Culture

One of the weirdest objects in the Milky Way just got weirder. Scientists have discovered a new source of the highest-energy photons in the cosmos: a strange system known as a microquasar, located in our neck of the galaxy a neighborly 15,000 light years from Earth. The discovery could shed light on some of the biggest, baddest phenomena in the known universe.

Their findings appear in the Oct. 4, 2018, issue of Nature. Among the coauthors are Petra Huentemeyer, a professor of physics; Henrike Fleischhack, a postdoctoral research associate; and PhD candidates Chad Brisbois and Binita Hona, all of Michigan Technological University.

The gamma rays beaming from this microquasar, known as SS 433, are among the brawniest photons ever observed--about 25 trillion times more energetic than visible light--and were detected at the High-Altitude Water Cherenkov Gamma-Ray (HAWC) Observatory, in Mexico. Such photons are born only in the most extreme environments, including quasars, the massive black holes at the centers of galaxies billions of light years away. But if you wanted to find a gamma-ray birthplace closer to home, microquasars might be one of the first places you'd look.

Microquasars behave like quasars, but in miniature. Quasars suck up dust and gas, while astronomers believe that SS 433 contains a black hole that sucks up stuff from a nearby companion star. They both blast out powerful jets of material in opposite directions. SS 433's jets extend over 130 light years into space. To put that into perspective, our entire solar system is not quite two light years across.

Scientists have been studying SS 433 since the 1980s and have already detected electromagnetic radiation in the form of X-rays and radio waves coming from the ends of its jets. But they had not found any high-energy gamma rays until now and HAWC's technology made it possible.

"The HAWC Observatory is the most sensitive instrument for photons at these very high energies, and it did not begin collecting data until 2015," Huentemeyer says, the HAWC science coordinator.

The new evidence strongly suggests that the powerful gamma rays were produced at the ends of the jets and not another source nearby.

"SS 433 is located in the same region of the sky as other bright sources that also emit gamma rays," Hao Zhou says, galactic science coordinator of HAWC and a lead author on the Nature paper. "With its wide field of view, HAWC is uniquely capable of separating the gamma-ray emission due to SS 433 from other background photons." Zhou is a former doctoral student of Huentemeyer and a 2015 Michigan Tech PhD graduate now at Los Alamos National Laboratory.

In addition, the data show that the high-energy gamma rays were generated by electrons colliding with background microwave radiation left over from the Big Bang. That means that electrons in the SS 433 jets attain energies that are about 1,000 times higher than those achieved by the most powerful earthbound particle accelerators, such as the city-sized Large Hadron Collider, in Switzerland. This is a new mechanism for generating high-energy gamma rays in this type of system and is different than what scientists have previously observed.

The finding is also somewhat mysterious. "These electrons are some of the highest-energy particles in our galaxy, and it's hard to explain how something that small got so much energy," Huentemeyer says. "However, the electromagnetic radiation emitted by SS 433 over a broad energy range is consistent with a single population of electrons."

Scientists hope that studying messengers from this microquasar may offer a glimpse into the secrets of their larger cousins. Quasars are millions of times bigger than the sun and the brightest known objects in the universe. Most have been found billions of light years away, and because it takes light time to travel, studying them is like going back in a time machine; we see the object as it was billions of years ago.

Because they are so far away, most of the quasars detected by telescopes have their jets aimed at Earth, so observing them is like looking directly into a flashlight. In contrast, SS 433's jets are oriented sideways, pointing away from Earth, which makes them easier to study.

"The new findings improve our understanding of particle acceleration in the jets of microquasars," Zhou says. "They may also shed light on the physics underlying the much larger and more powerful extragalactic jets in quasars."

The genomes of 25 UK species* have been read for the first time by scientists at the Wellcome Sanger Institute and their collaborators**. The 25 completed genome sequences, announced today (4 October) on the Sanger Institute's 25th anniversary, will lead to future studies to understand the biodiversity of the UK and aid the conservation and understanding of our species.

The newly-sequenced genomes will enable research into why some brown trout migrate to the open ocean, whilst others don't, or investigations into the magneto receptors in robins' eyes that allow them to 'see' the magnetic fields of the Earth. The genomes could also help to shed light on why red squirrels are vulnerable to the squirrel pox virus, yet grey squirrels can carry and spread the virus without becoming ill.

The Sanger Institute was founded in 1993 by Professor Sir John Sulston as part of the Human Genome Project. The Institute made the largest single contribution*** to the gold- standard sequence of the first human genome, which was published in 2003.

A genome is an organism's complete set of genetic instructions written in DNA. Each genome contains all of the information needed to build that organism and allow it to grow and develop.

Since the landmark completion of the human genome, the Sanger Institute has become a globally recognised leader in the field of genomics. Many more important reference genomes have already been sequenced - from the mouse and zebrafish genomes to the pig, gorilla, mosquito and many others. Beyond animal species, infectious diseases and bacteria also feature prominently on the list of reference genomes, from salmonella and MRSA to chlamydia and malaria. All of these have offered up important insights about these species in health and disease.

Now, the Sanger Institute and its partners have comprehensively sequenced 25 UK species for the first time. The first human genome took 13 years and billions of dollars to complete. With the great advances in technology and falling costs of sequencing, scientists have been able to newly sequence 25 species' genomes in less than one year and at a fraction of the cost.

