Culture

Herbivores developed powerful jaws to digest tougher plants after the mass extinctions

image: Triassic herbivore

Image: 
James Ormiston

Researchers at the University of Bristol found that plant eaters diversified quickly after mass extinctions to eat different kinds of plants, and the ones that were able to chew harsher materials, which reflected the drying conditions of the late Triassic, became the most successful. These tougher herbivores included some of the first dinosaurs.

Following the largest mass extinction of all time, the end-Permian mass extinction, ecosystems rebuilt from scratch during Triassic times, from 252-201 million years ago paving the way for new species, and many new kinds of plants and animals emerged. In a new study published in Nature Communications and led by Dr Suresh Singh of Bristol's School of Earth Sciences, fresh evidence has emerged of the complexity of the post-extinction recovery.

"I wanted to focus on the plant-eaters, including some of the first dinosaurs," says Dr Suresh Singh. "The main animals in any ecosystem tend to be the herbivores, and we found that they show remarkable evidence of specialisation in the turbulent times after the great mass extinction. In fact, the environmental shocks that killed so many species, such as global warming and acid rain, were still returning from time to time, but the survivors were set on exploring new diets."

"We were surprised to be able to identify definite specialisations among the herbivores," said Dr Tom Stubbs, a collaborator. "We call these groups, the ingestion generalists, prehension specialists, durophagous specialists, shearing pulpers, and heavy oral processors; these names reflect the power of their jaws, their teeth, and the kinds of plants they would likely have been eating."

"It might seem to be a speculative enterprise to identify the diets of animals that died over 200 million years ago," said Professor Emily Rayfield, who also co-led the project. "But we measured hundreds of fossil jaws and compared their shapes with living animals, and we estimated key functional values from the fossil jaws such as mechanical advantage and bite force, measuring the leverage of the jaws and how fast or forcefully they could shut."

Results were studied through the 80 million years following the mass extinction and including the diversification of the first plant-eating dinosaurs. "We were able to map the evolution of all the functional characters relating to feeding across the evolutionary tree and through time," said Dr Armin Elsler, collaborator. "We found to our surprise that, during this time, several new groups diversified as herbivores, and they seemed to take over their roles by pushing potential competitors aside, not necessarily by wiping them out."

The plants were also diversifying through the Triassic, and some of the evolution of herbivores relates to the availability of new kinds of plant food. "One key thing was the expansion of groups that were able to handle tough plant material, with powerful jaws for chopping and chomping," says Dr Singh. "This reflects the drying conditions especially in the Late Triassic, when many softer plant groups became less common, and dry-adapted conifers for example, spread worldwide. These changes combined with strictly enforced niche separation drove patterns of extinction as the generalist, hardy herbivores thrived, as other herbivores died out."

"This kind of macroecological analysis represents a huge amount of work," said Professor Mike Benton, who co-led the study. "But it sheds real light on key processes at an ecological level and helps explain why some groups died out and were replaced by others such as the first dinosaurs. We can be reasonably certain of the results because we have excellent data on the geological ages of the specimens, their relationships to each other, and the key features of their jaws and teeth that correspond to their ancient diets. What was once quite a speculative kind of project has now become much more analytical and testable."

Credit: 
University of Bristol

The eyes offer a window into Alzheimer's disease

While it has been said that the eyes are a window to the soul, a new study shows they could be a means for understanding diseases of the brain. According to new research by scientists at the UCSF Weill Institute for Neurosciences, retinal scans can detect key changes in blood vessels that may provide an early sign of Alzheimer's, while offering important insights into how one of the most common Alzheimer's risk genes contributes to the disease.

"The most prevalent genetic risk for Alzheimer's disease is a variant of the APOE gene, known as APOE4," said lead author Fanny Elahi, MD, PhD. "We still don't fully understand how this variant increases risk of brain degeneration, we just know that it does, and that this risk is modified by sex, race, and lifestyle. "Our research provides new insights into how APOE4 impacts blood vessels and may provide a path forward for early detection of neurodegenerative disease."

Studies in mice have explored the effect of APOE4 on capillaries in the brain. Elahi, an assistant professor of neurology and member of the UCSF Memory and Aging Center (MAC), has long suspected these tiny blood vessels may play a significant role in Alzheimer's disease, since they deliver nutrients and oxygen, carry away waste, and police immune system responses through the protective shield known as the blood-brain barrier. Damage to these blood vessels could cause a host of problems, she says, including the protein buildup and cognitive decline seen in individuals affected by Alzheimer's disease.

Because the technology does not exist to visualize individual capillaries in living people's brains, Elahi and colleagues turned to the eye. In the new study, which published May 11, 2021, in the journal Alzheimer's and Dementia: Diagnosis, Assessment & Disease Monitoring, Elahi and her team have shown that APOE4-associated capillary changes can be detected in humans through an easy, comfortable eye scan. As a light-penetrating tissue that shares biology with the brain, the retina, researchers believe, may help determine what APOE4 variants may be doing to similar capillaries inside the brain, even in those without dementia.

