Oncotarget: Genomic and Neoantigen Evolution in Head and Neck Squamous Cell Carcinoma (Medicine)

Oncotarget published “Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma” which reported that prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution.

These authors characterized genomic and neoantigen changes between 23 paired primary and recurrent head and neck squamous cell carcinoma (HNSCC) tumors.

Within these tumors, they identified 6 genes which have predicted neoantigens in 4 or more patients.

Within HNSCC tumors examined in this Oncotarget research paper, there are neoantigens in shared genes by a subset of patients.

The presence of neoantigens in these shared genes may promote an anti-tumor immune response which controls tumor progression.

Dr. Brian A. Van Tine from The Washington University in St. LouisThe St. Louis Children’s Hospital as well as The Siteman Cancer Center said, “Head and neck cancer are a group of heterogeneous tumors with an estimated 644,000 new cases per year worldwide.

The infiltration of immune cells, including T cells, into tumors is associated with improved outcomes and longer survival in HNSCC.

The infiltrating T cells release granules containing perforin and granzyme A and B which directly kill tumor cells or release other cytokines and chemokines that promote the anti-tumor immune response and alter the tumor microenvironment.

For example, infiltrating T cells release interferon gamma which increases expression of PD-L1 and CTLA-4, which may increase the efficacy of immune checkpoint therapy.

Multiple studies have characterized changes in mutation burden in HNSCC, when comparing primary and metastatic tumors, no studies have characterized the shifting neoantigen burden between primary and metastatic tumors within HNSCC.

In this Oncotarget study, the authors characterized the mutational and neoantigen burden between primary and first recurrence tumors in 23 patients with HNSCC.

In this Oncotarget study, the authors characterized the mutational and neoantigen burden between primary and first recurrence tumors in 23 patients with HNSCC

The Van Tine Research Team concluded in their Oncotarget Research Output that there is a shifting neoantigen burden as there are unique neoantigens in primary tumors and different unique neoantigens in the recurrent/metastatic tumors.

The patients which have these neoantigens in shared genes are patients which have higher total numbers of neoantigens.

What is clear is that patients with neoantigens in these shared genes also tend to have increased duration of survival with disease.

The increase in neoantigens and duration of survival with disease tends to be associated with increased CD3 CD8 density in the tumor and CD8A expression.

This suggests that patients with these shared neoantigens are associated with increased CD8 T cell infiltration and increased cytotoxic activity, which extends the patient’s life.

Featured image: Properties of patients who have neoantigens in shared genes. (A) The total number of neoantigens was graphed for primary tumors with neoantigens in Ryr3 (n = 4), DNAH7 (n = 5), TTN (n = 5), or no neoantigens (Pri neoAg-, (n = 13)) or relapse tumors with neoantigens in TTN (n = 4), PIK3CA (n = 5), USH2A (n = 5), or no neoantigens (Rel neoAg-, (n = 12)). The numbers under the X axis are the mean of neoantigens. *indicates p < 0.05. (B) The duration of disease for patients with predicted neoantigens in the Primary tumor (Ryr3 (n = 4), DNAH7 (n = 5), TTN (n = 4)) and relapse tumor (TTN (n = 4), PIK3CA (n = 4), and USH2A (n = 5)), or no predicted neoantigens in these genes (neoAg-, (n = 9)). Patients with neoantigens in multiple genes are placed in all neoantigens. The asterisks indicate patients who were alive as of writing. (C) The density of CD3+ CD8+ cells in the tumor graphed by presence of neoantigens in shared genes. Primary RYR3 (n = 4), Primary DNAH7 (n = 5), Primary TTN (n = 5), Primary no neoantigens (n = 11), relapse TTN (n = 4), relapse PIK3CA (n = 5), relapse USH2A (n = 5) relapse no neoantigens (n = 10)). Numbers under the X axis are the mean of the density. (D) The Log2 (TPM +1) expression of CD8A was graphed by the presence of neoantigens in shared genes. Pri NeoAg- (n = 10), Pri Ryr3+ (n = 2), Pri DNAH7+ (n = 1), Pri TTN+ (n = 4), Rel neoAg- (n = 8), Rel TTN+ (n = 2), Rel PIK3CA+ (n = 5), Rel USH2A+ (n = 1). The number under the X axis is the mean for each column. (E) The CTL activity was graphed by neoantigen status. CTL activity was calculated as described in Figure 4. Pri NeoAg- (n = 10), Pri Ryr3+ (n = 2), Pri DNAH7+ (n = 1), Pri TTN+ (n = 3), Rel neoAg- (n = 8), Rel TTN+ (n = 2), Rel PIK3CA+ (n = 5), Rel USH2A+ (n = 1). The number under the X axis is the mean for each column.


