Culture

Recurrent, unplanned readmissions to the hospital -- which happen when patients return shortly after discharge and are readmitted for the same or a related condition -- are a challenge worldwide. Many researchers have examined how to predict them and how to understand the factors that contribute to them. A new study looked at how the risk of readmission progressed over multiple visits to emergency departments (EDs) in Israel by patients with chronic diseases. The study explored a way to identify distinct groups of patients who are more likely to be readmitted so medical professionals can intervene to prevent or reduce the possibility of future readmissions.

The study, by researchers at Carnegie Mellon University in Pittsburgh and Ono Academic College in Kiryat Ono, appears in MIS Quarterly.

"Understanding the differences in disease progression in people who have frequent hospital admissions and predicting the likelihood of their readmission as they move from ED visit to hospitalization are critical steps in developing policies and interventions to minimize adverse outcomes to patients and society," explains Rema Padman, professor of management science and healthcare informatics at Carnegie Mellon University's Heinz College, who coauthored the study.

"Our goal was to see if we could predict each readmission to prevent future readmissions. We hope that if doctors had additional information early in the process, they could intervene earlier to avoid having patients return."

Patients who have unplanned readmissions not just once or twice, but multiple times, are costly and challenging for the health care system. Many prior studies have looked at this issue by focusing on one condition, such as congestive heart failure. This study looked at the risk of readmission among patients with more than one chronic condition. Studies show that patients with multiple underlying chronic conditions are more likely to be readmitted to hospitals within 30 days of discharge than those without chronic conditions.

Most prior studies have also used information based on patients' most recent visit to the hospital or first readmission to predict the likelihood of a subsequent readmission. This study followed patients over multiple visits: To predict patients' risk of future readmission, researchers applied statistical and machine learning methods to information from the electronic health records of patients with multiple chronic conditions and frequent readmissions that began with a visit to the ED and continued from 2005 to 2008.

Specifically, using information from 16,117 patients enrolled in a large Israeli Health Management Organization, the study sought to understand how the risk of readmission progressed over 5 to 12 separate visits to the ED by chronic patients who were readmitted 1 to 11 times. Researchers clustered patients into high-, medium-, and low-risk groups, and then generated predictions about their likelihood of subsequent readmissions based on a range of characteristics of each patient, such as age, gender, and number of chronic conditions and prior stays in the hospitals.

The researchers found that tracking multiple readmissions over time can help to identify specific groups of patients early based on their patterns of seeking emergency care and being readmitted. The data led researchers to discover three distinct trajectories related to the progression of readmissions, with a small group of patients displaying increasing likelihood of readmission over time, a large group having low likelihood of readmission, and a third group showing varying likelihoods of readmission over time, which captured the heterogeneity of the patient population.

The study also found that 30-day readmission rates differed significantly by age, gender, levels of creatinine (a waste product from wear and tear of muscles), chronic conditions, and length of stay, measured at each visit to the ED. This finding may allow earlier identification of patients who are more likely to be readmitted and this, in turn, could lead to targeted interventions and individualized post-discharge plans for these patients.

"Based on the results of our study, high-risk patients can be identified earlier, which will result in better care in the ED, appropriate and timely interventions for coordinated and personalized care in inpatient and ambulatory settings, and better allocation of resources," suggests Ofir Ben-Assuli, senior lecturer at Ono Academic College, who coauthored the study.

The authors acknowledge that their study was limited to patients with multiple chronic conditions, so additional research is needed to investigate multiple readmissions in patients without chronic conditions. In addition, lack of availability of data on patient mortality prevented investigation of this important outcome.

The research was funded in part by a grant from the United States-Israel Binational Science Foundation.

Think dietary fiber is just for digestive health? Think again.

Specific fibers known as prebiotics can improve sleep and boost stress resilience by influencing gut bacteria and the potent biologically active molecules, or metabolites, they produce, new University of Colorado Boulder research shows.

The research could ultimately lead to new approaches to treating sleep problems, which affect 70 million Americans.

"The biggest takeaway here is that this type of fiber is not just there to bulk up the stool and pass through the digestive system," said Robert Thompson, a postdoctoral researcher in the Department of Integrative Physiology and lead author of the study, published today in the journal Scientific Reports. "It is feeding the bugs that live in our gut and creating a symbiotic relationship with us that has powerful effects on our brain and behavior."

Food for our bugs

Most people are familiar with probiotics, friendly bacteria present in fermented foods like yogurt and sauerkraut. More recently, scientists have taken an interest in prebiotics - dietary compounds that humans cannot digest but serve as nourishment for our microbiome, or the trillions of bacteria residing within us. While not all fibers are prebiotics, many fibrous foods like leeks, artichokes, onions and certain whole grains are rich in them.

For the study, the researchers started adolescent male rats on either standard chow or chow infused with prebiotics and tracked an array of physiological measures before and after the rats were stressed.

As reported in the researchers' previous study, those on the prebiotic diet spent more time in restorative non-rapid-eye-movement (NREM) sleep. After stress, they also spent more time in rapid-eye-movement (REM) sleep, which is believed to be critical for recovery from stress.

While rats eating standard chow saw an unhealthy flattening of the body's natural temperature fluctuations and a drop in healthy diversity of their gut microbiome after stress, those fed prebiotics were buffered from these effects.

The new study sheds light on how prebiotics can help bust stress.

"We know that this combination of dietary fibers helps promote stress robustness and good sleep and protects the gut microbiome from disruption. With this new study, we wanted to try to identify the signal," said senior author and Integrative Physiology Professor Monika Fleshner, director of the Stress Physiology Laboratory.