The team - which includes Ari Green, MD, a neuro-ophthalmologist, professor, and director of the UCSF Neurodiagnostics Center, and Amir Kashani, MD, PhD, associate professor of ophthalmology at the Johns Hopkins Wilmer Eye Institute - used an advanced retinal imaging technique known as optical coherence tomography angiography (OCTA) to peer into the eyes of aging people with and without APOE4 mutations to evaluate the smallest blood vessels at the back of the eye.

The team leveraged the well-characterized cohorts of people enrolled in ongoing studies of brain aging and neurodegenerative disease at the MAC. By adding OCTA scans to existing MRI and PET scan data, they gain comparative insights without putting volunteer participants through additional discomfort. "That's the beauty of this technique," Elahi said. "It's very easy, noninvasive and participant-friendly."

Analyzing the retinal scans, the researchers found reduced capillary density in APOE4 carriers, an effect that increased with participant age. To test whether those scans accurately reflected what was happening in the brain, the team then compared the abnormalities seen in OCTA scans of retinal capillaries to measurements of brain perfusion, or the flow of blood through the brain, as measured via MRI. They found that people with higher retinal capillary density also had greater blood flow in the brain.

Finally, the team looked to participants with prior PET scans of beta-amyloid, the protein associated with Alzheimer's disease, to see how their retinal capillary measurements related to the burden of amyloid plaques in the brain, which is the major focus of Alzheimer's disease diagnosis, research and treatment to date. They found that capillary density did not differ between groups with and without amyloid plaques, nor did it vary along with amyloid burden. According to Elahi, that independence suggests that capillary abnormalities are unlikely to be driven by amyloid pathology, or that their relation may at most be indirect.

"This is the first time that we have demonstrated in living, asymptomatic humans that the smallest blood vessels are affected in APOE4 gene carriers," said Elahi. That's important, she added, because it suggests that the increased risk of brain degeneration and Alzheimer's disease in APOE4 carriers may be through its effect on blood vessels.

Elahi and her colleagues plan to follow their study participants to better understand blood vessel dysfunction at a molecular level. That work could help detect the onset of Alzheimer's disease before significant damage occurs to the brain and identify new vascular targets for early treatment.

"This is just the beginning," Elahi said. "But the implications for early detection and possible intervention can be significant in combatting Alzheimer's disease and other neurodegenerative disorders. It's much harder to regenerate neurons than to stop their degeneration from happening in the first place. Similar to cancer, early detection can save lives,"

Credit: 
University of California - San Francisco

New screening method could lead to microbe-based replacements for chemical pesticides

video: Microbe-Based Replacements for Chemical Pesticide Replacement.
A team of scientists from Tokyo University of Science has developed a screening method based on cultured plant cells that makes such testing easier. This may lead to microorganism-based crop protection methods that reduce the need for chemical pesticides.

Image: 
Tokyo University of Science

Plants have evolved unique immunity mechanisms that they can activate upon detecting the presence of a pathogen. Interestingly, the presence of some nonpathogenic microorganisms can also prompt a plant to activate its systemic immunity mechanisms, and some studies have shown that pretreating agricultural crops with such "immunity-activating" nonpathogenic microorganisms can leave the crops better prepared to fight off infections from pathogenic microorganisms. In effect, this means that immunity-activating nonpathogenic microorganisms can function like vaccines for plants, providing a low-risk stimulus for the plant's immune system that prepares it for dealing with genuine threats. These are exciting findings for crop scientists because they suggest the possibility of using such pretreatment as a form of biological pest control that would reduce the need for agricultural pesticides.

However, before pretreatment with nonpathogenic microorganisms can become a standard agricultural technology, scientists need a way to screen microorganisms for the ability to stimulate plant immune systems without harming the plants. There is currently no simple method for evaluating the ability of microorganisms to activate plant immune systems. Conventional methods involve the use of whole plants and microorganisms, and this inevitably makes conventional screening a time-consuming and expensive affair. To address this problem, Associate Professor Toshiki Furuya and Professor Kazuyuki Kuchitsu of Tokyo University of Science and their colleagues decided to develop a screening strategy involving cultured plant cells. A description of their method appears in a paper recently published in Scientific Reports.

The first step in this screening strategy involves incubating the candidate microorganism together with BY-2 cells, which are tobacco plant cells known for their rapid and stable growth rates. The next step is to treat the BY-2 cells with cryptogein, which is a protein secreted by fungus-like pathogenic microorganisms that can elicit immune responses from tobacco plants. A key part of the cryptogein-induced immune responses is the production of a class of chemicals called reactive oxygen species (ROS), and scientists can easily measure cryptogein-induced ROS production and use it as a metric for evaluating the effects of the nonpathogenic microorganisms. To put it simply, an effective pretreatment agent will increase the BY-2 cells' ROS production levels (i.e., cause the cells to exhibit stronger immune system activation) in response to cryptogein exposure.

