Culture

WASHINGTON--Black and Hispanic people with COVID-19 and diabetes are more likely than Caucasians to die or have serious complications, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Health disparities refer to unequal health status or health care between groups of people due to differences in their background, physical traits or their environment. These differences include race/ethnicity, country of origin, sex, income and disability. Minorities are disproportionately affected by diabetes and COVID-19 and are more likely to develop serious complications like diabetic ketoacidosis, a condition that occurs when your body produces high levels of blood acids.

"This is the first major study to examine racial-ethnic inequities for people with type 1 diabetes and COVID-19 that are brought on by structural and systemic racism," said study author Osagie Ebekozien, M.D., M.P.H., of the T1D Exchange in Boston, Mass. "We used a diverse cohort of patients with type 1 diabetes and found there is a significantly increased risk of worse outcomes for Black and Hispanic patients with COVID-19 and diabetes."

The researchers analyzed data from 180 people with type 1 diabetes and COVID-19 from 52 clinical sites in the United States. The study found Black patients were four times more likely to be hospitalized for diabetic ketoacidosis than Caucasians. Black and Hispanic patients were also less likely to use diabetes technology like continuous glucose monitors (CGMs) and insulin pumps, and they had worse glycemic control than Caucasian patients.

"Our findings of troubling and significant inequities call for urgent and targeted interventions, such as culturally appropriate diabetic ketoacidosis awareness campaigns, increased continuous glucose monitoring coverage for minority patients and health care provider participation in a Quality Improvement Collaborative," Ebekozien said.

New research by scientists at the University of Bristol explains how a 'stop-start' pattern of evolution, governed by environmental change, could explain why crocodiles have changed so little since the age of the dinosaurs.

Crocodiles today look very similar to ones from the Jurassic period some 200 million years ago. There are also very few species alive today - just 25. Other animals such as lizards and birds have achieved a diversity of many thousands of species in the same amount of time or less.

Prehistory also saw types of crocodile we don't see today, including giants as big as dinosaurs, plant-eaters, fast runners and serpentine forms that lived in the sea.

In the new research, published today in the journal Nature Communications Biology, the scientists explain how crocodiles follow a pattern of evolution known as 'punctuated equilibrium'.

The rate of their evolution is generally slow, but occasionally they evolve more quickly because the environment has changed. In particular, this new research suggests that their evolution speeds up when the climate is warmer, and that their body size increases.

Lead author Dr Max Stockdale from the University of Bristol's School of Geographical Sciences, said: "Our analysis used a machine learning algorithm to estimate rates of evolution. Evolutionary rate is the amount of change that has taken place over a given amount of time, which we can work out by comparing measurements from fossils and taking into account how old they are.

"For our study we measured body size, which is important because it interacts with how fast animals grow, how much food they need, how big their populations are and how likely they are to become extinct."

The findings show that the limited diversity of crocodiles and their apparent lack of evolution is a result of a slow evolutionary rate. It seems the crocodiles arrived at a body plan that was very efficient and versatile enough that they didn't need to change it in order to survive.

This versatility could be one explanation why crocodiles survived the meteor impact at the end of the Cretaceous period, in which the dinosaurs perished. Crocodiles generally thrive better in warm conditions because they cannot control their body temperature and require warmth from the environment.

The climate during the age of dinosaurs was warmer than it is today, and that may explain why there were many more varieties of crocodile than we see now. Being able to draw energy from the sun means they do not need to eat as much as a warm-blooded animal like a bird or a mammal.

Dr Stockdale added: "It is fascinating to see how intricate a relationship exists between the earth and the living things we share it with. The crocodiles landed upon a lifestyle that was versatile enough to adapt to the enormous environmental changes that have taken place since the dinosaurs were around."

The next step for the team's research is to find out why some types of prehistoric crocodile died out, while others didn't.

With an estimated lifespan between 25 to 40 years, the queen conch (Strombus gigas) is a prized delicacy long harvested for food and is revered for its beautiful shell. Second only to the spiny lobster, it is one of the most important benthic fisheries in the Caribbean region. Unfortunately, the species faces a challenge of survival: how to endure and thrive, as populations are in a steady state of decline from overfishing, habitat degradation and hurricane damage. In some places, the conch populations have dwindled so low that the remaining conch cannot find breeding partners. This dire situation is urgent in ecological and economic terms.

