use on a search for life.”
In the Yungay region of the Atacama desert, the scientists found the clay layer, a previously unreported habitat for microbial life, is inhabited by at least 30 salt-loving microbial species of metabolically active bacteria and archaea (single-cell organisms).
The researchers’ Atacama discovery reinforces the notion that early Mars may have had a similar subsurface with protected habitable niches, particularly during the first billion years of its history.
“That’s why clays are important,” he said. “They preserve organic compounds and biomarkers extremely well and they are abundant on Mars.”
Unrelated mutations, when present in the blood, can lead to false positive results in men with advanced prostate cancer who are undergoing liquid biopsies. Such tests, which look for variants in the cell-free DNA that tumors shed into the blood plasma, help determine suitable treatment options.
“You can actually measure what’s happening with a patient’s tumor by taking a blood draw,” said Dr. Colin Pritchard, associate professor of laboratory medicine and pathology at the University of Washington School of Medicine in Seattle. He also is the associate director of the Genetics and Solid Tumors Laboratory at UW Medicine.
The testing can guide therapy for already-diagnosed cancers by finding mutations that can suggest precision medicine choices. Cell-free DNA testing offers the ease and convenience of testing a blood sample for patients with advanced cancer.
Nonetheless, Pritchard and his team point to the urgency of evaluating the performance of cell-free DNA testing in actual practice and understanding sources of potential interferences with the accuracy of test results.
Two cancer treatment medications, recently approved by the U.S. Food and Drug Administration, or FDA, in fact, are indicated for possible use if certain cell-free DNA mutations appear in the plasma of men whose prostate cancer has spread.
However, other kinds of non-cancer DNA mutations can exit blood cells and get into the plasma.
Pritchard said that precision medicine scientists are learning more about a phenomenon called “clonal hematopoiesis” that can often interfere with cancer liquid biopsy findings. Mutations in some DNA repair genes – BRCA1, BRCA2, and ATM – are associated with male and female cancers.
“Unfortunately, these same genes are also commonly mutated as a result of clonal hematopoiesis,” Pritchard said.
He and his research team at UW Medicine and the Brotman Baty Institute for Precision Medicine, a partnership among UW Medicine, Seattle Children’s and Fred Hutchinson Cancer Research Center, looked at the degree to which clonal hematopoiesis was confounding prostate cancer liquid biopsy results.
They examined both the prevalence and the gene spectrum of this interference in patients undergoing cell-free DNA testing.
Their research paper appears this week in the Nov. 5 edition of the medical journal, JAMA Oncology.
The researchers discovered that CHIP (clonal hematopoiesis of indeterminant potential) variants accounted for almost half of the somatic DNA repair mutations that the liquid biopsy detected. The presence of these CHIP variants became exponentially more common with advancing age of the patients.
False positives have become an even greater concern as two new classes of PARP inhibitors for prostate cancer became approved in May of 2020 – rucaparib and olaparib. People with a positive liquid biopsy test can be candidates for these drugs. A false positive for these biomarker-guided treatments can lead to misdiagnosis and to patients receiving unnecessary, unhelpful therapy.
About half the time when the plasma is thought to contain a mutation that would guide therapy with these drugs, it actually contains CHIP variants, not prostate cancer DNA variants.
That means that in about half of those tested, a patient could be told that he should be administered a drug that is not indicated to treat to his cancer, Pritchard explained.
Solving this problem of potential misdiagnosis and misguided treatment is fortunately quite simple. Pritchard said that at UW Medicine and at Brotman Baty Institute for Precision Medicine, the laboratory medicine staff examine a sort of paired control: the whole blood cells where the clonal hematopoiesis is and the plasma.
“The good news is that, by looking at the blood cellular compartment, you can tell with pretty good certainty whether something is cancer or something is hematopoiesis,” he said.
The research team noted that some of the limitations of their study were the small sample size (69 men), its retrospective approach, and the similarities within their patient population, including the men’s prior therapies.
