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Pollen Levels Might Trigger Flares of Urologic Chronic Pelvic Pain (Medicine)

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As anyone living with hay fever can attest, days with high pollen counts can bring attacks of sneezing, nasal congestion and other allergy symptoms. Now, a new study suggests rising pollen levels may also trigger flare-ups of pain and other symptoms in patients with urologic chronic pelvic pain syndrome (UCPPS), reports The Journal of Urology®, Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.

“Our study provides evidence to suggest increased pollen counts may trigger symptom flares in people living with UCPPS,” comments Siobhan Sutcliffe, PhD, ScM, MHS, of Washington University School of Medicine, St Louis. “If the association with pollen levels is confirmed through future studies, it may help us to understand how flares occur in individuals with urologic chronic pelvic pain, as well as how to prevent or treat these otherwise unpredictable attacks.”

Patients with UCPPS experience flares of pelvic or bladder pain and urinary symptoms, which can be frequent and disabling. The cause of UCPPS is unknown, but talking to patients provides some intriguing clues – including the fact that patients with UCPPS report higher than average rates of allergies and asthma.

What’s more, some patients find their symptoms are improved when they take allergy medications. Some drugs used for allergy treatment, such as antihistamines and mast cell inhibitors, are also used for treating patients with UCPPS and other chronic pelvic pain diagnoses. If there is a link between UCPPS and allergies, then symptom flares might be more common when pollen counts are higher.

Dr. Sutcliffe and colleagues explored this association using data on patients with UCPPS enrolled in an ongoing study (Multidisciplinary Approach to the Study of Chronic Pelvic Pain, or MAPP). In 290 participants, pollen levels were compared for times when the patients were versus were not having symptom flares. They were part of an overall group of 409 patients followed up with over time to assess the overall relationship between flare rates and pollen levels. Patients were drawn from eight study sites across the United States. Information on UCPPS flares was compared with pollen levels, based on local air quality monitoring data from each study area.

Day-to-day changes in pollen counts were not related to UCPPS flares, either on the day of a flare or the preceding three days. This was the case for all participants and on analysis of those reporting allergies or respiratory tract disorders.

However, when pollen counts rose beyond the medium or high threshold, UCPPS flares significantly increased. One to two days after pollen counts exceeded the “medium” or higher threshold, the odds of a symptom flare increased by 22 percent in all patients with UCPPS, and by 33 percent in those with allergies.

Flare rates also increased in the three weeks after pollen counts exceeded medium or high thresholds, with a significant 23 percent increase in risk for patients with allergies. The results remained about the same on analysis excluding patients who were taking UCPPS medications with anti-allergy effects.

“Our results are consistent with patients reporting that higher pollen counts trigger their flares and with case series and report data suggesting allergy and asthma medications relieve UCPPS symptoms,” Dr. Sutcliffe and coauthors write. The findings are also supported by evidence that UCPPS and allergies share common biological factors, i.e., mast cell activation and histamine release. After histamine is released in response to allergens, levels remain elevated in the urine for some time – which might contribute to bladder-related symptoms in UCPPS.

While the findings provide new evidence of a link between allergies and UCPPS, the researchers note some limitations of their study – not all of the observed associations were statistically significant. “If pollen does indeed trigger flares for some patients with urologic chronic pelvic pain, that might have implications for further research and patient care,” Dr. Sutcliffe adds. “For example, patients may benefit from taking antihistamines on days with high pollen levels, or from allergy testing and immunotherapy.”

Reference: Irum Javed, Tiange Yu, Jieni Li, Ratna Pakpahan, Melissa Milbrandt, Gerald L. Andriole, Jerry L. Lowder, H. Henry Lai, Graham A. Colditz, and Siobhan Sutcliffe, “Does Pollen Trigger Urologic Chronic Pelvic Pain Syndrome Flares? A Case-Crossover Analysis in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network”, Journal of Urology, 2020.
https://doi.org/10.1097/JU.0000000000001482 https://www.auajournals.org/doi/10.1097/JU.0000000000001482?utm_source=press&utm_medium=press&utm_campaign=ju_pollen_pr_010521

Provided by Wolters Kluwer Health

Medicine

Heat Treatment May Make Chemotherapy More Effective (Medicine)

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Heating up cancer cells while targeting them with chemotherapy is a highly effective way of killing them, according to a new study led by UCL researchers.

The study, published in the Journal of Materials Chemistry B, found that “loading” a chemotherapy drug on to tiny magnetic particles that can heat up the cancer cells at the same time as delivering the drug to them was up to 34% more effective at destroying the cancer cells than the chemotherapy drug without added heat.

An artist’s conception of the doxorubicin-loaded nanocomposite carriers being internalized by cells (at the top) and remaining outside cells (at the bottom), with a blood vessel at the centre. © Journal of Materials Chemistry B / Nguyen T. K. Thanh / Florian Aubrit / Olivier Sandre / Lilin Wang

The magnetic iron oxide nanoparticles that carry the chemotherapy drug shed heat when exposed to an alternating magnetic field. This means that, once the nanoparticles have accumulated in the tumour area, an alternating magnetic field can be applied from outside the body, allowing heat and chemotherapy to be delivered simultaneously.