To preserve this most significant molluscan fishery in the Caribbean, a scientist from Florida Atlantic University's Harbor Branch Oceanographic Institute has dedicated more than four decades of research into the science and art of growing queen conch. Her latest contribution - an 80-page, step-by-step user manual that provides complete illustrations and photos of how to culture queen conch. The "Queen Conch Aquaculture: Hatchery and Nursery Phases User Manual," was recently published in the National Shellfisheries Association's Journal of Shellfish Research.

The manual is a deliverable of the Puerto Rico Saltonstall-Kennedy National Oceanic and Atmospheric Administration (NOAA) Fisheries grant, which is a two-year collaboration and project with Conservación Conciencia, the Naguabo Commercial Fishing Association and fishers in Puerto Rico.

"I wrote this edition for the Puerto Rican fishers of the Naguabo Fishing Association who are learning to operate the Naguabo Queen Conch Hatchery and Nursery," said Megan Davis, Ph.D., author and a research professor of aquaculture and stock enhancement, FAU's Harbor Branch, who collaborated with Victoria Cassar, a science communicator who designed the manual. "However, the majority of the information presented in this new manual can be applied to other queen conch hatchery and nursery projects to produce conch for sustainable seafood, conservation and restoration."

Last year, Davis teamed up with Conservación ConCiencia in Puerto Rico to assist with stock enhancement fisheries of the queen conch. The goal: to produce up to 2,000 queen conch juveniles in a fishers-operated aquaculture facility for release into conch juvenile habitats. The Saltonstall-Kennedy NOAA-funded project includes aiding sustainable fisheries practices through aquaculture. The team is working with the fishery communities, utilizing the commercial Fishing Association's working waterfront for conch aquaculture infrastructure, helping provide diversified incomes for the fishery communities, promoting aquaculture practices, and ensuring the conch population is available for future fishing and food security through aquaculture and restoration.

"Aquaculture, along with conservation of breeding populations and fishery management, are ways to help ensure longevity of the species," said Davis. "Our queen conch aquaculture project in Puerto Rico will serve as a model to ensure that conch populations are available for future fishing and to aid food security for Puerto Rico and elsewhere in the Caribbean region."

With requests for queen conch mariculture know-how coming from many communities throughout the Caribbean including The Bahamas, Puerto Rico, Curacao, Antigua, and Turks and Caicos Islands, and with the recent release of this manual, Davis and partners are expanding their Caribbean-wide queen conch conservation, education and restorative mariculture program.

Desired outcomes include establishing protected areas where conch breeding populations can spawn egg masses for future populations; raising queen conch for education, conservation, restoration and sustainable seafood through the establishment of in-classroom, research, pilot-scale or commercial size hatcheries; and locating protected habitats to release hatchery-reared juvenile conch to help repopulate seagrass beds to rebuild conch stocks.

"Forty years of queen conch mariculture research and pilot-scale to commercial application conducted by Dr. Davis holds promise as a way of addressing this critical situation with the queen conch through community-based solutions," said James Sullivan, Ph.D., executive director of FAU's Harbor Branch. "There are no other mariculture labs with the knowledge and capacity that she brings to the table to tackle the plight of the queen conch."

This new, in-depth manual will be used to support the eLearning platform that includes place-based experiential activities and workshops that can be accessed by anyone, which is featured in FAU Harbor Branch's crowd funding initiative, Save the Queen of the Sea.

Osaka, Japan - Medical professionals all want to be able to quickly and correctly diagnose diseases. Their future ability to do so will depend on identifying what biochemicals are present in tissue sections, where the biomolecules are, and at what concentrations. For this purpose, mass spectrometry imaging—which can identify multiple biochemicals in a single experiment—will be useful. However, the stability of biomolecular sampling needs improvement to obtain the chemical distribution information with high spatial resolution.

In the recent study published in Analytical Chemistry, researchers from Osaka University used mass spectrometry to image the distribution of fat molecules in mouse brain tissue. They acquired data at a spatial resolution of 6.5 micrometers, enabling analysis on a cellular level.

The researchers used a very small capillary to gently extract lipid molecules from a tissue section, and a carefully designed setup for fine 3D directional control. Although biological tissue may often seem smooth to the naked eye, on an ultrasmall scale it's rather rough. The ability to account for this ultrasmall-scale roughness is central to obtaining reproducible biochemical data at high spatial resolution.

"In our experiments, the probe's vibration amplitude is constant even when the sample height changes," says Yoichi Otsuka, first author. "We can also measure changes in sample height up to 20 micrometers, and it can be increased up to 180 micrometers."

The researchers' first experiments were to measure irregular distributions of molecules across an uneven surface: microwells filled with various concentrations of a dye. The measured concentrations correlated with the known concentrations, and the measured surface topography was close to the actual microwell diameter. Experiments with mouse brain sections yielded a multi-dimensional data of multiple molecules such as the distribution of certain hexosylceramides—lipids that are important in aging.