To test the practicability of their screening strategy, Dr. Furuya and his colleagues used the strategy on 29 bacterial strains isolated from the interior of the Japanese mustard spinach plant (Brassica rapa var. perviridis), and they found that 8 strains boosted cryptogein-induced ROS production. They then further tested those 8 strains by applying them to the root tips of seedlings from the Arabidopsis genus, which contains species commonly used as model organisms for studies of plant biology. Interestingly, 2 of the 8 tested strains induced whole-plant resistance to bacterial pathogens.

Based on the proof-of-concept findings concerning those 2 bacterial strains, Dr. Furuya proudly notes that his team's screening method "can streamline the acquisition of microorganisms that activate the immune system of plants." When asked how he envisions the screening method affecting agricultural practices, he explains that he expects his team's screening system "to be a technology that contributes to the practical application and spread of microbial alternatives to chemical pesticides."

In time, the novel screening method developed by Dr. Furuya and team may make it significantly easier for crop scientists create greener agricultural methods that rely on the defense mechanisms that plants themselves have evolved over millions of years.

Credit: 
Tokyo University of Science

Hanging by a thread: Imaging and probing chains of single atoms

image: (left) Schematic illustration of the technique. The stiffness of nanomaterials such as platinum (Pt) atomic chains can be measured using a length-extension resonator (LER) made with a quartz crystal. The atomic structure of the chain can be observed using a transmission electron microscope (TEM). We found that the atomic bond strength in the Pt monoatomic chains is 25 N/m, which is higher than the bulk value (20 N/m). (right) Experimental and simulated TEM images of a monoatomic Pt chain and time evolution of its electrical conductance and stiffness during stretching. The maximum strain was 24% on average.

Image: 
Yoshifumi Oshima

Ishikawa, Japan - Today, many well-studied materials in various fields, such as electronics and catalysis, are close to reaching their practical limits. To further improve upon modern technology and outperform state-of-the-art devices, researchers looking for new functional materials have to push the boundaries and explore more extreme cases. A clear example of this is the study of low-dimensional materials, such as monoatomic layers (2D materials) and monoatomic chains (1D materials).

It has been proved time and time again that low-dimensional materials exhibit exotic properties that are absent in their 3D bulk counterparts. For example, monoatomic chains of metals like gold and platinum (Pt) can exhibit the contribution of certain quantum phenomena, such as magnetic order or thermal transport, in ways that could find practical applications. However, it is very difficult to experimentally observe what goes on in monoatomic chains composed of five or less atoms, and the mechanical properties of single-atom bonds remain elusive.

To tackle this issue, a research group lead by Professor Yoshifumi Oshima from Japan Advanced Institute of Science and Technology (JAIST), Japan, is pioneering a novel and promising technique to measure the strength of individual atomic bonds. Their latest study, which was published in Nano Letters and showcased their strategy, involved researchers from JAIST (Dr. Zhang, Dr. Ishizuka, Prof. Tomitori, Prof. Maezono and Prof. Hongo), as well as Prof. Arai from Kanazawa University and Prof. Tosatti from the International School for Advanced Studies (SISSA) and The Abdus Salam International Centre for Theoretical Physics (ICTP).

This new technique, which Oshima named the "microscopic nanomechanics measurement method," combines transmission electron microscopy (TEM) with a quartz length-extension resonator (LER). TEM is a widely used imaging technique with incredibly high spatial resolution--enough to make out individual atoms--whereas the LER is a device that can oscillate at incredibly small amplitudes of a few ten trillionths of a meter and serves as a force sensor.

The researchers devised an experimental setup in which a small Pt juncture was stretched to its absolute breaking point, that is, when the two pieces of Pt were linked by a monoatomic chain of two to five atoms. By carefully aligning the pieces in the TEM, they observed the formation and breaking of the monoatomic Pt chains in real time. Moreover, using the quartz LER, they measured the conductance across the chain and its stiffness, from which the strength of individual Pt bonds was calculated with success. "We found the bond strength of 25 N/m in the monoatomic Pt chains to be remarkably high, especially compared to the 20 N/m normally found in bulk Pt crystals," comments Zhang. ""Moreover, these single-atom bonds could be stretched about 24% of their regular distance, in stark contrast to the 5% that bonds between Pt atoms in bulk can be stretched," he adds.

The results of the study showcase the potential of this novel technique to probe monoatomic chain bonds, which could lead to a better understanding of the interfaces or surfaces of low-dimensional materials. "Our method could greatly contribute to the design of advanced materials and catalysts as well as shed light on nanoscale phenomena in terms of surface or interface nanomechanics," highlights Oshima. In turn, more sophisticated materials and a better understanding of their surface properties will undoubtedly advance the fields of electronics, chemistry, and nanotechnology, paving the way to innovative and hopefully sustainable designs.