The effects of the two treatments were synergistic – that is, each treatment enhanced the effectiveness of the other, meaning they were more potent when combined than when separate. The study was carried out on cells in a lab and further research is needed ahead of clinical trials involving patients.

Senior author Professor Nguyen T. K. Thanh (Biophysics Group, UCL Physics & Astronomy) said: “Our study shows the enormous potential of combining chemotherapy with heat treatment delivered via magnetic nanoparticles.

“While this combination of therapy is already approved for the treatment of fast-growing glioblastomas, our results suggest it has potential to be used more widely as a broad anti-cancer therapy.

“This therapy also has potential to reduce the side effects of chemotherapy, by ensuring it is more highly targeted on cancer cells rather than healthy tissue. This needs to be explored in further pre-clinical tests.”

In the study, researchers combined the magnetic nanoparticles with a commonly used chemotherapy drug, doxorubicin, and compared the effects of this composite in various scenarios on human breast cancer cells, glioblastoma (brain cancer) cells, and mouse prostate cancer cells.

In the most successful scenario, they found that heat and doxorubicin together killed 98% of brain cancer cells after 48 hours, when doxorubicin without heat killed 73%. Meanwhile, for the breast cancer cells, 89% were killed by heat and doxorubicin together, while 77% were killed after 48 hours by doxorubicin alone.

Cancer cells are more susceptible to heat than healthy cells – they undergo a slow death (apoptosis) once the temperature reaches 42 degrees Celsius, whereas healthy cells are able to withstand temperatures up to 45 degrees Celsius.

The researchers found that heating cancer cells by only a few degrees, to 40 degrees Celsius, enhanced the effectiveness of the chemotherapy, meaning the treatment could be effective with lower doses of nanoparticles.

They found the combination of therapies was most effective when the nanoparticles were absorbed, or internalized, by the cancer cells, but they found the chemotherapy was also enhanced when the nanoparticles shed heat while remaining outside the cancer cells (which would be an easier form of treatment to deliver). However, the effects at lower temperatures only occurred when the iron oxide nanoparticles were internalized or tightly deposited on to the surface of the cancer cells.

The nanoparticles also have a polymer coating that prevents the chemotherapy drug from leaching out into healthy tissue. The coating is heat and pH-sensitive, and is designed to release the drug when temperature rises and the nanoparticles are internalized within tiny pockets in cells called “lysosomes”, which have a lower pH than the rest of the cell medium. This intracellular delivery of the drug was particularly effective for the mouse prostate cancer cells, which showed superior and synergetic cell death effect, especially when the temperature reached 42°C.

Co-author Dr Olivier Sandre, of the University of Bordeaux, said: “Since heat can be generated through the alternating magnetic field, the release of the drug can be highly localised to cancer cells, potentially reducing side effects.”

Researchers received funding from the Engineering and Physical Sciences Research Council (EPSRC), the Asian Office of Aerospace Research and Development (AOARD), the European Cooperation in Science and Technology (COST), UCL, the University of Bordeaux, and collaborated with Resonant Circuits Limited.

Provided by University College London

Paleontology

Leaf Fossils Show Severe End-Cretaceous Plant extinction in southern Argentina (Paleontology)

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The asteroid impact 66 million years ago that ushered in a mass extinction and ended the dinosaurs also killed off many of the plants that they relied on for food. Fossil leaf assemblages from Patagonia, Argentina, suggest that vegetation in South America suffered great losses but rebounded quickly, according to an international team of researchers.

The scientists examined more than 3,500 fossils to identify survivor pairs – plants that grew in both the Cretaceous and Paleogene periods. The two fossils on the left are from the Cretaceous, and the two on the right are from the Paleogene. © Elena Stiles

“Every mass extinction event is like a reset button, and what happens after that reset depends on which organisms survive and how they shape the biosphere,” said Elena Stiles, a doctoral student at the University of Washington who completed the research as part of her master’s thesis at Penn State. “All the biodiversity that we observe today is related to the organisms that made it past the last big reset 66 million years ago.”

Stiles and her colleagues examined more than 3,500 leaf fossils collected at two sites in Patagonia to identify how many species from the geologic period known as the Cretaceous survived the mass extinction event into the Paleogene period. Although plant families in the region fared well, the scientists found a surprising species-level extinction rate that may have reached as high as 92% in Patagonia, higher than previous studies have estimated for the region.

“There’s this idea that the Southern Hemisphere got off easier from the Cretaceous-Paleogene extinction than the Northern Hemisphere because we keep finding plant and animal groups that no one thought survived,” said Peter Wilf, professor of geosciences at Penn State and associate in the Earth and Environmental Systems Institute. “We went into this study expecting that Patagonia was a refuge, and instead we found a complex story of extinction and rebound.”