"Principle component analysis helped us integrate our wide-ranging data," explains Takuya Matsumoto, senior author. "For example, we could assign the classes of lipids that are primarily present in the cortex and brainstem."

Correlating such data with disease progression will require further study and perhaps additional development of the researchers' biomolecule extraction setup. The researchers anticipate that their approach will be useful for quantitatively imaging the myriad neural networks in brain tissue. Ultimately, they hope to help medical practitioners reliably diagnose diseases such as brain cancer in a tissue section with the support of molecular information in high spatial resolution.

A scalpel-free alternative to brain surgery has the potential to benefit people with Parkinson's disease symptoms that are much more severe on one side of the body, new research suggests.

More testing is needed, but the approach, which uses a technology called focused ultrasound, could offer a new option for patients whose symptoms are poorly controlled by medications and those who cannot or do not wish to undergo traditional brain surgery.

"This small brain region, the subthalamic nucleus, had a very strong and potent effect on parkinsonian symptoms when we targeted it with precise, focused ultrasound energy," said researcher Jeff Elias, MD, a neurosurgeon at UVA Health and a pioneer in the field of focused ultrasound. "The key for the ultimate adoption of this new procedure will be further refinements of the technology to ensure reliability and safety."

About Focused Ultrasound

Focused ultrasound offers a minimally invasive alternative to traditional surgery approaches. The technology focuses sound waves inside the body, much like a magnifying glass focuses light. This allows doctors to interrupt faulty brain circuits or destroy unwanted tissue. Magnetic-resonance imaging (MRI) allows doctors to monitor the procedure in real time - and to make adjustments as needed to obtain the best patient outcomes.

To determine if the technology could benefit patients with "asymmetrical" Parkinson's symptoms, Elias and Binit Shah, MD, from UVA's Department of Neurology, collaborated with Spain's Centro Intregral de Neurociencias to evaluate the approach in 40 volunteers in a randomized, double-blinded study. Twenty-seven study participants received treatment with focused ultrasound, while 13 others received a simulated treatment, so that the researchers could compare the results between the real procedure and the placebo. The average age of study participants was 57.

The volunteers' symptoms before and after the procedure were assessed on a scale of 1-44. Those who received the focused ultrasound procedure saw an improvement of 10 points, while those who received the sham treatment saw a difference of less than two points.

The study also looked at the safety of the procedure. Side effects included unwanted movements, muscle weakness, speech disturbances and difficulty walking. In most cases, these were temporary, but some effects persisted in six patients a year later.

The results warrant additional studies in larger numbers of volunteers conducted over longer periods of time, the researchers conclude.

"Parkinson's disease affects patients in more ways than just tremor," Shah said. "The current FDA approval for focused ultrasound in Parkinson's disease treats only tremor. Targeting this new area allows us to improve tremor but also get more overall benefit for our patients than we previously were able to achieve."

By comparing thousands of bacterial genomes, scientists in Gothenburg, Sweden have traced back the evolutionary history of antibiotic resistance genes. In almost all cases where an origin could be determined, the gene started to spread from bacteria that, themselves, can cause disease.

While human DNA is only passed down from parent to child, bacteria also have the habit of sharing some of their genes across species. This often applies to genes that make the bacteria resistant to antibiotics.

The use and overuse of antibiotics provide an advantage to those bacteria that have acquired resistance genes, thus further promoting the spread of resistance and making it more difficult to treat infections. This development threatens large parts of modern healthcare.

The rapid advances in DNA sequencing during the last decade has made it possible to study bacterial evolution much more effectively than ever before. This is an important background to the new study, published in the scientific journal Communications Biology.

The team from Gothenburg explored the scientific literature for claims of recent origins for antibiotic resistance genes, added information from public DNA-sequence-databases, and scrutinized the evidence at hand. While antibiotic-producing bacteria often are speculated to be the source for antibiotic resistance genes (as self-defence), this was not what the scientists found. None of the origin species found are known antibiotic producers. Strikingly, all verified origin species, except one, are known to cause disease, at least from time to time.

Professor Joakim Larsson, senior author of the study and director of the Centre for Antibiotic Resistance Research at University of Gothenburg, CARe, comments on the finding:

"Given that the overwhelming majority of bacteria are harmless to us, it was quite surprising that these genes almost exclusively came from bacteria causing disease. On the other hand, it makes some sense since such bacteria often trigger antibiotic use when we become infected, and other pathogens are often nearby, ready to engage in gene-transfer. These findings underscores the microbial-rich gut flora humans and domestic animals given antibiotics as arenas for resistance evolution" he says.