Reference: Schutt C. R., Sun H., Pradham J. Sarin, Saenger Y., Ley J., Adkins D., Ingham M., Ding L., Van Tine B. A. Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma. Oncotarget. 2021; 12: 534-548. Retrieved from https://www.oncotarget.com/article/27907/text/


Provided by Impact Journals LLC

First-order Transition Triggered By U(1) Symmetry Breaking Can Generate Gravitational Waves (Quantum)

An extra U(1) gauge interaction is one of the promising and interesting extensions of the standard model (SM) of particle physics. Since tiny but non-vanishing neutrino masses are a clear evidence for the existence of the beyond the SM, one of the simplest and the most interesting models is the one based on the gauge group SU(3)c×SU(2)L× U(1)Y× U(1)BL, where the additional interaction is from the gauged U(1)BL (baryon number minus lepton number) symmetry. In the standard U(1)BL charge assignment, three right-handed (RH) neutrinos have to be introduced to fulfill the gauge and gravitational anomaly cancellation conditions. After Majorana masses of RH neutrinos are generated by the spontaneous U(1)BL gauge symmetry breaking at a high energy scale, the observed tiny neutrino masses are naturally explained by the so-called seesaw mechanism with the heavy Majorana RH neutrinos through their Yukawa interactions with the SM left-handed neutrinos. In addition, one of the three RH neutrinos can be a candidate for the dark matter in our universe.

Although it is very difficult for any collider experiments to test an additional gauge symmetry if it is broken at very high energies, the detection of a gravitational wave (GW) can be a probe for such an extra U(1) symmetry breaking. This is because the first-order phase transition in the early universe is one of the promising sources of stochastic GW background. If a first-order phase transition occurred in the early universe, the dynamics of bubble collision followed by the turbulence of the plasma and sonic waves would have generated GWs, which can be detected by the future experiments, such as Big Bang Observer (BBO), DECi-hertz Interferometer Observatory (DECIGO), Advanced LIGO (aLIGO), and Einstein Telescope (ET).

Now, Nobuchika and colleagues in their recent paper, considered the U(1)X extended SM and studied the spectrum of stochastic GWs generated by the first-order phase transition associated with the extra U(1)X, symmetry breaking in the early universe. This breaking is responsible for the generation of Majorana masses of RH neutrinos. They have investigated a UV completion of the U(1)X extended SM by an SO(10) GUT. In this UV completion, the extra U(1) gauge coupling is unified with the SM gauge couplings, and thus the extra U(1) gauge coupling at the phase transition epoch is no longer a free parameter and g_χ ∼ 0.4 from the gauge coupling unification condition. They have found that the first-order phase transition triggered by this extra U(1) symmetry breaking can be strong enough to generate GWs with a detectable size of amplitude if the U(1)X Higgs quartic coupling is small enough and the symmetry breaking scale (the bubble nucleation temperature T⋆) is smaller than about 105 (104) TeV.

FIG. 1: The predicted GW spectrum for various values of Y_N and λ_2 for g_χ = 0.463 and v_2 = 1 PeV. Parameters in the legend denote (Y_N , λ_2 × 10³) © Nobuchika et al.

They have also clarified the dependence of the resultant GW spectrum on the RH neutrino Majorana Yukawa couplings, in other words, the mass scale of RH neutrinos. As the Yukawa couplings increase, the amplitude of GW background reduces and the peak frequency slightly increases. They have found a similar behavior in the GW spectrum as they change the U(1)X Higgs quartic coupling. Thus, different combinations of the Yukawa and the quartic couplings can result in almost the same GW spectrum. In order to extract the information about RH neutrino masses from the spectral shape of GW background, the information on the U(1)X Higgs quartic coupling is necessary.

Featured image: The predicted GW spectrum for various symmetry breaking scales for λ_2 = 6 × 10¯4. The difference of the symmetry breaking scale is indicated by colors as shown in the legends. Black solid curves are the expected sensitivities of each indicated experiments derived in K. Schmitz (2021) © Nobuchika et al.