Using a technology called mass spectrometry to analyze the rats' fecal samples, the researchers measured metabolites, or bioactive small molecules produced by bacteria as food is broken down.

They found rats on the prebiotic diet had a substantially different "metabolome", or make-up of metabolites. Theirs was higher in dozens of them, including fatty acids, sugars and steroids which may, via gut-brain signaling pathways, influence behavior. The rats' metabolome also looked different after stress.

For instance, the rats on the standard chow diet saw dramatic spikes in allopregnanolone precursor and Ketone Steroid, potentially sleep-disrupting metabolites, while those on the prebiotic diet saw no such spike.

"Our results reveal novel signals that come from gut microbes that may modulate stress physiology and sleep," said Fleshner.

In search of a better sleeping pill

While prebiotic dietary fiber is certainly healthy, it's uncertain whether just loading up on foods rich in it can promote sleep. The rats were fed very high doses of four specific prebiotics, including: galactooligosaccharides, which are present in lentils and cabbage; polydextrose (PDX) an FDA-approved food additive often used as a sweetener; lactoferrin, found in breast milk; and milk fat globular protein, abundant in dairy products.

"You'd probably have to eat a whole lot of lentils and cabbage to see any effect," said Thompson.

Prebiotic supplements already abound on natural food store shelves. But Fleshner said it's too soon to say whether a supplement or drug containing such compounds would be safe and effective for everyone. Depending on what their microbial make-up is, different people might respond differently.

"These are powerful molecules with real neuroactive effects and people need to exercise some caution," she said.

Human studies are already in the works at CU Boulder.

Ultimately, Fleshner believes what they are learning in her lab could lead to a new class of options for people who can't sleep but don't like taking narcotics.

"Armed with this information, we might be able to develop a targeted therapeutic that boosts the molecules that buffer against stress and tamps down the ones that seem to disrupt sleep," she said. "It's exciting to think about."

In animals, releasing eggs in a timely manner is vital to maximize the chances of successful fertilization.

However, how this process evolved and is controlled in different species is poorly understood. A new regulator of egg release has been identified in jellyfish in a new study published March 3 in the open-access journal PLOS Biology by Gonzalo Quiroga Artigas and Evelyn Houliston of Sorbonne University, France, and colleagues. The finding sheds light on how the complex hormonal control of sexual reproduction in animals evolved.

Clytia hemisphaerica is a small marine jellyfish, common across the world's oceans. It is part of the phylum Cnidaria, a large and diverse group of invertebrate animals that includes jellies, anemones, corals, and sea urchins. While the cellular events of meiosis (chromosome shuffling and genome reduction) are similar in eggs of all animals including cnidarians and vertebrates, the hormonal control of the process to ensure that eggs are produced at the best time to maximize fertilization success differs considerably, and key steps in the regulation of cnidarian gametogenesis are only partially understood.

In Clytia, formation of mature eggs (which have one set of chromosomes) from immature oocytes (which have four) is triggered every morning by release of a maturation-inducing hormone (MIH) from the surrounding tissue when it is stimulated by light at dawn. Previous studies had identified this neuropeptide hormone, but its receptor was unknown. However, the authors knew that stimulation by MIH produced a rise in levels of the signaling molecule cyclic AMP within oocytes, and that such a rise is typically associated with activation of a type of receptor called a G-protein coupled receptor (GPCR).

From that clue, they identified 16 GPCRs from the Clytia genome that are made in oocytes. Using a synthetic MIH neuropeptide as bait, they then identified the GPCR that it stuck to most strongly, on the grounds that it was likely to be the MIH receptor (MIHR). To confirm that this receptor was involved in MIH-stimulated signaling, they mutated the MIHR gene using CRISPR/Cas9 genome editing. This mutation produced severe defects in development or release of eggs in females and of sperm in males. These effects could be mimicked by injection of an antibody that blocked part of the normal receptor, and mitigated by treatment of the mutant with an analogue of cyclic AMP, bypassing the mutant receptor and restoring the downstream signal.

The family tree of the receptor sequence showed that it is related to a large set of GPCRs in other cnidarians, and also to a set of peptide hormone receptors in vertebrates . These include receptors for hormones that regulate both sexual reproduction and feeding, including neuropeptide Y and gonadotrophin inhibitory hormone in humans.

"The discovery of this receptor will help us understand the critical process that transforms animal oocytes into eggs," Houliston said, "and may help reveal important steps in the evolution of the hormone systems that regulate and link sexual reproduction to nutrition in animals."

BIRMINGHAM, Ala. - A new culprit -- hydrogen sulfide -- has been found for the deadly infectious disease tuberculosis. Hydrogen sulfide gas is known for its rotten egg smell, yet it has normal physiological roles in the human body to communicate among cells.

When tuberculosis bacteria invade the lung, however, the amounts of hydrogen sulfide in the lung microenvironment appear to greatly increase, and this makes the microbe more virulent and better able to block the body's protective immune response, according to research led by Andries "Adrie" Steyn, Ph.D., a University of Alabama at Birmingham professor of microbiology.

The source of this hydrogen sulfide? Mycobacterium tuberculosis bacteria, or Mtb, are able to induce human macrophage immune cells to produce more hydrogen sulfide. Thus, Mtb exploits macrophage metabolism to increase Mtb virulence. During the disease, Mtb grows and safely persists inside macrophages, the immune cells that normally should have protected the lungs by killing the engulfed bacteria. In a bacterial sense, the Mtb become wolves in sheep's clothing.

"To the best of our knowledge," Steyn said, "no study has yet reported a role for host hydrogen sulfide in the control of bacterial disease."