Knowing where resistance genes come from can inform measures to delay the emergence of additional resistance genes in the clinics. Importantly, the authors conclude that the origin is still unknown for more than 95% of all known resistance genes.

"Most likely, most of them come from un-sequenced bacterial species. We know the majority of the species that frequently tend to reside in the gut or on the skin of ourselves and of domestic animals. Therefore, this points to an important role of a much less explored gene reservoir - the environmental microbiota. The role of the environment as a likely source for antibiotic resistance also stress the need reduce risks for resistance development in the environment, for example by limiting discharges of antibiotics though wastewaters", says Larsson.

The genomes of egg-laying monotreme mammals, platypus and echidna, have been published in the prestigious journal Nature, providing a valuable public resource for research in mammalian biology and evolution, with applications for their conservation and health.

Monotremes display a unique mix of mammalian and reptilian features and form the most distantly related, and least understood, group of living mammals. Their genetic blueprint provides fundamental insights into their unique biology and into the evolution of all mammals.

"The platypus and echidna are the only egg-laying mammals, and so provide the key to understanding the change in reproductive strategy from egg-laying to the production of live young in all other mammals," Professor Marilyn Renfree from the University of Melbourne's School of BioSciences said.

"During their short in egg incubation, they have kept one of the three major egg proteins that is used to make the yolk in chickens, but after hatching both platypus and echidna have a complex milk like other mammals to support their young during their long lactation."

The research was the result of an international collaboration involving Australian scientists from the Universities of Melbourne, Adelaide, Sydney, LaTrobe University, as well as researchers from China, Japan, USA and Denmark.

The 40 researchers brought together expertise in bioinformatics, cytogenetics, developmental and molecular biology to produce and analyse the first ever echidna genome and a greatly improved, high quality platypus genome sequence.

University of Adelaide Professor Frank Grutzner, who co-led the study, said the findings were significant.

"More than 15 years ago we discovered that monotremes have different sex chromosomes to all other mammals," Professor Grutzner said.

"This finding revolutionised our understanding of mammalian sex chromosome evolution but also raised fundamental new questions. With the new genomes we can now tackle important questions about how sex chromosomes control monotreme sexual development and reproduction, and how they evolved."

Co-first author of the study, University of Adelaide Dr Linda Shearwin-Whyatt, said the system for safe removal of the oxygen carrier, haemoglobin from blood was thought to be common to all mammals.

"We were surprised when we discovered the system was missing from monotremes, implying that it arose quite recently in the ancestor of all other mammals," she said.

In contrast, University of Melbourne Dr Fenelon points out that monotremes have lost several key tooth genes and their adult teeth.

LaTrobe University's Professor Jenny Graves said the egg-laying monotremes, unique to Australia, help to answer some of our deepest questions of mammal evolution.

"We last shared a common ancestor with the platypus and echidna about 180 million years ago, so comparing the monotreme and human genomes can tell us about our common ancestor," Professor Graves said.

Knowledge of monotreme reproduction is also relevant for conservation and captive breeding programs. Researchers are excited that the new genome sequences also provide a roadmap for genetic management of threatened echidna populations and exciting new leads for drug development via the discovery of novel peptides in platypus venom.

Professor Renfree said the new understanding would help conserve these iconic and unique Australian mammals.

Infectious diseases are caused by pathogenic viruses, bacteria, fungi or parasites. The treatment of bacterial and fungal infections relies particularly on antimicrobial drugs, while the focus in treating viral infections is the alleviation of symptoms.

Initial therapy for infection is often empiric and guided by clinical presentation. Its efficacy on the pathogen is, however, only seldom understood at therapy initiation. Although methods for assessing treatment responses exist, the effectiveness is mainly determined through monitoring symptoms and signs of infections.

Advances in sequencing technology have made characterization of genomes and gene expression products increasingly practical. The technology has also made it possible to identify microbiota components up to species- and gene-level. Nevertheless, microbiota sequencing is only occasionally employed in infection treatment.

Now, researchers at the University of Helsinki have, together with their collaborators at the Helsinki University Hospital, developed a new sequencing-based approach for pathogen discovery from challenging samples. The approach and preliminary results on its usage in burn wound infection clearance assessment have been published in the Clinical Microbiology and Infection journal.