Reference: Nobuchika Okada, Osamu Seto, Hikaru Uchida, “Gravitational waves from breaking of an extra U(1) in SO(10) grand unification”, Progress of Theoretical and Experimental Physics, Volume 2021, Issue 3, March 2021, 033B01, https://doi.org/10.1093/ptep/ptab003


Copyright of this article totally belongs to our author S. Aman. One is allowed to reuse it only by giving proper credit either to him or to us that

Aspirin Use May Decrease Ventilation, ICU admission and Death in COVID-19 Patients (Medicine)

Researchers from the George Washington University found that aspirin may have lung-protective effects and reduce the need for mechanical ventilation, ICU admission and in-hospital mortality in hospitalized COVID-19 patients

George Washington University researchers found low dose aspirin may reduce the need for mechanical ventilation, ICU admission and in-hospital mortality in hospitalized COVID-19 patients. Final results indicating the lung protective effects of aspirin were published today in Anesthesia & Analgesia. 

“As we learned about the connection between blood clots and COVID-19, we knew that aspirin – used to prevent stroke and heart attack – could be important for COVID-19 patients,” Jonathan Chow, MD, assistant professor of anesthesiology and critical care medicine and director of the Critical Care Anesthesiology Fellowship at the GW School of Medicine and Health Sciences, said. “Our research found an association between low dose aspirin and decreased severity of COVID-19 and death.” 

Over 400 patients admitted from March to July 2020 to hospitals around the United States, including those at GW Hospital, the University of Maryland Medical Center, Wake Forest Baptist Medical Center and Northeast Georgia Health System, were included in the study. After adjusting for demographics and comorbidities, aspirin use was associated with a decreased risk of mechanical ventilation (44% reduction), ICU admission (43% reduction), and in-hospital mortality (47% reduction). There were no differences in major bleeding or overt thrombosis between aspirin users and non-aspirin users. 

Preliminary findings were first published as a preprint in fall 2020. Since then, other studies have confirmed the impact aspirin can have on both preventing infection and reducing risk for severe COVID-19 and death. Chow hopes that this study leads to more research on whether a causal relationship exists between aspirin use and reduced lung injury in COVID-19 patients. 

“Aspirin is low cost, easily accessible and millions are already using it to treat their health conditions,” said Chow. “Finding this association is a huge win for those looking to reduce risk from some of the most devastating effects of COVID-19.”  

In addition to Chow, study authors include David Yamane, MD, assistant professor of emergency medicine and anesthesiology and critical care medicine at the GW School of Medicine and Health Sciences; Ivy Benjenk, RN, MPH, lead research coordinator for the Department of Anesthesiology and Critical Care Medicine at GW Hospital; and Shannon Cain, MD, third-year resident in the Department of Emergency Medicine at the GW School of Medicine and Health Sciences; as well as researchers from the University of Maryland Medical Center, Wake Forest Baptist Medical Center and Northeast Georgia Health System. 

Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019” was published in Anesthesia & Analgesia.


Reference: Chow, Jonathan H. MD; Khanna, Ashish K. MD, FCCP, FCCM†,‡; Kethireddy, Shravan MD§; Yamane, David MD∥; Levine, Andrea MD¶; Jackson, Amanda M. MD#; McCurdy, Michael T. MD¶; Tabatabai, Ali MD¶,; Kumar, Gagan MD§; Park, Paul MD††; Benjenk, Ivy RN, MPH; Menaker, Jay MD; Ahmed, Nayab MD§§; Glidewell, Evan MD∥∥; Presutto, Elizabeth MD††; Cain, Shannon MD¶¶; Haridasa, Naeha BS; Field, Wesley MD§§; Fowler, Jacob G. BS∥∥; Trinh, Duy MD††; Johnson, Kathleen N. BS∥∥; Kaur, Aman DO§§; Lee, Amanda BS††; Sebastian, Kyle MD∥∥; Ulrich, Allison MD††; Peña, Salvador MD, PhD∥∥; Carpenter, Ross MD††; Sudhakar, Shruti MD††; Uppal, Pushpinder MD††; Fedeles, Benjamin T. MD, Capt, USAF, MC††; Sachs, Aaron MD††; Dahbour, Layth MD††; Teeter, William MD,##; Tanaka, Kenichi MD‡‡‡; Galvagno, Samuel M. DO, PhD; Herr, Daniel L. MD; Scalea, Thomas M. MD,‡‡; Mazzeffi, Michael A. MD, MPH Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019, Anesthesia & Analgesia: April 2021 – Volume 132 – Issue 4 – p 930-941
doi: 10.1213/ANE.0000000000005292


Provided by George Washington University

Missing Baryons Found in Far-Out Reaches of Galactic Halos (Planetary Science)

Berkeley Lab physicists play key role in studies that solve a cosmological mystery

Researchers have channeled the universe’s earliest light – a relic of the universe’s formation known as the cosmic microwave background (CMB) – to solve a missing-matter mystery and learn new things about galaxy formation. Their work could also help us to better understand dark energy and test Einstein’s theory of general relativity by providing new details about the rate at which galaxies are moving toward us or away from us.