Dr Julia Wilson, associate director of the Sanger Institute, said: "We are thrilled to announce the completion of 25 genomes from UK species. Sequencing these species for the first time didn't come without challenges, but our scientists and staff repeatedly came up with innovative solutions to overcome them. We have learned much through this project already and this new knowledge is flowing into many areas of our large scale science. Now that the genomes have been read, the pieces of each species puzzle need to be put back together during genome assembly before they are made available."

Dan Mead, co-ordinator of Sanger's 25 Genomes Project, said: "We are already discovering the surprising secrets these species hold in their genomes. We've found that King scallops are more genetically diverse than we are, and the Roesel's bush cricket's genome is four times the size of the human genome. Similar to when the Human Genome Project first began, we don't know where these findings could take us."

The 25 Genomes Project has been made possible by PacBio® long-read sequencing technology, which generates high-quality genomes. The Institute partnered with PacBio and other leaders in the technology sector, 10x Genomics and Illumina, to create the most comprehensive view of these genomes.

The high-quality genomes will be made freely available to scientists to use in their research. Researchers could discover how UK species are responding to environmental pressures, and what secrets they hold in their genetics that enables them to flourish, or flounder.

Dr Tim Littlewood, Head of Life Sciences at the Natural History Museum, London and a partner of the 25 Genomes Project, said: "The 25 Genomes Project has uncovered the blueprints of a diversity UK life, which will effectively re-write what we know about these species. By comparing those blueprints within and between species we can understand the genetic diversity of fauna and flora from the UK and beyond. These newly-sequenced genomes are a starting point that will reveal aspects of evolution we've not even dreamt of."

This project is a small contribution to a much larger undertaking, where scientists from around the world are coming together to form a plan to sequence all life on Earth.

Professor Sir Mike Stratton, director of the Sanger Institute, said: "DNA sequencing technology has advanced over the last number of years to a point at which we can at least discuss the possibility of sequencing the genomes of all of life on Earth. From those DNA sequences we will obtain inestimable insights into how evolution has worked, and to how life has worked."

By analysing survey data from 1999-2001 and 2010-2012, researchers have estimated the demand for commercial sex among British men.

The Scottish Journal of Political Economy study found that men traveling abroad, men living in London, drug users, religious men, and men with middle-class income are more often together with prostitutes than other men.

The most notable finding from a policy point of view was that learning about sex in school had a significant and sizeable negative effect on the expected number of times with a prostitute. The authors noted that requiring sex education in all schools could therefore help in reducing prostitution in Britain.

Both sexes of a songbird called the blue-capped cordon-bleu intensify courtship performances that involve singing and dancing in the presence of an audience, especially if it is a member of the opposite sex, an international team of researchers has discovered.

Mutual courtship displays have generally been understood as a form of private communication between a male and a female, and many researchers have focused on this aspect. The cordon-bleu is a socially monogamous songbird found in Africa. In its courtship display, both sexes sing and sometimes add a unique dance that resembles tap dancing.

Birds that live in flocks like cordon-bleus are thought to carry out courtship communications in the presence of other birds. However, very little research has been conducted on whether the individuals performing courtship displays are influenced by the presence of other birds. In the present study published in Science Advances, researchers from Hokkaido University in Japan and the Max Planck Institute for Ornithology in Seewiesen, Germany, focused on this so-called audience effect.

In the experiment, the researchers placed paired couples in situations with and without an audience and observed their behavior.

The researchers found that cordon-bleu couples tended to sing more courtship songs accompanied by dancing when an audience -- especially if it is a member of the opposite sex -- is present. In contrast, courtship displays without dancing were suppressed. As the birds were directing their courtship dancing toward their partners rather than the audience, Nao Ota of the research team concludes: "Performing a more elaborate courtship display toward a partner likely is meant to advertise the relationship to other individuals, which is a significant act among birds who live in flocks." Researchers hypothesize that loyalty and bonding are necessary for cordon-bleu pairs to maintain long-term coupling relationships.

"This could provide insights into how complex communication signals have developed among animals, including human beings, that establish coupling relationships," Nao Ota added.

(NEW YORK -October 3, 2018) - In a study published today in Science Translational Medicine, Mount Sinai researchers describe for the first time a mechanism that may shrink collections of immune cells in the gastrointestinal (GI) tract, called lymphoid aggregates, where HIV may lay sequestered. These findings may be of interest to scientists who are involved in researching the cure for HIV infection in light of the strong role that the intestines play in it.

The study builds on research by the same team which found in 2004 that the intestines are specifically targeted by HIV at the earliest stage of infection. "We know from our earlier research that intestinal immune cells called CD4+ T cells are profoundly depleted during the earliest stages of HIV infection. Newer research from other groups has found that CD4 + T cells that migrate to the gut, and bear a receptor called a4b7, are highly susceptible to HIV," says Saurabh Mehandru, MD, Associate Professor of Medicine (Gastroenterology) at the Icahn School of Medicine at Mount Sinai and the senior author on this study. Dr. Mehandru directs
an immunology lab, part of the Division of Gastroenterology at the Icahn School of Medicine. The Mehandru Lab studies mucosal immunology as it pertains to immune deficiency states such as HIV infection and inflammatory disorders, with inflammatory bowel disease (IBD) being a focal point.