Researchers from Penn State; the Museo Paleontologico Egidio Feruglio (MEF), Chubut, Argentina; Universidad Nacional del Comahue INIBIOMA, Rio Negro, Argentina; and Cornell University had been collecting the fossils for years from the two sites, in what is now Chubut province. Unlike North America, where the Cretaceous-Paleogene (K-Pg) boundary is well known from many sites in the western United States, the fossil record from this period is fragmented across the Southern Hemisphere, a result of rapidly changing ancient environments.

Researchers collect fossils cliffside in the Lefipan formation in southern Argentina. The scientists pictured mid-cliff are searching a layer of the late Cretaceous period, while the sandstone ledge above them marks the beginning of the Paleogene period. © Peter Wilf, Penn State

“Most of the Cretaceous-Paleogene boundary interval known from the Southern Hemisphere is marine,” said Ari Iglesias, a researcher at Universidad Nacional del Comahue INIBIOMA. “We were interested in obtaining the continental record, what happened on land. So, in this study we tried to get as close to the K-Pg boundary as possible, and we reached it in a small area in Chubut province. There we found floras right before the K-Pg boundary, or Maastrichtian floras, and right after the K-Pg boundary, so Danian age floras.”

The assemblages that the team obtained constitute the most complete collection of late Cretaceous and early Paleogene fossil floras in the Southern Hemisphere, added Iglesias.

The researchers studied the assemblages for survivor pairs — plants that grew in both the Cretaceous and Paleogene periods — and found few species-level matches. They then compared their findings to previous pollen and insect herbivory studies from the same area and to North American fossil records. Their study, which is the first of its kind in the Southern Hemisphere, appears in the journal Paleobiology.

“The 92% extinction estimate we get when we consider fossil leaf species across the K-Pg boundary should be taken as a maximum” Stiles said. “We were surprised to find such high extinction levels compared with the 60% extinction rate seen in North America. Nonetheless, we observed a sharp drop in plant species diversity and a high species-level extinction.”

Ecosystem recovery likely took millions of years, added Stiles, which is a small fraction of Earth’s nearly 4.5-billion-year history.

Stiles also led a novel morphospace analysis to identify changes in leaf shape from the Cretaceous to the Paleogene, as such changes could provide clues to the kinds of environmental and climatic occurrences that took place across the boundary interval. She studied each leaf fossil for nearly 50 features, including shape, size and venation patterns.

The analysis showed a higher diversity of leaf forms in the Paleogene, which surprised the researchers given the high species-level extinction and drop in number of species at the end of the Cretaceous. They also found an increase in the proportion of leaf shapes typically found in cooler environments, which suggests that climatic cooling occurred after the end-Cretaceous extinction event.

The researchers’ findings, combined with those of previous studies, suggest that despite the high species-level extinction at the end of the Cretaceous, South American plant families largely survived and grew more diverse during the Paleogene. Among the survivors were the laurel family, which today includes plants such as bay leaves and avocados, and the rose family, which includes fruit like raspberries and strawberries.

“Plants are often overlooked in these big events in geologic history,” Stiles said. “But really, because plants are the primary producers on terrestrial landscapes and sustain all other life forms on Earth, we should be paying closer attention to the plant fossil record. It can tell us how the landscape changed and how those changes affected different groups of organisms.”

Reference: http://dx.doi.org/10.1017/pab.2020.45

Provided by Penn State

Planetary Science

Remote Sensing Data Sheds Light on When And How Asteroid Ryugu Lost its Water (Planetary Science)

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Last month, Japan’s Hayabusa2 mission brought home a cache of rocks collected from a near-Earth asteroid called Ryugu. While analysis of those returned samples is just getting underway, researchers are using data from the spacecraft’s other instruments to reveal new details about the asteroid’s past.

Japan’s Hayabusa2 spacecraft snapped pictures of the asteroid Ryugu while flying alongside it two years ago. The spacecraft later returned rock samples from the asteroid to Earth. © JAXA

In a study published in Nature Astronomy, researchers offer an explanation for why Ryugu isn’t quite as rich in water-bearing minerals as some other asteroids. The study suggests that the ancient parent body from which Ryugu was formed had likely dried out in some kind of heating event before Ryugu came into being, which left Ryugu itself drier than expected.

“One of the things we’re trying to understand is the distribution of water in the early solar system, and how that water may have been delivered to Earth,” said Ralph Milliken, a planetary scientist at Brown University and study co-author. “Water-bearing asteroids are thought to have played a role in that, so by studying Ryugu up close and returning samples from it, we can better understand the abundance and history of water-bearing minerals on these kinds of asteroids.”