"The approach enables to capture the real-time functional activities of even minuscule amounts of microbes. It can be used to reliably investigate the activity of microbial drug resistance mechanisms and other microbial mechanisms relevant to infection or its treatment. This helps to understand whether causative microbes are alive or dying and what they do," says bioinformatician Matti Kankainen, PhD, from the University of Helsinki.

Technique sheds light on pathogen activities

The underlying principle of the technique is as follows: a clinical sample is taken from the patient and its RNA, the underlying foundation of biological processes, is extracted. Next, the microbial RNA is enriched to magnify pathogen information. The RNA is sequenced and the extensive amounts of data gained are analysed by novel algorithms.

To understand the value of the approach in clinical practice, the researchers applied their solution to a complicated wound infection case. The study subject was a wound infection patient that had been treated with several antibiotic therapies for almost one hundred days unsuccessfully. In spite of the therapies, the infection recurred. Briefly following the start of the fourth antibiotic regimen, the researchers collected samples from the infection site. The samples were analysed using their approach as well as with the help of the more common 16S DNA-gene profiling. Corresponding samples were collected also from a control subject.

The fourth antibiotic regimen proved to be effective and alleviated symptoms. The results gained using the new approach agreed the clinical presentation and confirmed the elimination of the pathogen. Furthermore, they demonstrated the recovery of the normal microbiota. A similar microbiota change was not seen in the 16S profiling. Instead, candidate pathogens of the infection were identified, due to the slow breakdown of DNA.

Metatranscriptomics may be the answer to diagnosing infectious diseases

The used approach is known as metatranscriptomics. It allows the comprehensive determination of microbial gene activity. Its use has become increasingly prevalent, but problems related to handling and analysis of challenging host-microbe samples have prevented the more widespread clinical use of metatranscriptomics.

"Our findings demonstrate that our solution suits also to challenging samples that contain minuscule amounts of microbes. On top of pathogen identification, it can be used to characterise host-microbe interaction. It may thereby shed light into yet-unidentified disease mechanisms. We will develop the technique further as a part of infection studies ongoing at our laboratory. Further work will also focus on understanding its application spectrum," says Esko Kankuri, docent in pharmacology at the University of Helsinki.

Postdoctoral Researcher Teija Ojala from the University of Helsinki developed the new approach. Next, Ojala will utilise the technique to advance our understanding on COVID-19 coronavirus disease.

Combining electronic structure calculations and machine learning (ML) techniques has become a common approach in the atomistic modelling of matter. Using the two techniques together has allowed researchers, for instance, to create models that use atomic coordinates as the only inputs to inexpensively predict any property that can be computed by the first-principles calculations that had been used to train them.

While the earliest and by now most advanced efforts have focused on using predictions of total energies and atomic forces to construct interatomic potentials, more recent efforts have targeted additional properties of crystals and molecules such as ionization energies, NMR chemical shieldings, dielectric response properties and charge density. In the paper "Learning the electronic density of states in condensed matter," Ceriotti and colleagues focus on the electronic density of states (DOS), another quantity that underlies many useful materials properties, some of which can be observed experimentally.

The DOS is essentially the number of different states that electrons can occupy at a particular energy level and can be used, for instance, to calculate the electronic contribution to heat capacity in metals and the density of free charge carriers in semiconductors. It is an indirect proxy for properties such as the energy band gap, the band energy and the optical absorption spectrum.

"Predicting the DOS is an interesting exercise in itself because it is essentially the simplest possible description of the electronic structure beyond the ground state picture," Ceriotti said. "It's also useful because there are many properties that you can compute starting from the DOS, making it a great example of how the next generation of ML models can be used in a similar way as electronic structure calculations, using them in an indirect way to compute intermediate quantities that can then be easily processed to evaluate properties that are harder to learn directly."

In developing the model, the group looked to assure transferability across different phases as well as scalability to large system sizes. Their ultimate approach, which looks at how different atomic configurations affect the distribution of energy levels, meets these goals--it was able to learn and predict DFT-computed DOS for a diverse data set of silicon structures, covering a broad range of thermodynamic conditions and different phases. It also scales linearly, rather than with the cube of the number of atoms as with electronic structure calculations, making it applicable to large structures. Finally, the model allowed for an analysis of the local DOS, giving researchers the chance to examine the interplay between structural motifs and electronic structure.

The combination of transferability, and scalability of predictions to large system sizes, make the model applicable to address long-standing open questions in materials science. The new framework has already been used to elucidate the electronic properties of a 100'000-atoms simulation of amorphous silicon, undergoing a series of phase transitions when compressed to 20 Gpa, in a paper published in Nature today in collaboration with a team comprising researchers from Oxford, Cambridge, the US Naval Research Laboratory and Ohio University. The predicted DOS is also used to explain how the pressure-induced structural transformations couple to the electronic structure of the material.

