Culture

Researchers from McGill University have revealed the steps by which two very distinct organisms - bacteria and carpenter ants - have come to depend on one another for survival to become a single complex life form. The study, published today in Nature, shows that the two species have collaborated to radically alter the development of the ant embryo to allow this integration to happen. Understanding how such grand unifications originate and evolve is a major puzzle for biologists. Ehab Abouheif, a biologist and senior author on the paper believes that these insights may lead to a better understanding of the origin of complex organisms.

The bacteria Blochmannia and members of the hyper-diverse ant tribe Camponotini have forged a symbiotic relationship that goes back 51 million years in which each species can no longer survive without the other (termed obligate endosymbiosis by biologists). The ants are thought to have initially ingested the bacteria from sap-sucking insects called hemipteran bugs, with whom they share an ecological niche. The bacteria, which live inside the cells of the ant, helps regulate the size distribution of workers in the colony by enhancing the ants' ability to synthesize nutrition. The ants, in turn, provide the bacteria with a protected cellular environment and ensure their survival from one generation to the next. But how they came together has been unclear until now.

A radically reorganized embryo development

The researchers began to look closely at genes that regulate the germline, the material that contains the genetic information (such as ova and sperm in humans) that is passed from one generation to the next, after observing that the bacteria completely surrounds the germline.

"Instead of the germline genes being localized in just one location in the egg like all other insects, now they are in four. No one has ever seen anything like this in any other insect," says Arjuna Rajakumar, a senior PhD student in Prof. Abouheif's lab and a first co-author of the paper with Ab. Matteen Rafiqi, a former postdoc in the Abouheif lab who is now based at Bezmialem Vakif University in Istanbul. "We were also surprised that the hox genes, which set up the layout of the body and normally come on late in embryo development appeared very early and localize in the same four locations as the germline genes." says Rafiqi.

"The localization of these genes in these 4 different areas creates a system of coordinates in the ant embryo, where each performs a different function to integrate the bacteria." says Abouheif.

Uncovering the steps towards a major evolutionary transition

Working with over 30 closely-related species of ants allowed the researchers to reconstruct the steps in this unification. They discovered that the merger happened in a series of steps, going from embryos where germline genes were localized in only one location, until eventually both germline and hox genes could be found in all four. However, a major surprise was that embryos with two locations of these genes evolved prior to the merger between the two species. This means that there was a pre-existing capacity to evolve new locations within the ant embryos, which the bacteria were then able to exploit to make radical alterations to embryo development and integrate the two species.

"We propose the bold idea that the steps we uncovered for the way these bacteria and ants got together to form an obligate endosymbiotic relationship will help us understand other major unifications that gave rise to complex life forms, like when unicellular organisms got together to form multicellular organisms" said Abouheif.

BOSTON - Kidneys from deceased donors with hepatitis C virus (HCV) infection can be safely transplanted into noninfected recipients when a regimen of direct-acting antiviral therapies is initiated as early as two days after the transplant, according to a study from Massachusetts General Hospital (MGH). In a multi-center clinical trial reported in the Journal of the American Society of Nephrology, MGH researchers found that each of 30 kidney recipients were cured of HCV with no serious side effects attributable to the antiviral therapy, and that nearly all maintained excellent allograft function at six months.

"We successfully treated the hepatitis C virus in kidneys transplanted from HCV-positive donors by using the antiviral agents glecaprevir and pibrentasvir as part of an eight-week course of daily dosing," says Meghan Sise, MD, investigator in the Division of Nephrology at MGH and co-first author of the study. "These findings could carry a strong message to the many transplant centers that are still wary about or resistant to using kidneys from HCV-infected donors. We've shown that these so-called donor positive to recipient negative transplants can be done safely and effectively through early antiviral intervention."

Nearly 95,000 people in the U.S. are currently waiting for kidney transplant, most suffering progressive health deterioration. For some groups, including patients over 60, death is a greater certainty than a transplant. Given this significant public health problem, the U.S. Department of Health and Human Services set a goal of doubling the number of kidneys available for transplantation by 2030 as part of the Advancing American Kidney Health Initiative. One promising pathway toward that target is reducing the discard of viable human kidneys that now occurs, particularly from deceased individuals with hepatitis C virus infection. The number of those organs has soared over the past five years as a result of mounting deaths from the national opioid epidemic.

The MGH prospective trial is the first multi-center investigation to show the feasibility of donor positive to donor negative transplantation. Known as MYTHIC (Multi-Center Study to Transplant Hepatitis-C Infected Kidneys), the study was conceived and carried out in collaboration with the Perelman School of Medicine at the University of Pennsylvania. Each of the trial's 30 kidney recipients at seven U.S. transplant centers was given an eight-week course of a coformulation of glecaprevir and pibrentasvir, powerful antiviral agents that target two distinct proteins within the virus that are essential to its survival.

While one patient died of complications of sepsis deemed unrelated to trial participation, no severe side effects or liver disease were observed in any patient, and allograft function at six months was excellent. "Many of the patients showed a tiny amount of virus in their blood right after transplant, but that viral load became undetectable or unquantifiable in all recipients of HCV-viremic kidneys by four weeks of treatment, " notes Raymond Chung, MD, investigator in the Liver Center and Gastrointestinal Division at MGH and co-senior author of the study.

The trial's success extends to the development by the research team of an evidence-based clinical protocol for transplanting hepatitis C-infected kidneys that could be used by transplant centers anywhere. "We sought to replace the many homegrown protocols based on varying treatment regimens with one that is sound, uniform and reproducible," explains Chung. "We believe we have succeeded by creating a very simple approach that works in patients."