Invisible dark matter and dark energy account for about 95% of the universe’s total mass and energy, and the majority of the 5% that is considered ordinary matter is also largely unseen, such as the gases at the outskirts of galaxies that comprise their so-called halos.

Most of this ordinary matter is made up of neutrons and protons – particles called baryons that exist in the nuclei of atoms like hydrogen and helium. Only about 10% of baryonic matter is in the form of stars, and most of the rest inhabits the space between galaxies in strands of hot, spread-out matter known as the warm-hot intergalactic medium, or WHIM.

Because baryons are so spread out in space, it has been difficult for scientists to get a clear picture of their location and density around galaxies. Because of this incomplete picture of where ordinary matter resides, most of the universe’s baryons can be considered as “missing.”

Now, an international team of researchers, with key contributions from physicists at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) and Cornell University, has mapped the location of these missing baryons by providing the best measurements, to date, of their location and density around groups of galaxies.

It turns out the baryons are in galaxy halos after all, and that these halos extend much farther than popular models had predicted. While most of an individual galaxy’s stars are typically contained within a region that is about 100,000 light-years from the galaxy’s center, these measurements show that for a given group of galaxies, the most distant baryons can extend about 6 million light-years from their center.

Paradoxically, this missing matter is even more challenging to map out than dark matter, which we can observe indirectly through its gravitational effects on normal matter. Dark matter is the unknown stuff that makes up about 27% of the universe; and dark energy, which is driving matter in the universe apart at an accelerating rate, makes up about 68% of the universe.

“Only a few percent of ordinary matter is in the form of stars. Most of it is in the form of gas that is generally too faint, too diffuse to be able to detect,” said Emmanuel Schaan, Chamberlain Postdoctoral Fellow in Berkeley Lab’s Physics Division and lead author for one of two papers about the missing baryons, published March 15 in the journal Physical Review D (view the other paper at this link).

The researchers made use of a process known as the Sunyaev–Zel’dovich effect that explains how CMB electrons get a boost in energy via a scattering process as they interact with hot gases surrounding galaxy clusters.

“This is a great opportunity to look beyond galaxy positions and at galaxy velocities,” said Simone Ferraro, a Divisional Fellow in Berkeley Lab’s Physics Division who participated in both studies. “Our measurements contain a lot of cosmological information about how fast these galaxies move. It will complement measurements that other observatories make, and make them even more powerful,” he said.

A team of researchers at Cornell University, comprised of research associate Stefania Amodeo, assistant professor. Professor Nicholas Battaglia, and graduate student Emily Moser, led the modeling and the interpretation of the measurements, and explored their consequences for weak gravitational lensing and galaxy formation.

The computer algorithms that the researchers developed should prove useful in analyzing “weak lensing” data from future experiments with high precision. Lensing phenomena occur when massive objects such as galaxies and galaxy clusters are roughly aligned in a particular line of site so that gravitational distortions actually bend and distort the light from the more distant object.

Weak lensing is one of the main techniques that scientists use to understand the origin and evolution of the universe, including the study of dark matter and dark energy.  Learning the location and distribution of baryonic matter brings this data within reach.

“These measurements have profound implications for weak lensing, and we expect this technique to be very effective at calibrating future weak-lensing surveys,” Ferraro said.

Schaan noted, “We also get information that’s relevant for galaxy formation.”

In the latest studies, researchers relied on a galaxies dataset from the ground-based Baryon Oscillation Spectroscopic Survey (BOSS) in New Mexico, and CMB data from the Atacama Cosmology Telescope (ACT) in Chile and the European Space Agency’s space-based Planck telescope. Berkeley Lab played a leading role in the BOSS mapping effort, and developed the computational architectures necessary for Planck data-processing at NERSC.

The algorithms they created benefit from analysis using the Cori supercomputer at Berkeley Lab’s DOE-funded National Energy Research Scientific Computing Center (NERSC). The algorithms counted electrons, allowing them to ignore the chemical composition of the gases.

“It’s like a watermark on a bank note,” Schaan explained. “If you put it in front of a backlight then the watermark appears as a shadow. For us the backlight is the cosmic microwave background. It serves to illuminate the gas from behind, so we can see the shadow as the CMB light travels through that gas.”