One of the reasons Ryugu was chosen as a destination, Milliken says, is that it belongs to a class of asteroids that are dark in color and suspected to have water-bearing minerals and organic compounds. These types of asteroids are believed to be possible parent bodies for dark, water- and carbon-bearing meteorites found on Earth known as carbonaceous chondrites. Those meteorites have been studied in great detail in laboratories around the world for many decades, but it is not possible to determine with certainty which asteroid a given carbonaceous chondrite meteorite may come from.

The Hayabusa2 mission represents the first time a sample from one of these intriguing asteroids has been directly collected and returned to Earth. But observations of Ryugu made by Hayabusa2 as it flew alongside the asteroid suggest it may not to be as water-rich as scientists originally expected. There are several competing ideas for how and when Ryugu may have lost some of its water.

Ryugu is a rubble pile — a loose conglomeration of rock held together by gravity. Scientists think these asteroids likely form from debris left over when larger and more solid asteroids are broken apart by a large impact event. So it’s possible the water signature seen on Ryugu today is all that remains of a previously more water-rich parent asteroid that dried out due a heating event of some kind. But it could also be that Ryugu dried out after a catastrophic disruption and re-formation as a rubble pile. It’s also possible that Ryugu had a few close spins past the sun in its past, which could have heated it up and dried out its surface.

The Hayabusa2 spacecraft had equipment aboard that could help scientists to determine which scenario was more likely. During its rendezvous with Ryugu in 2019, Hayabusa2 fired a small projectile into the asteroid’s surface. The impact created a small crater and exposed rock buried in the subsurface. Using a near-infrared spectrometer, which is capable of detecting water-bearing minerals, the researchers could then compare the water content of surface rock with that of the subsurface.

The data showed the subsurface water signature to be quite similar to that of the outermost surface. That finding is consistent with the idea that Ryugu’s parent body had dried out, rather than the scenario in which Ryugu’s surface was dried out by the sun.

“You’d expect high-temperature heating from the sun to happen mostly at the surface and not penetrate too far into the subsurface,” Milliken said. “But what we see is that the surface and subsurface are pretty similar and both are relatively poor in water, which brings us back to the idea that it was Ryugu’s parent body that had been altered.”

More work needs to be done, however, to confirm the finding, the researchers say. For example, the size of the particles excavated from the subsurface could influence the interpretation of the spectrometer measurements.

“The excavated material may have had a smaller grain size than what’s on the surface,” said Takahiro Hiroi, a senior research associate at Brown and study co-author. “That grain size effect could make it appear darker and redder than its coarser counterpart on the surface. It’s hard to rule out that grain-size effect with remote sensing.”

Luckily, the mission isn’t limited to studying samples remotely. Since Hayabusa2 successfully returned samples to Earth in December, scientists are about to get a much closer look at Ryugu. Some of those samples may soon be coming to the NASA Reflectance Experiment Laboratory (RELAB) at Brown, which is operated by Hiroi and Milliken.

Milliken and Hiroi say they’re looking forward to seeing if the laboratory analyses corroborate the team’s remote sensing results.

“It’s the double-edged sword of sample return,” Milliken said. “All of those hypotheses we make using remote sensing data will be tested in the lab. It’s super-exciting, but perhaps also a little nerve-wracking. One thing is for certain, we’re sure to learn a lot more about the links between meteorites and their parent asteroids.”

Reference: Kitazato, K., Milliken, R.E., Iwata, T. et al. Thermally altered subsurface material of asteroid (162173) Ryugu. Nat Astron (2021). https://www.nature.com/articles/s41550-020-01271-2 https://doi.org/10.1038/s41550-020-01271-2

Provided by Brown University

Biology

New Bacterial Culture Methods Could Result in the Discovery of New Species (Biology)

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The culture-dependent study allowed to isolate a surprisingly large number of diverse and previously unreported bacterial strains from the Tabernas Desert.

Microorganisms are the most abundant and diverse form of life on Earth. However, the vast majority of them remain unknown. Indeed, only a small fraction of the microorganisms of our planet can be cultured under traditional conditions, leaving a world of unculturable organisms out of our scope. This is especially true for bacteria thriving under extreme conditions as the harsh conditions are hardly reproducible in a lab. While some microbial studies have been performed in the Sahara, the Atacama, and the Gibson desert, European arid lands remain poorly studied.

The semi-arid Tabernas Desert in the province of Almería, Spain © Molina-Menor, Gimeno-Valero, Peretó and Porcar

To finally explore the microbial community of some European deserts, researchers from the University of Valencia and the Darwin Bioprospecting Excellence, here studied the bacterial diversity of the semi-arid Tabernas Desert. To this aim, the team developed new bacterial culture approaches.

“Culturomics of the Tabernas desert was the ideal crossroad between a rare, poorly studied environment, and the application of simple, yet powerful culturing techniques including long incubation times, diluted media, and careful colony picking”, says Dr Manuel Porcar, group leader at the University of Valencia, president of Darwin Bioprospecting Excellence, and last author of the study.