"Now, 14 years later, we have discovered how anti-a4b7 therapy can significantly, and rather unexpectedly, lead to the attenuation of lymphoid aggregates," continues Dr. Mehandru. This is the first report of reduction in GI-associated lymphoid aggregates by a therapeutic intervention in patients with HIV-1 infection. "As such, these data describe a new mechanism of action of treatments targeting the a4b7 receptor and define a rational basis for the use of these treatments in HIV-1 infection and beyond," says Dr. Mehandru.

Study authors, led by PhD student Mathieu Uzzan, designed a study that involved a cohort of six individuals with mild IBD and concomitant HIV-1 infection receiving anti-a4b7 treatment, specifically vedolizumab (VDZ). VDZ has become a frontline strategy in the management of patients with IBD, in whom it has demonstrated strong efficacy and an excellent safety profile. The investigators studied immune cells in the blood and the intestines and describe the immunological and virological effects of VDZ therapy over a 30-week period.

"The therapy was tolerated well, with only minor adverse events reported. We were surprised by the impact of treatment on lymphoid aggregates in the GI tract of patients with HIV-1 infection. We believe these initial findings could have significant implications for HIV-1 infection, perhaps in combination with other agents such as broadly neutralizing anti-HIV antibodies," says Dr. Mehandru.

Research was facilitated by scientists at the University of Hawaii, the Wistar Institute, the University of Montreal, and the University of Minnesota.

New York, NY, October 3, 2018 - A pair of Columbia University astronomers using NASA's Hubble Space Telescope and Kepler Space Telescope have assembled compelling evidence for the existence of a moon orbiting a gas-giant planet 8,000 light-years away.

In a paper published Oct. 3 in the journal Science Advances, Alex Teachey and David Kipping report that the detection of a candidate exomoon - that is, moons orbiting planets in other star systems - is unusual because of its large size, comparable to the diameter of Neptune. Such gargantuan moons do not exist in our own solar system, where nearly 200 natural satellites have been cataloged.

"This would be the first case of detecting a moon outside our solar system," said Kipping, an assistant professor of astronomy at Columbia. "If confirmed by follow-up Hubble observations, the finding could provide vital clues about the development of planetary systems and may cause experts to revisit theories of how moons form around planets."

In looking for exomoons, the researchers analyzed data from 284 Kepler-discovered planets that were in comparatively wide orbits, with periods greater than 30 days, around their host star. The observations measured the momentary dimming of starlight as a planet passed in front of its star, called a transit. The researchers found one instance, in Kepler 1625b, that had intriguing anomalies.

"We saw little deviations and wobbles in the light curve that caught our attention," Kipping said.

The Kepler results were enough for the team to get 40 hours of time with Hubble to intensively study the planet, obtaining data four times more precise than that of Kepler. The researchers monitored the planet before and during its 19-hour-long transit across the face of the star. After it ended, Hubble detected a second and much smaller decrease in the star's brightness 3.5 hours later, consistent with "a moon trailing the planet like a dog following its owner on a leash," Kipping said. "Unfortunately, the scheduled Hubble observations ended before the complete transit of the moon could be measured."

In addition to this dip in light, Hubble provided supporting evidence for the moon hypothesis by measuring that the planet began its transit 1.25 hours earlier than predicted. This is consistent with the planet and moon orbiting a common center of gravity (barycenter) that would cause the planet to wobble from its predicted location.

"An extraterrestrial civilization watching the Earth and Moon transit the Sun would note similar anomalies in the timing of Earth's transit," Kipping said.

The researchers note that in principle this anomaly could be caused by the gravitational pull of a hypothetical second planet in the system, although Kepler found no evidence for additional planets around the star during its four-year mission.

"A companion moon is the simplest and most natural explanation for the second dip in the light curve and the orbit-timing deviation," said lead author Teachey, NSF Graduate Fellow in astronomy at Columbia. "It was a shocking moment to see that light curve, my heart started beating a little faster and I just kept looking at that signature. But we knew our job was to keep a level head testing every conceivable way in which the data could be tricking us until we were left with no other explanation."

The moon is estimated to be only 1.5 percent the mass of its companion planet, which itself estimated to be several times the mass of Jupiter. This value is close to the mass-ratio between the Earth and its moon. But in the case of the Earth-Moon system and the Pluto-Charon system - the largest of the five known natural satellites of the dwarf planet Pluto - an early collision with a larger body is hypothesized to have blasted off material that later coalesced into a moon. Kepler 1625b and its satellite, however, are gaseous, not rocky, and, therefore, such a collision may not lead to the condensation of a satellite.

Exomoons are difficult to find because they are smaller than their companion planet and so their transit signal is weak; they also shift position with each transit because the moon is orbiting the planet. In addition, the ideal candidate planets hosting moons are in large orbits, with long and infrequent transit times. In this search, the Neptune-sized moon would have been among the easiest to first detect because of its large size.

The host planet and its moon lie within the solar mass star's (Kepler 1625) habitable zone, where moderate temperatures allow for the existence of liquid water on any solid planetary surface. "Both bodies, however, are considered to be gaseous and therefore unsuitable for life as we know it," Kipping said.

Future searches will target Jupiter-sized planets that are farther from their star than Earth is from the Sun. There are just a handful of these in the Kepler database. NASA's upcoming James Webb Space Telescope could really "clean-up" in the satellite search, Kipping said. "We can expect to see really tiny moons."

