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ITHACA, N.Y. - Bernie Sanders and Joe Biden lead Democratic presidential nominees among registered Latino voters heading into the Feb. 22 Nevada caucuses, the first contest in a diverse state. Nationally, registered Latino voters favor any of the Democratic contenders over President Donald Trump by large margins, and rate health care and racism as significant concerns.

Those are some of the key findings from the latest Univision News poll led by Sergio Garcia-Rios, assistant professor of government at Cornell University.

The results showed Sanders leading other Democratic candidates with 33% support in Nevada and 30% nationally, followed by Biden at 22% and 21%, respectively. In head-to-head matchups with Trump, Michael Bloomberg also fared well in Nevada, with 78% planning on or leaning toward voting for him, second to Sanders' 80% total.

Four out of five Nevada respondents disapproved of Trump, with 60% "strongly" disapproving. Nationally, 73% disapproved of the president, 49% strongly. At the same time, Trump's approval rating among Latinos rose from 22% to 27% since September.

Latinos this year are projected to be the largest racial or ethnic minority voting group for the first time with a record 32 million voters, according to the Pew Research Center. They make up nearly 20% of Nevada's eligible voters, up from about 3% in Iowa and New Hampshire.

Latino voter turnout surged in the 2018 midterm elections, compared to four years earlier. If that trend continues, Garcia-Rios said, Latinos could potentially play a decisive role in battleground states such as Florida, Nevada, Ohio, Texas and Wisconsin.

"A big Latino turnout," he said, "could have a big impact in the general election."

Garcia-Rios, a self-described "fronterizo" who grew up in both Mexico and Texas, said he and Univision shared a desire to accurately capture Latino public opinion with a scientific and bipartisan approach.

Broader polls and exit polls, he said, often fail to reach representative samples of a diverse Latino population. Latinos' varying geographic, generational and political backgrounds, he said, shape different attitudes across the country - more conservative in Florida, for example, than California.

"Being aware that it's not monolithic, and being able to capture that full picture, is important to us," said Garcia-Rios.

Garcia-Rios employs a hybrid approach that reaches out bilingually to potential voters by cellphone, landline telephone and online, confirming if they are registered voters. He writes the poll questions - seeking opinions on key issues as well as candidate preferences - and oversees the data analysis.

The new poll, produced in partnership the Latino Community Project, surveyed 1,000 registered Latino voters nationally and 306 in Nevada from Feb. 9-14. The margins of error were plus or minus 3.1 percentage points nationally and 5.6 percentage points in Nevada. Democratic primary preferences were asked of 667 respondents nationally and 210 in Nevada, with margins of error of plus or minus 3.8 percentage points and 6.7 percentage points, respectively.

The loss of the identity of insulin-secreting beta cells in the islet of Langerhans, a process also called beta cell dedifferentiation, has been proposed to be a main reason for the development of diabetes. If and how dedifferentiated beta cells can be targeted by pharmacological intervention for beta cell regeneration is unknown. In a new study in mice, Helmholtz Zentrum München in collaboration with Novo Nordisk, demonstrated for the first time that a targeted combinatorial drug treatment is able to restore beta cell function, achieve beta cell redifferentiation and therefore potentially open new ways for diabetes remission.

Under certain conditions, beta cells can lose their identity and regress to a less differentiated state in which they lose most of their prior functions. It has been proposed that this dedifferentiation contributes to an ongoing degenerative process of beta cell dysfunction. Current pharmacological diabetes treatments are not able to stop the decline of functional beta cell mass loss. The earlier this decline can be prevented, ideally already when first diabetic symptoms appear, the higher the amount and the level of beta cell function that will be preserved.

New target: Dedifferentiated beta cells

To investigate whether dedifferentiated beta cells can be targeted pharmacologically to restore beta cell function, the researchers used streptozotocin-induced diabetes in mice. Streptozotocin kills insulin-producing beta cells and causes severe diabetes. When injected in multiple low doses, however, some beta cells survive which replicates the decline in function the researchers wanted to establish for their experiment. Using single cell RNA sequencing the researchers could show that after streptozotocin treatment, the surviving beta cells dedifferentiate into a dysfunctional state. The simplicity of the model used (no genetic lesions nor autoimmunity) would help them better monitor the effect of the pharmacological treatment.