Ferraro said, “It’s the first really high-significance measurement that really pins down where the gas was.”

The new picture of galaxy halos provided by the “ThumbStack” software that researchers created: massive, fuzzy spherical areas extending far beyond the starlit regions. This software is effective at mapping those halos even for groups of galaxies that have low-mass halos and for those that are moving away from us very quickly (known as “high-redshift” galaxies).

New experiments that should benefit from the halo-mapping tool include the Dark Energy Spectroscopic Instrument, the Vera Rubin Observatory, the Nancy Grace Roman Space Telescope, and the Euclid space telescope.

NERSC is a DOE Office of Science user facility.

In addition to the lead authors from Berkeley Lab, UCB and Cornell, researchers from 41 institutions in seven countries participated in the new studies. The work was supported in part by the U.S. Department of Energy Office of Science, the National Science Foundation, Princeton University, the University of Pennsylvania, and the Canada Foundation for Innovation. Funding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutions.

Featured image: A new study has found that a share of particles that has been challenging to locate is most likely sprinkled across the distant bounds of galaxy halos. The study found some of these particles of baryonic matter are located up to 6 million light-years from their galactic centers. This color-rendered image shows the halo of the Andromeda galaxy, which is the Milky Way’s largest galactic neighbor. (Credit: NASA)


Reference: Emmanuel Schaan et al. (Atacama Cosmology Telescope Collaboration), “Atacama Cosmology Telescope: Combined kinematic and thermal Sunyaev-Zel’dovich measurements from BOSS CMASS and LOWZ halos”, Phys. Rev. D 103, 063513 – Published 15 March 2021. https://journals.aps.org/prd/abstract/10.1103/PhysRevD.103.063513


Provided by Berkeley Lab

Immune Receptor Protein Could Hold Key to Treatment of Autoimmune Diseases (Biology)

Scientists show how a receptor protein plays a role in the immune response, yielding a potential therapeutic target for diseases like rheumatoid arthritis

TARM1 is a receptor protein whose role in the functioning of the immune system is unknown. In a new study, scientists from Japan have explored the potential role of TARM1 in the pathogenesis of rheumatoid arthritis by analyzing mouse models. They found that TARM1 activated dendritic cells, and development of collagen-induced arthritis (CIA) was notably suppressed in TARM1-deficient mice and by treatment with TARM1-inhibitory soluble TARM1 proteins. This makes the protein a potential therapeutic target.

Autoimmune diseases are typically caused when the immune system, whose purpose is to deal with foreign threats to the body, incorrectly recognizes the body’s own proteins and cells as threats and activates immune cells to attack them. In the case of rheumatoid arthritis, a well-known autoimmune disease, immune cells erroneously attack the body’s own joint components and proteins, causing painful inflammation and even the destruction of bone! Scientists from Japan have now taken a massive step toward understanding and, potentially, treating rheumatoid arthritis better, with their discovery in a brand-new study. Read on to understand how!

The development of autoimmune diseases is an incredibly complex process, involving several key players including genetic and environmental factors. Dendritic cells (DCs), which are responsible for kick-starting the immune response against infections, are one of the main immune cells involved in the pathogenesis of autoimmune diseases. All immune cells, including DCs, are equipped with a variety of receptors on their surfaces, which can either amplify or suppress the immune response. One such receptor is the T cell-interacting, activating receptor on myeloid cells-1 (TARM1). It is a member of the leukocyte immunoglobulin-like receptor family, and helps in the activation of other immune cells such as neutrophils and macrophages. TARM1’s functions suggest that it may have an important role to play in the immune response, but the possibility of its role in the pathogenesis of rheumatoid arthritis remains largely unexplored.

The aforementioned team of scientists, led by Professor Yoichiro Iwakura from Tokyo University of Science, and Rikio Yabe and Shinobu Saijo from Chiba University, wanted to find out more about this association. In their study published in Nature Communications, they identified genes that were overexpressed in various mouse models of arthritis. Interestingly, they found that Tarm1 was one of many such genes. As Prof. Iwakura explains, “Tarm1 expression is elevated in the joints of rheumatoid arthritis mouse models, and the development of collagen-induced arthritis (CIA) is suppressed in TARM1-deficient mice.”