It's very likely that the expression "hanging by a thread" will soon get a more positive meaning in nanomaterials science!

Credit: 
Japan Advanced Institute of Science and Technology

Charting the expansion history of the universe with supernovae

image: Schematical representation of the expansion of the Universe over the course of its history.

Image: 
NAOJ

An international research team analyzed a database of more than 1000 supernova explosions and found that models for the expansion of the Universe best match the data when a new time dependent variation is introduced. If proven correct with future, higher-quality data from the Subaru Telescope and other observatories, these results could indicate still unknown physics working on the cosmic scale.

Edwin Hubble's observations over 90 years ago showing the expansion of the Universe remain a cornerstone of modern astrophysics. But when you get into the details of calculating how fast the Universe was expanding at different times in its history, scientists have difficulty getting theoretical models to match observations.

To solve this problem, a team led by Maria Dainotti (Assistant Professor at the National Astronomical Observatory of Japan and the Graduate University for Advanced Studies, SOKENDAI in Japan and an affiliated scientist at the Space Science Institute in the U.S.A.) analyzed a catalog of 1048 supernovae which exploded at different times in the history of the Universe. The team found that the theoretical models can be made to match the observations if one of the constants used in the equations, appropriately called the Hubble constant, is allowed to vary with time.

There are several possible explanations for this apparent change in the Hubble constant. A likely but boring possibility is that observational biases exist in the data sample. To help correct for potential biases, astronomers are using Hyper Suprime-Cam on the Subaru Telescope to observe fainter supernovae over a wide area. Data from this instrument will increase the sample of observed supernovae in the early Universe and reduce the uncertainty in the data.

But if the current results hold-up under further investigation, if the Hubble constant is in fact changing, that opens the question of what is driving the change. Answering that question could require a new, or at least modified, version of astrophysics.

These results will appear as M.G. Dainotti et al. "On the Hubble Constant Tension in the SNe Ia Pantheon Sample" in the Astrophysical Journal on May 17, 2021.

Credit: 
National Institutes of Natural Sciences

Researchers develop first-in-class inhibitors against key leukemia protein

image: An X-ray crystallography image showing an ASH1L inhibitor developed at U-M in complex with the protein.

Image: 
Grembecka / Cierpicki Labs

The protein made by the ASH1L gene plays a key role in the development of acute leukemia, along with other diseases. The ASH1L protein, however, has been challenging to target therapeutically.

Now a team of researchers led by Jolanta Grembecka, Ph.D., and Tomasz Cierpicki, Ph.D., from the University of Michigan has developed first-in-class small molecules to inhibit ASH1L's SET domain -- preventing critical molecular interactions in the development and progression of leukemia.

The team's findings, which used fragment-based screening, followed by medicinal chemistry and a structure-based design, appear in Nature Communications.

In mouse models of mixed lineage leukemia, the lead compound, known as AS-99, successfully reduced leukemia progression.

"This work points to a new, exiting avenue to develop new therapeutic agents against acute leukemia, as well as providing a new approach to further study the biological functions of ASH1L and its role in the development of the disease," says Grembecka, associate professor of pathology at Michigan Medicine and co-director of the developmental therapeutics program at the U-M Rogel Cancer Center.

The study was a close collaboration between her lab and the lab of co-senior author Cierpicki, an associate professor of biophysics and pathology.

Credit: 
Michigan Medicine - University of Michigan

Pancreatic cancer trials fail to include minorities despite worse outcomes

Bethesda, MD (May 14, 2021) -- Despite the fact that certain racial and ethnic minorities get pancreatic cancer more often, are diagnosed at a younger age and die sooner, clinical trials fail to include representative proportions of non-White patients at every phase of study, according to research that was selected for presentation at Digestive Disease Week® (DDW) 2021.

"We see disparities in representation across all kinds of clinical trials, so we were not surprised to see that it also occurs in pancreatic cancer trials. But hopefully we can make a change in that arena in the future," said Kelly Herremans, MD, lead researcher on the study and surgical research fellow at the University of Florida College of Medicine, Gainesville.

Researchers analyzed data from 8,429 participants in 207 clinical trials in the U.S. for treatments for pancreatic ductal adenocarcinoma on ClinicalTrials.gov, a national registry of clinical trial data. Gender was reported in 99 percent of the trials, while race and ethnicity were reported in 49.3 percent and 34.7 percent of trials, respectively.

Minorities were substantially underrepresented in trials:

Black patients represented 8.2 percent of trial participants vs. 12.4 percent of the U.S. incident cases.

Hispanic patients represented 6 percent of trial participants compared to 8.5 percent of the U.S. incident cases.

Asian or Pacific Islander patients represented 2.4 percent of trial participants vs. 3.3 percent of the U.S. incident cases.

American Indians and Alaska Native patients represented 0.3 percent of trial participants compared to 0.4 percent of the U.S. incident cases.

