The Secret of How Frogs See the World (Biology)

It’s clear to see that species like tree frogs have gigantic eyes, but the visual systems of most frogs have gone largely unstudied by scientists.

Leptopelis brevirostris, Bioko Island, Equatorial Guinea.Source: Christian Irian. See ‘Eye size and investment in frogs and toads correlate with adult habitat, activity pattern and breeding ecology’ by Thomas et al., published in Proc. R. Soc. B.

An international, interdisciplinary team of researchers is starting to change that. In the first study to come out of the collaboration, the team examined museum specimens representing all 55 frog families to test hypotheses about the evolution of frog eye size and its relationship to different aspects of their lifestyles. The results show that, overall, frogs are investing a lot of energy in maintaining their eyes and that vision is likely important to their survival and reproductive success.

Rayna Bell, assistant curator of herpetology at the California Academy of Sciences and one of the new paper’s authors, says that although frogs were an early model for studying vision at the turn of the 20th century, the research was limited to a small number of easily accessible species.

“It was not reflective of the enormous diversity of frogs that we know exist today,” she says. “Our understanding of vision in frogs has lagged behind such research in other vertebrates, such as fishes, birds, and mammals.”

There are more than 7,000 frog species living in a variety of different habitats and ecosystems: Some spend their entire lives underwater, others live in the treetops, and others burrow underground.

Ceratophrys cornuta, the Amazonian Horned Frog from Kaw, French Guiana.Source: Christian L. Cox. See ‘Eye size and investment in frogs and toads correlate with adult habitat, activity pattern and breeding ecology’ by Thomas et al., published in Proc. R. Soc. B.

The first goal of Bell and her colleagues was to broaden out from those initial frog species whose vision had been characterized historically and document the diversity in eye size among frogs. To do this, her team depended primarily on specimens preserved in natural history collections around the world. They measured eye size in 220 frog species representing all 55 families.

The study revealed that frogs have relatively large eyes for their body size, with certain species of tree frog coming out on top. Bell says that relative eye size is an indication of how much of an organism’s energy budget is invested in eye tissue.

“Eyes are metabolically expensive to maintain, so if you have large eyes, that suggests you are relying pretty heavily on vision and investing energy in maintaining that eye tissue,” she says.

Incilus alvarius, the Sonoran Desert Toad from Sonora, Mexico.Source: Jeffrey W. Streicher. See ‘Eye size and investment in frogs and toads correlate with adult habitat, activity pattern and breeding ecology’ by Thomas et al., published in Proc. R. Soc. B.

The team also tested whether eye sizes were correlated with life history traits like where the frogs lived or whether they are active at day or night. As is seen in other animals, there was a strong association between habitat type and eye size, with species that live underground or in murky water having reduced eyes. It’s likely that in these light-deficient environments, animals are not relying as much on vision and it’s not worth it to invest in growing large eyes.

Bell says this study is an important first step in understanding the diversity of eye size in frogs. Next, she and her colleagues are looking at the genetic underpinnings of this variation and characterizing photoreceptor sensitivity in different frogs. She’s also interested in how frogs’ visual systems change as they develop from aquatic tadpoles into adults who might live in a very different habitat.

“It’s interesting from an evolutionary perspective but also from a behavioral perspective, in terms of understanding how frogs are sensing and interacting with their environment,” says Bell.

“We know that they have big eyes. We don’t know specifically why but we’re working on it.”

References: Thomas KN, Gower DJ, Bell RC, Fujita MK, Schott RK, and Streicher JW. (2020). Eye size and investment in frogs and toads correlate with adult habitat, activity pattern and breeding ecology. Proceedings of the Royal Society B 287: 20201393. Doi: 10.1098/rspb.2020.1393.

This article is republished here from psychology today under common creative licenses

The First Demonstration Of Braiding In Photonic Topological Zero Modes (Physics)

Physics theory suggests that exotic excitations can exist in the form of bound states confined in the proximity of topological defects, for instance, in the case of Majorana zero modes that are trapped in vortices within topological superconducting materials. Better understanding these states could aid the development of new computational tools, including quantum technologies.