A research group from Chalmers University of Technology, Sweden, has made great, rapid strides towards the development of a specially designed molecule which can store solar energy for later use. These advances have been presented in four scientific articles this year, with the most recent being published in the highly ranked journal Energy & Environmental Science.

Around a year ago, the research team presented a molecule that was capable of storing solar energy. The molecule, made from carbon, hydrogen and nitrogen, has the unique property that when it is hit by sunlight, it is transformed into an energy-rich isomer - a molecule which consists of the same atoms, but bound together in a different way.

This isomer can then be stored for use when that energy is later needed - for example, at night or in winter. It is in a liquid form and is adapted for use in a solar energy system, which the researchers have named MOST (Molecular Solar Thermal Energy Storage). In just the last year, the research team have made great advances in the development of MOST.

"The energy in this isomer can now be stored for up to 18 years. And when we come to extract the energy and use it, we get a warmth increase which is greater than we dared hope for," says the leader of the research team, Kasper Moth-Poulsen, Professor at the Department of Chemistry and Chemical Engineering.

The research group have developed a catalyst for controlling the release of the stored energy. The catalyst acts as a filter, through which the liquid flows, creating a reaction which warms the liquid by 63 degrees Celsius. If the liquid has a temperature of 20C when it pumps through the filter, it comes out the other side at 83C. At the same time, it returns the molecule to its original form, so that it can be then reused in the warming system.

During the same period, the researchers also learned to improve the design of the molecule to increase its storage abilities so that the isomer can store energy for up to 18 years. This was a crucial improvement, as the focus of the project is primarily chemical energy storage.

Furthermore, the system was previously reliant on the liquid being partly composed of the flammable chemical toluene. But now the researchers have found a way to remove the potentially dangerous toluene and instead use just the energy storing molecule.

Taken together, the advances mean that the energy system MOST now works in a circular manner. First, the liquid captures energy from sunlight, in a solar thermal collector on the roof of a building. Then it is stored at room temperature, leading to minimal energy losses. When the energy is needed, it can be drawn through the catalyst so that the liquid heats up. It is envisioned that this warmth can then be utilised in, for example, domestic heating systems, after which the liquid can be sent back up to the roof to collect more energy - all completely free of emissions, and without damaging the molecule.

"We have made many crucial advances recently, and today we have an emissions-free energy system which works all year around," says Kasper Moth-Poulsen.

The solar thermal collector is a concave reflector with a pipe in the centre. It tracks the sun's path across the sky and works in the same way as a satellite dish, focusing the sun's rays to a point where the liquid leads through the pipe. It is even possible to add on an additional pipe with normal water to combine the system with conventional water heating.

The next steps for the researchers are to combine everything together into a coherent system.

"There is a lot left to do. We have just got the system to work. Now we need to ensure everything is optimally designed," says Kasper Moth-Poulsen.

The group is satisfied with the storage capabilities, but more energy could be extracted, Kasper believes. He hopes that the research group will shortly achieve a temperature increase of at least 110 degrees Celsius and thinks the technology could be in commercial use within 10 years.

U of T scientists use nanoparticles to improve chemotherapy response and boost anti-tumor immunity in breast cancer

Scientists at the University of Toronto's Leslie Dan Faculty of Pharmacy have seen remarkable success combining tumor modulating nanoparticles with doxorubicin to enhance chemotherapy response in pre-clinical model breast cancer. This combination approach also appears to boost anti-tumor immunity, contributing to the growing excitement surrounding immunotherapy as an avenue to treat cancer.
Chemotherapy is a first-line treatment for many cancers; however, the makeup of tumor microenvironments is often a key barrier to the effectiveness of treatment, requiring that patients receive higher doses in order to get the desired result. The adverse effects of repeated high-dose chemotherapy can have significant detrimental effects on a patient's health, such as damaging healthy tissues and organs, which can themselves be fatal.
"The challenge is to find new ways to get better treatment outcomes with lower doses of chemotherapy," says Xiao Yu (Shirley) Wu, senior investigator and professor at the Leslie Dan Faculty of Pharmacy, University of Toronto. "Our combination approach outlined in this study appears to reduce tumor resistance to doxorubicin, making the chemotherapy effective even at a low dose."
In fact, the research team found that a single treatment with the tumor-modulating nanoparticles and the commonly-used chemotherapy drug led to an astonishing 60 per cent cure rate in the pre-clinical animal models, meaning a complete tumor regression and enhanced life expectancy by five-fold compared to treating with chemotherapy alone.
"By using the nanoparticles to target and change the tumor environment before administering drug treatment, we were able to knockout the tumor's ability to resist the treatment -it's a game changer," says Mohammad Ali Amini, first co-author on the study recently published in the Journal of the National Cancer Institute, and a PhD candidate in the Department of Pharmaceutical Sciences at the Leslie Dan Faculty of Pharmacy.