Researchers are now hopeful that transplant centers will take notice of these encouraging results and the opportunity they afford to increase access to high quality organs by patients in critical need of a kidney transplant. "By showing that these procedures are effective," says Sise, "we're hoping that insurance companies will also see the enormous benefit of making transplants with hepatitis-C infected kidneys uniformly covered and reimbursable. The ultimate goal of everyone should be to increase the quality and quantity of life for patients waiting for a kidney transplant."

AMES, Iowa - A recently published analysis of data on tagged monarch butterflies migrating from the United States to Mexico emphasizes the importance of creating new habitat to ensure the future of the species' iconic migratory pattern.

The study, published this month in the peer-reviewed journal Frontiers in Ecology and Evolution, drew on data collected on 1.4 million monarch butterflies that were tagged in the United States Midwest from 1998 to 2015. The study presents evidence that the migration success of monarchs hasn't declined and thus cannot explain the steep decline in the monarch population over the last few decades.

Several lines of evidence support the primary hypothesis for the monarch population decline, which is the loss of milkweed habitat. John Pleasants, an adjunct associate professor in Iowa State University's Department of Ecology, Evolution and Organismal Biology, said the analysis should put to rest this persistent alternative explanation for the population decline that posits monarch butterflies are experiencing increasing mortality during their fall migration to Mexico, Pleasants said.

"If there was some problem with migration, we should have found fewer tagged monarchs recovered in Mexico over time, but that was not the case," he said.

Monarch butterflies carry out a remarkable migration pattern year after year. Monarchs born in Midwestern states move south during the late summer and fall and arrive in central Mexico for the winter. The monarchs then move northward again in the spring. But the monarch population has dwindled to such an extent over the last two decades that scientists worried the migratory system could collapse forever.

Focus on milkweed

In response, the Iowa Monarch Conservation Consortium, a diverse partnership of 45 organizations supported by Iowa State University, the Iowa Department of Agriculture and Land Stewardship, and the Iowa Department of Natural Resources, is spearheading an effort to plant between 480,000 and 830,000 acres of new habitat by 2038. This effort focuses on milkweed, the only plant on which monarchs will lay eggs.

Pleasants said some researchers looked at yearly surveys of monarch adults and did not find a decline at the same time the overwintering population in Mexico was falling and hypothesized that increasing mortality during the southward migration may be driving the overall population decline. Those researchers suggested increased parasite load or declining nectar availability in Texas might contribute to migratory mortality. However, Pleasants said no reliable data show a decline in those factors. Instead, Pleasants said the data show no trend in the tag recovery rate, an indication the migratory journey hasn't become more dangerous over the years.

Pleasants said the discrepancy between the surveys of the summer populations and the overwintering population likely stems from the loss of milkweed habitat on agricultural land in the Midwest. Milkweed was once plentiful in farm fields, providing plenty of habitat for monarchs in rural areas, until about 2006 when it had all but disappeared due to herbicide use. Surveys done in the late 1990s and early 2000s did not include field habitat and therefore missed the monarchs in fields, underestimating the true size of the population, Pleasants said. Since 2006, population estimates from those surveys have been highly correlated with overwintering numbers.

"Our analysis points us back to the idea that the loss of milkweeds, particularly from agricultural fields, is most responsible for this decline," he said. "If you want to bring the monarch butterfly back, you need to bring the milkweeds back."

Our gut microbiota can crucially influence our behaviour and neurodevelopment. New research of the Ethology Department at the Faculty of Science at Eötvös Loránd University indicates that dogs' aging mechanism and memory performance are also linked to their gut microbiome composition. According to the study, dogs and humans may have similar mechanisms in cognitive aging.

Dogs have become a valuable model for complex human traits and disorders

In humans, intestinal microbiome composition has been linked to psychiatric conditions such as depression, anxiety, and autism, as well as neurodegenerative disorders, including Parkinson's and Alzheimer's disease through metabolites produced by gut-inhabiting bacteria. The wide range of expected lifespans, a natural inclination to develop dementia, and an environment shared with humans have made companion dogs a promising model organism in aging research. The gut microbiome of dogs is more similar to that of humans than that of mice and pigs. "Next-generation DNA sequencing techniques have enabled the identification of the taxonomic composition and also the potential functions of the microorganisms, gaining a better understanding of microbial-host interactions" - says Tamás Felföldi, assistant professor at the Department of Microbiology, ELTE, Budapest, who usually studies the microbial communities of natural waters, such as the Lake Balaton.

Collecting and analyzing the samples

Eniko Kubinyi, the principal investigator of the Senior Family Dog Project at ELTE, funded by the European Research Council, teamed up with microbiologists to investigate the gut microbiome of a group of companion dogs and examined possible links with age and cognitive performance. "After we tested the memory performance of the dogs at the Department of Ethology, ELTE, we took them for a walk, and collected fecal samples. We had to immediately freeze the excrement in storage containers to ensure they would provide a valid picture about the bacteria that lived in the dogs guts before defecation." According to Sara Sandor, geneticist, "the time limit is important, as some species of bacteria can continue proliferation after defecation, and therefore may falsely outnumber other bacteria in the sample".

Overall, the involvement of family dogs represented a relatively novel approach in this field as it included a huge variety of animals, regarding breed, diet, and life history. This leads to a large statistical variance in their bacterial communities' composition, yet, this approach is crucial if researchers aim to model the natural variability of human populations. "A main limitation of the current study is the relatively low number of subjects, 29 dogs. However, the results of such exploratory studies can facilitate new research efforts, especially if they indicate medically relevant trends in the data" - points out Soufiane Bel Rhali, PhD student.