Two research papers by Steyn and colleagues -- the first descriptions of this unexpected role for host-generated hydrogen sulfide in bacterial pathogenesis -- are published in Nature Communications and Proceedings of the National Academy of Sciences, or PNAS.

"Tuberculosis is responsible for about a million and a half deaths each year, and roughly 2 billion people are latently infected with Mtb worldwide," Steyn said. "Our results indicate that Mtb exploits host-derived hydrogen sulfide to promote growth and disease and suggest that host-directed therapies targeting hydrogen sulfide production may be useful for the management of tuberculosis and other microbial infections."

Steyn oversees labs at UAB and at the Africa Health Research Institute, or AHRI, in Durban, KwaZulu Natal, South Africa, an area that is the worldwide epicenter for tuberculosis infections. The experimenters used two different mouse models and also showed clinical relevance by examining the spatial distribution of human hydrogen sulfide-generating enzymes in excised lung samples from South African tuberculosis patients. The samples come from a Durban hospital whose surgeons often resect diseased portions of an infected lung; this surgery provides nearly immediate symptomatic relief for seriously ill patients.

The human tuberculosis lung tissue experiments, described in the PNAS paper, showed that hydrogen sulfide is produced at a spectrum of tuberculosis lesions that are the sites of Mtb infection.

Study details

Hydrogen sulfide has roles in normal physiology as one of three gasses -- along with nitric oxide and carbon monoxide -- that can diffuse from producer cells to send a signal to nearby cells. However, when Mtb invades macrophage cells, Steyn and colleagues found a 34-fold increase in the level of the macrophage enzyme cystathionine beta-synthase, or CBS, a major producer of hydrogen sulfide in mammalian cells.

So, in the Nature Communications paper, the researchers examined the roles of CBS and different levels of hydrogen sulfide using a variety of approaches.

One was mice that have one of their two genes for CBS inactivated, so they make only half as much CBS enzyme. When these mice were infected with Mtb, they survived a significantly longer time compared to wild-type mice. They also had fewer Mtb bacilli in their lungs and spleen, and their lungs showed less pathology.

In another approach, the researchers found that exposing Mtb cells to increasing concentrations of hydrogen sulfide significantly increased the rate of Mtb growth.

Mechanistically, hydrogen sulfide stimulates Mtb respiration and bioenergetics, acting at a protein called cytochrome bc oxidase. It also reverses one of the body's immune defense mechanisms -- the inhibition of Mtb respiration by increased amounts of nitric oxide produced by host cells. Furthermore, exposure of Mtb to hydrogen sulfide regulated bacterial genes involved in sulfur and copper metabolism and a 48-gene regulon involved in bacterial dormancy during latent infections.

"This suggested that Mtb infection of host cells upregulates CBS production, leading to increased hydrogen sulfide levels, which exacerbates disease as indicated by reduced host survival, and to a lesser extent by increased organ burden," Steyn said. "These ?ndings identify a new phenotypic category of host genes that exacerbates tuberculosis disease, whereas their disruption prolongs survival during infection."

Importantly, as seen in the PNAS paper, the increased hydrogen sulfide also alters host immunometabolism in a way that increases Mtb burden -- and hence disease -- in the lungs and other organs.

This was shown with mice that lacked a second major hydrogen sulfide producing enzyme, macrophage cystathionine gamma-synthase, or CSE.

Similar to what was shown for the CBS-deficient mice, the Mtb-infected CSE-knockout mice survived longer than wild-type mice and showed reduced pathology and lowered bacterial burdens in the lung, spleen and liver. Thus, they were more resistant to Mtb infection.

For CSE-knockout macrophages grown outside of mice, Mtb infection of macrophages resulted fewer live bacteria in the macrophages. Experiments with a chemical that slowly releases hydrogen sulfide or experiments with a CSE inhibitor showed that hydrogen sulfide was the effector molecule regulating Mtb survival in macrophages.

Comparison of the immune responses in wild-type mice or CSE-knockout mice showed that CSE promoted an excessive innate immune response and pathological inflammation, as measured by levels of various cytokines in the serum and numbers and types of immune cells in the lungs. This change exacerbated disease. The CSE-knockout mice also had a reduced adaptive immune response; a functional adaptive immune response is needed to control Mtb infection.

Mechanistically, hydrogen sulfide appears to induce these changes by reprogramming central metabolism in the macrophages, including decreasing flux through glycolysis and the pentose phosphate pathway, which causes dysfunctional immunity.

Steyn and colleagues note that their findings highlight the hydrogen sulfide-producing enzyme CSE as a potential therapeutic target to restrain tuberculosis disease; one current drug that is used to treat rheumatoid arthritis, D-penicillamine, targets CSE.

Leesburg, VA, March 3, 2020--A multi-center study (n=101) of the relationship between chest CT findings and the clinical conditions of coronavirus disease (COVID-19) pneumonia--published ahead-of-print and open-access in the American Journal of Roentgenology (AJR)--determined that most patients with COVID-19 pneumonia have ground-glass opacities (GGO) (86.1%) or mixed GGO and consolidation (64.4%) and vascular enlargement in the lesion (71.3%).

In addition, lead authors Wei Zhao, Zheng Zhong, and colleagues revealed that lesions present on CT images were more likely to have peripheral distribution (87.1%) and bilateral involvement (82.2%) and be lower lung predominant (54.5%) and multifocal (54.5%).

Zhao, Zhong, et al. collected their 101 cases of COVID-19 pneumonia across four institutions in China's Hunan province, comparing clinical characteristics and imaging features between two groups: nonemergency (mild or common disease) and emergency (severe or fatal disease).

