Culture

New technique shows promise in preventing recurrent stroke

image: A surgical procedure advanced and studied by vascular neurosurgeons at Cedars-Sinai dramatically reduced the rate of recurrent strokes among patients with atherosclerotic disease, a new study shows.

Image: 
Cedars-Sinai

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LOS ANGELES -- A surgical procedure advanced and studied by vascular neurosurgeons at Cedars-Sinai dramatically reduced the rate of recurrent strokes among patients with atherosclerotic disease, a new study shows.

Atherosclerotic disease, also known as hardening of the arteries, is a buildup of plaque that narrows the arteries leading to the brain. The condition is known to increase patients' risk of having a series of strokes.

Exciting new results from a Phase II clinical trial conducted at Cedars-Sinai demonstrated that a new procedure reduced recurrent stroke rates from 37% to 10.7%. Encephaloduroarteriosynangiosis, or EDAS for short, is a new procedure that was used and recently published in the journal Neurosurgery.

"The EDAS procedure is unique in that it involves rerouting arteries from the scalp and membranes that cover the brain, to segments of the brain at risk of stroke," said Nestor Gonzalez, MD, director of the Cedars-Sinai Neurovascular Laboratory. "Similar to gardening, over time, new blood vessels form and create a fresh path for blood oxygen to reach the brain."

This gardening-like surgical technique differs from current, conventional approaches to reduce recurrent stroke, which include intensive medical management and various procedures, ranging from angioplasty and stenting to direct bypass surgery.

"Your brain needs a steady supply of oxygen-rich blood in order to function properly," said Keith Black, MD, professor and chair of the Department of Neurosurgery. "This work is an important step in increasing the vital vessels in the brain and ensuring that patients with this complex condition have an innovative and minimally invasive option for care."

The Neurovascular Center and Department of Neurosurgery at Cedars-Sinai provide personalized care for aneurysms, strokes and other neurovascular problems, using state-of-the-art imaging technology, a dedicated intensive care unit, advanced therapies and new surgical techniques.

Nestor Gonzalez, MD

As a next step, Gonzalez and his team are working with the National Institutes of Health--a funder of this work--to launch a large, multicenter Phase III clinical trial at medical centers across the nation. These sites will allow willing patients with atherosclerotic disease to participate in clinical research.

"Clinical research is a critical component and a necessary step to advance the science and treatments available to patients with this unique yet common condition," said Gonzalez. "As the trial expands from Los Angeles to other parts of the country, I hope patients consider participating in the study of this promising technique."

Credit: 
Cedars-Sinai Medical Center

Uncovers the molecular mechanism behind synapse loss in Alzheimer's disease

image: Schematic model for the role of RAPGEF2 in Aβ oligomer-induced synaptic degeneration

Image: 
KOREA BRAIN RESEARCH INSTITUTE

Korea Brain Research Institute (KBRI, Pann-Ghill Suh (President)) announced that Dr. Kea Joo Lee and Dr. You-Na Jang of the Neural Circuits Research Group have identified the mechanism causing synaptic loss in Alzheimer's disease as the aberrant expression of RAPGEF2, a synaptic protein.

- The results were published on January 2021, in the online Early View of Neuropathology and Applied Neurobiology.
* (Title) RAPGEF2 mediates oligomeric Aβ-induced synaptic loss and cognitive dysfunction in the 3xTg-AD mouse model of Alzheimer's disease

Alzheimer's disease (AD) accounts for about 75% of dementia cases and is the most common type of degenerative brain disease. AD is a devastating because disease progression can cause memory loss, mood disorder, slurred speech, confusion, and impaired movement.

- With the conventional treatment available today, AD patients may expect to see some temporary improvement of symptoms, but nothing exists at the moment that can halt or reverse the progression. Instead, preventive strategies are emphasized, with health care professionals commonly suggesting physical exercise and continued learning programs as options.

- AD is a tricky condition that has constantly thwarted the best efforts to unravel the inner workings of the disease. In the leading hypothesis, abnormal aggregation of amyloid beta (Aß) and tau proteins are identified as a possible cause of the illness. Amyloid beta is known to degrade synapses and drive cognitive impairment such as memory loss.

In their work unveiling the complex processes by which amyloid beta brings about synaptic loss, Dr. Kea Joo Lee and his team have been studying the brain tissue of both deceased Alzheimer's patients and genetically modified mouse models for the disease, and have found "RAPGEF2 protein overexpression" to be the common phenomenon.

* RAPGEF2(Rap guanin nucleotide exchange factor 2) is an essential protein involved in multiple critical biological pathways such as synaptic remodeling, neural plasticity, and embryo neural development

- Employing various neurobiological methodologies that utilize neuronal cell culture models and brain tissue from mouse models of Alzheimer's, the researchers arrived at the conclusion that "amyloid beta facilitates the overexpression of the RAPGEF2 protein," and "the RAPGEF2 protein, in turn, activates downstream effectors RAP2 and JNK to ultimately induce synaptic loss."

- Intriguingly, electron microscopy and behavioral tests conducted by the team showed the silencing of RAPGEF2 as having a preventive effect on synapse loss and cognitive impairment even in the presence of increased amyloid beta.

The potential significance of these findings is great. Having a detailed understanding of the molecular mechanisms behind synaptic damage that occurs in the early stages of the Alzheimer's disease can be invaluable in developing treatments for neurodegenerative diseases such as dementia which have continued to plague humanity despite scientific advancement.

Credit: 
Korea Brain Research Institute

Scientists describe earliest primate fossils

image: Shortly after the extinction of the dinosaurs, the earliest known archaic primates, such as the newly described species Purgatorius mckeeveri shown in the foreground, quickly set themselves apart from their competition -- like the archaic ungulate mammal on the forest floor -- by specializing in an omnivorous diet including fruit found up in the trees.

Image: 
Andrey Atuchin

A new study published Feb. 24 in the journal Royal Society Open Science documents the earliest-known fossil evidence of primates.