Novel methods for culturing previously “unculturable” bacteria © Molina-Menor, Gimeno-Valero, Peretó and Porcar

The researchers experimented with different culture methods to find permissive conditions for some unculturable species. Their strategy lied in combining different media, using serial dilutions of the nutrients (up to a hundred times), and extending incubation time (up to a month). In total, 254 bacterial strains were isolated. Most of the species isolated from the concentrated media were previously described as soil inhabitants or species isolated from other deserts. However, 60% of the strains isolated from the highly diluted media are non-identified and possibly new bacteria species. Besides, playing on incubation times also allowed, after a month, to isolate some oligotrophic strains (slow-growing bacteria living under low nutrient conditions) otherwise difficult to growth under lab conditions.

Altogether, this study highlights the potential of simple strategies to obtain higher microbial diversity from natural samples, especially if taken from extreme environments. But the unexploited bacterial biodiversity of the Tabernas Desert could have impacts well beyond ecology and bacteriology:

“We are currently characterising several of the unidentified bacteria, three of them being new Kineococcus species. I am certain that some bacterial strains produce biotechnologically relevant products. It is just a matter to carry out the right screening”, says Porcar.

Reference: http://dx.doi.org/10.3389/fmicb.2020.583120

Provided by Frontiers

Engineering

On the Road to Invisible Solar Panels: How Tomorrow’s Windows Will Generate Electricity (Engineering)

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A new study led by scientists from Incheon National University in Korea shows how to make a fully transparent solar cell.

In a new study in Journal of Power Sources, an international team of researchers, led by Prof. Joondong Kim from Korea, demonstrate the first transparent solar cell. Their innovative technique rests on a specific part of the solar cell: the heterojunction, made up of thin films of materials responsible for absorbing light. By combining the unique properties of titanium dioxide and nickel oxide semiconductors, the researchers were able to generate an efficient, transparent solar cell.

Five years after the Paris climate agreement, all eyes are on the world’s progress on the road to a carbon-free future. A crucial part of this goal involves the energy transition from fossil fuels to renewable sources, such as sun, water, wind and wave energy. Among those, solar energy has always held the highest hope in the scientific community, as the most reliable and abundant energy source on Earth. In recent decades, solar cells have become cheaper, more efficient, and environment friendly. However, current solar cells tend to be opaque, which prevents their wider use and integration into everyday materials, constrained to being lined up on roofs and in remote solar farms.

But what if next-generation solar panels could be integrated to windows, buildings, or even mobile phone screens? That is the hope of Professor Joondong Kim from the Department of Electrical Engineering at Incheon National University, Korea. In a recent study published in Journal of Power Sources, he and his colleagues detail their latest invention: a fully transparent solar cell. “The unique features of transparent photovoltaic cells could have various applications in human technology,” says Prof. Kim.

The idea of transparent solar cells is well known, but this novel application where scientists have been able to translate this idea into practice is a crucial new finding. At present, the materials making the solar cell opaque are the semiconductor layers, those responsible for capturing light and translating it into an electrical current. Hence, Prof. Kim and his colleagues looked at two potential semiconductor materials, identified by previous researchers for their desirable properties.

The first is titanium dioxide (TiO2), a well-known semiconductor already widely used to make solar cells. On top of its excellent electrical properties, TiO2 is also an environment-friendly and non-toxic material. This material absorbs UV light (a part of the light spectrum invisible to the naked eye) while letting through most of the visible light range. The second material investigated to make this junction was nickel oxide (NiO), another semiconductor known to have high optical transparency. As nickel is one of the mist abundant elements on Earth, and its oxide can easily be manufactured at low industrial temperatures, NiO is also a great material to make eco-friendly cells.

The solar cell created by the team is transparent, allowing its use in a wide range of applications
Photo courtesy: Joondong Kim from Incheon National University

The solar cell prepared by the researchers was composed of a glass substrate and a metal oxide electrode, on top of which they deposited thin layers of the semiconductors (TiO2 first, then NiO) and a final coating of silver nanowires, acting as the other electrode in the cell. They ran several tests to evaluate the device’s absorbance and transmittance of light, as well as its effectiveness as a solar cell.

Their findings were encouraging; with a power conversion efficiency of 2.1%, the cell’s performance was quite good, given that it targets only a small part of the light spectrum. The cell was also highly responsive and worked in low light conditions. Furthermore, more than 57% of visible light was transmitted through the cell’s layers, giving the cell this transparent aspect. In the final part of their experiment, the researchers demonstrated how their device could be used to power a small motor. “While this innovative solar cell is still very much in its infancy, our results strongly suggest that further improvement is possible for transparent photovoltaics by optimizing the cell’s optical and electrical properties,” suggests Prof. Kim.

Now that they have demonstrated the practicality of a transparent solar cell, they hope to further improve its efficiency in the near future. Only further research can tell whether they will indeed become a reality, but for all intents and purposes, this new technology opens a—quite literal—window into the future of clean energy.