Accordingly, most of the cohort (70.2%) were 21-50 years old, and most patients (78.2%) had fever as the onset symptom. Only five patients showed disease associated with a family outbreak.

While the emergency group patients were older than the patients in the nonemergency group, the rate of underlying disease was not significantly different in the two groups--suggesting that viral load could be a better reflection of the severity and extent of COVID-19 pneumonia.

As Zhao and Zhong explained further: "Architectural distortion, traction bronchiectasis, and pleural effusions, which may reflect the viral load and virulence of COVID-19, were statistically different between the two groups and may help us to identify the emergency type disease."

The authors of this AJR article also noted that CT involvement score can help evaluate the severity and extent of COVID-19 pneumonia.

A team of researchers led by the Biology Department at the University of Hawai'i at Hilo has its new study on animal biodiversity patterns on the planet featured in the February 28, 2020 issue of the journal Science.

Dr. Matthew Knope, assistant professor of biology, is lead author of "Ecologically diverse clades dominate the oceans via extinction resistance," which demonstrates that animal biodiversity in the modern oceans is best explained by lower extinction rates in animal groups that are ecologically diverse, rather than by higher origination rates, as previously predicted. Co-authors include Andrew M. Bush, University of Connecticut, Luke O. Frishkoff, University of Texas at Arlington, Noel A. Heim, Tufts University, and Jonathan L. Payne, Stanford University.

"Animals in the oceans today are more diverse than they have ever been in the history of life on Earth and scientists have long worked to describe how they have come to be that way," Knope said. The study examined approximately 20,000 genera of fossil marine animals across the past 500 million years, and approximately 30,000 genera of living marine animals.

"Our findings clearly show that the most ecologically diverse animal groups are also the most dominate animals in terms of numbers of genera in the modern oceans," Knope noted. "Being a member of an ecologically flexible group makes you resistant to extinction, particular during mass extinctions, that primarly impacted ecologically homogenous groups. The oceans we see today are filled with a dizzying array of species in groups like fishes, arthropods, and mollusks, not because they had higher origination rates than groups that are less common, but because they had lower extintion rates over very long intervals of time."

Rosemary Gillespie, professor of evolutionary biology at the University of California, Berkeley, who was not involved in the study, explained, "Understanding how biodiversity is structured, both in space and time, has always been a major focus in biology. A significant difficulty in doing so is that current patterns of biodiversity are dictated both by origination and extinction, and while we can infer origination rates through examination of extant biodiversity, elucidating the role of extinction is notoriously difficult. This study represents some of the most detailed and careful analyses of the fossil record to date, showing very clearly the importance of the 'slow and steady' development of lineages through time has been a key factor in dictating which lineages have achieved the highest diversity."

Further, Michal Kowalewski, professor of invertebrate paleontology at the University of Florida, who was also not involved with the study, said, "In a clever analysis of massive data derived from the fossil record, Knope and colleagues directly address one of the critical questions of biology, as to why do certain types of animals occupy exceptionally broad spectra of ecological niches. As importantly, the study highlights the truly unique value of paleontological data for assessing core questions of biology and exploring historical roots of the modern biosphere."

Knope further explained, "Perhaps the fable of the tortoise and the hare is apt in explaining marine animal diversification: some groups jumped out to an early diversity lead only to be surpassed by other groups that were more ecologically diverse and less evolutionarily volatile, with steady diversification rates and strong resistance to mass extinctions."

The entire study is available at: https://science.sciencemag.org/cgi/doi/10.1126/science.aax6398.

American culture values the freedom to change and reinvent one's self. A new study, however, reveals that Americans who do change tend to report a lower sense of well-being.

University of Georgia psychologists compared individual self-concepts between Americans and Japanese counterparts and uncovered this essential contradiction about the heroic myth of American individualism.

The findings were published in the journal Social Psychological and Personality Science.

"In Western and particularly American culture there is a notion that we have a lot of freedom, and that you can reinvent yourself and that's a positive thing," said Brian Haas, associate professor in the Franklin College of Arts and Sciences department of psychology and lead author on the new study. "But when you apply it to one's self-concept and reinventing one's self, are they better off? Are they happier than people who do not change? We found that it's not the case."

The researchers sourced publicly available longitudinal self-reported personality data from the United States and Japan, and found that in the United States, any type of self-concept changes occurring over the course of several years tended to be associated with a marked decrease in well-being. Conversely Japanese respondents did not show a similar link between self-concept changes and decreased well-being. Self-concept refers to how individuals think about their identity.

"One way to think about this is in political debates, where one of the worst things you can call somebody out on in the United States is being a flip-flopper," Haas said. "Changing your mind, and not being consistent, tends to be thought of as a very negative characteristic in the United States political culture. We found that when people change their identity and likely change their minds, there are many profound negative consequences in our culture."

These notions contrast sharply with cultures such as Japan that tend to have an interdependent identity within a relatively collective culture.

"Changes are perceived as being adaptable in an interdependent context. Social relationships are stronger, concrete, and don't change so quickly. And one way to ensure harmony in those strong social relationships is to be adaptable and flexible so you can make sure that the social relationship remains positive," Haas said.

Individual liberty and self-reinvention may be promoted as a good thing in the U.S., but American people who change tend to be worse off than those that remain consistent.

"In the United States, people who are being inconsistent, experience lower well-being, report that they are less happy, have less meaning in life and have poorer relationships with their family members."

Self-reported emotions and emotional experience in Japan, their sense of value and meaning in life, and also the strength of relationships within families suggest that more stable Japanese culture can withstand changes in individual self-concept.