Combining the new model with one of the well-established potential energy models also makes it possible to compute the electronic contributions to macroscopic properties such as the heat capacity of metals and to perform simulations that take into account finite-electronic-temperature effects - as demonstrated in another soon-to-be published article discussing the high-temperature properties of nickel. Indeed, the new model is a critical step towards MARVEL's goal of developing integrated machine learning models that augment - and perhaps eventually replace - costly electronic structure calculations.

"There are other properties aside from the electron density of states, such as optical excitations, and NMR response, which we have been able to accurately predict with machine learning." Ceriotti said. "If we can use them all in combination with cheap and accurate interatomic potentials it will allow us to describe all of the properties of materials with the same accuracy achieved with electronic structure calculation, but at a tiny fraction of the cost."

It is during rare merging events that galaxies undergo dramatic changes in their appearance and in their stellar content. These systems are excellent laboratories to trace the formation of star clusters under extreme physical conditions.

The Milky Way typically forms star clusters with masses that are 10 thousand times the mass of our Sun. This doesn't compare to the masses of the star clusters forming in colliding galaxies, which can reach millions of times the mass of our Sun.

These dense stellar systems are also very luminous. Even after the collision, when the resulting galactic system begins to fade into a more quiescent phase, these very massive star clusters will shine throughout their host galaxy, as long-lasting witnesses of past merging events.

By studying the six galaxy mergers shown here, the Hubble imaging Probe of Extreme Environments and Clusters (HiPEEC) survey has investigated how star clusters are affected during collisions by the rapid changes that drastically increase the rate at which new stars are formed in these galaxies. Hubble's capabilities have made it possible to resolve large star-forming "knots" into numerous compact young star clusters. Hubble's ultraviolet and near-infrared observations of these systems have been used to derive star cluster ages, masses, and extinctions and to analyse the star formation rate within these six merging galaxies. The HiPEEC study reveals that the star cluster populations undergo large and rapid variations in their properties, with the most massive clusters formed towards the end of the merger phase.

When ridesourcing companies Uber and Lyft show up in urban areas, vehicle registrations per capita increase by 0.7% on average, increasing even more in car-dependent cities. Researchers reporting in the journal iScience on January 6 made this discovery by analyzing data from major US cities between 2011 to 2017, comparing trends in cities where Uber and Lyft entered with those where they didn't. They also found that Uber and Lyft displace transit more in cities with higher income and fewer children.

"I would have expected people to own fewer vehicles once they gain access to this alternative transportation mode," says Jeremy Michalek, a professor of engineering and public policy at Carnegie Mellon University and co-author on the study. "But that's not what we see in the data. One possible explanation could be that there's an effect on the other side, where somebody who was on the verge of being able to afford a vehicle now has an incentive to buy one and earn some money with it. So vehicle adoption by Uber and Lyft drivers may outweigh the effect of riders getting rid of their personal vehicles."

The researchers also investigated the impact of ridesourcing services on transit use. While there wasn't a significant effect on average, they did find that cities with higher income and fewer children see a bigger reduction in transit use.

"What this suggests to me is that in a city where people have disposable income and fewer children, they don't mind paying more for a more convenient mode of transportation, and they don't have to worry about logistics like bringing a car seat," says Michalek.

While the researchers were able to identify trends across cities in their data analysis, they are also interested in investigating how these trends stack up in specific cities. Additionally, their analysis only accounts for pre-pandemic patterns that have certainly changed because of COVID-19.

"Of course, the pandemic has caused enormous changes in ridesourcing, public transit, and transportation trends in general. With many employees working from home, and many others opting to use personal vehicles for travel, ridesourcing services have seen a drop in riders," says Michalek. "The question is, once the pandemic is behind us, do we return to the kinds of travel patterns and choices we saw before the pandemic, or are there systemic changes that won't go back to normal because people have permanently changed their behavior? We won't know for sure until it happens."

Researchers have successfully used a DNA-editing technique to extend the lifespan of mice with the genetic variation associated with progeria, a rare genetic disease that causes extreme premature aging in children and can significantly shorten their life expectancy. The study was published in the journal Nature, and was a collaboration between the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health; Broad Institute of Harvard and MIT, Boston; and the Vanderbilt University Medical Center, Nashville, Tennessee.?