A link between cognitive performance, age and gut microbiome composition

The researchers found a negative correlation between the abundance of Fusobacteria phylum and the chronological age in dogs. Interestingly, in humans, Fusobacteria were shown to increase with aging and elevated abundance of these microbes have been linked to serious illnesses, like inflammatory bowel disease and colorectal cancer. Therefore, the current finding seems to support an already formed hypothesis that Fusobacteria play a fundamentally different, beneficial role in carnivores as compared with humans. "The identification of such differences between dogs and humans are at least as important as exploring the shared patterns in gut microbial composition, since ungrounded assumptions of similarity can lower the translational value of intervention studies." - notes Kubinyi.

Moreover, the current study found that dogs performing worse in a short-term memory test had relatively more Actinobacteria. This finding can indicate a shared mechanism underlying dogs' and humans' cognitive aging, since Actinobacteria were also shown to be more abundant in the intestines of Alzheimer patients.

A link between cognitive performance, age and gut microbiome composition in companion dogs was hypothesized but not described before. The new research, although preliminary regarding the association between cognition and gut microbiome composition, opens up new venues in canine aging and neurodevelopmental research.

The humble ink in a tattoo artist's needle could be the key to improving the detection of cancer, thanks to new research from the USC Viterbi Department of Biomedical Engineering.

WiSE Gabilan assistant professor in the department with a lab at the USC Michelson Center for Convergent Bioscience, Cristina Zavaleta and her team recently developed new imaging contrast agents using common dyes such as tattoo ink and food dyes. When these dyes are attached to nanoparticles, they can illuminate cancers, allowing medical professionals to better differentiate between cancer cells and normal adjacent cells. The work has been published in Biomaterials Science.

Early detection is crucial for patients to have the best possible outcomes from cancer; a disease that will affect over 38% of Americans at some point in their lifetime.

However, detection is challenging without good imaging agents; contrast materials which when injected into patients, allow for imaging such as MRI and CT to function with better sensitivity and specificity, enabling medical professionals to diagnose with accuracy, and for surgeons to identify the exact margins of tumors.

"For instance, if the problem is colon cancer, this is detected via endoscopy," Zavaleta said. "But an endoscope is literally just a flashlight on the end of a stick, so it will only give information about the structure of the colon ­- you can see a polyp and know you need to take a biopsy."

"But if we could provide imaging tools to help doctors see whether that particular polyp is cancerous or just benign, maybe they don't even need to take it," she said.

Illuminated nanoparticles move through a blood vessel to find cancer. The coloring dyes were incorporated into nanoparticles to allow for more sensitive imaging contrast when identifying cancerous cells.

To achieve this, the team has discovered a unique source of optical contrasting agents from the household coloring dyes and pigments that we routinely encounter. These "optical inks" can be attached to cancer-targeting nanoparticles to improve cancer detection and localization.

The dyes and pigments were discovered from common coloring agents that already have U.S. Food and Drug Administration (FDA) approval, which the team hopes may enable them to be more easily and safely implemented in imaging practice.

For Zavaleta, inspiration struck in an unusual place -- an animation class with Pixar artists in Emeryville, California, the home of the famed studio. Zavaleta, who enjoys art and animation among her hobbies, said she was intrigued by the inks and paints that the artists brought to class.

"I was thinking about how these really high pigment paints, like gouache watercolors, were bright in a way I hadn't seen before, and I was wondering if they had interesting optical properties," Zavaleta said.

The idea led her to tattoo artist in nearby San Francisco, Adam Sky, another artisan working with bright dyes.

"I remember I brought a 96-well plate and he squirted tattoo ink into each of the wells," Zavaleta said. "Then I took the inks to our Raman scanner (used to sensitively detect our tumor-targeting nanoparticles) and discovered these really amazing spectral fingerprints that we could use to barcode our nanoparticles. It was super cool."

One of the safety challenges of imaging using nanoparticles, is that often these nanoparticles can have a prolonged retention in organs like the liver and the spleen, which are responsible for trying to break down the nanoparticle. Because of these safety concerns, it's crucial to consider biodegradable nanomaterials. Currently, there are a limited amount of optical contrast agents approved for clinical use.

With this in mind, Zavaleta's team considered common food dyes that could be used to decorate the nanoparticles, such as the dyes found in colorful candies like Skittles and M&Ms. These brightly colored food products that humans routinely consume have been deemed by the FDA as safe for human consumption.

"We thought, let's look at some of the FDA-approved drug, cosmetic and food dyes that exist and see what optical properties are amongst those dyes," Zavaleta said. "And so that's where we ended up finding that many of these FDA-approved dyes have interesting optical properties that we could exploit for imaging."

The team has developed a nanoparticle that will carry these highly pigmented imaging agents as a "payload." Zavaleta said the particles are of a specific size that enables them to passively penetrate into tumor areas, but can also be retained due to their size.

Most of the imaging contrast agents used in the clinic today are small molecule dyes.

"With small molecules, you may be able to see them accumulate in tumor areas initially, but you'd have to be quick before they end up leaving the tumor area to be excreted," Zavaleta said. "Our nanoparticles happen to be small enough to seep through, but at the same time big enough to be retained in the tumor, and that's what we call the enhanced permeability and retention effect."

The nanoparticle can also be "decorated" with a larger payload of the dye than previous small molecule imaging agents, which the team has shown under fluorescence imaging leads to brighter signal and significant localization of the nanoparticles in tumors.