A good match: GLP-1/estrogen and insulin have additive effects in preclinical models

The team then tested treatments for their potential to restore beta cell function. To this end, they stratified seven cohorts of severely diabetic mice and treated them daily for 100 days with single and combinatorial pharmacology. The researchers showed that a stable Glucagon-like peptide-1 (GLP-1)/estrogen conjugate (provided by Novo Nordisk) enables targeted and selective delivery of the nuclear hormone cargo to beta cells. The combination of GLP-1/estrogen and a long acting insulin was superior to mono-treatments to both normalize glycemia, glucose tolerance, to increase pancreatic insulin content and to increase the number of beta cells. Importantly, administration of high doses of GLP-1/estrogen did not show signs of systemic toxicity in rats, a pre-requisite for any future clinical testing. In a collaboration with the biotech company InSphero, the researchers could also show that GLP-1/estrogen, but not GLP-1 or estrogen alone, increases human beta cell function when human pancreatic islets are exposed to cytokine stress, which is known to impair human beta cell function.

"Not only does our study describe paths and processes of beta cell dedifferentiation, it also demonstrates the potential of single and combinatorial drug treatments to achieve diabetes remission by targeting dedifferentiated beta cells" explains Prof. Dr. Heiko Lickert, director of the Institute for Diabetes and Regeneration Research at Helmholtz Zentrum München and Professor of Beta Cell Biology at TUM School of Medicine. "This is the first study that shows beta cell redifferentiation with targeted pharmacology performed by an interdisciplinary team that used cutting edge single cell technology, computational biology, pharmacology and regeneration biology" says Lickert who, together with Susanna M. Hofmann, Fabian Theis and Timo D. Müller at Helmholtz Zentrum München, lead this research project.

Future clinical studies?

This study brought together scientists from Helmholtz Zentrum München (Helmholtz Diabetes Center and Institute for Computational Biology), the German Center for Diabetes Research (DZD), Technical University of Munich (TUM) as well as InSphero AG and Novo Nordisk with the aim to explore the potential therapeutic benefits of GLP1/estrogen treatment in an animal models and in human cells in vitro. The results from this study as well as future studies to support translation to humans and safety of the compound may pave the way for clinical studies that use GLP-1 as a carrier peptide for estrogen but potentially also other, novel cargos to directly target beta cells for regenerative therapy and diabetes remission.

A growing body of research shows that birds' spring migration has been getting earlier and earlier in recent decades. New research from The Auk: Ornithological Advances on Black-throated Blue Warblers, a common songbird that migrates from Canada and the eastern U.S. to Central America and back every year, uses fifty years of bird-banding data to add another piece to the puzzle, showing that little-studied fall migration patterns have been shifting over time as well.

Loyola Marymount University's Kristen Covino and her colleagues used data housed at the USGS Bird Banding Laboratory on migrating Black-throated Blue Warblers between 1965 and 2015. Across the United States, researchers working with this program safely capture migrating birds, collect data on them, and fit them with metal leg bands with unique codes that allow them to be identified if they're captured again. Analyzing almost 150,000 individual records, Covino and her colleagues found that the timing of the birds' spring migration has advanced over the last fifty years, with early migrants passing through banding sites approximately one day earlier each decade. Crucially, their data also covered fall migration, which has been less well-studied, and found that while the timing of the peak of fall migration hasn't changed, fall migration takes longer today than it did fifty years ago.

The North American Bird Banding Program is one of the most expansive historical datasets on migratory birds, including records for over 38 million songbirds banded since 1960. "My coauthor Sara Morris and I were already working together on another paper on Blackpoll Warblers using data we'd requested from banding stations across North America. We wanted to take a similar large-scale approach for this study, but we wanted to demonstrate that we could do this approach with data that is completely available from the Bird Banding Lab," says Covino. "We selected Black-throated Blue Warblers because it's relatively straightforward to determine their age and sex, which means that the data this species generates are both accurate and powerful."

Although the researchers emphasize that their findings can't be explicitly linked to climate change without incorporating climate or environmental data, they believe similar methods could be useful for tracking the effects of climate change on birds. "The protraction of fall migration means that the season is getting longer overall, but it could also mean that the breeding season may be shifting, ending earlier for some individuals but later for others. To determine what this means in the context of breeding season shifts in timing, additional studies that incorporate both arrival on the breeding grounds and, importantly, departure from them are needed," says Covino. "More studies of these patterns of fall migration timing and, even more so, both spring and fall migration timing across years are needed to gain the complete picture of how species are changing migration timing."

Bottom Line: The loss of one copy of the miR15a/miR16-1 gene cluster promoted initiation and progression of multiple myeloma in mice.