Even Americans who were changing in a socially desirable direction - becoming, for example, more conscientious, or more extroverted - were not experiencing positive consequences in terms of their well-being.

"It's all negative - any type of change in any direction in the U.S. tended to be linked to negative well-being," Haas said.

Individualism is strongly characterized by behavior in social scenarios, with freedom to choose friends, romantic partners, and the freedom to leave our hometown and family.

"That sense of freedom might mean we don't need to keep those relationships in check, and that's likely what is contributing to this effect. Americans do not need to be adaptable to be able keep their social relationships consistent and positive, because we can just start new relationships or opt out of them easily, we have the freedom to be able to do so," said Michelle vanDellen, associate professor and co-author of the study.

"In the United States, we have a strong tendency to hold up on a pillar those that remain consistent and don't change their identity or minds. It's really something we hold as a high value here," Haas said.

ITHACA, N.Y. - Gene drives use genetic engineering to create a desired mutation in a few individuals that then spreads via mating throughout a population in fewer than 10 generations.

In theory, such a mechanism could be used to prevent malarial mosquitoes from transmitting disease, or possibly to wipe out an invasive species by disabling its ability to reproduce.

Though scientists have had success proving the concept in the lab, they have found that wild populations invariably adapt and develop resistance to the scheme. And when gene drives work, they are all or nothing - without nuance - they spread to all individuals, which can be a drawback.

Now, a Cornell study, "A Toxin-Antidote CRISPR Gene Drive System for Regional Population Modification," published Feb. 27 in the journal Nature Communications, describes a new type of gene drive with the potential to delay resistance. The method could also be applied to a regional population, limiting its spread other populations where it could have undesired effects.

"Those are two things that this new drive that we developed here addresses to some extent," said Philipp Messer, an assistant professor of computational biology, and the paper's senior author. Jackson Champer, a postdoctoral researcher in Messer's lab, is the first author.

In a classic gene drive, called a homing drive, an offspring inherits one set of genes, or genome, from the mother and another from the father. If an offspring inherits a gene with a drive from one parent and not the other, the drive copies itself into the genome from the parent without the drive.

"Now that individual has that drive in both of its genomes and it will pass it on to every offspring," Messer said.

The drives are engineered with CRISPR-Cas9 gene-editing technology, so when the drive copies itself into a new genome, the CRISPR machinery makes a cut into the chromosome without the drive, and pastes in the new code. But sometimes, cells will repair the incision and, in doing so, randomly delete DNA letters. When this happens, the CRISPR gene drive can no longer find a genetic sequence it recognizes in order to make the incision, which creates a resistance and stops the gene drive from spreading.

Natural genetic variation - another source of changes in DNA sequences - can also create resistance, since CRISPR gene drives must recognize short genetic sequences in order to make incisions.

"We were among the first labs to show that this is a tremendous problem," Messer said.

The paper describes a new gene drive, called TARE (Toxin-Antidote Recessive Embryo), which works by targeting a gene that is essential for an organism to function. At the same time, the organism can survive with only one intact copy of this essential gene. Instead of cutting and pasting DNA as homing drives do, the TARE drive simply cuts the other parent's gene, disabling it.

Meanwhile, the engineered TARE drive gene has a DNA sequence that has been recoded; the gene works but it won't be recognized or cut in future generations. If an offspring inherits two disabled genes, those individuals won't survive, thereby removing those copies from the population. Meanwhile, as viable individuals mate, more and more surviving offspring will carry TARE drive genes.

Just a few individuals with homing drives can spread a trait through an entire population. TARE drives, on the other hand, do not cut and paste a drive into a target gene; instead they destroy one of the target gene copies in the offspring. Because of this, the drive requires a higher frequency of engineered individuals in the population to spread. For this reason, TARE drives are less likely to transfer from one distinct population to another.

In lab experiments, when fruit flies with TARE gene drives were released in cages of wild-type fruit flies, all the flies in the cage had the TARE drive in just six generations.

The researchers pointed out that resistance can indeed evolve with a TARE drive in the wild, especially in very large populations, but they believe it will take longer and evolve at a much lower rate, Messer said.

ROCHESTER, Minn. -- The toxic protein tau is a key biological feature in the brains of people with Alzheimer's disease. Yet the factors that make people susceptible or resistant to tau accumulation are not well-understood. A preliminary Mayo Clinic study shows that inherited DNA variants may be associated with developing tau deposits in older adults. The research will be presented at the American Academy of Neurology's 72nd Annual Meeting in Toronto April 25-May 1.

"The location and burden of tau in the brain is closely related to cognitive symptoms in Alzheimer's disease, but we don't know nearly enough about how and why tau accumulates the way it does," says first author Vijay Ramanan, M.D., Ph.D., a behavioral neurology fellow at Mayo Clinic. "These findings point to genetic factors being key in that process, which may help us better predict who will develop symptoms and hopefully identify new targets for treatment," Dr. Ramanan says.

The study included 754 people over 50, with an average age of 72, from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota. Of those, 87% had no memory or thinking problems. Researchers studied the participants' genetic profiles and used positron emission tomography (PET) scans to look for tau proteins in their brains.

The study found that participants with novel genetic variants on chromosomes 1 and 5 had a higher amount of tau in their brains, compared with people who had more typical gene sequences in those regions. The genetic variants were found in 2% to 3% of the group, and those participants had about 10% higher tau levels than those without the variants.

The data also confirmed that variants in the microtubule-associated protein tau (MAPT) gene, which produces tau protein, were associated with tau levels and suggested that genes previously linked to risk of Alzheimer's disease dementia, including apolipoprotein E (APOE), are not associated with tau accumulation.