"If you encapsulate a bunch of dyes in a nanoparticle, you're going to be able to see it better because it is going to be brighter," Zavaleta said. "It's like using a packet of dyes rather than just one single dye."

Tropical Depression 15 strengthened into a tropical storm late on Sept. 1 and was renamed Omar. Visible imagery from NASA-NOAA's Suomi NPP satellite was compiled into an animation that showed the system's formation and strengthening. NASA's Terra satellite also provided temperature data on Omar that revealed wind shear was affecting the storm.

Another Record-Breaker

Omar is the 15th named storm of the 2020 Atlantic hurricane season, and is the earliest 15th storm on record, besting the previous mark by about a week from Ophelia of 2005.

NASA Animates Omar's Development

At NASA's Goddard Space Flight Center in Greenbelt, Md. using the NASA Worldview platform an animation of satellite imagery was created to show Omar over three days. Using visible imagery from the Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard NASA-NOAA's Suomi NPP satellite, an animation shows the development, organization and movement of Tropical Depression 15 from Aug. 30 to Sept. 1 off the coast of North Carolina. On Sept. 2, it became Tropical Storm Omar.

This animation of visible imagery from the VIIRS instrument aboard NASA-NOAA's Suomi NPP satellite shows the organization and movement of Tropical Depression 15 from Aug. 30 to Sept. 1 off the coast of North Carolina. On Sept. 2, it became Tropical Storm Omar. Courtesy: NASA Worldview, Earth Observing System Data and Information System (EOSDIS).

Infrared Data Reveals Wind Shear Battering Omar

Strong upper-level winds are battering Omar and pushing the strongest storms to the southeastern quadrant. Those northwesterly winds are not expected to let up, putting Omar on a weakening trend. NASA's infrared data showed how those outside winds were displacing the strongest storms in Omar's circulation.

On Sept. 1 at 10 p.m. EDT (Sept. 2 at 0200 UTC), the Moderate Resolution Imaging Spectroradiometer or MODIS instrument aboard NASA's Terra satellite gathered temperature information about Tropical Storm Omar's cloud tops. MODIS found the most powerful thunderstorms were on the southeastern side of the storm, where temperatures were as cold as or colder than minus 70 degrees Fahrenheit (minus 56.6 Celsius). Cloud top temperatures that cold indicate strong storms with the potential to generate heavy rainfall.

"Satellite images show that the system remains sheared with a bursting pattern on satellite, occasionally exposing the center, and a large area of curved bands in the southeastern quadrant of the circulation," Eric Blake wrote in the 5 a.m. EDT Omar Discussion. Blake is a senior hurricane specialist at NOAA's National Hurricane Center (NHC) in Miami, Florida.

Omar's Status on Sept. 2

At 5 a.m. EDT (0900 UTC), NOAA's NHC noted the center of Tropical Storm Omar was located near latitude 36.2 degrees north and longitude 68.7 degrees west. Omar was centered about 350 miles (560 km) northwest of Bermuda. The storm is moving toward the east-northeast near 14 mph (22 kph), and this general motion is expected to continue through this afternoon. Maximum sustained winds are near 40 mph (65 km/h) with higher gusts. Little change in strength is expected through tonight. The estimated minimum central pressure is 1003 millibars.

Omar's Bleak Forecast

The NHC forecast calls for Omar to turn toward the east during the evening hours on Sept. 2, with a reduction in forward speed occurring through Friday, Sept. 4. Weakening should begin by Thursday, Sept. 3, with Omar likely to become a remnant low-pressure area by Thursday night.

Alzheimer's disease is a neurodegenerative condition that is characterized by the buildup of clumps of beta-amyloid protein in the brain. Exactly what causes these clumps, known as plaques, and what role they play in disease progression is an active area of research important for developing prevention and treatment strategies.

Recent studies have found that beta-amyloid has antiviral and antimicrobial properties, suggesting a possible link between the immune response against infections and the development of Alzheimer's disease.

Chemical biologists at the Sloan Kettering Institute have now discovered clear evidence of this link: A protein called IFITM3 that is involved in the immune response to pathogens also plays a key role in the accumulation of beta-amyloid in plaques.

"We've known that the immune system plays a role in Alzheimer's disease -- for example, it helps to clean up beta-amyloid plaques in the brain," says Yue-Ming Li, a chemical biologist at SKI. "But this is the first direct evidence that immune response contributes to the production of beta-amyloid plaques -- the defining feature of Alzheimer's disease."

In a paper published September 2 in Nature, Dr. Li and his team show that IFITM3 alters the activity of an enzyme called gamma-secretase, which chops up precursor proteins into the fragments of beta-amyloid that make up plaques.

They found that removing IFITM3 decreased the activity of the gamma-secretase enzyme and, as a result, reduced that number of amyloid plaques that formed in a mouse model of the disease.

Mounting Evidence for a New Hypothesis

Neuroinflammation, or inflammation in the brain, has emerged as an important line of inquiry in Alzheimer's disease research. Markers of inflammation, such as certain immune molecules called cytokines, are boosted in Alzheimer's disease mouse models and in the brains of people with Alzheimer's disease. Dr. Li's study is the first to provide a direct link between this inflammation and plaque development -- by way of IFITM3.

Scientists know that the production of IFITM3 starts in response to activation of the immune system by invading viruses and bacteria. These observations, combined with the new findings from Dr. Li's lab that IFITM3 directly contributes to plaque formation, suggest that viral and bacterial infections could increase the risk of Alzheimer's disease development. Indeed, Dr. Li and his colleagues found that the level of IFITM3 in human brain samples correlated with levels of certain viral infections as well as with gamma-secretase activity and beta-amyloid production.