Reference: Thanh Tai Nguyen, Malkeshkumar Patel, Sangho Kim, Rameez Ahmad Mir, Junsin Yi, Vinh-Ai Dao, Joondong Kim, “Transparent photovoltaic cells and self-powered photodetectors by TiO2/NiO Heterojunction”, Journal of Power Sources, 2020. 10.1016/j.jpowsour.2020.228865

Provided by Incheon National University

Biology

Magnets Dim Natural Glow of Human Cells, May Shed Light on How Animals Migrate (Biology)

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First direct observation of magnetic field affecting autofluorescence of flavins in living cells.

Researchers in Japan have made the first observations of biological magnetoreception – live, unaltered cells responding to a magnetic field in real time. This discovery is a crucial step in understanding how animals from birds to butterflies navigate using Earth’s magnetic field and addressing the question of whether weak electromagnetic fields in our environment might affect human health.

Professor Jonathan Woodward (left) and doctoral student Noboru Ikeya working with their custom-built microscope to observe how magnetic fields affect autofluorescence of living cells. (Masks are worn as a COVID-19 precaution.) © Photo by Xu Tao, CC BY-SA.

“The joyous thing about this research is to see that the relationship between the spins of two individual electrons can have a major effect on biology,” said Professor Jonathan Woodward from the University of Tokyo, who conducted the research with doctoral student Noboru Ikeya. The results were recently published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Researchers have suspected since the 1970s that because magnets can attract and repel electrons, Earth’s magnetic field, also called the geomagnetic field, could influence animal behavior by affecting chemical reactions. When some molecules are excited by light, an electron can jump from one molecule to another and create two molecules with single electrons, known as a radical pair. The single electrons can exist in one of two different spin states. If the two radicals have the same electron spin, their subsequent chemical reactions are slow, while radical pairs with opposite electron spins can react faster. Magnetic fields can influence electron spin states and thus directly influence chemical reactions involving radical pairs.

Over the past 50 years, chemists have identified multiple reactions and specific proteins called cryptochromes that are sensitive to magnetic fields in test tube environments. Biologists have even observed how genetically interfering with cryptochromes in fruit flies and cockroaches can eliminate the insects’ ability to navigate according to geomagnetic cues. Other research has indicated that birds’ and other animals’ geomagnetic navigation is light sensitive. However, no one has previously measured chemical reactions inside a living cell changing directly because of a magnetic field.

Woodward and Ikeya worked with HeLa cells, human cervical cancer cells that are commonly used in research labs, and were specifically interested in their flavin molecules.

Flavins are a subunit of cryptochromes that are themselves a common and well-studied group of molecules that naturally glow, or fluoresce, when exposed to blue light. They are important light-sensing molecules in biology.

When flavins are excited by light, they can either fluoresce or produce radical pairs. This competition means that the amount of flavin fluorescence depends on how quickly the radical pairs react. The University of Tokyo team hoped to observe biological magnetoreception by monitoring cells’ autofluorescence while adding an artificial magnetic field to their environment.

Researchers at the University of Tokyo detected changes in cells’ autofluorescence in response to magnetic fields, a crucial step in understanding how animals from birds to butterflies navigate using Earth’s geomagnetic field. A short burst of blue light shines on a specific area (blue circle) of a single HeLa (human cervical cancer) cell and then the light that the cell emits back is measured (center). The cellular autofluorescence occurs only in the area that was irradiated with blue light (center, right). © Photo by Ikeya and Woodward, CC BY, originally published in PNAS DOI: 10.1073/pnas.2018043118

Autofluorescence is common in cells, so to isolate flavin autofluorescence, the researchers used lasers to shine light of a specific wavelength onto the cells and then measured the wavelengths of the light that the cells emitted back to ensure that it matched the characteristic values of flavin autofluorescence. Standard magnetic equipment can generate heat, so the researchers took extensive precautions and performed exhaustive control measurements to verify that the only change in the cells’ environment was the presence or absence of the magnetic field.

“My goal even as a Ph.D. student has always been to directly see these radical pair effects in a real biological system. I think that is what we’ve just managed,” said Woodward.

The cells were irradiated with blue light and fluoresced for about 40 seconds. Researchers swept a magnetic field over the cells every four seconds and measured changes in the intensity of the fluorescence. Statistical analysis of the visual data from the experiments revealed that the cell’s fluorescence dimmed by about 3.5% each time the magnetic field swept over the cells.

The researchers suspect that the blue light excites the flavin molecules to generate radical pairs. The presence of a magnetic field caused more radical pairs to have the same electron spin states, meaning that there were fewer flavin molecules available to emit light. Thus, the cell’s flavin fluorescence dimmed until the magnetic field went away.

“We’ve not modified or added anything to these cells. We think we have extremely strong evidence that we’ve observed a purely quantum mechanical process affecting chemical activity at the cellular level,” Woodward remarked.