Schematic depiction of the structure that performs the braiding process with light. (a) Waveguide array structure, where light is braided opposite directions in the two arrays, and then interfered; (b) diagram showing the displacement of waveguide array coordinates required to perform the braiding operation, where \alpha denotes the angle of a ‘vortex at infinity’ that is braided around the array. Credit: Noh et al.

One phenomenon that has attracted attention over the past few years is “braiding,” which occurs when electrons in particular states (i.e., Majorana fermions) are braided with one another. Some physicists have theorized that this phenomenon could enable the development of a new type of quantum technology, namely topological quantum computers.

Researchers at Pennsylvania State University, University of California-Berkeley, Iowa State University, University of Pittsburgh, and Boston University have recently tested the hypothesis that braiding also occurs in particles other than electrons, such as photons (i.e., particles of light). In a paper published in Nature Physics, they present the first experimental demonstration of braiding using photonic topological zero modes.

“The idea was inspired by a well-known architecture for building a quantum computer; one that has been theoretically predicted but never experimentally realized,” Mikael C. Rechtsman, one of the researchers who carried out the study, told Phys.org. “To perform operations in this previously theorized type of quantum computer, Majorana fermions are moved around one another—this is called braiding. In a previous theoretical study, some of my colleagues predicted that braiding is a general phenomenon that can be applied not only to electrons, but to photons, as well. In our new paper, we demonstrate this experimentally, using an array of waveguides that are similar to fiber optic cables.”

Rechtsman and his colleagues measured the geometric phase of the braiding phenomenon by conducting an experiment in which two different braiding processes interfered with one another. In one of these processes, topological defects were braided clockwise, while in the other one, they were braided counterclockwise.

Interference is a feature of wave mechanics that is often used to study physical systems. This feature is responsible for countless wave-related phenomena, ranging from rainbow swirls on soap bubbles to gravitational waves.

“We observed that the light from the two opposite braiding processes interfered destructively, which confirmed our theoretical prediction that the processes have a relative braiding phase of pi,” Thomas Schuster, another researcher involved in the study, told Phys.org. “Crucially, due to the particularly simple action of braiding, the measurement we collected allows us to extrapolate the behavior of any braiding process. In particular, it verifies that when performing multiple braids in a row, the order of the braiding matters.”

Rechtsman, Schuster and their colleagues demonstrated the existence of a generalizable braiding process that they refer to as non-Abelian braiding, which is a simple manifestation of a feature that researchers have sought for in electronic systems for several years. Their results suggest that braiding may, in fact, be a common phenomenon that reaches beyond electrons and also applies to light, sound, water and potentially even seismic waves.

In addition to highlighting the possibility of using photonic lattices as a platform to study topological defects and their braiding, this study could inspire other research teams to examine braiding in the context of other phenomena that involve the production of waves. Rechtsman, Schuster and their colleagues now plan to continue investigating the braiding of photonic topological zero modes, along with other topological phenomena that could also be applied to light-related systems.

“Braiding is a topological phenomenon that has been traditionally associated with electronic devices,” Rechtsman said. “We now hope to show that a whole class of topological phenomena can potentially be useful not only for electronic devices, but also photonic devices, such as lasers, medical imaging devices, telecommunications systems, and others. We also expect that this new type of topological physics could be applied to quantum information systems, particularly those based on photons.”

References: (1) Noh, J., Schuster, T., Iadecola, T. et al. Braiding photonic topological zero modes. Nat. Phys. 16, 989–993 (2020). Doi: https://doi.org/10.1038/s41567-020-1007-5 (2) Thomas Iadecola, Thomas Schuster, and Claudio Chamon, “Non-Abelian Braiding of Light”, Physical Review Letters, Phys. Rev. Lett. 117, 073901 – Published 10 August 2016. Link: https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.117.073901.