Researchers at the Hong Kong University of Science and Technology (HKUST) have identified new therapeutic targets for Alzheimer’s disease (AD) by studying the patients’ brain with a newly-developed methodology. This novel approach also enables researchers to measure the effects of potential drugs on AD patients, opening new directions for AD research and drug development.
Although the pathological mechanisms of AD have been studied for decades, the disease remains incurable. One reason is that conventional research approaches have limited capability to identify molecular targets for drug development. Molecular and pathological pathway analysis generally examines AD patients’ brain as a single unit, which usually underestimates the contributions of different brain cell types to AD and any abnormalities in them. This is especially the case with less-common cell types such as microglia (the brain’s resident immune cells) and neurovascular cells (specifically endothelial cells), which only account for less than 5% and 1% of the total brain cell population, respectively.
However, a team led by Prof. Nancy Ip, Vice-President for Research and Development, Director of the State Key Laboratory of Molecular Neuroscience, and Morningside Professor of Life Science at HKUST, has more than circumvented this problem–they have also identified several new potential molecular targets in endothelial cells and microglia for AD drug development.
The team examined the functions of specific cell types in the postmortem brains of AD patients, which is typically impossible with conventional approaches, by using cutting-edge, single-cell transcriptome analysis, which can be used to characterize of the molecular changes in single cells. This yielded a comprehensive profile of the cell-type-specific changes in the transcriptome in the brains of AD patients. Subsequent analysis identified cell subtypes and pathological pathways associated with AD, highlighting a specific subpopulation of endothelial cells found in the brains’ blood vessels. Accordingly, the team discovered that increased angiogenesis (the formation of new blood vessels from current ones) and immune system activation in a subpopulation of endothelial cells are associated with the pathogenesis of AD, suggesting a link between the dysregulation of blood vessels and AD. The researchers also identified novel targets for restoring neural homeostasis (the ability to maintain a relatively stable internal state despite external changes) in AD patients.
The team also leveraged their single-cell transcriptome analysis to study the mechanism by which the cytokine interleukin-33 (IL-33), an important protein for immune signaling, exerts beneficial actions, making it a possible AD therapeutic intervention. The researchers found that IL-33 reduces AD-like pathology by stimulating the development of a specific subtype of microglia that helps clear amyloid-beta, a neurotoxic protein found in AD brains. The team is also the first to capture data on the mechanisms by which microglia transform into an amyloid-beta-consuming phagocytic state, which is a major cellular mechanism for the removal of pathogens.
“The complex and heterogeneous cell composition within the brain makes it difficult to study disease mechanisms,” Prof. Ip explained. “The advancement of single-cell technology has enabled us to identify specific cell subtypes and molecular targets, which is critical for developing new interventions for Alzheimer’s disease.”
The team has recently published their work in the prestigious scientific journals Proceedings of the National Academy of Sciences U S A (PNAS) and Cell Reports.
AD, the predominant form of dementia, currently affects over 50 million individuals worldwide and is projected to afflict 150 million people by 2050. Its pathological hallmarks include the accumulation of extracellular amyloid-beta depositions and neurofibrillary tangles. Over time, ineffective clearance of these pathological hallmarks leads to cellular dysfunction in AD, resulting in memory loss, communication problems, reduced physical abilities, and eventually death.
References: Shun-Fat Lau, Han Cao, Amy K. Y. Fu, Nancy Y. Ip, “Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease”, PNAS October 13, 2020 117 (41) 25800-25809; first published September 28, 2020; https://doi.org/10.1073/pnas.2008762117 link: https://www.pnas.org/content/117/41/25800/tab-article-info
The renin-angiotensin system (RAS) becomes active at low blood pressure and forms angiotensin II, a hormone that causes blood vessels to constrict, causing blood pressure to rise again. The enzyme dipeptidyl peptidase 3 (DPP3) is significantly involved in the metabolism of angiotensin II.