The scientists observed that the immune system’s response to type 2 collagen (IIC), a protein crucial for the development of CIA in mice, was suppressed in TARM1-deficient mice. They also found that the antigen-presenting ability of DCs in TARM1-deficient mice was impaired. With respect to the significance of these findings, Prof. Iwakura explains, “We have shown that TARM1 plays an important role for the maturation and activation of DCs through interaction with IIC”. Finally, they injected TARM1-inhibitory soluble TARM1 proteins into the knee of a mouse with CIA. Notably, this suppressed the progression of CIA in the mouse, suggesting that TARM1 inhibition is effective in weakening autoimmune arthritis.

The team’s findings about the TARM1 protein have wide implications with respect to the treatment of rheumatoid arthritis as well as other autoimmune and allergic diseases. Commenting on their important discoveries, Prof. Iwakura states, “Because excess DC activation is suggested in many autoimmune and allergic diseases, our observations suggest that TARM1 is a good target for the development of new drugs to treat such diseases.”

The findings of this exciting new study surely indicate that there still remains much to be understood about autoimmune diseases like rheumatoid arthritis―and that the more we understand them, the better we can fight them!


Reference

Titles of original papers: TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens, Journal: Nature Communications, DOI: 10.1038/s41467-020-20307-9


Provided by Tokyo University of Science

Electromagnetic Fields Hinder Spread of Breast Cancer, Study Shows (Medicine)

Lab tests suggest the fields interfere with the inner workings of cancer cells

Electricity may slow – and in some cases, stop – the speed at which breast cancer cells spread through the body, a new study indicates.

The research also found that electromagnetic fields might hinder the amount of breast cancer cells that spread. The findings, published recently in the journal Bioelectricity, suggest that electromagnetic fields might be a useful tool in fighting cancers that are highly metastatic, which means they are likely to spread to other parts of the body, the authors said.

Vish Subramaniam © Ohio State news

We think we can hinder metastasis by applying these fields, but we also think it may be possible to even destroy tumors using this approach,” said Vish Subramaniam, senior author of the paper and former professor of mechanical and aerospace engineering at The Ohio State University. Subramaniam retired from Ohio State in December.

“That is unclear at this stage, but we are working on understanding that – how big should the electromagnetic field be, how close should it be to the tumor? Those are the next questions we hope to answer.”

The study is among the first to show that electromagnetic fields could slow or stop certain processes of a cancer cell’s metabolism, impairing its ability to spread. The electromagnetic fields did not have a similar effect on normal breast cells.

Travis Jones, lead author of the paper and a researcher at Ohio State, compared the effects to what might happen if something interfered with a group running together down a path.

Travis Jones © Ohio State news

The effect, Subramaniam said, is that some of the cancer cells slow down when confronted with electromagnetic fields.

“It makes some of them stop for a little while before they start to move, slowly, again,” he said. “As a group, they appear to have split up. So how quickly the whole group is moving and for how long they are moving becomes affected.”

The electromagnetic fields are applied to cancerous cells without touching them, said Jonathan Song, co-author of the paper, associate professor of mechanical and aerospace engineering at Ohio State and co-director of Ohio State’s Center for Cancer Engineering.

Song compared the cancer cells with cars. Each cell’s metabolism acts as fuel to move the cells around the body, similar to the way gasoline moves vehicles.

“Take away the fuel, and the car cannot move anymore,” Song said.

The work was performed on isolated human breast cancer cells in a lab and has not been tested clinically.

Jonathan Song © Ohio State news

The electromagnetic fields appear to work to slow cancer cells’ metabolism selectively by changing the electrical fields inside an individual cell. Accessing the internal workings of the cell, without having to actually touch the cell via surgery or another more invasive procedure, is new to the study of how cancer metastasizes, Subramaniam said.

“Now that we know this, we can start to answer other questions, too,” Subramaniam said. “How do we affect the metabolism to the point that we not only make it not move but we choke it, we completely starve it. Or can we slow it down to the point where it will always remain weak?”

This research is an extension of two previous pioneering studies, published in 2015 and 2019, that showed electromagnetic fields could hinder breast cancer metastasis. (Read an Ohio State News story about the 2019 study here.)

Other Ohio State researchers who authored this study include Kirti Kaul, Ayush Garg and Ramesh Ganju.

Featured image: An illustration of a migrating breast cancer cell. New research suggests electromagnetic fields might hinder both the number of breast cancer cells that spread through the body, and the speed at which they spread. Illustration: Getty Images


Reference: Travis H. Jones, Kirti Kaul, Ayush A. Garg, Jonathan W. Song, Ramesh K. Ganju, and Vish V. Subramaniam, “Directional Migration of Breast Cancer Cells Hindered by Induced Electric Fields May Be Due to Accompanying Alteration of Metabolic Activity“, Bioelectricity, 2021.