A team of 10 researchers from across the U.S. analyzed several fossils of Purgatorius, the oldest genus in a group of the earliest-known primates called plesiadapiforms. These ancient mammals were small-bodied and ate specialized diets of insects and fruits that varied by species. These newly described specimens are central to understanding primate ancestry and paint a picture of how life on land recovered after the Cretaceous-Paleogene extinction event 66 million years ago that wiped out all dinosaurs -- except for birds -- and led to the rise of mammals.

Gregory Wilson Mantilla, a University of Washington professor of biology and curator of vertebrate paleontology at the UW's Burke Museum of Natural History & Culture, co-led the study with Stephen Chester of Brooklyn College and the City University of New York. The team analyzed fossilized teeth found in the Hell Creek area of northeastern Montana. The fossils, which are now part of the collections at the University of California Museum of Paleontology, are estimated to be 65.9 million years old, about 105,000 to 139,000 years after the mass extinction event. Based on the age of the fossils, the team estimates that the ancestor of all primates --including plesiadapiforms and today's primates such as lemurs, monkeys and apes -- likely emerged by the Late Cretaceous and lived alongside large dinosaurs.

"It's mind blowing to think of our earliest archaic primate ancestors," said Wilson Mantilla. "They were some of the first mammals to diversify in this new post-mass extinction world, taking advantage of the fruits and insects up in the forest canopy."

The fossils include two species of Purgatorius: Purgatorius janisae and a new species described by the team named Purgatorius mckeeveri. Three of the teeth found have distinct features compared to any previously known Purgatorius species and led to the description of the new species.

Purgatorius mckeeveri is named after Frank McKeever, who was among the first residents of the area where the fossils were discovered, and also the family of John and Cathy McKeever, who have since supported the field work where the oldest specimen of this new species was discovered.

"This was a really cool study to be a part of, particularly because it provides further evidence that the earliest primates originated before the extinction of non-avian dinosaurs," said co-author Brody Hovatter, a UW graduate student in Earth and space sciences. "They became highly abundant within a million years after that extinction."

"This discovery is exciting because it represents the oldest dated occurrence of archaic primates in the fossil record," said Chester. "It adds to our understanding of how the earliest primates separated themselves from their competitors following the demise of the dinosaurs."

Credit: 
University of Washington

Revive the map: 4D building reconstruction with machine learning

image: Revive the map

Image: 
Farella E.M, et al./ MDPI Applied Sciences

A research team from Skoltech and FBK (Italy) presented a methodology to derive 4D building models using historical maps and machine learning. The implemented method relies on the geometric, neighbourhood, and categorical attributes to predict building heights. The method is useful for understanding urban phenomena and changes contributing to defining our cities' actual shapes. The results were published in the MDPI Applied Sciences journal.

Historical maps are the most powerful source used to analyze changes in urban development. Nevertheless, maps represent the 3D world in the 2D space, which describes the main features of the urban environment but fails to incorporate other spatial information, such as building heights. In 3D/4D city modeling applications based on historical data, the lack of building heights is a major obstacle for accurate space representation, analysis, visualization, or simulations.

Scientists from Skoltech and 3DOM research unit of FBK Trento explored machine learning solutions for inferring building heights from historical maps.

Their method tested on four historical maps of Trento (years 1851, 1887, 1908, and 1936) and Bologna (years 1884 and 1945), reflecting the biggest changes in the urban structures over the last centuries, helped reconstruct multi-temporal (4D) versions of these cities.

"The implemented learning and predictive procedures tested on historical data have proven to be effective and promising for many other applications. Based on a few attributes for the prediction, it will soon be expanded to diverse real-life contexts with missing elevation data. The resulting models will be a great help in bridging the geospatial knowledge gap in past or remote situations," Emre Ozdemir, a Skoltech and FBK Trento PhD student, explains.

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

Diabetes patients use of mobile health app found to improve health outcomes, lower medical costs

Emerging smart mobile health (or mHealth) technologies are changing the way patients track information related to diagnosed conditions. A new study examined the health and economic impacts of mHealth technologies on the outcomes of diabetes patients in Asia. The study concluded that compared to patients who did not use mHealth applications, patients who used the apps had better health outcomes and were able to regulate their health behavior more effectively. They also had fewer hospital visits and lower medical costs.

The study was conducted by researchers at Carnegie Mellon University (CMU) and New York University (NYU). It has been accepted into publication and is forthcoming in MIS Quarterly, a publication of the Management Information Systems Research Center.

"Given the importance of health behaviors to well-being, health outcomes, and disease processes, mHealth technologies offer significant potential to facilitate patients' lifestyle and behavior modification through patient education, improved autonomous self-regulation, and perceived competence," explains Beibei Li, professor of information systems and management at CMU's Heinz College, who coauthored the study.

The relatively new area of mHealth includes mobile computing, medical sensor, and communications technologies used for health care services (e.g., managing chronic diseases). mHealth applications can operate on smart phones, tablets, sensors, and cloud-based computing systems, all of which collect health data on individuals. The global mHealth market was estimated to have reached $49 billion by the end of 2020. Yet few studies have assessed the technology's effectiveness in changing patients' behaviors and outcomes.

In this study, researchers sought to determine how mHealth applications persuade individuals to modify their behavior to comply with recommended approaches to obtain certain health goals. The researchers measured compliance by looking at detailed patient activities (e.g., daily walking steps, exercise time, sleeping pattern, food intake) as measured by the app, as well as general health outcomes, hospital visits, and medical expenses.

The researchers partnered with a top mHealth firm that provides one of the largest mobile health platforms in Asia specializing in diabetes care. The study randomly assigned 1,070 adult patients to different groups for three months: Some patients used the mHealth app, some did not, and some used a web-based version of the app. Among the patients in the group that used the mHealth app, some received personalized text message reminders, while others received non-personalized text messages. Researchers interviewed all participants before the study began and five months after it ended. Among the questions asked were those about demographics, medication and medical history, blood glucose and hemoglobin levels, frequency of hospital visits, and medical costs.