The head of the Institute of Biochemistry at Graz University of Technology, Peter Macheroux, and his team are world leaders in DPP3 research: “For example, we now know that people who suffer a heart attack, blood poisoning or acute kidney injury have elevated levels of DPP3 in their bloodstream. This increase correlates with increased mortality.” However, little is known about the physiological function of DPP3. For this reason, the working group led by Macheroux, together with researchers from the University of Graz and Med Uni Graz, investigated how DPP3 affects the RAS. The results were published in the Journal of Biological Chemistry.
Effects of DPP3 deficiency
The DPP3 gene was specifically switched off in a mouse model at the University of Graz (knock-out mouse model). Using mass spectroscopic analyses, the researchers discovered that DPP3 regulates RAS processes and the water balance by breaking down angiotensin peptides. The DPP3 deficiency led to increased fluid and food intake. Nevertheless, the knock-out mice had a lower body weight and less fat mass than the mice of the control group (wild type mice). Furthermore, the concentration of angiotensin II was significantly higher in knock-out mice. This increased angiotensin II level caused oxidative stress and reduced metabolism. “The exact effects of these changes are still unclear, however, and will have to be examined in more detail in follow-up studies. For example, the blood pressure did not change measurably,” said Macheroux.
Gender-specific differences
For the first time it was also possible to prove that there are gender-specific differences. While major changes in RAS were found in male mice, female mice were hardly affected by DPP3 knock-out. “This documents a direct connection between the hormone system and the physiological role of DPP3. Oestrogen in particular is likely to inhibit the production of angiotensin II,” say the two first authors Shalinee Jha and Ulrike Taschler from the Institute of Biochemistry at TU Graz and the Institute of Molecular Biosciences at the University of Graz.
Development of an inhibitor
The characterization of DPP3 in this study shows that DPP3 can modulate metabolic and cellular processes in RAS. This property could be of great benefit in the treatment of various cardiovascular diseases in the future. Macheroux: “In a next step, we would like to advance the development of an enzyme-inhibiting substance (inhibitor) for DPP3. Work on this has already begun at the Institutes of Biochemistry and Organic Chemistry at TU Graz.”
Evgeny Popov (Senior Research Associate, Laboratory of the Stratigraphy Oil and Gas Bearing Reservoirs) partook in researching Canadodus suntoki.
A dental plate was found by Canadian national Stephen Suntok on the Pacific coast of British Columbia. Evgeny Popov, a renowned expert in chimaerids, was asked to assist in classification.
“The new species and genus is most close to the extant members of Chimaeridae – Chimaera and Hydrolagus. They are quite widely present in the oceans and comprise about 82% of the existing Holocephali fish,” explains Popov.
The dental plate shows that the extinct Canadodus was close in appearance to the extant relatives, with length between 83 and 125 centimeters. Its diet most likely consisted of worms, mollusks, and crustaceans. The dental plate never left Canada – it was studied in Russia via high-definition photos, adds Popov.
As the scientists report, the finding was rather lucky, because vertebrate fossils are rarely found on the shores of Juan de Fuca Strait.
The research significantly contributes to the understanding of chimaerid fauna of the late Paleogene in the Pacific Ocean.
New research from Tel Aviv University will allow cameras to recognize colors that the human eye and even ordinary cameras are unable to perceive.
The technology makes it possible to image gases and substances such as hydrogen, carbon and sodium, each of which has a unique color in the infrared spectrum, as well as biological compounds that are found in nature but are “invisible” to the naked eye or ordinary cameras. It has groundbreaking applications in a variety of fields from computer gaming and photography as well as the disciplines of security, medicine and astronomy.
The research was conducted by Dr. Michael Mrejen, Yoni Erlich, Dr. Assaf Levanon and Prof. Haim Suchowski of TAU’s Department of Physics of Condensed Material. The results of the study were published in the October 2020 issue of Laser & Photonics Reviews.