Provided by Ohio State news

‘We Marry Disorder With Order’ (Material Science / Physics)

Physicists able to determine properties of mesoporous materials more precisely

He and his research group have found a way to more precisely determine the properties of these materials, because they can better account for the underlying disorder. Their article has been designated “ACS Editors’ Choice” by the editors of the American Chemical Society journals, who recognise the “importance to the global scientific community” of the Leipzig researchers’ work and see it as a breakthrough in the accurate description of phase transition phenomena in disordered porous materials.

In mesoporous materials, the pore openings are far smaller than in a normal sponge: their diameters range from 2 to 50 nanometres and are invisible to the naked eye. Nevertheless, they have a number of interesting properties, including with regard to separating substances. This occurs as a function of molecule and pore size, for example.

Until now, scientific experiments have only been able to approximate the desired properties of these materials. “So it is more down to experience whether you can determine which of the structures can be used for which applications,” says the physicist. The problem is that these materials are mostly disordered, which means that pores of different sizes in the material form a complex network structure.

Researchers at Leipzig University developed a model that determines the features that can be observed in such complex pore networks. Professor Valiullin describes the approach as follows: “We can statistically describe how the individual pores in these networks are coupled to each other. We marry disorder with order.” This makes it possible to determine the physical phenomena that need to be understood in gas-liquid and solid-liquid phase transitions, for example. And not only in theory: using special mesoporous modelling, it was possible to prove with the aid of modern nuclear magnetic resonance methods that the theoretical results can also be directly applied in practice.

This should make it easier to use such materials in the future, for example to help release drugs into the human body over an extended period – precisely when necessary and desired. Other potential applications for such materials include sensor technology or energy storage and conversion.

Featured image: Professor Rustem Valiullin with a nuclear magnetic resonance spectrometer. © Photo: Swen Reichhold, Leipzig University


Reference: Henry R. N. B. Enninful, Daniel Schneider, Dirk Enke, and Rustem Valiullin, “Impact of Geometrical Disorder on Phase Equilibria of Fluids and Solids Confined in Mesoporous Materials”, Langmuir 2021. https://pubs.acs.org/doi/10.1021/acs.langmuir.0c03047
https://doi.org/10.1021/acs.langmuir.0c03047


Provided by Leipzig University

Artificial Light Also Influences Plant Pollination During the Day (Botany)

Street lamps change the number of times insects visit flowers not only at night, but also during the day. Artificial light at night thus indirectly influences the entire community of pollinators and plants – with unknown consequences for the ecosystem, as researchers from the University of Zurich and Agroscope have shown for the first time.

In the last few years the spread of artificial light has increased massively worldwide. This has negative consequences for the survival and reproduction of nocturnal organisms. Important ecological processes such as the pollination of plants by nocturnal insects are impaired by artificial light – which can have consequences for the yield of agricultural crops and the reproduction of wild plants.

Scientists from the University of Zurich and Agroscope are now showing for the first time that artificial light also affects the pollination behavior of insects during the day. In an experiment they illuminated natural plant-pollinator communities on six natural meadows at night with commercial street lamps. Six other natural meadows remained in the dark. In their analysis, the research team focused on 21 naturally occurring plant species as well as on the insect groups of the two-winged (Diptera), the hymenoptera (Hymenoptera) and the beetle (Coleoptera).

Different interactions depending on the type of plant

“Our results suggest that artificial light at night changes the number of plant-pollinator interactions during the day, depending on the type of plant,” says Eva Knop from the University Research Center on Global Change and Biodiversity at the University of Zurich and Agroscope. Three plant species received significantly fewer pollination visits during the day and another species slightly fewer. Another plant species, on the other hand, was visited a lot more with LED light and another a little more.

Interestingly, the activity of the nocturnal pollinators was also different in artificial light: For example, the forest cranesbill (Geranium sylvaticum) was visited equally often in lighted and dark meadows, but the insects differed: while the two-winged birds avoided the lighting, the beetles were more likely attracted. There were similar trends in two other plant species.

Indirect ecological consequences of light pollution

So far, indirect ecological effects of light pollution have been neglected. “Since insects play a central role in the pollination of cultivated and wild plants and are threatened by habitat destruction and climate change regardless of artificial light, it is important to clarify these indirect mechanisms,” says Knop.