Age is the number one risk factor for Alzheimer's, and the levels of both inflammatory markers and IFITM3 increased with advancing age in mice, the researchers found.

They also discovered that IFITM3 is increased in a subset of late onset Alzheimer's patients, meaning that IFITM3 could potentially be used as a biomarker to identify a subset of patients who might benefit from therapies targeted against IFITM3.

The researchers next plan is to investigate how IFITM3 interacts with gamma-secretase at the molecular and atomic levels and how it is involved in neuroinflammation in animal models. They will also explore IFITM3 as a biomarker for the disease and as a potential target for new drugs designed to treat it.

House sparrows can be found on nearly every continent including North America, South America, Africa and Australia, where they are not native but an invasive species. New research into these highly social songbirds reveals that they can learn from each other and adapt their behavior.

"Our study demonstrates that house sparrows can extrapolate information gleaned from the social environment and apply it to new experiences," said Tosha Kelly, LSU Department of Biological Sciences post-doctoral researcher and lead author in this study published in Biology Letters.

House sparrows can often be observed in large flocks and this research suggests they may watch and learn from each other. The ability of house sparrows to adjust their behavior after a social experience provides evidence of social learning.

"This is really important because as humans encroach upon and develop wildlife habitats, animals are exposed to a variety of environments and objects that they wouldn't naturally be exposed to. It's critical to understand how quickly new information can pass through a population, which can affect how a species, as a whole, is going to persevere in this era of human-induced environmental change," Kelly said.

Kelly and colleagues video recorded, in a lab environment, how individual house sparrows reacted to a new object placed near the food bowl in their cage. Some sparrows did not hesitate to feed at their bowl despite the new object, while others were more reluctant to approach the bowl with the unusual object nearby. The new objects were harmless to the birds and were introduced one at a time. The objects included a blinking light, a white cover over part of the dish, yellow pipe cleaners, a purple plastic egg, a red-painted dish, a tinfoil hood, three gold bells, pink puffs and an open blue cocktail umbrella. Each bird was exposed to three of these objects one at a time to determine its "personality type."

The researchers paired 10 individual birds with similar responses to the new objects and 14 birds with contrasting responses to the objects. Then, the pairs were exposed to unusual objects near the food dish that were new to both individuals in each pair's shared cage. Kelly and colleagues observed through video recordings that the more wary individual had the opportunity to observe the more daring individual feed at the bowl near the new object. Then, all of the birds were returned to their individual cages and a week later, they were tested alone again with new objects near the food dish. Surprisingly, the birds that had previously been more cautious but had watched a daring partner began to be more daring when feeding alone at their food bowl, even with a completely new object they had never seen before nearby.

A week after being housed with a more daring partner, cautious house sparrows were on average 2.6 times more likely to feed in the presence of a new object than compared to when initially tested alone. This demonstrates that they learned from their partners that novel objects near the food dish were not a threat, write the authors.

"A lot of species that get introduced don't become established, but house sparrows are very successful. Our findings from this study might be part of what explains their success as an invasive species," said LSU Department of Biological Sciences Assistant Professor Christine Lattin, who is the senior author on this study. "How an individual species responds to novelty can have a big impact on whether or not they can coexist with people in cities and other human-altered environments. It may also indicate whether they are going to be able to benefit from increased food availability and other kinds of opportunities that humans bring along with them or if they are going to just be shut out."

Like humans, bacteria live together in communities, sometimes lending a hand -- or in the case of bacteria, a metabolite or two -- to help their neighbors thrive. Understanding how bacteria interact is critical to solving growing problems such as antibiotic resistance, in which infectious bacteria form defenses to thwart the medicines used to fight them.

Now, researchers at the University of Delaware have discovered that bacteria do more than just work together. Bacterial cells from different species can combine into unique hybrid cells by fusing their cell walls and membranes and sharing cellular contents, including proteins and ribonucleic acid (RNA), the molecules which regulate gene expression and control cell metabolism. In other words, the organisms exchange material and lose part of their own identity in the process.

This unprecedented observation, which was reported on Tuesday, Sept. 1 in mBio, a journal of the American Society for Microbiology, has the potential to shed light on unexplained phenomena affecting human health, energy research, biotechnology and more.

The research team, led by Eleftherios (Terry) Papoutsakis, Unidel Eugene Du Pont Chair of Chemical and Biomolecular Engineering, studied interactions between Clostridium ljungdahlii and C. acetobutylicum. These species of bacteria work together in a syntrophic system, producing metabolites that are mutually beneficial to each other's survival.

The team found that C. ljungdahlii invades C. acetobutylicum. The two organisms combine cell walls and membranes and exchange proteins and RNA to form hybrid cells, some of which continue to divide and in fact differentiate into the characteristic sporulation program.

"They mix their machinery to survive or do metabolism, and that's kind of extraordinary, because we always assumed that each and every organism has its own independent identity and machinery," said Papoutsakis.

Previously, researchers have observed that bacteria could exchange some material through nanotubes. The combination into hybrid cells was unexpected.

"This is the first time we've shown this in this bacteria, and it's also a new mechanism of how material is exchanged," said Kamil Charubin, a doctoral student in chemical and biomolecular Engineering and first author of the paper.

Although this phenomenon of interspecies microbial fusion is now being reported for the first time, it is likely ubiquitous in nature among many bacterial pairs.

So why do bacteria bother to fuse together? The simple answer is likely because this process allows the microbes to share machinery that will increase their odds of survival.