Lab experiments and real-world magnetoreception

The experimental magnetic fields were 25 millitesla, which is roughly equivalent to common refrigerator magnets. The magnetic field of the Earth varies by location, but is estimated to be about 50 microtesla, or 500 times weaker than the magnetic fields used in the experiments.

Woodward states that Earth’s very weak magnetic field could still have a biologically important influence due to a phenomenon known as the low field effect. Although strong magnetic fields make it difficult for radical pairs to switch between states in which the two electron spins are the same and states in which they are different, weak magnetic fields can have the opposite effect and make the switch easier than when there is no magnetic field.

The authors are now investigating the effect in other types of cells, the potential role of the cells’ health and surroundings, and testing candidate magnetic receptors, including cryptochromes directly inside cells. Interpreting any potential environmental or physiological significance of the results will require developing more specialized and highly sensitive equipment to work with much weaker magnetic fields and more detailed cellular analysis to connect the magnetic field-sensitive response to specific signaling pathways or other consequences within the cell.

Reference: Noboru Ikeya, Jonathan R. Woodward. 4 Jan 2021. Cellular autofluorescence is magnetic field sensitive. Proceedings of the National Academy of Sciences of the United States of America (PNAS). DOI: 10.1073/pnas.2018043118 https://doi.org/10.1073/pnas.2018043118

Provided by University of Tokyo

Food

Danish and Chinese Tongues Taste Broccoli and Chocolate Differently (Food)

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Two studies from the University of Copenhagen show that Danes aren’t quite as good as Chinese at discerning bitter tastes. The research suggests that this is related to anatomical differences upon the tongues of Danish and Chinese people.

The tongue-coordinate system which the researchers developed for mapping papillae. © University of Copenhagen

For several years, researchers have known that women are generally better than men at tasting bitter flavours. Now, research from the University of Copenhagen suggests that ethnicity may also play a role in how sensitive a person is to the bitter taste found in for example broccoli, Brussels sprouts and dark chocolate. By letting test subjects taste the bitter substance PROP, two studies demonstrate that Danish and Chinese people experience this basic taste differently. The reason seems to be related to an anatomical difference upon the tongue surfaces of these two groups.

“Our studies show that the vast majority of Chinese test subjects are more sensitive to bitter tastes than the Danish subjects. We also see a link between the prominence of bitter taste and the number of small bumps, known as papillae, on a person’s tongue,” says Professor Wender Bredie of the University of Copenhagen’s Department of Food Science (UCPH FOOD).

A taste of artificial intelligence

Using a new artificial intelligence method, researchers from UCPH FOOD, in collaboration with Chenhao Wang and Jon Sporring of UCPH’s Department of Computer Science, analysed the number of mushroom-shaped “fungiform” papillae on the tongues of 152 test subjects, of whom half were Danish and half Chinese.

Fungiform papillae, located at the tip of the tongue, are known to contain a large portion of our taste buds and play a central role in our food and taste experiences. To appreciate the significance of papillae in food preferences across cultures and ethnicities, it is important to learn more about their distribution, size and quantity.

The analysis demonstrated that the Chinese test subjects generally had more of these papillae than the Danish subjects, a result that the researchers believe explains why Chinese people are better at tasting bitter flavours.

However, Professor Bredie emphasizes that larger cohorts need to be examined before any definitive conclusions can be drawn about whether these apparent phenotypical differences between Danes and Chinese hold at the general population level.

More knowledge about differences in taste impressions can be important for food development. According to Professor Bredie:

“It is relevant for Danish food producers exporting to Asia to know that Asian and Danish consumers probably experience tastes from the same product differently. This must be taken into account when developing products.”

Danes prefer foods that require a good chew

Professor Wender Bredie points out that genetics are only one of several factors that influence how we experience food. Another significant factor has to do with our preferences — including texture. Think, for example, of the difference between munching on crispy potato chips from a newly opened bag, compared to eating softened ones from a bag opened the day before. Here, many Danes would probably prefer the crispy ones over the soft ones, even if the taste is similar. According to the UCPH studies, there seems to be a difference between the Danish and Chinese test subjects on this point as well.

While the vast majority of Chinese subjects (77%) prefer foods that don’t require much chewing, the opposite holds true for the Danish subjects. Among the Danes, 73% prefer eating foods with a harder consistency that require biting and chewing – rye bread and carrots, for example.

The reason for this difference remains unknown, but the researchers suspect that it stems from differences in food culture and the ways in which we learn to eat. The studies do not point to tongue shape as making any difference.

THE NEW METHOD:

Because the counting of tongue papillae is usually done manually, and a tongue has hundreds of tiny fungiform papillae, it is a demanding job in which mistakes are easily made.

The new method, based on artificial intelligence and developed by image analysis experts Chenhao Wang and Jon Sporring of the Department of Computer Science, automates the counting and delivers precision. Using an algorithm, they have designed a tongue-coordinate system (see figure) that can map papillae on individual tongues using image recognition.