“The human eye picks up photons at wavelengths between 400 nanometers and 700 nanometers — between the wavelengths of blue and red,” explains Dr. Mrejen. “But that’s only a tiny part of the electromagnetic spectrum, which also includes radio waves, microwaves, X-rays and more. Below 400 nanometers there is ultraviolet or UV radiation, and above 700 nanometers there is infrared radiation, which itself is divided into near-, mid- and far-infrared.
“In each of these parts of the electromagnetic spectrum, there is a great deal of information on materials encoded as ‘colors’ that has until now been hidden from view.”
The researchers explain that colors in these parts of the spectrum are of great importance, since many materials have a unique signature expressed as a color, especially in the mid-infrared range. For example, cancer cells could be easily detected as they have a higher concentration of molecules of a certain type.
Existing infrared detection technologies are expensive and mostly unable to render those “colors.” In medical imaging, experiments have been performed in which infrared images are converted into visible light to identify the cancer cells by the molecules. To date, this conversion required very sophisticated and expensive cameras, which were not necessarily accessible for general use.
But in their study, TAU researchers were able to develop cheap and efficient technology that could mount on a standard camera and allows, for the first time, the conversion of photons of light from the entire mid-infrared region to the visible region, at frequencies that the human eye and the standard camera can pick up.
“We humans can see between red and blue. If we could see in the infrared realm, we would see that elements like hydrogen, carbon and sodium have a unique color,” explains Prof. Suchowski. “So an environmental monitoring satellite could ‘see’ a pollutant being emitted from a plant, or a spy satellite would see where explosives or uranium are being hidden. In addition, since every object emits heat in the infrared, all this information could be seen even at night.”
After registering a patent for their invention, the researchers are developing the technology through a grant from the Innovation Authority’s KAMIN project, and they have already met with a number of both Israel-based and international companies.
Study shows music volume has a major impact on how the listener experiences the acoustics of a concert hall.
The volume and timbre of music have a significant impact on how people perceive the acoustics in a concert hall, according to two recent studies carried out by the research group of Aalto University Professor Tapio Lokki. Both have been published in the Journal of the Acoustical Society of America, one of the most prestigious journals in its field.
The first study demonstrated that, based on the music alone, it is difficult to distinguish which concert hall a piece of music is being played in. The test subjects listened to recordings of a single violin and of part of Beethoven’s Seventh Symphony, all played in four different concert halls: the rectangular Concertgebouw in Amsterdam and Herkulessaal in Munich, the vineyard-shaped Berlin Philharmonic, and the fan-shaped Cologne Philharmonic. They first heard a sample from the reference location, after which they tried to identify the reference location from four music samples.
It was easier to identify the hall when the same music sample played in each concert halls. If the reference sample was from a slightly different part of the same piece of music as used in the control locations, it was harder to identify the hall.
‘Even small differences in the music listened to made it very difficult to identify concert halls of similar size and architecture. Halls that were very different to each other were clearly more easily identified regardless of the music,’ explains postdoctoral researcher Antti Kuusinen.
Another study showed that the acoustics of a concert hall are experienced differently depending on the volume at which the orchestra is playing. The concert halls used in the study were the Helsinki’s Musiikkitalo, Munich Herkulessaal, Berlin Philharmonic and Berlin Konzerthaus.
The subjects listened to the orchestra playing at different volume levels, from the quietest piano pianoissimo to the strongest forte fortissimo, after which they placed the concert halls in order according to how loud and enveloping they experienced the music to be. The order of the concert halls changed in some cases related to the volume of the music.
‘Traditionally, the acoustics of concert halls are studied by using objective measurements to calculate acoustic parameters, such as reverberation time, which is independent of the characteristics or dynamics of the music. Our research clearly shows that this is insufficient for understanding the acoustics in its entirety, because both the timbre of the sound and the listeners’ perceptions shift as the volume changes,’ Lokki explains.
Lokki’s research group has also previously studied how the acoustics of concert halls affect the emotional reactions evoked by the music. The studies indicated that halls with acoustics that support large dynamic fluctuations evoke the strongest emotional experiences in listeners.