© 2020 Science X Network

Scientists Find Upper Limit For The Speed Of Sound (Physics)

A research collaboration between Queen Mary University of London, the University of Cambridge and the Institute for High Pressure Physics in Troitsk has discovered the fastest possible speed of sound.

The result- about 36 km per second—is around twice as fast as the speed of sound in diamond, the hardest known material in the world.

Waves, such as sound or light waves, are disturbances that move energy from one place to another. Sound waves can travel through different mediums, such as air or water, and move at different speeds depending on what they’re travelling through. For example, they move through solids much faster than they would through liquids or gases, which is why you’re able to hear an approaching train much faster if you listen to the sound propagating in the rail track rather than through the air.

Einstein’s theory of special relativity sets the absolute speed limit at which a wave can travel which is the speed of light, and is equal to about 300,000 km per second. However until now it was not known whether sound waves also have an upper speed limit when travelling through solids or liquids.

The study, published in the journal Science Advances, shows that predicting the upper limit of the speed of sound is dependent on two dimensionless fundamental constants: the fine structure constant and the proton-to-electron mass ratio.

These two numbers are already known to play an important role in understanding our Universe. Their finely-tuned values govern nuclear reactions such as proton decay and nuclear synthesis in stars and the balance between the two numbers provides a narrow ‘habitable zone’ where stars and planets can form and life-supporting molecular structures can emerge. However, the new findings suggest that these two fundamental constants can also influence other scientific fields, such as materials science and condensed matter physics, by setting limits to specific material properties such as the speed of sound.

The scientists tested their theoretical prediction on a wide range of materials and addressed one specific prediction of their theory that the speed of sound should decrease with the mass of the atom. This prediction implies that the sound is the fastest in solid atomic hydrogen. However, hydrogen is an atomic solid at very high pressure above 1 million atmospheres only, pressure comparable to those in the core of gas giants like Jupiter. At those pressures, hydrogen becomes a fascinating metallic solid conducting electricity just like copper and is predicted to be a room temperature superconductor. Therefore, researchers performed state-of-the-art quantum mechanical calculations to test this prediction and found that the speed of sound in solid atomic hydrogen is close to the theoretical fundamental limit.

Professor Chris Pickard, Professor of Materials Science at the University of Cambridge, said: “Soundwaves in solids are already hugely important across many scientific fields. For example, seismologists use sound waves initiated by earthquakes deep in the Earth interior to understand the nature of seismic events and the properties of Earth composition. They’re also of interest to materials scientists because sound waves are related to important elastic properties including the ability to resist stress.”

References: K. Trachenko, B. Monserrat, “Speed of sound from fundamental physical constants”, Science Advances 09 Oct 2020, Vol. 6, no. 41, eabc8662 DOI: 10.1126/sciadv.abc8662 link: https://advances.sciencemag.org/content/6/41/eabc8662

Provided by Queen Mary, University of London

Planting Parasites: Unveiling Common Molecular Mechanisms Of Parasitism And Grafting (Botany)

β-1,4-glucanase, a cell wall degrading enzyme, is integral for plant parasitism and cross-species grafting in the plant family Orobanchaceae.

Using the model Orobanchaceae parasitic plant Phtheirospermum japonicum, scientists from Nagoya University and other research institutes from Japan have discerned the molecular mechanisms underlying plant parasitism and cross-species grafting, pinpointing enzyme β-1,4-glucanase (GH9B3) as an important contributor to both phenomena. Targeting this enzyme may help control plant parasitism in crops. Also, this mechanism can be exploited for novel cross-species grafting techniques to realize the goal of sustainable agricultural technologies.

(Left) Parasitism between the roots of P. japonicum and Arabidopsis. (Right) Grafting of P. japonicum with Arabidopsis. Yellow arrow heads indicate the grafted points. ©Michitaka Notaguchi

Plant parasitism is a phenomenon by which the parasite plant latches onto and absorbs water and nutrients from a second host plant, with the help of a specialized organ called the “haustorium.” Once the haustorium forms, specific enzymes then help in forming a connection between the tissues of the parasite and host plants, known as a “xylem bridge,” which facilitates the transport of water and nutrients from the host to the parasite.