For example, some pathogenic bacteria -- those that can cause disease -- may borrow proteins from other antibiotic-resistant bacteria in order to shore up their own resistance. Some bacteria might borrow machinery from others in order to evade detection by the immune system. This could also help to explain why some bacteria are difficult to culture, or grow for study or medical diagnostic purposes. These difficult-to-culture bacteria might combine with or work with and depend on other microorganisms for their existence instead of growing and multiplying on their own.

The team's findings may influence understanding of the evolution of biology because once bacterial species share machinery, they can evolve together instead of only evolving on their own, said Papoutsakis.

September 2, 2020 - States that have expanded Medicaid eligibility under the Affordable Care Act have seen an "early surge in demand" for hip and knee replacement surgery, reports a study in the September 2, 2020 issue of The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

"Patients with Medicaid expansion plans have a shorter time from enrollment to the surgical procedure, suggesting that there may be an unmet need for total hip arthroplasty [THA] and total knee arthroplasty [TKA] among newly enrolled Medicaid expansion beneficiaries," according to the new research by Christopher J. Dy MD, MPH, and colleagues of Washington University School of Medicine, St. Louis, Mo. "This need should be considered by surgeons, hospitals, and policymakers in ensuring access to care."

Shorter Times to THA and TKA in Medicaid-Expansion Patients

With use of data from a Medicaid managed care program, the researchers analyzed the timing of primary THA and TKA procedures in adults under age 65 between 2008 to 2015. The study included patients in four states that expanded Medicaid eligibility in 2014 (Illinois, Ohio, Oregon, and Washington) and four states without Medicaid expansion (Louisiana, Mississippi, Texas, and Wisconsin).

Times to joint replacement surgery were compared for Medicaid-expansion patients, a relatively healthy group of adults without dependent children; Medicaid patients with Supplemental Security Income (SSI), a group of relatively unhealthy adults with disabilities; and patients receiving Temporary Assistance for Needy Families (TANF), who are parents of children with Medicaid insurance. The analysis included a total of 4,117 patients across groups.

The median time to THA or TKA surgery for Medicaid-expansion patients (7.5 months) was significantly shorter than for SSI patients (16.1 months) and TANF patients (12.2 months).

A further analysis was adjusted for other factors, including patient age and sex, social deprivation, surgeon supply and reimbursement, and state-level Medicaid enrollment. The results of that analysis suggested that the time to THA or TKA was 70 percent shorter for Medicaid-expansion patients than for SSI patients. For TANF patients, the time to THA or TKA was 24 percent shorter than for SSI patients.

Expansion of state Medicaid programs has led to dramatic increases in insurance coverage among Americans. In August, Medicaid expansion was approved by voters in Missouri, making it the 38th state to expand Medicaid coverage.

Medicaid-expansion states have seen increases in certain "elective" but medically indicated surgical procedures, including THA and TKA, which raises questions of whether pent-up demand will strain the capacity of the health-care system or exceed the supply of orthopaedic surgeons willing to accept Medicaid insurance.

The new study finds a significantly shorter time from enrollment to THA and TKA for Medicaid-expansion patients compared with those with other routes of access to Medicaid coverage. "Our findings may represent an unmet need for THA and TKA among newly enrolled beneficiaries with Medicaid expansion plans," Dr. Dy and coauthors write. They suggest that Medicaid expansion is likely to lead to "an early surge in demand rather than a gradual increase."

"This need should be considered by surgeons, hospitals, and policymakers in ensuring access to care," Dr. Dy and coauthors conclude. They believe that healthcare policy and resource planning should also consider the existing disparities in access to orthopedic care already faced by Medicaid patients, as surges in demand may exacerbate these differences.

The human brain has about 100 billion neurons, linked in intricate ways, that the Spanish neuroanatomist Ramón y Cajal compared to "the impenetrable jungles where many investigators have lost themselves."

But to decipher how the brain works and understand how it can go awry in many diseases, it is essential to figure out how many classes of neurons it actually has and how they are connected with each other.

Now, in a paper published recently in Nature Neuroscience, a Columbia-led international group has proposed a unified nomenclature of the neurons of the cerebral cortex, the outermost layer of the brain that plays a key role in attention, perception, awareness, memory, language, and consciousness.

"A broadly agreed-upon classification is essential to archiving the hundreds of neuron types and their properties," said Rafael Yuste, a professor in the Department of Biological Sciences at Columbia University. "If we could decipher how the cortex is built and what it does, one could scientifically understand our minds."

How to classify neurons has been much debated since the inception of modern neuroscience. Many efforts to describe their anatomical, physiological, and molecular features have been unsuccessful due to their cellular diversity, Yuste said.

During the last two decades, however, the Human Genome Project has produced a host of molecular methods that enable identifying and phenotyping cells in great numbers.

"This molecular revolution is generating databases that are complete, accurate, and permanent--a triumvirate considered the golden standard of biology," Yuste said.

In particular, using highly automated techniques that sequence the RNA of individual cells rapidly and cost-effectively, several groups have started to assemble datasets to classify cell types in the cortex. "The approach enables sampling tens of thousands of cells, generating what could be an essentially complete coverage of all the existing cell types in the cortex," Yuste said.

Two years ago, during discussions at an international meeting on cortical neurons in Copenhagen, participants agreed that the time was right to finally tackle the creation of a unified classification.

A group of 74 scientists proposed the use of single-cell RNA sequencing as the skeleton for a unified classification of cortical neurons. Known as the "Copenhagen Classification," the proposal is described in the Nature Neuroscience article.

"This could be a historic event, as it tackles one of the core problems in neuroscience," Yuste said. "A unified framework is important not only for researchers and clinicians interested in understanding how the cortex works but also could inspire similar community classifications of cells."