ABOUT THE RESEARCH:

  • The 152 study participants were all healthy non-smokers between the ages of 18 and 55. Of them, 75 were from Denmark and 77 from China. 71% of participants were women and 29% men.
  • Test subject sensitivity to bitter taste was examined by allowing subjects to taste the bitter substance 6-n-propylthiouracil (PROP), considered a genetic marker for differences in taste perception.
  • The research was conducted by: Jing Liu and Wender Bredie from the Department of Food Science; Chenhao Wang and Jon Sporring from the Department of Computer Science; Camilla Cataneo and Ella Pagliarini from the University of Milan; and Anne C. Bech from Arla Innovation Centre. The research received support from Arla Foods amba and the Capital Region of Denmark.
  • Research articles for the two studies can be found here:https://link.springer.com/chapter/10.1007/978-3-030-59722-1_4
    https://www.sciencedirect.com/science/article/pii/S0950329319304653

Provided by Faculty of Science- University of Copenhagen

Biology

Integrator: A Guardian of the Human Transcriptome (Biology)

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In a joint collaboration, Danish and German researchers have characterized a cellular activity that protects our cells from potentially toxic by-products of gene expression. This activity is central for the ability of multicellular organisms to uphold a robust evolutionary ‘reservoir’ of gene products.

Manufacturing processes need quality control systems in order to ensure proper assembly of functional products. Moreover, space-consuming, and perhaps even toxic, by-products of such processes need to be properly discarded or recycled by efficient waste handling systems.

RNA polymerase II (RNAPII) initiates transcription at a multitude of positions in the human genome. However, only a fraction of these sites is associated with genes that give rise to functional RNA. The ‘Integrator’ complex by default terminates RNAPII shortly after its initiation (top), unless specific gene-defining elements are present allowing for transition to productive elongation (bottom). In the latter case, transcription is typically terminated by the ‘Cleavage & Polyadenylation’ Complex that recognizes specific ‘terminator’ sequence elements in the genome (bottom, red box). In the former case the produced short RNA is by default rapidly degraded by the RNA exosome, whereas snRNAs constitute a special case that avoids degradation. Figure: Søren Lykkke-Andersen.

By analogy, transcription of our genome is an imperfect process that produces large quantities of non-functional and potentially harmful transcripts both from within and outside of conventional genes. The RNA polymerase II enzyme transcribes the majority of our genes, and it also generates pervasive transcripts from multiple non-genic regions. Over the past decade, it has become increasingly clear that the enzyme is relatively promiscuous when it comes to where it starts, and there are transcription initiation sites scattered everywhere in the genome. However, not all these sites are associated with a ‘proper’ gene, and this requires the presence of specific gene-defining elements.

Discovery of new activity of the protein complex ‘Integrator’

In a new article published in the international journal Molecular Cell, a Danish-German research team has now demonstrated that the multi-protein complex ‘Integrator’ – which was previously described as the transcription termination factor for a specific class of genes encoding small nuclear (sn)RNAs – is in fact a default ‘early’ termination factor for most, if not all RNA polymerase II initiation events (Figure, top panel).

The resulting short transcripts are in most cases rapidly degraded by the ribonucleolytic RNA exosome. This mechanism is also at play to varying degrees inside conventional genes, but these have evolved elements, counteracting such early termination, to facilitate productive transcription elongation, which eventually produces functional transcripts such as protein-coding ‘messenger’ (m)RNA (Figure, bottom panel).

Through this newly discovered mechanism of action, Integrator ensures that production of wasteful transcripts remains limited, while at the same time allowing maintenance of thousands of transcription start sites under neutral selection in the human genome. These provide a reservoir of transcription units that may turn into functional genes over time, exemplified by the evolution of the currently known functional RNAs of our genome. As a curious example, snRNA genes appear to be a special case, taking advantage of the general early termination activity of Integrator and fend off the ensuing RNA exosome activity to allow production of stable functional RNAs (Figure, top panel).

Inactivating mutations in Integrator subunits lead to severe neurodevelopmental disorders, and elevated expression of some integrator subunits is associated with increased epithelial-to-mesenchymal transition – a key step in tumor metastasis. This duality highlights the need for a tight control of the Integrator activity. Moreover, the realization that Integrator is a general attenuator of nonproductive transcription may inform the molecular characterization and potential treatment of such ailments.

The work was carried out in a collaboration between researchers from Max Planck Institute in Göttingen and Aarhus University.  

Reference: Søren Lykke-Andersen, Kristina Zumer, Ewa Šmidová Molska, Jérôme O. Rouvière, Guifen Wu, Carina Demel, Björn Schwalb, Manfred Schmid, Patrick Cramer and Torben Heick Jensen, “Integrator is a genome-wide attenuator of nonproductive transcription”, Molecular Cell, 2020. DOI: https://doi.org/10.1016/j.molcel.2020.12.014 DOI: https://doi.org/10.1016/j.molcel.2020.12.014

Provided by Aarhus University