A similar mechanism is involved in the process of artificial stem grafting, during which, the cell walls of the two different plant tissues at the graft junction become thinner and compressed, a phenomenon made possible by specific cell wall modifying enzymes. Cell wall modification has also been implicated to play a role in parasitism in different lineages of parasitic plants.

Therefore, the research team, led by Dr Ken-ichi Kurotani of Nagoya University, hypothesized that similar genes and enzymes should be involved in the process of parasitism and cross-species grafting. “To investigate molecular events involved in cell-cell adhesion between P. japonicum and the host plant, we analyzed the transcriptome for P. japonicum-Arabidopsis parasitism and P. japonicum-Arabidopsis grafting,” reports Dr Kurotani. When a gene in a cell is activated, it produces an RNA “transcript” that is then translated into an active protein, which is then used by the cell to perform various activities. A “transcriptome” is the complete set of RNA transcripts that the genome of an organism produces under various diverse conditions. The findings of their experiments are published in Nature’s Communications Biology.

Comparison of the parasitism and graft transcriptomes revealed that genes associated with wound healing, cell division, DNA replication, and RNA synthesis were highly upregulated during both events, indicating active cell proliferation at both the haustorium and graft interface.

“What’s more, we found an overlap between the transcriptome data from this study and that from grafting between Nicotiana and Arabidopsis, another angiosperm,” reports Dr Michitaka Notaguchi, the co-corresponding author of the study. Glycosyl hydrolases are enzymes that specifically target the breakdown of cellulose, the primary component of plant cell walls. A β-1,4-glucanase identified in P. japonicum belongs to the glycosyl hydrolase 9B3 (GH9B3) family; an enzyme from the same family was recognized to be crucial for cell-cell adhesion in Nicotiana by Dr Notaguchi’s group.

Further experiments showed that GH9B3-silenced P. japonicum could form the haustorium with Arabidopsis but could not form a functional xylem bridge, meaning that the P. japonicum β-1,4-glucanase is integral for the plant’s parasitic activity. Further, high GH9B3 RNA transcript levels were observed during artificial grafting experiments, thereby proving that the enzyme plays an integral role in both parasitism and grafting mechanisms.

The transcriptome data generated in this study can be used to unearth additional genes and enzymes involved in plant parasitism. Additionally, further research along these directions will help scientists develop specific molecular approaches to arrive at sustainable cross-species grafting alternatives.

References: Kurotani, K., Wakatake, T., Ichihashi, Y. et al. Host-parasite tissue adhesion by a secreted type of β-1,4-glucanase in the parasitic plant Phtheirospermum japonicum. Commun Biol 3, 407 (2020). https://doi.org/10.1038/s42003-020-01143-5 link: https://www.nature.com/articles/s42003-020-01143-5

Provided by Nagoya University

Hydroxychloroquine Does Not Counter SARS-CoV-2 In Hamsters, High Dose Of Favipiravir Does (Medicine)

Virologists at the KU Leuven Rega Institute have been working on two lines of SARS-CoV-2 research: searching for a vaccine to prevent infection, and testing existing drugs to see which one can reduce the amount of virus in infected people.

Lab technicians have to wear protective suits when working with infectious SARS-CoV-2 samples. ©Layla Aerts – KU Leuven

To test the efficacy of the vaccine and antivirals preclinically, the researchers use hamsters. The rodents are particularly suitable for SARS-CoV-2 research because the virus replicates itself strongly in hamsters after infection. Moreover, hamsters develop a lung pathology similar to mild COVID-19 in humans. This is not the case with mice, for example.