In fact, he added, "there are major consortia worldwide charted with classifying all the cells in the body something that could be a breakthrough for biology and medicine."

With neuroscience rapidly transitioning to digital data, the researchers propose the classification be updated regularly using a type of algorithm often employed by the software industry for automatic data aggregation.

"It's exciting to think that neuroscientists in the not-too-distant future could finally, through technology, break the impasse that has plagued us for centuries," Yuste said.

CATONSVILLE, MD, September 2, 2020 - If you are a budget-conscious traveler, there is a chance you've used a travel site aggregator like Orbitz to book your air transportation. Or, perhaps you shopped around on multiple aggregators, and made your final booking on an airline website. Did you ever wonder if you were presented with all airline options, or what kind of itineraries you could have received had you explored all airline sites one by one? Between aggregators and airlines, who ultimately has the upper hand?

Those questions were on the minds of two data scientists who conducted a comprehensive study on who has more clout: the airline or the aggregator? What they found was that the aggregator can come out losing the most when its site is not comprehensive.

The research study, to be published in the September issue of the INFORMS journal Marketing Science, titled "Value of Aggregators," is authored by Selin Akca of the University of Zurich and Anita Rao of the University of Chicago.

"Search aggregators, such as Google, Kayak, Expedia, and Orbitz, improve consumers' search experience by providing a quick and comprehensive view of all available options," said Rao. "But those aggregators are facing increased scrutiny by regulatory authorities who fear that many firms are now at the mercy of aggregators and their ranking algorithms. This can pose significant operational, and even survival challenges for firms that are not part of an aggregator."

At the same time, some firms like Southwest Airlines have consistently bypassed aggregators, choosing instead to sell directly to consumers. This has given successful firms more market power.

To determine who benefits the most in the airline-aggregator relationship, the study's authors conducted an in-depth analysis of a 2011 dispute between American Airlines and aggregators Orbitz and Expedia, which centered on distribution fees on flight reservation systems.

"That dispute created a clear shift in the choice set available to consumers visiting Orbitz, with the timing being driven entirely by the contract renegotiation deadline," said Akca. "Expedia then delisted American's flights for a shorter three-month period in 2011. During that time, by bypassing the aggregators, American saved on its distribution costs, and its fares were not being presented on either Orbitz or Expedia."

The researchers revealed that loyalty to airlines is more common than loyalty to aggregators. According to the authors, nearly 52% of aggregator users browse only one airline, while most users use multiple aggregators in their searches. This means that more consumers tend to express loyalty to a specific airline over a specific aggregator, and they will use multiple aggregators to get the best option on the airline to which they are most loyal from a brand perspective. This further underscores the need for aggregators to be more comprehensive.

"When we studied the dispute between American Airlines and the aggregators, we found that the aggregator was negatively impacted in both site visits and purchases," said Rao. "Site visits at both Orbitz and Expedia dropped by nearly 11%, and purchases declined 2%."

Akca added, "Our results suggest that aggregators and search engines do not always have substantial market power. We learned that where consumers can choose between multiple aggregators and fewer airlines, the aggregator does not have as much market power as many might assume."

New Rochelle, NY, September 2, 2020—A meta-analysis of non-human primate (NHP) studies showed that adeno-associated virus (AAV) gene therapy often caused dorsal root ganglion (DRG) pathology. There were no clinical effects. The study is reported in the peer-reviewed journal Human Gene Therapy. Click here to read the full-text article free on the Human Gene Therapy website through October 2, 2020.

The dorsal root ganglion is a cluster of neurons in the dorsal root of a spinal nerve. DRG pathology was present in 83% of NHP given AAV through the cerebrospinal fluid and 32% of NHP that received an intravenous injection.

 The data suggest that “DRG pathology is almost universal after AAV vectors are delivered into the cerebral spinal fluid of nonhuman primates. However, none of the animals receiving a vector expressing a therapeutic transgene displayed any clinical signs,” stated James M. Wilson, MD, PhD, a professor of Medicine and director of the Gene Therapy Program and the Orphan Disease Center, and coauthors from the Perelman School of Medicine at the University of Pennsylvania. 

“The DRG pathology associated with AAV has triggered an increase in the intensity of preclinical evaluation of AAV vectors prior to initiation of clinical trials of new vectors,” according to Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School. “The insights offered by Dr. Wilson’s paper provide an excellent summary perspective on this phenomenon, which could potentially eliminate the need for a number of redundant preclinical safety studies and thus shorten the path to the clinic for new vectors.”

Individual studies utilized for data extraction were supported by REGENXBIO (all studies previously published), Biogen (some studies previously published), Passage Bio, Amicus Therapeutics, ODC MPS I pilot grant MPS-18-D010-01 and MPS-19-001-0, Janssen, Cure FA, Rett Syndrome Research Trust and Elaaj Bio. These entities funded the original studies whose samples were later run through the comparative meta-analysis covered in the manuscript. The studies, company sponsor, and transgenes representing each data point are not disclosed.

About the Journal
Human Gene Therapy ,the Official Journal of the European Society of Gene and Cell Therapy and eight other international gene therapy societies, was the first peer-reviewed journal in the field and provides all-inclusive access to the critical pillars of human gene therapy: research, methods, and clinical applications. The Journal is led by Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, and an esteemed international editorial board. Human Gene Therapy is available in print and online. Complete tables of contents and a sample issue are available on the Human Gene Therapy website.

About the Publisher
Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s 90 journals, books, and newsmagazines is available on the  Mary Ann Liebert, Inc., publishers website.