"We are excited that the availability of tau imaging in the Mayo Clinic Study of Aging has allowed us to investigate the genetic architecture underlying tau deposition that may be distinct from the genetic architecture underlying amyloid deposition ? both key proteins underlying Alzheimer's disease dementia," says Prashanthi Vemuri, Ph.D., an Alzheimer's researcher at Mayo Clinic and senior author.

Through a technique known as DNA origami, scientists have created the fastest, most persistent DNA nano motor yet. Angewandte Chemie published the findings, which provide a blueprint for how to optimize the design of motors at the nanoscale -- hundreds of times smaller than the typical human cell.

"Nanoscale motors have tremendous potential for applications in biosensing, in building synthetic cells and also for molecular robotics," says Khalid Salaita, a senior author of the paper and a professor of chemistry at Emory University. "DNA origami allowed us to tinker with the structure of the motor and tease out the design parameters that control its properties."

The new DNA motor is rod-shaped and uses RNA fuel to roll persistently in a straight line, without human intervention, at speeds up to 100 nanometers per minute. That's up to 10 times faster than previous DNA motors.

Salaita is also on the faculty of the Wallace H. Coulter Department of Biomedical Engineering, a joint program of Georgia Institute of Technology and Emory. The paper is a collaboration between the Salaita lab and Yonggang Ke, assistant professor at Emory's School of Medicine and the Wallace H. Coulter Department of Biomedical Engineering.

"Our engineered DNA motor is fast," Ke says, "but we still have a long way to go to achieve the versatility and efficiency of nature's biological motors. Ultimately, the goal is to make artificial motors that match the sophistication and functionality of proteins that move cargo around in cells and allow them to perform various functions."

Making things out of DNA, nicknamed DNA origami after the traditional Japanese paper folding craft, takes advantage of the natural affinity for the DNA bases A, G, C and T to pair up with one another. By moving around the sequence of letters on the strands, researchers can get the DNA strands to bind together in ways that create different shapes. The stiffness of DNA origami can also easily be adjusted, so they remain straight as a piece of dry spaghetti or bend and coil like boiled spaghetti.

Growing computational power, and the use of DNA self-assembly for the genomics industry, have greatly advanced the field of DNA origami in recent decades. Potential uses for DNA motors include drug delivery devices in the form of nanocapsules that open up when they reach a target site, nanocomputers and nanorobots working on nanoscale assembly lines.

"These applications may seem like science fiction now, but our work is helping move them closer to reality," says Alisina Bazrafshan, an Emory PhD candidate and first author of the new paper.

One of the biggest challenges of DNA motors is the fact that rules governing motion at the nanoscale are different than those for objects that humans can see. Molecular-scale devices must fight their way through a constant barrage of molecules. These forces can cause such tiny devices to drift randomly like grains of pollen floating on the surface of a river, a phenomenon known as Brownian motion.

The viscosity of liquids also makes a much larger impact on something as tiny as a molecule, so water becomes more like molasses.

Many prior DNA motors "walk" with a mechanical leg-over-leg motion. The problem is that two-legged versions tend to be inherently unstable. Walking motors with more than two legs gain stability but the extra legs slow them down.

The Emory researchers solved these problems by designing a rod-shaped DNA motor that rolls. The rod, or "chassis" of the motor consists of 16 DNA strands bound together in a four-by-four stack to form a beam with four flat sides. Thirty-six bits of DNA protrude from each face of the rod, like little feet.

To fuel its motion, the motor is placed on a track of RNA, a nucleic acid with base pairs that are complementary to DNA base pairs. The RNA pulls at the DNA feet on one face of the motor and binds them to the track. An enzyme that targets only RNA that is bound to DNA then quickly destroys the bound RNA. That causes the motor to roll, as the DNA feet on the next face of the motor get pulled forward by their attraction to RNA.

The rolling DNA motor forges a persistent path, so it continues to move in a straight line, as opposed to the more random motion of walking DNA motors. The rolling motion also adds to the new DNA motor's speed: It can travel the length of a human stem cell within two or three hours. Previous DNA motors would need about a day to cover that same distance, and most lack the persistence to make it that far.

One of the biggest challenges was measuring the speed of the motor at the nanoscale. That problem was solved by adding fluorescent tags on either end of the DNA motor and optimizing imaging conditions on a fluorescent microscope.

Through trial and error, the researchers determined that a stiff rod shape was optimal for moving in a straight line and that 36 feet on each face of the motor provided optimal density for speed.

"We provided a tunable platform for DNA origami motors that other researchers can use to design, test and optimize motors to further advance the field," Bazrafshan says. "Our system allows you to test the effects of all kinds of variables, such as chassis shape and rigidity and the number and density of legs to fine tune your design."

For instance, what variables would give rise to a DNA motor that moves in circles? Or a motor that turns to go around barriers? Or one that turns in response to a particular target?

"We hope other researchers will come up with other creative designs based on these findings," Bazrafshan says.

COLUMBUS, Ohio - A new child can spark feelings of jealousy in a person who already fears being abandoned by his or her partner, research suggests.

A new study found that partners who showed signs of relationship anxiety before the birth of their first child were more likely to be jealous of the child after it was born.

"You might think, who could be jealous of a baby? But if you already have fears of rejection, it may be scary to see how much attention your partner showers on your new child," said Anna Olsavsky, lead author of the study and a doctoral student in human sciences at The Ohio State University.

This jealousy can make an already difficult period for couples' relationships even more stressful.

The study found that when either partner was jealous of the baby, couples experienced a decline in their satisfaction with their relationship after becoming parents.