The study found that patients who used the mHealth app reduced their blood glucose and hemoglobin levels, even after controlling for individual-level fixed effects. Patients who used the app also exercised more, slept more, and ate healthier food. And they had fewer hospital visits and lower medical expenses.

The authors suggest that patients' adoption of and use of the mHealth app was associated with significant behavioral modifications toward a healthier diet and lifestyle. In this way, users became more autonomously self-regulated with their health behavior, and this increasing intrinsic motivation helped them become more engaged, persistent, and stable in their behavior, which led to improved health outcomes. The mHealth platform also facilitated an increased usage of telemedicine, which in turn led to reduced hospital visits and medical expenses for the patients.

The study also found that the mHealth platform was more effective in improving patients' health outcomes than a web-based (PC) version of the same app. And non-personalized text messages tended to be more effective in changing patients' behavior than personalized messages, possibly because personalized messages can be viewed as intrusive, coercive, and annoying.

Among the study's limitations, the authors note that this study focused mainly on participants with Type II diabetes which, different from Type I diabetes or Gestational diabetes, is directly tied to dietary or lifestyle self-management. Hence, the research is not necessarily applicable to patients with other types of diabetes.

"Our findings provide important insights on the design of mHealth apps through a better understanding of patients' health behavior and interactions with the platform," suggests Anindya Ghose, professor of business at NYU's Stern School of Business, who coauthored the study. "Such knowledge can be very valuable for health care mobile platform designers as well as policymakers to improve the design of smart and connected health infrastructures through sustained usage of the emerging technologies."

Credit: 
Carnegie Mellon University

Bearded seals are loud - but not loud enough

ITHACA, N.Y. - During mating season, male bearded seals make loud calls to attract a mate. How loud? Well, even their "quiet" call can still be as ear-rattling as a chainsaw.

These elaborate vocalizations are essential for bearded seal reproduction, and have to be loud enough to be heard over the cacophony of their equally loud brethren.

But in the rapidly changing Arctic soundscape, where noise from industrial activities is predicted to dramatically increase in the next 15 years, bearded seals may need to adjust their calling behavior if they are going to be heard above the noise generated by ships and commercial activities.

The bearded seals, however, can only do so much. A study conducted by the Cornell Lab of Ornithology's Center for Conservation Bioacoustics (CCB) found that when ambient underwater noise gets too loud, the bearded seals are no longer able to compensate in order to be heard.

The results of the study, "Limited Vocal Compensation for Elevated Ambient Noise in Bearded Seals: Implications for an Industrializing Arctic Ocean," published Feb. 24 in Proceedings of the Royal Society: Biological Science.

"We wanted to know whether bearded seals would call louder when their habitat grew noisy from natural sound sources," said CCB postdoctoral researcher Michelle Fournet, who led the study. "The goal was to determine if there was a 'noise threshold' beyond which seals either couldn't or wouldn't call any louder in order to be heard. By identifying this naturally occurring threshold, we can make conservation recommendations about how loud is too loud for human activities."

From spring through early summer, the under-ice habitat near Utqiagvik, Alaska, is flooded with the vocalizations of male bearded seals - a sound that can be best described as "otherworldly."

Fournet and colleagues listened to thousands of recorded bearded seal vocalizations from Arctic Alaska spanning a two-year period. Each call was carefully measured and compared with the concurrent ambient noise conditions. They found bearded seals do call louder as their underwater acoustic habitat gets noisier, but there is an upper limit to this behavior. As expected, when ambient noise gets too high, bearded seals are no longer able to compensate in order to be heard.

As a result, as ambient noise conditions increase, the distance over which individuals can be detected goes down.

"Given that these are reproductive calls, it is likely that the seals are already calling as close to as loudly as possible - the males very much want to be heard by the females," Fournet said. "So it is unsurprising that there is an upper limit. I'm grateful that we have been able to identify that limit so we can make responsible management choices moving forward."

Bearded seals - or ugruk in the Inupiaq language - are highly valued by Alaska Native communities in the high Arctic. Since bearded seals are at the center of subsistence and cultural activities in Inupiaq communities, threats to them threaten the communities that rely on them.

"This work never would have happened without the insight and guidance of Arctic communities," Fournet said. "It was their energy that led the Cornell Lab to place hydrophones in the water. It is our job to continue listening."

Credit: 
Cornell University

'Miracle poison' for novel therapeutics

image: Liu and his lab engineered botulinum toxin to target new proteins, a critical advance that could lead to new treatments for a range of maladies, including nerve and brain damage, muscle injury, and rampant inflammation.

Image: 
Casey Atkins Photography, courtesy of Broad Institute

When people hear botulinum toxin, they often think one of two things: a cosmetic that makes frown lines disappear or a deadly poison.

But the "miracle poison," as it's also known, has been approved by the F.D.A. to treat a suite of maladies like chronic migraines, uncontrolled blinking, and certain muscle spasms. And now, a team of researchers from Harvard University and the Broad Institute have, for the first time, proved they could rapidly evolve the toxin in the laboratory to target a variety of different proteins, creating a suite of bespoke, super-selective proteins called proteases with the potential to aid in neuroregeneration, regulate growth hormones, calm rampant inflammation, or dampen the life-threatening immune response called cytokine storm.

"In theory, there is a really high ceiling for the number and type of conditions where you could intervene," said Travis Blum, a postdoctoral researcher in the Department of Chemistry and Chemical Biology and first author on the study published in Science. The study was the culmination of a collaboration with Min Dong, an associate professor at the Harvard Medical School, and David Liu, the Thomas Dudley Cabot Professor of the Natural Sciences, a Howard Hughes Medical Institute Investigator, and a core faculty member of the Broad Institute.

Together, the team achieved two firsts: They successfully reprogrammed proteases--enzymes that cut proteins to either activate or deactivate them--to cut entirely new protein targets, even some with little or no similarity to the native targets of the starting proteases, and to simultaneously avoid engaging their original targets. They also started to address what Blum called a "classical challenge in biology": designing treatments that can cross into a cell. Unlike most large proteins, botulinum toxin proteases can enter neurons in large numbers, giving them a wider reach that makes them all the more appealing as potential therapeutics.