White patients were overrepresented, making up 84.7 percent of the total trial participants, while they account for 82.3 percent of the total U.S. incident cases. In all, 54.8 percent of trial participants were male, and 45.2 percent female.

Pancreatic ductal adenocarcinoma is particularly deadly, with an estimated 5-year survival rate of only 9 percent. Diversity is important for clinical trials because previous research has shown racial differences in tumor biology, Dr. Herremans said. For example, Black patients have different rates of both somatic and germline mutations when compared to other racial subgroups, which means they may respond differently to treatment.

"We are treating everybody as if they were the same and their tumors would react the same to treatments, but it's important to look at the ancestral differences of tumor biology and therapeutic response," Dr. Herremans said.

Lack of diversity in clinical trials is often attributed to reluctance to participate due to historic wrongs such as the infamous 1932 Tuskegee Syphilis Study that left Black men untreated for many years to study the long-term impact of syphilis. But research has shown that Black patients are just as willing as White patients to be part of a clinical trial, Dr. Herremans said.

Lack of representation may be a result of systemic racism, provider biases that interfere with recruitment as well as study inclusion criteria, which can create impediments to enrollment, such as turning away patients with obesity and diabetes, which have increased prevalence in minority populations.

"It is multifaceted, and regulations have been put in place that have tried to combat this problem, but over the last 15 years, we really haven't made much headway," Dr. Herremans said.

DDW Presentation Details

Dr. Herremans will present data from the study, "Trials and tribulations: Diversity and inclusion in pancreatic ductal adenocarcinoma clinical trials," abstract 901, on Sunday, May 23, at 6 p.m. EDT. For more information about featured studies, as well as a schedule of availability for featured researchers, please visit http://www.ddw.org/press.

Credit: 
Digestive Disease Week

Gimmicky or effective? The effects of imaginative displays on customers' purchase behavior

Researchers from Monash University, Queensland University of Technology, and Capital University of Economics and Business published a new paper in the Journal of Marketing that examines the effects of imaginative product displays in retail stores on customers' purchase behavior.

The study, forthcoming in the Journal of Marketing, is titled "Gimmicky or Effective? The Effects of Imaginative Displays on Customers' Purchase Behavior" and is authored by Hean Tat Keh, Di Wang, and Li Yan.

Imaginative displays are constructed using multiple units of the same product in a novel, yet aesthetically appealing, form. Results from six studies show that, relative to standard displays (i.e., non-novel and neutral aesthetics), imaginative displays can increase customers' purchase intention, actual purchases, product sales, and ROI.

Importantly, the effects of imaginative displays can be explained by the dual mechanisms of affect-based arousal and cognition-based inferred benefits. That is, an imaginative display increases customer arousal and a themed imaginative display leads customers to infer benefits from the display, which increases their purchase behavior. Moreover, the researchers identify a theoretically meaningful and managerially relevant moderator--congruence between display form and perceived product benefit, which can enhance or attenuate the core effects.

There are three major takeaways:

First, an imaginative display represents a cost-effective way to enhance customers' purchase behavior and increase product sales and ROI. This effect applies to both familiar and less familiar brands.

Second, effective imaginative displays have to be both novel and aesthetically appealing, which highlights the overlooked aesthetic element in innovative design.

Third, the inferred benefits of imaginative displays are context-dependent. For a themed imaginative display (i.e., has a particular shape mimicking an object), the retailer should ensure that the display form is congruent with the perceived product benefit to increase purchase behavior. Incongruence between display form and product benefit would backfire.

The authors observe that "Our findings not only explain why some retailers utilize 'gimmicky' imaginative displays, but also provide evidence on the processes and boundary conditions of these displays to favorably influence customers' purchase behavior and increase product sales at relatively low costs."

Credit: 
American Marketing Association

Our dreams' weirdness might be why we have them, argues new AI-inspired theory of dreaming

image: This illustration represents the overfitted brain hypothesis of dreaming, which claims that the sparse and hallucinatory quality of dreams is not a bug, but a feature, since it helps prevent the brain from overfitting to its biased daily sources of learning

Image: 
Georgia Turner

The question of why we dream is a divisive topic within the scientific community: it's hard to prove concretely why dreams occur and the neuroscience field is saturated with hypotheses. Inspired by techniques used to train deep neural networks, Erik Hoel (@erikphoel), a research assistant professor of neuroscience at Tufts University, argues for a new theory of dreams: the overfitted brain hypothesis. The hypothesis, described May 14 in a review in the journal Patterns, suggests that the strangeness of our dreams serves to help our brains better generalize our day-to-day experiences.

"There's obviously an incredible number of theories of why we dream," says Hoel. "But I wanted to bring to attention a theory of dreams that takes dreaming itself very seriously--that says the experience of dreams is why you're dreaming."