DNA is made up of four chemical bases -- A, C, G and T. Progeria, which is also known as Hutchinson-Gilford progeria syndrome, is caused by a mutation in the nuclear lamin A?(LMNA) gene in which one DNA base C is changed to a T. This change increases the production of the toxic protein progerin, which causes the rapid aging process.

Approximately 1 in 4 million children are diagnosed with progeria within the first two years of birth, and virtually all of these children develop health issues in childhood and adolescence that are normally associated with old age, including cardiovascular disease (heart attacks and strokes), hair loss, skeletal problems, subcutaneous fat loss and hardened skin.

For this study, researchers used a breakthrough DNA-editing technique called base editing, which substitutes a single DNA letter for another without damaging the DNA, to study how changing this mutation might affect progeria-like symptoms in mice.

"The toll of this devastating illness on affected children and their families cannot be overstated," said Francis S. Collins, M.D., Ph.D., a senior investigator in NHGRI's Medical Genomics and Metabolic Genetics Branch, NIH director and a corresponding author on the paper. "The fact that a single specific mutation causes the disease in nearly all affected children made us realize that we might have tools to fix the root cause. These tools could only be developed thanks to long-term investments in basic genomics research."

The study follows another recent milestone for progeria research, as the U.S. Food and Drug Administration approved the first treatment for progeria in November 2020, a drug called lonafarnib. The drug therapy provides some life extension, but it is not a cure. The DNA-editing method may provide an additional and even more dramatic treatment option in the future.

David Liu, Ph.D., and his lab at the Broad Institute developed the base-editing method in 2016, funded in part by NHGRI.

"CRISPR editing, while revolutionary, cannot yet make precise DNA changes in many kinds of cells," said Dr. Liu, a senior author on the paper. "The base-editing technique we've developed is like a find-and-replace function in a word processor. It is extremely efficient in converting one base pair to another, which we believed would be powerful in treating a disease like progeria."

To test the effectiveness of their base-editing method, the team initially collaborated with the Progeria Research Foundation to obtain connective tissue cells from progeria patients. The team used the base editor on the?LMNA?gene within the patients' cells in a laboratory setting. The treatment fixed the mutation in 90% of the cells.

"The Progeria Research Foundation was thrilled to collaborate on this seminal study with Dr. Collins's group at the NIH and Dr. Liu's group at Broad Institute," said Leslie Gordon, M.D., Ph.D., a co-author and medical director of The Progeria Research Foundation, which partially funded the study. "These study results present an exciting new pathway for investigation into new treatments and the cure for children with progeria."

Following this success, the researchers tested the gene-editing technique by delivering a single intravenous injection of the DNA-editing mix into nearly a dozen mice with the progeria-causing mutation soon after birth. The gene editor successfully restored the normal DNA sequence of the?LMNA?gene in a significant percentage of cells in various organs, including the heart and aorta.

Many of the mice cell types still maintained the corrected DNA sequence six months after the treatment. In the aorta, the results were even better than expected, as the edited cells seemed to have replaced those that carried the progeria mutation and dropped out from early deterioration. Most dramatically, the treated mice's lifespan increased from seven months to almost 1.5 years. The average normal lifespan of the mice used in the study is two years.

"As a physician-scientist, it's incredibly exciting to think that an idea you've been working on in the laboratory might actually have therapeutic benefit," said Jonathan D. Brown, M.D., assistant professor of medicine in the Division of Cardiovascular Medicine at Vanderbilt University Medical Center. "Ultimately our goal will be to try to develop this for humans, but there are additional key questions that we need to first address in these model systems."

A new class of protein material that interacts with living cells without being absorbed by them can influence cell signaling, a new study shows. The material does this by binding and sequestering cell surface receptors.

The discovery could have far-reaching implications for stem cell research and enable the development of new materials designed to modulate the behavior of living systems.

The research, reported in the January 6 edition of Nature, was led by the Baker lab at the University of Washington School of Medicine and the Derivery lab at the Medical Research Council Laboratory of Molecular Biology in Cambridge, U.K. Their paper is titled, Design of Biologically Active Binary Protein 2D Materials.

Cells interact with their environment via receptors at their surface. These receptors can bind to hormones, neurotransmitters, drugs, and toxins. When such molecules bind to a receptor, this triggers a response inside the cell, a process known as signaling.

But for the cell, it is important that this response be transient, to still be responsive to the signal later on. To achieve this, cells will commonly terminate signaling by absorbing both an activated receptor and the molecule that stimulated it, thereby targeting both for destruction inside the cell.