Now, the team's technology can evolve custom proteases with tailor-made instructions for which protein to cut. "Such a capability could make 'editing the proteome' feasible," said Liu, "in ways that complement the recent development of technologies to edit the genome."

Current gene-editing technologies often target chronic diseases like sickle cell anemia, caused by an underlying genetic error. Correct the error, and the symptoms fade. But some acute illnesses, like neurological damage following a stroke, aren't caused by a genetic mistake. That's where protease-based therapies come in: The proteins can help boost the body's ability to heal something like nerve damage through a temporary or even one-time treatment.

Scientists have been eager to use proteases to treat disease for decades. Unlike antibodies, which can only attack specific alien substances in the body, proteases can find and attach to any number of proteins, and, once bound, can do more than just destroy their target. They could, for example, reactivate dormant proteins.

"Despite these important features, proteases have not been widely adopted as human therapeutics," said Liu, "primarily because of the lack of a technology to generate proteases that cleave protein targets of our choosing."

But Liu has a technological ace in his pocket: PACE (which stands for phage-assisted continuous evolution). A Liu lab invention, the platform rapidly evolves novel proteins with valuable features. PACE, Liu said, can evolve dozens of generations of proteins a day with minimal human intervention. Using PACE, the team first taught so-called "promiscuous" proteases--those that naturally target a wide swath of proteins--to stop cutting certain targets and become far more selective. When that worked, they moved on to the bigger challenge: Teaching a protease to only recognize an entirely new target, one outside its natural wheelhouse.

"At the outset," said Blum, "we didn't know if it was even feasible to take this unique class of proteases and evolve them or teach them to cleave something new because that had never been done before." ("It was a moonshot to begin with," said Michael Packer, a previous Liu lab member and an author on the paper). But the proteases outperformed the team's expectations. With PACE, they evolved four proteases from three families of botulinum toxin; all four had no detected activity on their original targets and cut their new targets with a high level of specificity (ranging from 218- to more than 11,000,000-fold). The proteases also retained their valuable ability to enter cells. "You end up with a powerful tool to do intracellular therapy," said Blum. "In theory."

"In theory" because, while this work provides a strong foundation for the rapid generation of many new proteases with new capabilities, far more work needs to be done before such proteases can be used to treat humans. There are other limitations, too: The proteins are not ideal as treatments for chronic diseases because, over time, the body's immune system will recognize them as alien substances and attack and defuse them. While botulinum toxin lasts longer than most proteins in cells (up to three months as opposed to the typical protein lifecycle of hours or days), the team's evolved proteins might end up with shorter lifetimes, which could diminish their effectiveness.

Still, since the immune system takes time to identify foreign substances, the proteases could be effective for temporary treatments. And, to side-step the immune response, the team is also looking to evolve other classes of mammalian proteases since the human body is less likely to attack proteins that resemble their own. Because their work on botulinum toxin proteases proved so successful, the team plans to continue to tinker with those, too, which means continuing their fruitful collaboration with Min Dong, who not only has the required permission from the Centers for Disease Control (CDC) to work with botulinum toxin but provides critical perspective on the potential medical applications and targets for the proteases.

"We're still trying to understand the system's limitations, but in an ideal world," said Blum, "we can think about using these toxins to theoretically cleave any protein of interest." They just have to choose which proteins to go after next.

Credit: 
Harvard University

The risks of communicating extreme climate forecasts

For decades, climate change researchers and activists have used dramatic forecasts to attempt to influence public perception of the problem and as a call to action on climate change. These forecasts have frequently been for events that might be called "apocalyptic," because they predict cataclysmic events resulting from climate change.

In a new paper published in the International Journal of Global Warming, Carnegie Mellon University's David Rode and Paul Fischbeck argue that making such forecasts can be counterproductive. "Truly apocalyptic forecasts can only ever be observed in their failure--that is the world did not end as predicted," says Rode, adjunct research faculty with the Carnegie Mellon Electricity Industry Center, "and observing a string of repeated apocalyptic forecast failures can undermine the public's trust in the underlying science."

Rode and Fischbeck, professor of Social & Decision Sciences and Engineering & Public Policy, collected 79 predictions of climate-caused apocalypse going back to the first Earth Day in 1970. With the passage of time, many of these forecasts have since expired; the dates have come and gone uneventfully. In fact, 48 (61%) of the predictions have already expired as of the end of 2020.

Fischbeck noted, "from a forecasting perspective, the 'problem' is not only that all of the expired forecasts were wrong, but also that so many of them never admitted to any uncertainty about the date. About 43% of the forecasts in our dataset made no mention of uncertainty."

In some cases, the forecasters were both explicit and certain. For example, Stanford University biologist Paul Ehrlich and British environmental activist Prince Charles are serial failed forecasters, repeatedly expressing high degrees of certainty about apocalyptic climate events.

Rode commented "Ehrlich has made predictions of environmental collapse going back to 1970 that he has described as having 'near certainty'. Prince Charles has similarly warned repeatedly of 'irretrievable ecosystem collapse' if actions were not taken, and when expired, repeated the prediction with a new definitive end date. Their predictions have repeatedly been apocalyptic and highly certain...and so far, they've also been wrong."

The researchers noted that the average time horizon before a climate apocalypse for the 11 predictions made prior to 2000 was 22 years, while for the 68 predictions made after 2000, the average time horizon was 21 years. Despite the passage of time, little has changed--across a half a century of forecasts; the apocalypse is always about 20 years out.

Fischbeck continued, "It's like the boy who repeatedly cried wolf. If I observe many successive forecast failures, I may be unwilling to take future forecasts seriously.

That's a problem for climate science, say Rode and Fischbeck.