Journal

Human Gene Therapy

DOI

10.1089/hum.2020.167

BIRMINGHAM, Ala. - Why is the COVID-19 virus more dangerous in people with comorbidities?

Sadis Matalon, Ph.D., of the University of Alabama at Birmingham and colleagues in Texas and San Francisco asked that question in a hypothesis paper published online in Physiological Reviews. This study was made available online in March 2020 ahead of final publication in issue on July 1, 2020. They reviewed, in detail, research literature for comorbidities like hypertension, diabetes, coronary heart disease, cerebrovascular illness, chronic obstructive pulmonary disease and kidney dysfunction, as well as many viral studies, studies of COVID-19 pathology and clinical presentation, and literature on the life-threatening acute respiratory distress syndrome.

Twelve days later, UAB Professor Emeritus Timothy Ness, M.D., Ph.D., posted plans on ClinicalTrials.gov for an exploratory COVID-19 outpatient study to test Matalon's hypothesis and prevent worse clinical outcomes.

In the Physiological Reviews paper, the researchers noted that all those comorbidities feature elevated levels of the extracellular protease plasmin. Plasmin is able to nick proteins at amino acid sequences called furin sites. For many viruses, this nicking at furin sites increases their infectivity. Both SARS and MERS -- the two virulent coronaviruses that are related to the COVID-19 virus -- "have evolved an unusual two-step furin activation for fusion, suggestive of a role during the process of emergence into the human population," the researchers wrote.

They noted that the COVID-19 virus, SARS-CoV-2, also has a furin site on its spike protein, the vital, viral protein for viral attachment to a lung cell. The researchers proposed that plasmin may cleave that furin site in the spike protein to increase its infectivity and virulence, and they hypothesized that, "the plasmin system may prove a promising therapeutic target for combating COVID-19."

Ness already knew there is an inexpensive, commonly used drug -- tranexamic acid, or TXA -- that targets plasmin by inhibiting its conversion from the inactive precursor, plasminogen, to the active protease, plasmin.

TXA is approved by the U.S. Food and Drug Administration for treatment of heavy menstrual bleeding because having lower plasmin levels allows better clotting. TXA has a long track record of safety and is commonly given off-label. At UAB Hospital, TXA is used perioperatively as a standard-of-care for orthopedic and cardiac bypass surgeries; it is commonly used for hemorrhaging trauma patients and also has been used for spinal surgery, neurosurgery and corrective jaw surgeries. It is currently being studied for perioperative use in Cesarean section surgeries.

For the clinical trial, Ness and colleagues have started a double-blind study, giving either TXA or a placebo pill to COVID-19 outpatients who were recently diagnosed with COVID-19. Patients also receive an anticoagulant. The overall goal of the exploratory study is to assess both safety and efficacy of five days of TXA versus placebo in the COVID-19 population. Enrollment is ongoing.

Ness and colleagues hypothesize that the TXA treatment will reduce the infectivity and virulence of the virus, as measured by reduced need for hospitalization within a week if a patient's condition deteriorates. Adults 19 years old and older are eligible, and all patients -- whether in the control group or the TXA group -- receive standard care as directed by their primary caretakers.

BOSTON - Researchers from Boston Medical Center's Maxwell Finland Laboratory for Infectious Diseases have identified properties in placenta tissue that may play an important role in preventing the transmission of COVID-19 from a mother with the virus to her fetus. The study results demonstrate that the COVID-19 virus universally invades the placenta in cases with and without evidence of fetal infection, highlighting the protection that the placenta may offer against COVID-19 infection as current data indicates a less than five percent COVID-19 transmission rate in newborns from their mothers. Published in Placenta, these results underscore the importance of using placenta tissue in COVID-19 research studies aimed at developing novel ways to diagnose, treat and prevent COVID-19 virus transmission.

For this study, the researchers examined placental tissue, which shares many developmental and physiological similarities with the lung and the immune response of the small and large intestine, making it a key source of human tissue that can be used for ongoing COVID-19 research. It also contains a unique expression pattern of COVID-19 receptors that are different from other organs, which could be helpful in the development of COVID-19 treatments.

"The results of this study provide evidence for ongoing research of COVID-19 infection at the maternal-fetal interface as means to better understand virus transmission and infection in other human tissues," said Elisha Wachman, MD, a neonatologist at Boston Medical Center, associate professor of pediatrics at Boston University School of Medicine, and principal investigator of this study. "Previous research has shown that the placenta protects the fetus from various types of infection, and exploring the particular ways in which it protects the fetus from COVID-19 transmission may help identify new targets of COVID-19 prevention and treatment."

Throughout April and May 2020, samples from 15 COVID-19 positive maternal-fetal dyads were collected for this study; five cases had evidence of fetal transmission. The placental tissue of the positive cases was analyzed and compared with ten COVID-19 negative controls. The researchers found that the COVID-19 virus was present in the placental tissues in cases with and without evidence of fetal infection. They also found that the placenta contains a unique pattern of cell surface proteins (TMPRSS2 and ACE2) that are important for COVID-19 viral entry, which is different from other cell types. The demographics of mother-baby dyads were also studied and no differences were found to be significant, showing the fetal transmission does not discriminate.

"Determining how the placenta could be preventing COVID-19 infections during pregnancy can help provide clues on how to prevent infection in other organs, such as the lungs and gut," said Elizabeth Taglauer, MD, PhD, a neonatologist and placental biologist based at Boston Children's Hospital. "As a readily available tissue for research, the placenta can be a valuable source of scientific study for a variety of human diseases in pregnancy and beyond."