For this study, the team of Suzanne Kaptein (PhD), Joana Rocha-Pereira (PhD), Professor Leen Delang, and Professor Johan Neyts gave the hamsters either hydroxychloroquine or favipiravir – a broad-spectrum antiviral drug used in Japan to treat influenza – for four to five days. They tested several doses of favipiravir. The hamsters were infected with the SARS-CoV-2 virus in two ways: by inserting a high dose of virus directly into their noses or by putting a healthy hamster in a cage with an infected hamster. Drug treatment was started one hour before the direct infection or one day before the exposure to an infected hamster. Four days after infection or exposure, the researchers measured how much of the virus was present in the hamsters.

Hydroxychloroquine versus favipiravir

Treatment with hydroxychloroquine had no impact: the virus levels did not decrease and the hamsters were still infectious. “Despite the lack of clear evidence in animal models or clinical studies, many COVID-19 patients have already been treated with hydroxychloroquine,” explains Joana Rocha-Pereira. “Based on these results and the results of other teams, we advise against further exploring the use of hydroxychloroquine as a treatment against COVID-19.”

A high dose of favipiravir, however, had a potent effect. A few days after the infection, the virologists detected hardly any infectious virus particles in the hamsters that received this dose and that had been infected intranasally. Moreover, hamsters that were in a cage with an infected hamster and had been given the drug did not develop an obvious infection. Those that had not received the drug all became infected after having shared a cage with an infected hamster.

A low dose of the drug favipiravir did not have this outcome. “Other studies that used a lower dose had similar results,” Professor Delang notes. “The high dose is what makes the difference. That’s important to know, because several clinical trials have already been set up to test favipiravir on humans.”

Hamsters are particularly suitable for SARS-CoV-2 research. © Layla Aerts – KU Leuven.

Cautious optimism

The researchers are cautiously optimistic about favipiravir. “Because we administered the drug shortly before exposing the hamsters to the virus, we could establish that the medicine can also be used prophylactically, so in prevention,” Suzanne Kaptein notes.

“If further research shows that the results are the same in humans, the drug could be used right after someone from a high-risk group has come into contact with an infected person. It may likely also be active during the early stages of the disease.”

General preventive use is probably not an option, however, because it is not known whether long-term use, especially at a high dose, has side effects.

No panacea

Further research will have to determine whether humans can tolerate a high dose of favipiravir. “In the hamsters, we detected hardly any side effects,” says Delang. In the past, the drug has already been prescribed in high doses to Ebola patients, who appear to have tolerated it well.

“Favipiravir is not a panacea,” the researchers warn. This flu drug, nor any other drug, has not been specifically developed against coronaviruses. As a result, the potency of favipiravir is to be considered moderate at best.

The study also highlights the importance of using small animals to test therapies against SARS-CoV-2 in vivo. “Our hamster model is ideally suited to identify which new or existing drugs may be considered for clinical studies,” explains Professor Johan Neyts. “In the early days of the pandemic, such a model was not yet available. At that time, the only option was to explore in patients whether or not a drug such as hydroxychloroquine could help them. However, testing treatments on hamsters provides crucial information that can prevent the loss of valuable time and energy with clinical trials on drugs that don’t work.”

Not all research models are equal

Kaptein, Rocha-Pereira, Delang and Neyts recently contributed to a commentary in Nature Communications in which they give additional context to the contradictory messages that have been circulating about (hydroxy)chloroquine. In the early days of the pandemic, several studies were set up to test these drugs in cell cultures. The results suggested that they could have an antiviral effect. As a result, clinical trials were organised to test the drugs on humans. However, cell cultures are not the best proxy for the human body, and no conclusive effect was found in humans.

In their commentary, the authors describe several recent studies on human organ-on-chip and other complex in vitro models, mice, hamsters, and non-human primates. Each of these studies demonstrates that hydroxychloroquine and chloroquine do not have the efficacy suggested by the studies in cell cultures. Therefore, the authors conclude that these malaria drugs are very unlikely to be effective in humans as a COVID-19 treatment.