Based on the results, Eva Knop and her colleagues demand: “The ecological consequences of light pollution should be researched more closely and measures developed to prevent negative effects on the environment.” Even if it is hard to imagine populated areas without artificial light, there are possibilities for it: Public lighting in combination with new technologies could be carefully planned and reduced to a minimum.

Featured image: Artificial light at night also changes the number of plant-pollinator interactions during the day. (Image UZH / Agroscope)


Literature:

Giavi S., Fontaine C., Knop E. (2021) Impact of artificial light at night on diurnal plant-pollinator interactions. Nature Communications, March 16, 2021. Doi: 10.1038/s41467-021-22011-8


Provided by University of Zurich

Elusive Protein Complex Could Hold the Key to Treating Chromosomal Disorders (Biology)

Scientists report on the structural and molecular factors governing the stability of a protein complex involved in DNA repair pathways in cells

The cells in our body are constantly fighting off the threat of cancer by repairing damaged DNA. In a new study, scientists from Tokyo University of Science investigate the structure of an elusive protein complex that plays a key role in the activation of the “Fanconi anemia pathway” involved in DNA repair, and report on the factors governing its stability. Their insights can potentially help find novel treatments disorders involving chromosomal instability, including cancer.

One of the most vital functions performed by the cells in our body is DNA repair, a task so crucial to our well-being that failing to execute it can lead to consequences as dreadful as cancer. The process of DNA repair involves a complex interplay between several gene pathways and proteins. One such pathway is the “Fanconi anemia (FA) pathway,” whose genes participate in DNA repair. FANCM, a component of this pathway, is tasked with the elimination of harmful DNA “inter-strand cross-links,” and interacts with another component called MHF in order to function. The importance of the FANCM-MHF complex is well-documented: its loss can result in chromosomal instabilities that can lead to diseases such as FA itself and cancer. However, little is known about its structure and the basis of its stability.

Against this backdrop, Associate Professor Tatsuya Nishino and his colleague Dr. Sho Ito from Tokyo University of Science decided to explore the crystalline structure of this intriguing complex using X-ray diffraction techniques. “DNA damage and chromosome segregation are mechanisms necessary for the maintenance and inheritance of genes possessed by all organisms. MHF (also known as CENP-SX) is an enigmatic complex that plays a role in DNA repair and chromosome segregation. We wanted to find out how it performs these two different functions in the hope that it might give us insights into novel phenomena,” explains Prof. Nishino. Their findings are published in Acta Crystallographica Section F: Structural Biology Communications.

The scientists prepared a recombinant version of the FANCM-MHF complex, consisting of FANCM from chickens and MHF1 and MHF2. They were able to purify three different types of protein crystals―tetrahedral, needle-haped, and rod-shaped―from similar crystallization conditions. Surprisingly, upon determining the structure with X-ray crystallography, they found that two of the crystal forms (tetrahedral and needle-shaped) contained only the MHF complex without FANCM.

Intrigued by this discovery, the scientists used biochemical techniques to examine what caused the FANCM-MHF complex to disassemble. They attributed it to the presence of a compound called 2-methyl-2, 4-pentanediol (MPD), an organic solvent commonly used in crystallography, and exposure to an oxidizing environment.

But, how exactly does the dissociation happen? The scientists believe that this may have been caused partly by certain non-conserved amino acids in the chicken FANCM which causes the complex to aggregate with other FANCM-MHF complexes and disassemble. Additionally, they surmise that the small, flexible structure of MPD may have also allowed it to bind to and facilitate the release of FANCM, dismantling the complex.

The findings are extraordinary and can be used to improve the stability of the FANCM-MHF complex for future studies on its structure and function. Dr. Ito believes we have much to expect in the future from this complex. “A good understanding of this complex can help us treat cancer and genetic diseases, create artificial chromosomes, and even develop new biotechnological tools,” he speculates.

Thanks to Prof. Nishino and Dr. Ito’s efforts, we are already one step closer to that goal!

Featured image: Dissociation of the FANCM-MHF complex: After X-ray crystallography (XRC), scientists found that tetrahedral and needle-shaped forms of recombinant FANCM-MHF complex contained only MHF without FANCM. Upon biochemical analysis, they found that this was due to the organic solvent used in sample preparation for XRC and exposure to oxidizing conditions. Image credit: Tatsuya Nishino from Tokyo University of Science


Reference

Titles of original papers: Structural analysis of the chicken FANCM-MHF complex and its stability, Journal: Acta Crystallographica Section F: Structural Biology Communications, DOI: 10.1107/S2053230X20016003


Provided by Tokyo University of Science