"The underlying science of climate change has many solid results," says Fischbeck, "the problem is often the leap in connecting the prediction of climate events to the prediction of the consequences of those events." Human efforts at adaptation and mitigation, together with the complexity of socio-physical systems, means that the prediction of sea level rise, for example, may not necessarily lead to apocalyptic flooding.

"By linking the climate event and the potential consequence for dramatic effect," noted Rode, "a failure to observe the consequence may unfairly call into question the legitimacy of the science behind the climate event."

With the new Biden administration making climate change policy a top priority, trust in scientific predictions about climate change is more crucial than ever, however scientists will have to be wary in qualifying their predictions. In measuring the proliferation the forecasts through search results, the authors found that forecasts that did not mention uncertainty in their apocalyptic date tended to be more visible (i.e., have more search results available). Making sensational predictions of the doom of humanity, while scientifically dubious, has still proven tempting for those wishing to grab headlines.

The trouble with this is that scientists, due to their training, tend to make more cautious statements and more often include references to uncertainty. Rode and Fischbeck found that while 81% of the forecasts made by scientists referenced uncertainty, less than half of the forecasts made by non-scientists did.

"This is not surprising," said Rode, "but it is troubling when you consider that forecasts that reference uncertainty are less visible on the web. This results in the most visible voices often being the least qualified."

Rode and Fischbeck argue that scientists must take extraordinary caution in communicating events of great consequence. When it comes to climate change, the authors advise "thinking small." That is, focusing on making predictions that are less grandiose and shorter in term. "If you want people to believe big predictions, you first need to convince them that you can make little predictions," says Rode.

Fischbeck added, "We need forecasts of a greater variety of climate variables, we need them made on a regular basis, and we need expert assessments of their uncertainties so people can better calibrate themselves to the accuracy of the forecaster."

Credit: 
College of Engineering, Carnegie Mellon University

Apollo rock samples capture key moments in the Moon's early history, study find

PROVIDENCE, R.I. [Brown University] -- Volcanic rock samples collected during NASA's Apollo missions bear the isotopic signature of key events in the early evolution of the Moon, a new analysis found. Those events include the formation of the Moon's iron core, as well as the crystallization of the lunar magma ocean -- the sea of molten rock thought to have covered the Moon for around 100 million years after it formed.

The analysis, published in the journal Science Advances, used a technique called secondary ion mass spectrometry (SIMS) to study volcanic glasses returned from the Apollo 15 and 17 missions, which are thought to represent some of the most primitive volcanic material on the Moon. The study looked specifically at sulfur isotope composition, which can reveal details about the chemical evolution of lavas from generation, transport and eruption.

"For many years it appeared as though the lunar basaltic rock samples analyzed had a very limited variation in sulfur isotope ratios," said Alberto Saal, a geology professor at Brown University and study co-author. "That would suggest that the interior of the Moon has a basically homogeneous sulfur isotopic composition. But using modern in situ analytical techniques, we show that the isotope ratios of the volcanic glasses actually have a fairly wide range, and those variations can be explained by events early in lunar history."

The sulfur signature of interest is the ratio of the "heavy" sulfur-34 isotope to the lighter sulfur-32. Initial studies of lunar volcanic samples found that they uniformly leaned toward the heavier sulfur-34. The nearly homogeneous sulfur isotope ratio was in contrast with large variations in other elements and isotopes detected in the lunar samples.

This new study looked at 67 individual volcanic glass samples and their melt inclusions -- tiny blobs of molten lava trapped within crystals inside the glass. Melt inclusions capture the lava before sulfur and other volatile elements are released as gas during eruption -- a process called degassing. As such, they offer a pristine picture of what the original source lava was like. Using the SIMS at the Carnegie Institution for Science, Saal with his colleague, the late Carnegie scientist Eric Hauri, were able to measure the sulfur isotopes in these pristine melt inclusions and glasses, and use those results to calibrate a model of the degassing process for all the samples.

"Once we know the degassing, then we can estimate back the original sulfur isotope composition of the sources that produced these lavas," Saal said.

Those calculations revealed that the lavas had been derived from different reservoirs within the interior of the Moon with a wide range of sulfur isotope ratios. The researchers then showed that the range of values detected in the samples could be explained by events in the Moon's early history.

The lighter isotope ratio in some of the volcanic glasses, for example, is consistent with the segregation of the iron core from the early molten Moon. When an iron core separates from other material in a planetary body, it takes a bit of sulfur with it. The sulfur that's taken tends to be the heavier sulfur-34 isotope, leaving the remaining magma enriched in the lighter sulfur-32.

"The values we see in some of the volcanic glasses are fully consistent with models of the core segregation process," Saal said.

The heavier isotope values can be explained by the further cooling and crystallization of the early molten Moon. The crystallization process removes sulfur from the magma pool, producing solid reservoirs with heavier sulfur-34. That process is the likely source of the heavier isotope values found in some of the volcanic glasses and basaltic rocks returned from the Moon.

"Our results suggest that these samples record these critical events in lunar history," Saal said. "As we keep looking at these samples with newer and better techniques, we keep learning new things."

More work needs to be done -- and more samples need to be analyzed -- to fully understand the sulfur isotopic composition of the Moon, Saal says. But these new results help to clarify long-standing questions about the composition of the Moon's interior, and they bring scientists one step closer to understanding the formation and early history of the Moon.

Credit: 
Brown University

Bearded seals are loud -- but not loud enough

image: Bearded seal on ice

Image: 
Michael Cameron, NOAA

Ithaca, NY-- During mating season, male bearded seals make loud calls to attract a mate--even their "quiet" call could still be as ear-rattling as a chainsaw. Bearded seals have to be loud to be heard over the cacophony of their equally loud brethren. And, increasingly, the noise humans make is adding to the underwater din and could have serious consequences. A study conducted by the Cornell Lab of Ornithology's Center for Conservation Bioacoustics (CCB) aims to understand how resilient bearded seals can be to changes in ambient underwater noise. The results are published in Proceedings of the Royal Society: Biological Science.