References: Suzanne Kaptein, Johan Neyts, Joana Rocha-Pereira, Leen Delang et al., “Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity”, PNAS, 2020. Doi: https://doi.org/10.1073/pnas.2014441117 link: https://www.pnas.org/content/early/2020/10/08/2014441117

Provided by Ku Leuven

When It Comes To Genes, We’re All Much More Alike Than Different (Biology)

You’re 99.9 percent genetically identical to every human being you meet. George Clooney, Donald Trump, Serena Williams, your annoying coworker, the Pope — they’re all basically the same as you (genetically speaking).

Whether you’ve experienced culture shock in a foreign country or just sat down to dinner with your family and felt you couldn’t possibly be related to those weirdos, everyone has felt detached from other human beings at some point. At those moments, it’s good to remember the simple fact that we are all more alike than we are different.

Your genome is made up of 3 billion base pairs, the teeny-tiny chemical units that make up the genes that form the twisting, paired strands known as DNA. That means that between any two people, roughly 2.999 billion base pairs will be exactly the same. To put that another way, if you printed your genome, it would take up to 262,000 pages, and only 500 would differ from person to person.

Why is this? It’s because most of our genome does the same thing across the animal kingdom. Consider the differences between your house and the Notre Dame Cathedral. At first glance, they look very different, but they share a lot of similarities: both have foundations, doorways, windows, and a roof, to name just a few. The form these take differ, but their basic building blocks are the same. It’s similar with DNA. Most of the genetic building blocks are the same across species. The tiny differences between two organisms come down to a sliver of their genomes.

As a result, you’re 94 percent identical to your dog and 90 percent identical to your cat, genetically speaking. For cows, it’s 80 percent. You’re even strikingly similar to insects: the fruit fly, a popular subject of genomic research, shares 60 percent of your genes (including two-thirds of cancer genes!).

Humans are much more alike than they are different. In a world that seems to have more divisions every day, it’s important to remember our shared humanity. It’s right there in our genes.

Oncotarget: Characterization Of Porcine Hepatocellular Carcinoma For Liver Cancer (Medicine)

Volume 11, Issue 28 of Oncotarget features “Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation” by Gaba et, al. which reported that reliable development of Oncopig HCC cell lines was demonstrated through hepatocyte isolation and Cre recombinase exposure across 15 Oncopigs.

CRISPR/Cas9-mediated disruption of Oncopig KRASG12D and TP53R167H transgenes. (A) Schematic representation of the Oncopig transgene showing gRNA target sites and primers used for PCR. IRES, Internal ribosome entry site. (B) KRASG12D and TP53R167H editing efficiencies at multiple time points post transfection with Cas9 and gRNAs. (C) Frameshift mutations resulting in protein truncation for 2 Oncopig TP53R167H KO HCC cell lines developed via single cell clone isolation and screening. Dashed line marks the cleavage position, and dashed grey boxes represent nucleotide deletions. Dotted regions represent frameshifts in predicted protein sequences. (D) Positive arginase-1 staining (brown) of parental and TP53R167H KO cell lines (scale bar, 300 μm). (E) Cellular proliferation of Oncopig parental and TP53R167H KO HCC cell lines. Values represent mean ± S. D. (n ? 3). **indicates P < 0.001. ©Kyle M. Schachtschneider

Oncopig and human HCC cell lines displayed similar cell cycle lengths, alpha-fetoprotein production, arginase-1 staining, chemosusceptibility, and drug-metabolizing enzyme expression.

The ability of Oncopig HCC cells to consistently produce tumors in vivo was confirmed via subcutaneous injection into immunodeficient mice and Oncopigs.

Reproducible development of intrahepatic tumors in an alcohol-induced fibrotic microenvironment was achieved via engraftment of SQ tumors into fibrotic Oncopig livers.

Finally, Oncopig HCC cells are amenable to gene editing for the development of personalized HCC tumors.