A common problem when it comes to training AI is that it becomes too familiar with the data it's trained on--it starts to assume that the training set is a perfect representation of anything it might encounter. Data scientists fix this by introducing some chaos into the data; in one such regularization method, called "dropout," some data is randomly ignored. Imagine if black boxes suddenly appeared on the internal screen of a self-driving car: the car that sees the random black boxes on the screen and focuses on overarching details of its surroundings, rather than the specifics of that particular driving experience, will likely better understand the general experience of driving.

"The original inspiration for deep neural networks was the brain," Hoel says. And while comparing the brain to technology is not new, he explains that using deep neural networks to describe the overfitted brain hypothesis was a natural connection. "If you look at the techniques that people use in regularization of deep learning, it's often the case that those techniques bear some striking similarities to dreams," he says.

With that in mind, his new theory suggests that dreams happen to make our understanding of the world less simplistic and more well-rounded--because our brains, like deep neural networks, also become too familiar with the "training set" of our everyday lives. To counteract the familiarity, he suggests, the brain creates a weirded version of the world in dreams, the mind's version of dropout. "It is the very strangeness of dreams in their divergence from waking experience that gives them their biological function," he writes.

Hoel says that there's already evidence from neuroscience research to support the overfitted brain hypothesis. For example, it's been shown that the most reliable way to prompt dreams about something that happens in real life is to repetitively perform a novel task while you are awake. He argues that when you over-train on a novel task, the condition of overfitting is triggered, and your brain attempts to then generalize for this task by creating dreams.

But he believes that there's also research that could be done to determine whether this is really why we dream. He says that well-designed behavioral tests could differentiate between generalization and memorization and the effect of sleep deprivation on both.

Another area he's interested to explore is on the idea of "artificial dreams." He came up with overfitted brain hypothesis while thinking about the purpose of works of fiction like film or novels. Now, he hypothesizes that outside stimuli like novels or TV shows might act as dream "substitutions"--and that they could perhaps even be designed to help delay the cognitive effects of sleep deprivation by emphasizing their dream-like nature (for instance, by virtual reality technology).

While you can simply turn off learning in artificial neural networks, Hoel says, you can't do that with a brain. Brains are always learning new things--and that's where the overfitted brain hypothesis comes in to help. "Life is boring sometimes," he says. "Dreams are there to keep you from becoming too fitted to the model of the world."

Credit: 
Cell Press

Bio-inspired scaffolds help promote muscle growth

image: Aligned myotubes formed on electrospun extracellular matrix scaffolds produced at Rice University. The staining with fluorescent tags shows cells' expression of myogenic marker desmin (green), actin (red) and nuclei (blue) after seven days of growth.

Image: 
Mikos Research Group/Rice University

HOUSTON - (May 14, 2021) - Rice University bioengineers are fabricating and testing tunable electrospun scaffolds completely derived from decellularized skeletal muscle to promote the regeneration of injured skeletal muscle.

Their paper in Science Advances shows how natural extracellular matrix can be made to mimic native skeletal muscle and direct the alignment, growth and differentiation of myotubes, one of the building blocks of skeletal muscle. The bioactive scaffolds are made in the lab via electrospinning, a high-throughput process that can produce single micron-scale fibers.

The research could ease the burden of performing an estimated 4.5 million reconstructive surgeries per year to repair injuries suffered by civilians and military personnel.

Current methods of electrospinning decellularized muscle require a copolymer to aid in scaffold fabrication. The Rice process does not.

"The major innovation is the ability to prepare scaffolds that are 100% extracellular matrix," said Rice bioengineer and principal investigator Antonios Mikos. "That's very important because the matrix includes all the signaling motifs that are important for the formation of the particular tissue."

The scaffolds leverage bioactive cues from decellularized muscle with the tunable material properties afforded through electrospinning to create a material rich with biochemical signals and highly specific topography. The material is designed to degrade as it is replaced by new muscle within the body.

Experiments revealed that cells proliferate best when the scaffolds are not saturated with a crosslinking agent, allowing them access to the biochemical cues within the scaffold matrix.

Electrospinning allowed the researchers to modulate crosslink density. They found that intermediate crosslinking led to better retention of fiber alignment during cell culture.

Most decellularized matrix for muscle regeneration comes from such thin membranes as skin or small intestine tissue. "But for muscle, because it's thick and more complex, you have to cut it smaller than clinically relevant sizes and the original material properties are lost," said Rice graduate student and lead author Mollie Smoak. "It doesn't resemble the original material by the time you're done.

"In our case, electrospinning was the key to make this material very tunable and have it resemble what it once was," she said.

"It can generate fibers that are highly aligned, very similar to the architecture that one finds in skeletal muscle, and with all the biochemical cues needed to facilitate the creation of viable muscle tissue," Mikos said.

Mikos said using natural materials rather than synthetic is important for another reason. "The presence of a synthetic material, and especially the degradation products, may have an adverse effect on the quality of tissue that is eventually formed," he said.

"For eventual clinical application, we may use a skeletal muscle or matrix from an appropriate source because we're able to very efficiently remove the DNA that may elicit an immune response. We believe that may make it suitable to translate the technology for humans."