"We wanted to know whether bearded seals would call louder when their habitat grew noisy from natural sound sources," says CCB postdoctoral research associate Michelle Fournet who led the study. "The goal was to determine if there was a 'noise threshold' beyond which seals either couldn't-or wouldn't-call any louder in order to heard. By identifying this naturally occurring threshold, we can make conservation recommendations about how loud is too loud for human activities.'

From spring through early summer, the under-ice habitat near Utqiagvik, Alaska, is flooded with the vocalizations of male bearded seals--a sound that can be best described as "otherworldly." These elaborate vocalizations are essential for bearded seal reproduction, but in the rapidly changing Arctic soundscape, where noise from industrial activities is predicted to dramatically increase in the next 15 years, bearded seals may need to adjust their calling behavior if they are going to be heard above the noise generated by ships and commercial activities. But the bearded seals can only do so much.

Fournet and colleagues listened to thousands of recorded bearded seal vocalizations from Arctic Alaska spanning a two-year period. Each call was carefully measured and compared to the concurrent ambient noise conditions. What they found is that bearded seals do call louder as their underwater acoustic habitat gets noisier, but there is an upper limit to this behavior. As expected, when ambient noise gets too high, bearded seals are no longer able to compensate in order to be heard. As a result, as ambient noise conditions increase, the distance over which individuals can be detected goes down.

"Given that these are reproductive calls, it is likely that the seals are already calling as close to as loudly as possible-the males very much want to be heard by the females," Fournet says. "So, it is unsurprising that there is an upper limit. I'm grateful that we have been able to identify that limit so we can make responsible management choices moving forward."

While this work has intrinsic conservation value, a major impetus for pursuing this research is the value of bearded seals-or ugruk in the Inupiaq language-to Alaska Native communities in the high Arctic. Bearded seals are at the center of subsistence and cultural activities in Inupiaq communities. Threats to bearded seals are by extension threats to the communities that rely on them.

"This work never would have happened without the insight and guidance of Arctic communities," Fournet says. "It was their energy that led the Cornell Lab to place hydrophones in the water. It is our job to continue listening."

Credit: 
Cornell University

Fantastic voyage: Nanobodies could help CRISPR turn genes on and off

The genetic tool CRISPR has been likened to molecular scissors for its ability to snip out and replace genetic code within DNA.

But CRISPR has a capability that could make it useful beyond genetic repairs. "CRISPR can precisely locate specific genes," says Lacramioara Bintu, an assistant professor of bioengineering at Stanford. "What we did was attach CRISPR to nanobodies to help it perform specific actions when it reached the right spot on DNA."

Her lab recently used this combo technique to transform CRISPR from a gene-editing scissors into a nanoscale control agent that can toggle specific genes on and off, like a light switch, to start or stop the flow of some health-related protein inside a cell.

"There are a lot of things you can't fix with scissors," Bintu says. The novel technique her team describes in the journal Nature Communications could enable researchers to explore new therapeutic applications in the field of epigenetics -- which is the study of how genes behave inside cells.

As Bintu explains, every cell in the human body has the same DNA -- a full complement of genes -- but not every gene is switched on in every cell. Some cells have certain genes on, telling the cell to produce specific proteins. Others have those genes turned off, but others turned on. Sometimes, as with genetic diseases, things go awry in this switching. The Bintu lab's new tool has the potential to correct those mistakes.

The new tool is more complicated than scissors because ordinary CRISPR cannot turn genes on and off in a controlled manner without breaking the DNA. To make changes without harm to the DNA, CRISPR needs an assist from other large, complex proteins, known as "effectors." With the new combo tool, CRISPR finds the right gene, and the effector can flip the switch.

"But these effector molecules are usually too big to easily deliver into a cell for therapeutic use," says PhD student Mike Van, first author of the paper. Further complicating matters, several effectors are usually used in combination to efficiently regulate specific cell behaviors, making the CRISPR-effectors combo even bigger, hence harder to produce and deliver.

To get around this roadblock, Bintu's team turned to smaller proteins known as nanobodies. Nanobodies don't act as stand-ins for the effectors. Instead, they act like tiny hooks that snare the needed effectors that are already swimming about within the cell. Choose the right nanobody and it will recruit the right effector for the switching job.

The new technique could be used to correct epigenetic defects without the need to combine CRISPR to large effectors. "The cells already have these proteins," explains Bintu. "We thought: Why are we reattaching them? Let's use nanobodies to do that."

At this point the technique is at the proof-of-concept stage. The next step is for the team to sort through millions of potential nanobodies, and start figuring out how to attach them to CRISPR to target specific epigenetic breakdowns.

"We just came up with a method of testing hundreds of thousands at a time," says Bintu, who hopes to further develop the technique in future experiments.

Credit: 
Stanford University School of Engineering

Baby mice have a skill that humans want - and this microchip might help us learn it

image: A team of scientists including UNSW's Dr Vashe Chandrakanthan and Dr Hossein Tavassoli (pictured left to right) have developed a microchip that allows scientists to study the regenerative potential of mice heart cells.

Image: 
UNSW Sydney

Baby mice might be small, but they're tough, too.

For their first seven days of life, they have the special ability to regenerate damaged heart tissue.

Humans, on the other hand, aren't so lucky: any heart injuries we suffer could lead to permanent damage. But what if we could learn to repair our hearts, just like baby mice?

A team of researchers led by UNSW Sydney have developed a microchip that can help scientists study the regenerative potential of mice heart cells. This microchip - which combines microengineering with biomedicine - could help pave the way for new regenerative heart medicine research.

The study is featured on the cover of today's issue of the journal Small.

"We've developed a simple, reliable, cheap and fast way to identify and separate these important mouse heart cells," says lead author Dr Hossein Tavassoli, a biomedical engineer and stem cell researcher at UNSW Medicine & Health who conducted this work as part of his doctoral thesis.

"Our method uses a microchip that's easy to fabricate and can be made in any laboratory in the world."

The process for identifying and separating mice heart cells is rather complex.