"This jealousy can erode a couple's relationship," said Sarah Schoppe-Sullivan, study co-author and professor of psychology at Ohio State.

"There has been a lot of research that shows couples' satisfaction with their relationship goes down after the birth of a baby, and this could be part of the reason for some people," said Schoppe-Sullivan, who is a senior research associate on the board of the Council on Contemporary Families.

The study was published online today (March 3, 2020) in the Journal of Social and Personal Relationships.

The researchers used data from the New Parents Project, a long-term study co-led by Schoppe-Sullivan that is investigating how dual-earner couples adjust to becoming parents for the first time. In all, 182 couples, most of whom were married, participated in this study.

During the third trimester of pregnancy, mothers and fathers completed a variety of questionnaires, including one that examined "attachment anxiety." They were asked how much they agreed with statements like "I'm afraid that I will lose my partner's love" and "I worry about being abandoned."

Three months after their baby was born, the couples completed a measure of jealousy of the partner-infant relationship. They reported how much they agreed with statements like "I resent it when my spouse/partner is more affectionate with our baby than s/he is with me."

As they predicted, the researchers found that people with relationship anxiety before the child's birth were more jealous of the child three months after arrival.

But it wasn't just the anxious partner who felt jealous of the baby - even their spouses felt higher levels of jealousy.

The reason may be that spouses of anxious partners are used to receiving a lot of attention from their partner, and that responsiveness may lessen when the baby arrives.

"There may be two things happening to the spouses of people with relationship anxiety," Schoppe-Sullivan said.

"It is not just that you aren't receiving all the attention that you used to receive, but also that the child is receiving that extra devotion that once was given to you."

The researchers went into the study believing that anxious fathers may be most vulnerable to feeling jealousy of the new child, because dads tend to spend less time with infants than moms do, Olsavsky said.

But that's not what they found. Anxious moms and dads were equally likely to be jealous of the time their partners spent with the new baby.

The results suggest that expectant parents should be aware of their relationship style before their first baby is born.

"There are a lot of programs for expectant parents, and attachment anxiety might be a good thing to assess beforehand," Olsavsky said.

"If you make people aware of their relationship patterns, it may help them deal with the feelings more constructively."

INDIANAPOLIS--Each year, thousands of people in the United States experience a spinal cord injury, damaging the system of nerves that the brain and body use to communicate.

A team of researchers from Indiana University School of Medicine, in collaboration with the National Institute of Neurological Disorders and Stroke, have investigated how boosting energy levels within damaged nerve fibers or axons may represent a novel therapeutic direction for axonal regeneration and functional recovery.

The study, published March 3 in "Cell Metabolism," examined three central nervous system injury mouse models to determine how energy levels affect spinal cord injury repair.

Investigators from the Spinal Cord and Brain Injury Research Group at Stark Neurosciences Research Institute--led by Xiao-Ming Xu, PhD--and a team led by Zu-Hang Sheng, PhD at Porter Neuroscience Research Center at the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, collaborated on the research.

"Spinal cord injury is devastating, affecting patients, their families and our society," Xu said. "Although tremendous progress has been made in our scientific community, no effective treatments are available for patients with such disorders. There is definitely an urgent need for the development of new strategies for patients with spinal cord injury."

Xu, whose lab at IU School of Medicine is supported both through the NIH and the U.S. Department of Veterans Affairs, said researching the connection between cell energy and potential regeneration is a new direction for spinal cord injuries.

When a person suffers from a spinal cord injury, the axon, or nerve fibers, regenerate poorly, often leading to neurological impairment and eventual motor paralysis. In this study, Xu`s group found that the injured axons fail to regenerate due to energy deficits and disfunction in mitochondria--the power supply of the cell.

"The extremely polarized neurons face exceptional energy stress after traumatic insults," said researcher Qi Han, PhD, the first author of the publication. "Like eating spinach to give Popeye strength, we found that stimulating internal cellular power plants by enhancing mitochondrial transport or energy metabolism is key to power central nervous system axons regeneration and functional recovery after spinal cord injury."

Through three mouse model experiments, they found deleting a protein anchor in the mitochondria--syntaphilin--promoted axonal regeneration and improved recovery of motor functions. They also determined that increasing energy metabolism via creatine treatment promotes axonal regeneration and recovery of function following a spinal cord injury.

Xu said he hopes the strategy could be translated into future treatments of the injury.

With an estimated 10-15% of adults over the age of 60 having some degree of osteoarthritis, otherwise known as degenerative joint disease (DJD), many people will be familiar with, or will know someone who suffers from, this painful and debilitating condition. What is not well recognised is that DJD, where the protective cartilage that cushions the end of the bones wears down over time, affects a high proportion of pet cats of all age groups, but particularly those 10 years of age and over. A study published today in the Journal of Feline Medicine and Surgery (JFMS)1 provides a screening checklist to help veterinarians and owners to identify cats experiencing DJD-associated pain.

The team of researchers that developed the new tool are based at North Carolina State University (NCSU) in the USA, and led by Margaret Gruen and Duncan Lascelles. They were concerned that feline DJD remains underdiagnosed and undertreated in veterinary practice despite its high prevalence; earlier research has revealed, for example, that 90% of cats are likely to have radiographic signs of DJD, with at least 40% showing related signs of pain. The authors suggest that one possible reason for this is that while many people may associate limping with joint pain, this is actually a less common sign of DJD in cats. Meanwhile other, more typical behavioral signs of DJD (such as difficulty navigating stairs) may be misinterpreted as normal aging.