Smoak said the electrospinning process can produce muscle scaffolds in any size, limited only by the machinery.

"We're fortunate to collaborate with a number of surgeons, and they see promise in this material being used for craniofacial muscle applications in addition to sports- or trauma-induced injuries to large muscles," she said. "These would include the animation muscles in your face that are very fine and have very precise architectures and allow for things like facial expressions and chewing."

Credit: 
Rice University

Crowdsourcing for university community engagement COVID-19 safety strategies

What The Study Did: This is a qualitative study that evaluates a crowdsourcing open call to gather community input for engaging the university community in COVID-19 safety strategies.

Authors: Suzanne Day, Ph.D., of the University of North Carolina at Chapel Hill, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.10090)

Editor's Note: This article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Availability of US hospital price data

What The Study Did: Researchers evaluated the compliance of hospitals with a Centers for Medicare & Medicaid Services ruling mandating that a list of charges for services, procedures and items be publicly available and in a machine-readable file.

Authors: David Hsiehchen, M.D., of the University of Texas Southwestern Medical Center in Dallas, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.10109)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Fruit flies and mosquitos are 'brainier' than most people suspect, say scientists

image: (Left) Whole brain of a fruit fly. (Right) Nuclei of neurons in fruit fly brain tissue.

Image: 
Joshua Raji and Christopher Potter, Johns Hopkins Medicine.

In research made possible when COVID-19 sidelined other research projects, scientists at Johns Hopkins Medicine meticulously counted brain cells in fruit flies and three species of mosquitos, revealing a number that would surprise many people outside the science world.

The insects' tiny brains, on average, have about 200,000 neurons and other cells, they say. By comparison, a human brain has 86 billion neurons, and a rodent brain contains about 12 billion. The figure probably represents a "floor" for the number needed to perform the bugs' complex behaviors.

"Even though these brains are simple [in contrast to mammalian brains], they can do a lot of processing, even more than a supercomputer," says Christopher Potter, Ph.D., associate professor of neuroscience at the Johns Hopkins University School of Medicine. "They enable the insects to navigate, find food and perform other complicated tasks at the same time, and our study offers one answer to the question of how many brain cells come together to conduct these behaviors," Potter adds.

Results of the research are summarized May 14 in PLOS ONE.

Those who study insect behavior and brain function have long suspected these insects must have hundreds of thousands of brain cells, says Potter, but when he and postdoctoral fellow Joshua Raji, Ph.D., followed chains of scientific papers that referenced the count, they did not find proof for it.

In response, they report, they set out to find proof using a relatively simple counting method called an isotropic fractionator, a technique familiar to pathologists when they tally the number of any type of cell in a tissue.

First, Raji used a plastic pestle to break down all the brain tissue of the individual insects. Then, he used a pipette to break apart the tissue and distribute the cells evenly through a buffered solution.

Knowing the precise total volume of the solution, they could then count cells within a small fraction of the solution, and scale it up to account for and estimate the total number of cells in the entire solution.

To make the actual count, the small amount of solution was spread on a microscope slide and placed on top of a small grid. With painstaking precision, Raji counted the cells on each slide, one by one.

The researchers concluded that the total sum of brain cells was 199,380 plus or minus 3,400 for the fruit fly Drosophila melanogaster. For three species of mosquito, the researchers found 217,910 plus or minus 6,180 in Aedes aegypti; 223,020 plus or minus 4,650 in Anopheles coluzzii; and 225,911 plus or minus 7,220 in Culex quinquefasciatus.

Raji and Potter found that the brain cells in each species contained mostly neurons -- about 90%. The rest are most likely supportive cells called glia, they say.

Potter says that researchers have determined the number of brain cells in only a few species of insects, including wasps and ants. "It would be interesting to apply this approach to social insects like bees, and see if there are differences between queens and drones," he says.

Potter also notes that the counting technique is a simple one that most researchers could perform, and it's an opportunity for any researcher to perform the counts and contribute them to scientific literature.

Raji noted that he did most of the work for the study as a side project during times when COVID-19 restrictions halted his main research projects.

The most challenging part of the technique, says Potter, was the microdissection of a brain that is smaller than the tip of a pencil. "It takes a really steady hand and lots of practice," he says.

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Johns Hopkins Medicine

Fairness 'important - but not enough'

Being treated fairly is important - but fairness alone isn't enough to make people feel valued in a workplace or other groups, new research suggests.

Researchers found that "distinctive treatment" - where a person's talents and qualities are recognised - provides this sense of value while also reinforcing their sense of inclusion. It also promotes mental health.

The findings suggest there is no conflict between "fitting in" and "standing out" in groups - in fact, they complement each other.

But while the importance of fairness is widely accepted, the researchers say distinctive treatment is often overlooked.

The research was carried out by the University of Exeter, UCLA and Sonoma State University.