In 2014, Wu and her team published the first-ever use of the nanoparticles developed specifically to suppress a well-known drug resistance factor called tumor hypoxia, a term used to describe the lack of oxygen in a cancerous tumor and other hypoxia-induced factors.
"The nanoparticles we developed are made up of manganese dioxide, an oxide of the nutrient mineral manganese that already exists in our bodies," Wu explains. "They accumulate in the tumor and remodel the tumor environment by generating oxygen and changing the conditions to such an extent that, the chemotherapy becomes more effective."
While the team anticipated the nanoparticles would improve chemo-drug uptake and efficacy, the strikingly high cure rate was surprising and suggested that the nanoparticles were also triggering an anti-tumor immune response. Intriguingly, a few days after the combination treatment, an increased amount of specific anti-tumor T-cells was found in tumors. The team also re-challenged the cured models with the same type of cancer cells and found that 88 per cent of them showed resistance to new tumor growth.
"This means there was an additional, immunity-boosting effect of the treatment," says Amini, "which made sense because a key feature of nanoparticles is that they increase pH and decrease oxidative stress in the tumor, which also provides better conditions for immune cells to enter the tumor and become more active."
Taking the study one step further, the researchers then collected the anti-tumor T-cells and placed into completely new hosts that were subsequently exposed to the same cancer strain. Strikingly, they found 57 per cent of recipients showed no tumor generation at all.
"This means the T-cells were effectively fighting the breast cancer strain and that the immunity was actually transferred from a donor to a receiver," says Wu. "It was very exciting that a single combination treatment could produce T-cells for immunotherapy."
While very promising, these novel findings will need to be validated using different pre-clinical models and by further investigating the exact mechanisms and pathways that led to the initial cure rate and immunity-boosting response. "Once these are better understood, we can move on to designing a more clinically applicable treatment approach," says Wu.

BUFFALO, N.Y. -- University at Buffalo childhood obesity experts are praising a study published Monday in JAMA Pediatrics that rigorously assessed how the home environments of young children who are genetically at high risk for obesity can influence whether they become overweight or obese.

"The study's main finding was that genetic influences on children's body mass index (BMI) depends upon their home environment," said Myles S. Faith, PhD, professor of counseling, school and educational psychology in the UB Graduate School of Education.

PHOTO: http://www.buffalo.edu/news/releases/2018/10/006.html

He co-authored an editorial in JAMA Pediatrics with Leonard H. Epstein, PhD, SUNY Distinguished Professor of Pediatrics in the Jacobs School of Medicine and Biomedical Sciences at UB. They were invited to write it in response to a study by Valerie Schrempft of University College in London and her colleagues.

"The study found that for kids living in less 'obesogenic' homes--for example, who had more access to fruits and vegetables and who watched less television--the size of the genetic influence was cut roughly in half," said Faith. "Thus, genes are not destiny. Healthier homes can potentially offset obesogenic genes."

The UB professors commended the researchers for characterizing the relationship between genes and the environment "as one of nature interacting with nurture rather than nature vs. nurture."

"Most genetics studies have been positioned as 'nature versus nurture' in the onset of obesity in childhood, rather than nature and nurture working in combination," Faith said. "The study by Schrempft et al. took such an approach and had novel discoveries. It was an exciting opportunity to comment upon this study, and what it could mean for pediatricians and other health providers treating pediatric obesity."

According to the editorial, research has shown that children living in homes that are less "cognitively enriched"--that is, homes with fewer games, books and activities--are more likely to become obese. Faith noted that much childhood obesity research also has demonstrated the power of family interventions and the establishment of healthier homes and lifestyles.
"In terms of genetic research on childhood obesity, however, direct measures of the home environment rarely have been taken," he said. "By using rigorous measures of the home environment and strong behavioral theories as a compass, the door for new genetic research opens up.

"These findings imply that homes promoting healthy eating and activity, if sustained, can partially offset children's genetic susceptibilities to obesity. This can be a powerful and empowering message to families from health care providers, courtesy of genetics research."

Faith is an expert on childhood obesity and the eating behavior of kids, as well as on how parents can be agents of change for their children. Epstein is a renowned investigator in behavioral medicine and nutrition, and an internationally recognized expert on childhood weight control and family intervention.

While many cancer therapies initially can be very successful, tumors often return and spread when remaining cancer cells develop resistance to treatment. To combat this tendency, Frédéric Thomas of the French National Centre for Scientific Research proposes that cancer researchers take a lesson from our own immune system and explore "natural adaptive therapies." Such an approach would mimic the immune system's more restrained way of keeping cancer in check by gradually killing off cancerous cells. Ideally, these therapies would remove the evolutionary pressure that often leads to the spread of resistant tumors.

In Thomas' article, publishing 2nd October in the open access journal PLOS Biology, he and his colleagues reason that the body has evolved anti-cancer responses that direct and slow the evolution of life-threatening cancer cells by not killing off too many cells too quickly. Natural adaptive therapies would use a similar approach to keep tumor size stable, while slowing the evolution of resistance. This strategy may be especially useful to prolong lifespan and quality of life in patients after a cancer has metastasized.

The authors also explore the risk that cancer immunotherapies may force the immune system to rapidly kill malignant cells in a way that undermines the body's natural adaptive therapies, thus accelerating the evolution of immune resistance.

According to Thomas, further explorations into the mechanisms employed by the immune system to stabilize tumors could help researchers to identify new therapies to prevent tumor growth and metastasis.

AUGUSTA, Ga. (Oct. 2, 2018) - A member of a protein family known for protecting our cells also protects cancer cells in aggressive, metastatic breast cancer, scientists report.