In their study, the authors collated questionnaire data from five studies previously carried out at the Translational Research in Pain Program at NCSU. This enabled them to compare 249 cats with, and 53 cats without, DJD-associated pain, and, via a multistep process of analysis, develop a set of questions that can be answered with a straightforward 'yes' or 'no'. After some further refinement, they came up with a final checklist comprising six questions. These ask whether a cat can jump up and down normally, climb up and down stairs normally and run normally, and whether it chases moving objects such as toys and prey. The checklist can also be used for owners and cats living in a single-storey home by excluding the questions about stairs.

In developing this new tool, referred to as the 'Feline Musculoskeletal Pain Screening Checklist', the researchers compared the scoring of owners who were both aware or unaware of the link between DJD and pain in cats. Unsurprisingly, they found a gap in the responses between the groups, with a higher percentage of 'DJD-informed' owners scoring their cats as impaired for every question. The authors suggest that, given the high prevalence of feline DJD, many cats with undiagnosed DJD would nonetheless still be identified using the checklist; and, when coupled with owner education and engagement in watching for behavioural changes in their cats, the detection of DJD should improve even more.

The authors conclude that this checklist not only provides a clinically expedient tool likely to increase vets' ability to screen for DJD pain in cats, but it may also further provide a foundation for increasing awareness of DJD pain among cat owners. Cats being cats are more likely to display behavioural signs of DJD-associated pain at home compared with in the veterinary clinic, meaning owners are well placed to help in the diagnosis of this condition. The idea is that the checklist can be completed quickly by owners, and if 'no' is selected for any question, this will prompt further evaluation by the vet and treatment to improve the cat's comfort levels.

Scientists have made a breakthrough in the search for a new, sustainable permanent magnet.

Most permanent magnets are made from alloys of rare earth metals - but the mining and processing of these materials produces toxic by-products, leading to ecological challenges around rare-earth mines and refineries. At the same time, demand for permanent magnets is increasing as they are a common component in renewable energy, consumer electronics and electric-powered vehicles.

A team of scientists, led by the University of Leeds, has made a breakthrough in a new advanced material which may eventually replace rare-earth-based permanent magnets. The researchers have developed a hybrid film from a thin layer of cobalt, which is naturally magnetic, covered with molecules of Buckminsterfullerene, a form of carbon.

The presence of the carbon dramatically boosted cobalt's magnetic energy product, a measure of the strength of a magnet, by five times at low temperatures.

The findings have been published in Physical Review B, produced by the American Physical Society. Available at: https://journals.aps.org/prb/pdf/10.1103/PhysRevB.101.060408

The research team observed the increase in magnetic strength at minus 195 degrees Centigrade, but they hope by chemically manipulating the carbon molecules, they will be able to get the same effect at room temperature.

Dr Tim Moorsom, co-principal investigator from the School of Physics and Astronomy at Leeds, said: "This is the first indication I have seen that a rare-earth-free magnet could compare to something like samarium cobalt, a rare-earth-based permanent magnet.

"While we have only seen this effect at low temperatures thus far, I am hopeful that a hybrid magnetic material similar to this will one day replace rare earth permanent magnets, helping to mitigate the environmental damage they cause."

Although carbon is not magnetic, the way the molecules bond to the cobalt surface causes a magnetic pinning effect, which prevents the magnetism in the cobalt from changing direction, even in strong opposing fields. This surface interaction is the key to the unusually high magnetic energy of the hybrid material.

While it may be a long time before hybrid magnets are ready to be used in wind turbines or electric cars, there are other applications which are closer at hand.

Dr Oscar Cespedes, co-principal investigator, who is also at Leeds, said "Although room temperature applications in bulk permanent magnetism may be a long way off, the use of molecular coupling to tune the magnetic properties of thin films, for example in magnetic memories, is a tantalising prospect that is within easy reach."

Researchers at Western University are studying a molecule found in sweet oranges and tangerines called nobiletin, which they have shown to drastically reduce obesity and reverse its negative side-effects.

But why it works remains a mystery.

New research published in the Journal of Lipid Research demonstrates that mice fed a high-fat, high-cholesterol diet that were also given nobiletin were noticeably leaner and had reduced levels of insulin resistance and blood fats compared to mice that were fed a high-fat, high-cholesterol diet alone.

"We went on to show that we can also intervene with nobiletin," said Murray Huff, PhD, a Professor at Western's Schulich School of Medicine & Dentistry who has been studying nobiletin's effects for over a decade. "We've shown that in mice that already have all the negative symptoms of obesity, we can use nobelitin to reverse those symptoms, and even start to regress plaque build-up in the arteries, known as atherosclerosis."

But Huff says he and his team at Robarts Research Institute at Western still haven't been able to pinpoint exactly how nobiletin works. The researchers hypothesized that the molecule was likely acting on the pathway that regulates how fat is handled in the body. Called AMP Kinase, this regulator turns on the machinery in the body that burns fats to create energy, and it also blocks the manufacture of fats.

However, when the researchers studied nobiletin's effects on mice that had been genetically modified to remove AMP Kinase, the effects were the same.

"This result told us that nobiletin is not acting on AMP Kinase, and is bypassing this major regulator of how fat is used in the body," said Huff. "What it still leaves us with is the question - how is nobiletin doing this?"

Huff says while the mystery remains, this result is still clinically important because it shows that nobiletin won't interfere with other drugs that act on the AMP Kinase system. He says current therapeutics for diabetes like metformin for example, work through this pathway.

The next step is to move these studies into humans to determine if nobiletin has the same positive metabolic effects in human trials.

"Obesity and its resulting metabolic syndromes are a huge burden to our health care system, and we have very few interventions that have been shown to work effectively," said Huff. "We need to continue this emphasis on the discovery of new therapeutics."