Dr. Kyle M. Schachtschneider from The Department of Radiology and The Biological Resources Laboratory at The University of Illinois at Chicago as well as The National Center for Supercomputing Application at The University of Illinois at Urbana-Champaign said, “Hepatocellular carcinoma (HCC)–the most common type of primary liver cancer–is an aggressive cancer that spans more than 850,000 new yearly diagnoses and causes 800,000 annual deaths, representing the fifth most common cancer globally and the second most common cause of cancer-related death worldwide.”

The rabbit VX2 model has been considered the most relevant and widely used model to test HCC LRTs to date.

As such, there is a crucial need for more clinically relevant large animal models that faithfully recapitulate human HCC to address unmet clinical needs and serve as a bridge between murine studies and clinical practice.

This study describes the utilization of the Oncopig Cancer Model for the development of a clinically relevant, translational porcine HCC model.

The Oncopig Cancer Model is a transgenic pig model that develops site and cell-specific tumors following Cre recombinase induced expression of heterozygous KRASG12D and TP53R167H transgenes.

The large size of the pig and its similarities with humans in terms of anatomy, physiology, metabolism, immunity, and genetics make it an ideal model species for the development of a large animal cancer model.

Development of Oncopig HCC cell lines has been previously described, however, prior work was limited to characterization of HCC cell lines derived from three Oncopigs, minimal in vitro and in vivo profiling, and no description of intrahepatic tumors.

As such, this study was undertaken to test the hypothesis that phenotypically consistent Oncopig HCC cells that faithfully recapitulate the in vitro features of human HCC can be developed across a large Oncopig cohort and that these cells can be utilized to develop clinically relevant intrahepatic HCC tumors in Oncopigs.

The Schachtschneider Research Team concluded in their Oncotarget Research Paper, “the Oncopig HCC model offers a novel, physiologically and anatomically relevant cancer model for which a multitude of innovative therapeutic modalities can be applied and tested while significantly reducing the costs, confounding variables seen in human subjects, and lengthy conduct of human clinical trials. Importantly, the Oncopig can be utilized to conduct correlative studies for more efficient and consistent investigation of new therapies. Its size allows for utilization of the same methods and instruments used in human clinical practice, including CT and magnetic resonance imaging technologies. This model is thus amenable to developing and establishing medical imaging standards related to diagnosing HCC tumors and tracking treatment response using accepted radiologic criteria, a critical facet of therapeutic discovery and validation. Importantly, the Oncopig is also immunocompetent, lending itself to investigation of immunotherapies [32]. Therefore, the Oncopig fulfills the currently unmet clinical modeling needs for HCC, particularly for pilot investigations of experimental therapies or experimental therapeutic combinations not feasible in human subjects.”

“The Oncopig HCC model offers a novel, physiologically and anatomically relevant cancer model for which a multitude of innovative therapeutic modalities can be applied and tested while significantly reducing the costs, confounding variables seen in human subjects, and lengthy conduct of human clinical trials. Importantly, the Oncopig can be utilized to conduct correlative studies for more efficient and consistent investigation of new therapies. Its size allows for utilization of the same methods and instruments used in human clinical practice, including CT and magnetic resonance imaging technologies. This model is thus amenable to developing and establishing medical imaging standards related to diagnosing HCC tumors and tracking treatment response using accepted radiologic criteria, a critical facet of therapeutic discovery and validation. Importantly, the Oncopig is also immunocompetent, lending itself to investigation of immunotherapies [32]. Therefore, the Oncopig fulfills the currently unmet clinical modeling needs for HCC, particularly for pilot investigations of experimental therapies or experimental therapeutic combinations not feasible in human subjects.”

References: Gaba R. C., Elkhadragy L., Boas F. Edward, Chaki S., Chen H. H., El-Kebir M., Garcia K. D., Giurini E. F., Guzman G., LoBianco F. V., Neto M. F., Newson J. L., Qazi A., et al Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation. Oncotarget. 2020; 11: 2686-2701. Retrieved from https://www.oncotarget.com/article/27647/text/ link: https://www.oncotarget.com/article/27647/text/

Provided by Impact Journals LLC

Researchers 3D Print Unique Micro-Scale Fluid Channels Used For Medical Testing (Engineering / Medicine)

In a groundbreaking new study, researchers at the University of Minnesota, in collaboration with the U.S. Army Combat Capabilities Development Command Soldier Center, have 3D printed unique fluid channels at the micron scale that could automate production of diagnostics, sensors, and assays used for a variety of medical tests and other applications.