Induction of heat shock protein 70, or HSP70, - which protects cells from stress - appears to be a key difference between difficult-to-treat triple negative breast cancer and the more responsive estrogen-positive breast cancer, says Dr. Hasan Korkaya, tumor biologist at the Georgia Cancer Center and Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Augusta University.

"This aggressive breast cancer hijacks your normal protective physiological process to survive the toxic environment it has created," says Korkaya.

The finding illustrates at least one way tumor necrosis factor alpha, or TNFα - which as its name implies can cause cancer cells to self-destruct - is manipulated by cancer to instead aid its survival.

"Here we show that TNFα supports aggressive breast cancer by first upregulating A20, which induces HSP70, which protects cancer cells from TNFα-induced apoptosis," says first author Eunmi Lee, a PhD student in biochemistry and cancer biology in The Graduate School at AU working in Korkaya's lab.

It also provides evidence that targeting HSP70 could be an effective strategy for some of the most aggressive breast cancers, they report in the journal Oncogene.

The scientists, working in animal models and human breast cancer cell lines, already have started using HSP70 inhibitors, looking both at efficacy and toxicity, before also giving more TNFα, which should then be free to kill rather than protect cancer.

They've found that to aid cancer, TNFα first induces the protein A20, which in turn induces HSP70. A20 is a failsafe mechanism immune cells use after aggressively attacking an invader, like a bacterium, to stop expressing things like cytokines used to kill the invader so they do not instead begin attacking the body. In fact, for autoimmune diseases like lupus and rheumatoid arthritis, where the immune system is attacking the body, a major treatment is TNFα blockers, Korkaya notes.

A20 has not been linked to HSP70 in immune cells, but the new work indicates a powerful partnership in aggressive breast cancer cells that essentially shuts off cell death.

"We think A20 determines TNFα activity in different tumor types," Korkaya says. "The cancer cell cannot induce apoptosis, it cannot die."

To make matters worse, the partnership also promotes a cancer stem cell type that makes the durable cells more aggressive and able to spread.

"Not only are the breast cancer cells protected, they become more aggressive," Korkaya says. They are still investigating why TNFα induces A20 in this scenario. He notes that constant upregulation of HSP70 by A20 is important to cancer, because the heat shock protein is so rapidly degraded.

In less-aggressive luminal breast cancer, TNFα doesn't upregulate A20, rather helps cancer cells commit suicide, they report. But when the scientists overexpressed A20 in these luminal breast cancer cells, they started functioning more like their aggressive counterparts.

When they inhibited A20 expression, then gave more TNFα to the aggressive cells, the previously diligent cancer cells started dying off. But when they gave TNFα without first inhibiting A20, the cancer cells produced even more of the protective protein.

Why TNFα doesn't upregulate A20 and HSP70 in luminal breast cancer is another question they want to answer. They also want to look at whether A20 is upregulated in patients whose disease has progressed, and suspect they will find it is.

Study coauthor Dr. Jason E. Gestwicki, professor in the Institute for Neurodegenerative Diseases at the University of California, San Francisco, provided an HSP70 inhibitor he developed for the studies.

Breast cancer is the second leading cause of cancer death among women, just behind lung cancer, according to the American Cancer Society. Triple negative breast cancer accounts for about 15-20 percent of breast cancer cases, according to the Susan G. Komen® organization, and is typically treated with a combination of surgery, chemotherapy and radiation therapy.

Autoimmune diseases like lupus are known to have gene mutations in the multifunctional A20. Mice missing A20 experience multi-organ inflammation and death, but its usual skill at activating inflammation has been shown to promote regeneration of the liver.

HSP70 is found in high levels in a lot of tumor types and those high levels typically correlate with metastasis and a poor prognosis. HSP70 inhibitors already are in clinical trials for cancers like non-small cell lung cancer.

Many of our cell types use one or more of the heat shock proteins to protect themselves from extremes like cold, heat and too little oxygen. Their diverse functions include aiding the proper folding of proteins, the workhorse of cells, so the protein performs the proper job. Misfolding, for example, can result in a variety of conditions from Alzheimer's to cancer. Cancer cells use heat shock proteins to enable their successful growth and spread and even to help them become treatment resistant.

BOSTON (Oct. 2, 2018, 2:00 p.m. ET)--Poor eating is a major cause of illness, especially from cardiometabolic conditions such as heart disease, type 2 diabetes, and obesity. These diseases generate large economic burdens for both government and private insurance programs. For individuals and their families, additional burdens come in the form of personal illness, out-of-pocket costs, reduced quality of life, and a shortened lifespan. These diet-related diseases and costs disproportionately affect low-income families in the United States.

A new Food-PRICE study from researchers at the Friedman School of Nutrition Science and Policy at Tufts University and the Harvard T.H. Chan School of Public Health modeled the health effects and cost-effectiveness of three policy interventions to incentivize healthier eating in the Supplemental Nutrition Assistance Program (SNAP).

SNAP is the foremost U.S. program providing $70 billion each year for low-wage working families, low-income seniors, and people with disabilities to purchase food. SNAP is reauthorized every five years as part of the omnibus Farm Bill, with the 2018 Farm Bill currently being crafted by Congress. SNAP currently includes relatively few incentives, disincentives, or restrictions to encourage healthier eating.