"Organisations and other groups often recognise the importance of members treating each other fairly - with dignity and without bias," said lead author Dr Christopher Begeny, of the University of Exeter.

"In six studies of workplaces and other groups, we find that this is indeed key to fostering individuals' sense of belonging.

"However, individuals also need to be shown that they have some distinct value to the group.

"When colleagues or fellow group members show interest and appreciation for an individual's more distinguishing qualities, that individual benefits.

"This kind of distinctive treatment has real benefits for mental health too, including less anxiety and depression.

"To be clear, fair treatment is a must - but our studies show it's also woefully insufficient on its own.

"Individuals need to feel more than inclusion. As well as 'fitting in', they need to 'stand out' - to feel that they have some distinct value and worth that they bring to the group."

Asked how organisations could embed distinctive treatment in their workplace, Dr Begeny said: "It helps to have supervisors with the time and energy to recognise and tap into the particular skills and knowledge of the different people they supervise.

"Another method is to create well-developed systems of mentorship, allowing people to share their experience and expertise.

"This can also foster a workplace culture that is not just inclusive, but value-affirming - where people regularly seek each other out for advice, which is beneficial to both parties."

Dr Begeny added: "Expressing distinctive treatment does not simply mean sending out a mass email saying 'if anyone has any ideas about this project, please let me know'.

"It's about going to an individual, or small group of individuals, and saying, 'hey, I really think your insights and perspectives could be an asset to this project. Would you be willing to offer your thoughts?'

"It's not a passive process of hearing people when they have ideas to share.

"It involves actively seeking them out - taking the initiative to learn what an individual has to offer -and showing recognition and appreciation for it."

Of the six studies, four were based in workplaces, while the others examined fair and distinctive treatment in student communities, and in racial/ethnic minority communities.

In all cases, distinctive treatment provided clear benefits.

Credit: 
University of Exeter

Ventilating the rectum to support respiration

image: Based on the fact that loaches have intestinal respiration under hypoxic conditions, the efficacy of the EVA method was examined in mammals such as mice and pigs. The EVA method may be effective for patients with respiratory failure.

Image: 
Institute of Research,TMDU

Tokyo, Japan - Oxygen is crucial to many forms of life. Its delivery to the organs and tissues of the body through the process of respiration is vital for most biological processes. Now, researchers at Tokyo Medical and Dental University (TMDU) have shown that oxygen can be delivered through the wall of the intestine to compensate for the reduced availability of oxygen within the body that occurs in lung diseases that cause respiratory failure.

To breathe is to live; for higher animals, respiration involves absorbing oxygen and excreting carbon dioxide at gills or in the lungs. However, some animals have evolved alternative ventilatory mechanisms: loaches, catfish, sea cucumbers and orb-weaving spiders can absorb oxygen through their hindgut to survive in situations where the availability of oxygen is limited. Inspired by these unique adaptations, the team at TMDU devised strategies to allow gas exchange through the lining of the intestine, a process termed as enteral ventilation or EVA.

"The rectum has a mesh of fine blood vessels just beneath the surface of its lining, which means that drugs administered through the anus are readily absorbed into the bloodstream," first author Ryo Okabe explains. "This made us wonder whether oxygen could also be delivered into the bloodstream in the same way. We used experimental models of respiratory failure in mice, pigs and rats to try out two methods: delivering oxygen into the rectum in gas form, and infusing an oxygen-rich liquid via the same route."

The researchers prepared the lining of the rectum by rubbing it to cause inflammation and increase blood flow; these changes were confirmed by increased genetic markers and improved the effectiveness of the oxygen delivery. However, because such a preparation requirement would be unacceptable for human patients, the researchers also tried using oxygenated perfluorodecalin (PFD), a liquid that can be safely used in the human body and is already in selective clinical use, and that can carry large amounts of oxygen and carbon dioxide.

The team demonstrated that delivery of oxygen both as a gas and in liquid form was beneficial: oxygenation levels increased and behavior normalized, while survival was prolonged. The team also confirmed the improvement in oxygenation at the cellular level by immunochemical staining. Furthermore, they found that the minimal amount of PFD that was absorbed along with the oxygen caused no harm, and gut bacteria were not disrupted, indicating the safety of these methods in the animal models.

"Patients in respiratory distress can have their oxygen supply supported by this method to reduce the negative effects of oxygen deprivation while the underlying condition is being treated," foresees Takanori Takebe, corresponding author. "Enteral ventilation showed great promise in our asphyxia-like experimental model. The next steps will be to test safety of the EVA approach with more profound mechanistic understanding by which it works; and to establish effectiveness in humans in a clinical setting."

Conventional therapeutic respiratory support comprises complex technological protocols such as ventilators and artificial lungs. The current SARS-CoV-2 pandemic has highlighted the high need for development of less invasive alternatives such as EVA for short-term support of respiratory function. These new findings from the researchers at TMDU may pave the way for new ventilation strategies in the future.

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Tokyo Medical and Dental University