First, scientists need to separate the right kind of heart cells (called proliferative cardiomyocytes) from other types of cells present in the heart.

Their next challenge is keeping the cells alive.

"Newborn mice heart cells (called proliferative cardiomyocytes) are very sensitive," says Dr Vashe Chandrakanthan, a senior research fellow at UNSW Medicine & Health and co-senior author of the study.

"Only about 20 per cent usually survive the conventional isolation and separation process. If we want to study these cells, we need to isolate them before they undergo cell death."

Dr Tavassoli says that this new method is much more efficient.

"We reduced the stress applied on these cells by minimising the isolation and processing time," he says. "Our method can purify millions of cells in less than 10 minutes.

"Almost all of the cells survived when we used our microfluidic chip - over 90 per cent."

The spiral-shaped device is a microfluidic chip - that is, a chip designed to handle liquids on tiny scale. It filters cells according to their size, separating the cardiomyocytes from other cells. The chip costs less than $500 to produce, making it cheaper than other isolation and separation methods.

This tool will make it easier for researchers to study how baby mice repair their hearts - and whether humans might be able to use the same technique.

"Heart disease is the number one killer in the world," says Dr Tavassoli. "In Australia, someone dies of heart disease every 12 minutes, and every four hours a baby is born with a heart defect.

"We hope that our device will help accelerate heart disease research."

Characterising mice heart cells

Once the heart cells were separated from other cells with the help of their chip, the researchers seized the opportunity to study the cells' physico-mechanical properties - that is, the way they respond to force.

This involved asking questions like 'How do these individual heart cells beat?', 'Do the cells have distinct features?' and 'What are their differences in size, shape and elasticity?'.

The findings could provide new insights for developing materials that repair heart tissue, like cardiac patches, scaffolds and hydrogels.

"The fast, large-scale characterisation of cells' physico-mechanical features is a relatively new field of research," says Dr Tavassoli, who originally trained as an engineer before specialising in medicine.

"This is the first time microfluidic technology has been used to study mechanical properties of baby mouse heart cells."

A multipurpose microchip

Dr Chandrakanthan says that even though the microchip was created for baby mouse heart cells, it could potentially be adapted for use in other types of cell applications.

"The principles are compatible with isolating cardiomyocytes from mouse heart cells of all ages," he says.

"We could potentially also use this method to separate not only the heart cells, but all sorts of cells from different organs."

Dr Tavassoli says this method could also help other areas of medical research, including cardiac biology, drug discovery and nanoengineering. He is currently conducting research at the Garvan Institute and Lowy Cancer Research Centre on how this method could help cancer diagnosis.

"This microchip opens up the opportunity for new discoveries by researchers all over the world," he says.

Credit: 
University of New South Wales

New discoveries on the containment of COVID-19 finds travel bans are of limited value

BROOKLYN, New York, Wednesday, February 24, 2021 – Travel bans have been key to efforts by many countries to control the spread of COVID-19. But new research aimed at providing a decision support system to Italian policy makers, recently published in the Journal of the Royal Society Interface, suggests that reducing individual activity (i.e., social distancing, closure of non-essential business, etc.) is far superior in controlling the dissemination of Sars-CoV-2, the virus that causes COVID-19.

The research, which has implications for the United States and other countries, found that limiting personal mobility through travel restrictions and similar tactics is effective only in the first phases of the epidemic, and reduces in proportion to the spread of infection across a population.

In the study, “Modelling and predicting the effect of social distancing and travel restrictions on COVID-19 spreading” the researchers, led by Alessandro Rizzo, visiting professor in the Office of Innovation at NYU Tandon and professor at the Politecnico di Torino, and Maurizio Porfiri Institute Professor of mechanical and aerospace, biomedical and civil and urban engineering at NYU Tandon and a member of the Center for Urban Science and Progress (CUSP), detail a data modeling framework for isolating the differential efficacy of different COVID-19 intervention policies. Since their method benefits from a low computational load (it can easily run on a personal computer), it can be a valuable decision support system to policy makers, toward the implementation of combined containment actions that can protect citizens’ health, while avoiding total closures, with all their economic, social, and psychological consequences.

“While this project was focused specifically on Italy, the results are revelatory for virtually any country relying on travel restrictions to stem the spread of the pandemic. We look forward to using US data to tune the model and give specific answers to combat this delicate phase of the pandemic,” said Porfiri.

Added Rizzo, “We are particularly satisfied with this model, as it provides very detailed answers even though it relies only on aggregated sources of data – a further guarantee of people’s privacy.”

The work includes a realistic representation of demographic data and travel patterns of both commuters and those taking long-distance trips, using only aggregated and publicly available data, without resorting to individual tracking devices. It follows upon a study on the spread of Covid-19 in New Rochelle, New York predicting the diffusion of COVID-19 in medium sized cities and provinces, published as the cover of Advanced Modeling and Simulations (Wiley),

The investigators, including Francesco Parino of Politecnico di Torino and Lorenzo Zino of the University of Groningen, The Netherlands, also found that selective lockdown policies, for example restriction only on the activity of the elderly, seems not to have a great effect on the overall transmission of the epidemic.

Deploying their algorithmic framework to model scenarios in which restrictions are lifted, discovered that restrictions on social activity must be gradually removed to avoid a second wave, while the timing and swiftness of removal of travel restrictions seem not to have a great effect on the transmission.

In view of the scarce resources and the inherent slowness of vaccination campaigns, the research group is now engaged in the use of the model to assess the effect of different vaccination policies, toward the definition of vaccination rollouts that will aim at providing an optimal outcome in spite of the limited resources in terms of vaccine doses and operators.

Credit: 
NYU Tandon School of Engineering

Mangrove forests store more carbon when they're more diverse

image: Field survey. Hainan 2018.

Image: 
Guanghui Lin.

Mangrove forests with greater species diversity can store more carbon, according to new research published in the British Ecological Society journal Functional Ecology.