The study, published today in PLOS Medicine, estimated that $6.77 billion to $41.93 billion could be saved in healthcare costs over the model cohort's lifetime by incorporating specific food incentives, restrictions, and/or disincentives to improve food choices in SNAP. At the same time, up to 940,000 cardiovascular events and 146,600 diabetes cases could be prevented.

The three evaluated incentive/disincentive scenarios were:

A 30 percent subsidy for fruits and vegetables (F&V), similar to the USDA FINI program currently available for some SNAP participants in certain states.

A 30 percent F&V subsidy plus removal of sugar-sweetened beverages (SSBs) from the list of eligible purchases using SNAP funds.

A broader incentive/disincentive program including a 30 percent subsidy for F&V, nuts, whole grains, fish, and plant-based oils and a 30 percent disincentive for SSBs, junk food, and processed meats. This program, termed "SNAP-plus" by the researchers, incentivizes healthier intakes across a broader range of foods while preserving participant choice (i.e., not restricting any items from eligibility).

The impact on health outcomes, healthcare costs, and cost-effectiveness were evaluated over different time periods: 5 years, 10 years, 20 years, and lifetime. The research team estimated that, over the cohort's lifetime, the F&V incentive could prevent 303,900 cardiovascular events, add 649,000 quality-adjusted life-years (QALYs), and save $6.77 billion in healthcare costs. Adding a SSB restriction increased the benefits to 797,900 fewer cardiovascular events, 2.11 million QALYs gained, and $39.16 billion in healthcare savings.

The SNAP-plus incentive yielded the greatest corresponding gains:

940,000 fewer cardiovascular events;

2.47 million added QALYs; and

$41.93 billion healthcare savings.

Cost-effectiveness of each scenario was evaluated from a societal perspective (accounting for costs of implementing the program and healthcare costs) and from a government affordability perspective (further adding the direct costs of the food incentives or disincentives for everyone on SNAP, including children).

From a societal perspective, all three interventions were cost-saving, leading to societal savings of $6.77 billion, $39.16 billion, and $41.93 billion over the cohort's lifetime.

From a government affordability perspective, the incentive for fruits and vegetables showed marginal cost-effectiveness at five years but was cost-effective over a lifetime (i.e., with a cost lower than the conventional healthcare threshold of $150,000 per QALY gained). Adding the SSB restriction was cost-effective at 10 years, 20 years and lifetime.

In comparison, SNAP-plus was not only cost-effective but actually cost-saving - i.e., the government gained more dollars than it spent - with net cost-savings of $10.16 billion at five years and $63.33 billion over lifetime.

To evaluate the effects of the three incentive/disincentive protocols, the research team used a validated micro-simulation model (CVD Predict) to generate a sample representative of the U.S. adult SNAP population. The data included observations from the three most recent National Health and Nutrition Examination Surveys (NHANES 2009-2014), as well as data from national surveys, published sources, and meta-analyses that included demographics, food prices, diet-disease costs, policy costs and healthcare costs.

The research team constructed a data-driven simulation for the three incentive/disincentive policy interventions. Their analysis examined effects of such interventions on the number of cardiovascular events, QALYs, program costs, healthcare savings, and cost-effectiveness for the three scenarios, compared to the outcomes under the current SNAP program.

"Systems level changes are often the most efficient and cost-effective way to gain health and reduce healthcare costs. Our findings suggest that modest incentives for fruits and vegetables could dramatically reduce the burden of disease for individuals and the healthcare costs for businesses and the government," said co-senior author Thomas Gaziano, M.D., M.Sc., who was also corresponding author on the CVD Predict modeling study. He is an assistant professor in the department of health policy and management at Harvard T.H. Chan School of Public Health and director of the global cardiovascular health policy and prevention unit at Brigham and Women's Hospital.

"About one in seven Americans participate in SNAP, a crucial and effective program to reduce hunger. Our results suggest that SNAP can also be a powerful lever to improve nutrition, reduce major diseases, and lower healthcare spending," said corresponding and co-first author Dariush Mozaffarian, M.D., Dr.P.H., dean of the Friedman School of Nutrition Science and Policy at Tufts. "SNAP-plus, the combined food incentive/disincentive, showed the largest overall gains in health and cost-savings. Such a program could be implemented now using new technologies similar to those enjoyed in a growing number of U.S. worksite wellness and insurance programs."

At 11 am EDT (1500 UTC) on Oct 1 , Kong-rey was located near 16.8 north and 134.4 east, about 488 miles north-northwest of Yap. It was moving to the northwest and had maximum sustained winds near 125 knots gusting to 150 knots. Currently the only threatened landmasses are the Ryuku Islands.

This satellite image was taken on September 30, 2018 by NASA's Earth Observing System Data and Information System (EOSDIS) Worldview application which provides the capability to interactively browse over 700 global, full-resolution satellite imagery layers and then download the underlying data. Many of the available imagery layers are updated within three hours of observation, essentially showing the entire Earth as it looks "right now. "

Kong-rey will move northwest, intensifying steadily. The storm will peak at 135 knots later today, after which it will steadily weaken. The system will gradually veer north, into the Yellow Sea after three days.

ITHACA, NY - You might not have heard of the groundcherry, or at least, never tasted one. But that could soon change thanks to research from the Van Eck Laboratory at Boyce Thompson Institute (BTI).