Researchers at the University of Minnesota are the first to 3D print microfluidic channels on a curved surface, providing the initial step for someday printing them directly on the skin for real-time sensing of bodily fluids. Credit: McAlpine Group, University of Minnesota.

The team is the first to 3D print these structures on a curved surface, providing the initial step for someday printing them directly on the skin for real-time sensing of bodily fluids. The research is published in Science Advances, a peer-reviewed scientific journal published by the American Association for the Advancement of Science (AAAS).

Microfluidics is a rapidly growing field involving the control of fluid flows at the micron scale (one millionth of a meter). Microfluidics are used in a wide range of application areas including environmental sensing, medical diagnostics (such as COVID-19 and cancer), pregnancy testing, drug screening and delivery, and other biological assays.

The global microfluidics market value is currently estimated in the billions of dollars. Microfluidic devices are typically fabricated in a controlled-environment cleanroom using a complex, multi-step technique called photolithography. The fabrication process involves a silicone liquid that is flowed over a patterned surface and then cured so that the patterns form channels in the solidified silicone slab.

In this new study, the microfluidic channels are created in a single step using 3D printing. The team used a custom-built 3D printer to directly print the microfluidic channels on a surface in an open lab environment. The channels are about 300 microns in diameter—about three times the size of a human hair (one one-hundredth of an inch). The team showed that the fluid flow through the channels could be controlled, pumped, and re-directed using a series of valves.

Printing these microfluidic channels outside of a cleanroom setting could provide for robotic-based automation and portability in producing these devices. For the first time, the researchers were also able to print microfluidics directly onto a curved surface. In addition, they integrated them with electronic sensors for lab-on-a-chip sensing capabilities.

“This new effort opens up numerous future possibilities for microfluidic devices,” said Michael McAlpine, a University of Minnesota mechanical engineering professor and senior researcher on the study. “Being able to 3D print these devices without a cleanroom means that diagnostic tools could be printed by a doctor right in their office or printed remotely by soldiers in the field.”

But McAlpine said the future is even more compelling.

“Being able to print on a curved surface also opens up many new possibilities and uses for the devices, including printing microfluidics directly on the skin for real-time sensing of bodily fluids and functions,” said McAlpine, who holds the Kuhrmeyer Family Chair Professorship in the Department of Mechanical Engineering.

In addition to McAlpine, researchers involved in the study include University of Minnesota mechanical engineering graduate student Ruitao Su; University of Minnesota electrical and computer engineering researchers Jiaxuan Wen and Qun Su (both Ph.D. candidates); Professor Steven Koester, who is the Louis John Schnell Professor in Electrical and Computer Engineering; and U.S. Army Combat Capabilities Development Command Soldier Center researchers Dr. Michael S. Wiederoder and Dr. Joshua R. Uzarski.

The research was funded primarily by the U.S. Army Research Office via the Soldier Center, the National Institute of Health’s National Institute of Biomedical Imaging and Bioengineering, and the Minnesota Discovery, Research, and InnoVation Economy (MnDRIVE) Initiative through the State of Minnesota. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nanotechnology Coordinated Infrastructure (NNCI) Network.

References: Ruitao Su, Jiaxuan Wen, Qun Su, Michael S. Wiederoder, Steven J. Koester, Joshua R. Uzarski and Michael C. McAlpine, “3D printed self-supporting elastomeric structures for multifunctional microfluidics”, Science Advances 09 Oct 2020: Vol. 6, no. 41, eabc9846 DOI: 10.1126/sciadv.abc9846 link: https://advances.sciencemag.org/content/6/41/eabc9846/

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