Researchers studying mangrove forests in Hainan Island, China, have found that species diversity in mangrove forests enhances both biomass production (the quantity of organic matter) and soil carbon storage. The findings highlight the impotence of conserving mangrove biodiversity as a nature-based solution to mitigate climate change.

The East side of the island was found to have the highest mangrove biomass, diversity and carbon storage, with a mean of 537 tonnes of carbon per hectare (Mg C ha-1). This compared to a mean of 328 Mg C ha-1 across the entire island, and the world mangrove forest mean of 386Mg C ha-1.

This is the first study based on an intensive field study to verify the positive effect of biodiversity on mangrove biomass and carbon storage.

Mangroves grow in tropical regions and are one of the most carbon rich ecosystems on the planet. There are over 70 different species worldwide with 27 of these in China and 26 in the areas studied by the researchers.

Because of the large representation of mangrove species in the study area, the researchers believe the results can be applied to other regions of China and the rest of the world, especially other Asian countries which have similar mangrove species diversity.

The researchers also found that areas with high soil nitrogen content and annual rainfall had higher mangrove biomass and carbon storage potential, indicating that both soil fertility and climate factors determine areas of high mangrove diversity and carbon storage.

Dr Guanghui Lin of Tsinghua University and one of the authors of the study, said: "Our findings suggest that mangrove forests with greater diversity also have higher carbon storage capacities and conservation potential. Thus, mangrove biodiversity conservation is crucial for ensuring mangrove forests are able to mitigate climate change. We can increase mangrove diversity through restoration and conservation projects, especially those that promote local native species."

Professor Xiaoshan Zhu, also of Tsinghua University and another author of the study, said: "Worldwide, particularly in developing countries such as China, mangroves have been lost or degraded over the last several decades. Restoration of mangrove forests and their habitats are urgently needed not only for preservation of biodiversity but also to increase carbon storage potentials."

Another benefit of increasing mangrove species diversity is that it will help to maintain the stability of mangrove ecosystems against disturbances like climate change and extreme weather. This in turn ensures mangrove forests continue to provide a habitat for the hundreds of species that rely on them.

Mangrove forests consist of trees, shrubs and other woody plants growing in the tidal zones of tropical and sub-tropical coastlines. They provide numerous ecological services including water purification, coastal protection, habitat provision and carbon storage.

The 26 mangrove species found on Hainan Island, where the researchers conducted the study, ranged from 30m tall trees such as Sonneratia and Bruguerria species, to shrubs of only a few meters such as Avicennia marina.

A higher diversity of mangrove species leads to a more complex ecological community that can access more of the resources available. This is why species diversity leads to a faster accumulation of mangrove biomass.

In the study the researchers conducted an intensive field survey of mangrove biodiversity and carbon storage along the entire coastline of Hainan Island, which has nearly 20% of China's mangrove forest area.

Between 2017 and 2018 they collected data from 234 10m2 field plots along 30 transects distributed across the four main mangrove sites on the island. In each plot they collected data on the size, density and number of mangrove species, as well water and soil salinity and pH.

They then calculated the carbon storage of the plant biomass using known carbon concentrations for each species and soil carbon and nitrogen content using soil samples from each of the 30 transects.

A limitation of the study was that it was restricted to an isolated island. The authors are now compiling data for the rest of China and other countries with mangrove forests around the world. "This will allow us to test the relationship between plant species diversity and mangrove carbon storage found in this study." said Dr Guanghui Lin.

Credit: 
British Ecological Society

Red light put moths in the mood

image: Female of the yellow peach moth Conogethes punctiferalis

Image: 
Wei Xiao / Southwest University, China

Do you dim the lighting and turn on the red light for a romantic night in with your partner? It turns out moths aren't so different in that regard. A new study published in Frontiers in Genetics shows that dim red light boosts sexual activity in a model species, the yellow peach moth Conogethes punctiferalis (family Crambidae), by selectively activating a genetic pathway related to olfaction in the antennae. This pathway ultimately makes males more sensitive to the odor of the female sex pheromone and thus more motivated to mate.

"We usually use red lights when working with our moths as prolonged white light can prevent them from mating," says lead author Dr Wei Xiao, a scientist from Southwest University in Chongqing, China. "However, we realized that the moths laid more eggs when we shone red light during the dark phase of their daily light-dark cycle, and we wanted to determine the molecular mechanisms underlying this change."

Odorant binding proteins (OBPs) are small proteins secreted by auxiliary cells surrounding olfactory receptor neurons in the antennae of insects. Xiao and colleagues first used quantitative PCR (qRT-PCR) to show that two OBPs, encoded by the genes CpunOB2 and CpunPBP5, are more abundant in the antennae of male C. punctiferalis exposed to medium-intensity (around 2 lux) red light than in antennae exposed to darkness or light with other wavelengths. The authors speculate that the relatively long wavelength of red light enables it to enter tissues and cells and there stimulates the expression of CpunOB2 and CpunPBP5 by a yet to be determined mechanism.

Xioa et al. then used another molecular technique, fluorescence binding assay, to show that these OBPs, when recombinantly expressed in E. coli bacteria, selectively bind to molecules that are known to be components of the moth's female sex pheromone. With electroantennography, a technique that measures the electrical activity in antennae in response to stimuli, they went on to show that the antennae of males become more reactive to female sex pheromone after exposure to red light. Finally, they used behavioral experiments to confirm that the ultimate effect of red light on male and female C. punctiferalis is to stimulate mating and egg laying.

Xiao et al. conclude that for this species at least, dim red light is sufficient to cause olfactory receptor neurons in the antennae of males to become hypersensitive to components of the female sex pheromone, ultimately promoting reproductive behaviors in the adults moths.

Although the yellow peach moth itself isn't endangered, Xiao's study could potentially help to boost reproduction in at-risk species, or species that are economically important.

"Our study is the first to test the stimulatory effects of red light on mating behavior and is therefore a potential springboard for research into novel conservation techniques for endangered insects," says Xiao.

Credit: 
Frontiers