The groundcherry (Physalis pruinosa) is approximately the same size as a cherry tomato, but with a much sweeter flavor. The tropical-tasting fruit is also a powerhouse in terms of nutritional value. Packed with Vitamin C, Vitamin B, beta-carotene, phytosterols, and antioxidants, plus anti-inflammatory and medicinal properties, this tiny fruit might just be the next superfood.

"We feel there is potential for these to become a specialty fruit crop and to be grown on a larger scale in the US," said Joyce Van Eck, associate professor at BTI.

However, even with their delicious flavor and nutritional value, groundcherries remain an underutilized crop in the United States. Several characteristics make them unsuitable for large-scale agriculture. In the October 1, 2018 issue of Nature Plants, Van Eck and colleagues present research which could change that and make groundcherries a common household name thanks to the genome editing tool CRISPR.

CRISPR has great promise for increasing crop productivity, especially for orphan crops such as groundcherries, which often contain undesirable characteristics resembling wild relatives. Leveraging knowledge from model crops (such as the tomato) can improve plant architecture (growth habit), flower production, fruit size, and more.

Selections for mutations in tomatoes have led to improvements in yield and Van Eck and her collaborator, Zach Lippman, at the Cold Spring Harbor Laboratory hypothesized that groundcherry genes could be similarly modified for immediate improvements. One concern with the groundcherry is its weedy growth habit. Genetic alterations have led to changes in the hormone that regulates flowering, producing plants which are more compact with fruit in clusters. They also targeted ways to increase fruit size and weight through a CRISPR-generated mutation, leading to fifty-percent more fruit along a given stem and more seedy sections in each fruit.

"It's exciting that we can take what we have learned in tomato and apply it to distantly related species," said Van Eck.

Van Eck is also focused on fixing problems caused by fruit drop. Groundcherries drop to the ground, often before fully ripening.

This puts the fruit at risk for damage and creates a labor-intensive harvest process. In addition, fruit having to be gathered up from the ground causes concerns for food safety with potential for foodborne illness. A jointless mutation in tomatoes could provide the inspiration for using gene-editing to stop fruit drop in groundcherries.

"Physalis is the perfect candidate for looking at getting the fruit to not drop," said Van Eck. "Gene editing might be the only way to fix this in the groundcherry."

This study represents the first step towards improving the groundcherry and this work could be extended to target additional genes benefiting a range of consumer desirable traits.

BUFFALO, N.Y. - Being a good neighbor can have a powerful effect on residents' attitudes and behaviors even for those living in highly disadvantaged communities, according to the results of a new study by a University at Buffalo sociologist.

While most research examining the relationship between people and place has looked at individual characteristics reflecting lifecycle stages, such as marital status, size of the family and children's ages, Gregory Sharp, an assistant professor in UB's Department of Sociology, instead looks at the potential mechanisms that link neighborhood disadvantage with neighborly attitudes and behaviors.

Sharp says that under the right conditions, community matters in the 21st century -- and it can still positively affect lives.

"We know that living in disadvantaged neighborhoods is associated with dissatisfaction, but the effect is amplified by fear, isolation and a lack of social support," says Sharp, an expert in urban and community sociology. "Having frequent conversations with neighbors, doing favors for one another and watching each other's home makes a difference.
"This is neighboring," says Sharp. "And it makes a difference."

These neighborly interactions have a cumulative effect. The study's results suggest that neighboring encourages residents to become more active in their communities, regardless of the level of disadvantage.

"Policy makers need to hear this," says Sharp. "Neighborhoods and communities matter. They have consequences for people's lives and their life chances - and their attitudes often determine whether they'll be invested in the places they live."

The findings are published in the latest edition of the journal City & Community.

Sharp relies on data from the Los Angeles Family and Neighborhood Survey to examine how neighborhood disadvantage affects residents' satisfaction and interactions.

The survey's data provides researchers with unique information, according to Sharp. First, it's a longitudinal study that covers two waves of attitudes from 2000-02 and 2006-08 in 65 neighborhoods and more than 3,000 households.

"What better city to look at for this kind of work?" asks Sharp. "Los Angeles is a huge multiracial and multiethnic metropolis. And the survey digs into not only the attitudes and perceptions of residents about their neighborhood, but also their actual behaviors in the neighborhood."

Sharp says to realize the value of neighboring demands considering how perceptions and experiences with neighborhood danger factors into attitudes. Just as neighboring can snowball into neighborhood investment, Sharp says that living in the most disadvantaged neighborhoods can intensify fear and work against the advantages generated by consistent interactions.

"People exposed to pernicious neighborhood conditions that evoke fear and mistrust suffer an amplification effect that can result in social isolation and loneliness," he says.

But even demonstrating the importance of including neighborhood characteristics along with perceptions and experiences raises questions about the nature of neighborhoods in the 21st century.

Urban sociology is grounded in what's known as the Chicago School, a mindset emerging from the early 20th century that asked how the transition from agrarian to industrial centers would impact the vitality of community life.

Something similar is happening today with emerging digital technologies. But these new technologies are not creating an environment that's eclipsing today's communities, according to Sharp.

"Many neighborhoods are composed of residents who regularly connect with one another, foster meaningful bonds, and are ultimately satisfied with their surroundings," says Sharp. "Fully understanding how this occurs should help scholars and policy makers anticipate how communities will change in the future."