"This tendency of cells to internalize receptors likely lowers the efficiency of immunotherapies," said Emmanuel Derivery, assistant professor at the MRC Laboratory of Molecular Biology. "Indeed, when antibody drugs bind their target receptors and then become internalized and degraded, more antibody must always be injected."

To create a way around this, Baker lab postdoctoral scholar Ariel Ben-Sasson designed new proteins that assemble into large, flat patches. This molecular scaffolding was then further engineered to contain signaling molecules.

Graduate student Joseph Watson of the Derivery lab showed that such protein materials could latch onto cells, activate surface receptors, and resist being absorbed by the cell for hours or even days.

"This work paves the way towards a synthetic cell biology, where a new generation of multi-protein materials can be designed to control the complex behavior of cells," said David Baker, professor of biochemistry at the UW School of Medicine and director of the UW Medicine Institute for Protein Design.

By swapping out which cell surface receptors were targeted by the patch, the researchers showed that different cell types could be activated.

"We now have a tool that can interact with any type of cells in a very specific way," said Ben-Sasson. "This is what is exciting about protein engineering: it opens fields that people may not expect."

According to co-author Hannele Ruohola-Baker, professor of biochemistry at the UW School of Medicine and associate director of the UW Medicine Institute for Stem Cell and Regenerative Medicine, versions of these new materials could eventually help physicians alleviate the dangers of sepsis by controlling the inflammatory response to infection.

They might even enable entirely new ways to treat COVID-19, heart disease, and diabetes, and perhaps mitigate the downstream effects of strokes, including Alzheimer's disease.

"This breakthrough helps pave the way for the use of synthetic cell biology in regenerative medicine," said Ruohola-Baker.

The westerlies--or westerly winds--play an important role in weather and climate both locally and on a global scale, by influencing precipitation patterns, impacting ocean circulation and steering tropical cyclones. So, finding a way to assess how they will change as the climate warms is crucial.

Typically, the westerlies blow from west to east across the planet's middle latitudes. But scientists have noticed that over the last several decades, these winds are changing, migrating poleward. Research suggests this is because of climate change. But, scientists have been debating whether the poleward movement of the westerlies will continue as temperatures and atmospheric carbon dioxide (CO2) increase further under future warming scenarios. It's been difficult to resolve this scientific question because our knowledge of the westerlies in past warm climates has until now been limited.

In a paper published January 6 in Nature, climate researchers from Columbia University's Lamont-Doherty Earth Observatory describe a new method of tracking the ancient history of the westerly winds--a proxy for what we may experience in a future warming world. The lead author, Lamont graduate student Jordan Abell and his advisor, Gisela Winckler, developed a way to apply paleoclimatology--the study of past climate--to the question of the behavior of the westerly winds, and found evidence suggesting that atmospheric circulation patterns will change with climate warming.

The finding represents a breakthrough in our understanding of how the winds changed in the past, and how they may continue to change in the future.

By using dust in ancient, deep sea sediments as an indirect tracer of wind, the researchers were able to reconstruct wind patterns that occurred three to five million years ago. Knowing that winds--in this case the westerlies--transport dust from desert regions to faraway locations, the authors examined cores from the North Pacific Ocean. This area is downwind from Eastern Asia, one of the largest dust sources today and a known dust-generating region for the past several million years. By measuring the dust in cores from two different sites thousands of kilometers apart, the researchers were able to map changes in dust, and in turn the westerly winds.

"We could immediately see the patterns. The data are so clear. Our work is consistent with modern observations, and suggests that wind patterns will change with climate warming," said Abell.

They found that during the warm parts of the Pliocene (a period three to five million years ago, when the Earth was about two to four degrees Celsius warmer than today but had approximately the same concentration of CO2 in the air as we do now), the westerlies, globally, were located closer towards the poles than during the colder intervals afterwards.

"By using the Pliocene as an analogue for modern global warming, it seems likely that the movement of the westerlies towards the poles observed in the modern era will continue with further human-induced warming," explained Winckler.

The movement of these winds have huge implications for storm systems and precipitation patterns. And while this research does not indicate exactly where it will rain more or less, it confirms that the wind and precipitation patterns will change with climate warming.

"In the Earth history record, tracking down movements of wind and how they've changed, that's been elusive because we didn't have a tracer for it," said Winckler. "Now we do."

What The Study Did: The findings of this survey study suggest that simply providing maps with COVID-19 case information wasn't necessarily associated with improved public knowledge, risk perception or reported intent to adhere to health guidelines.

Authors: Angela Fagerlin, Ph.D., of the University of Utah in Salt Lake City, 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.2020.33538)

Editor's Note: The article includes conflict of interest 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.