Journal in Which the Study was Published: Published online in Blood Cancer Discovery, the latest journal of the American Association for Cancer Research

Author: Marta Chesi, PhD, associate professor of medicine at the Mayo Clinic

Background: Multiple myeloma is a cancer of antibody-producing cells called plasma cells. It is preceded by a premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS), in which abnormal plasma cells are present but do not expand. A hallmark of both MGUS and multiple myeloma is the detection of an M spike, which indicates the accumulation of an abnormal secreted antibody in the patient's blood.

"The risk of progression from MGUS to malignant multiple myeloma is approximately 1 percent each year, but the factors that contribute to progression are not well understood," said Chesi. "The purpose of our study was to model genetic risk factors that may contribute to initiation and progression of multiple myeloma. This understanding could eventually allow us to identify the mechanisms that increase the risk of progressing to multiple myeloma."

One copy of chromosome 13 is deleted in approximately half of patients with MGUS and multiple myeloma; however, the significance of this deletion on prognosis and disease progression remains controversial. Chesi and colleagues hypothesized that individual genes on chromosome 13 may promote disease initiation and/or progression.

The authors examined the impact of two genetic loci found on human chromosome 13 - RB1 and MIR15A/MIR16-1 - on disease initiation and progression. Both RB1 and MIR15A/MIR16-1 are considered tumor suppressor genes due to their roles in regulating cellular proliferation. The RB1 protein is known to be inactivated in many cancers, including multiple myeloma. A previous study demonstrated that deletion of MIR15A/MIR16-1 enhances proliferation of human B cells, and deletion of the gene in mice promotes development of another blood cancer, chronic lymphocytic leukemia.

How the Study was Conducted and Results: In this study, the authors deleted a single copy of either Rb1 or miR15a/miR16-1 in wild-type mice and in a transgenic mouse model of multiple myeloma they previously developed. The authors found that deletion of one copy of Rb1 did not affect disease initiation or progression. In contrast, deleting one copy of miR15a/miR16-1 in wild-type mice significantly accelerated the development of an M-spike. Furthermore, the deletion of one copy of miR15a/miR16-1 in mice with multiple myeloma significantly enhanced the aggressiveness of the disease and led to increased expression of genes that promote cellular proliferation.

The authors also analyzed a genetic dataset of multiple myeloma patients and found that deletion of one copy of MIR15A/MIR16-1 in patient tumors was associated with increased expression of the same cellular proliferation genes that were upregulated in mice.

Author's Comments: "Losing one copy of the MIR15A/MIR16-1 gene appears to promote tumor cell proliferation in both mice and patients," said Chesi. "For many years, we thought that deletion of chromosome 13 was just a byproduct of other genetic changes in the tumor and that it did not directly affect disease progression. Our study now demonstrates that deletion of chromosome 13, and specifically deletion of MIR15A/MIR16-1, appears to alter the biology of the tumor.

"However, the fact that the entire chromosome 13, and not just MIR15A/MIR16-1, is lost in many cases of MGUS or multiple myeloma suggests that other genes on this chromosome are also likely to be important for pathogenesis," added Chesi. In particular, Chesi is interested in studying DIS3, another gene located on chromosome 13 that is frequently mutated in multiple myeloma. The authors were not able to assess its contribution in this study due to the lack of relevant mouse models.

ANN ARBOR--A new study from University of Michigan biologists presents the first genetic evidence of resistance in some bats to white-nose syndrome, a deadly fungal disease that has decimated some North American bat populations.

The study involved northern Michigan populations of the little brown bat, one of the most common bats in eastern North America prior to the arrival of white-nose syndrome in 2006. Since then, some populations of the small, insect-eating bat have experienced declines of more than 90%.

U-M researchers collected tissue samples from wild little brown bats that survived the disease, as well as individuals killed by the fungal pathogen. They compared the genetic makeup of the two groups and found differences in genes associated with regulating arousal from hibernation, the breakdown of fats and echolocation.

"Because we found differences in genes associated with regulating hibernation and breakdown of fats, it could be that bats that are genetically predisposed to be a little bit fatter or to sleep more deeply are less susceptible to the disease," said U-M's Giorgia Auteri, first author of a paper scheduled for publication Feb. 20 in the journal Scientific Reports.

"Changes at these genes are suggestive of evolutionary adaptation, given that white-nose syndrome causes bats to arouse with unusual frequency from winter hibernation, contributing to premature depletion of fat reserves," said Auteri, a doctoral student in the Department of Ecology and Evolutionary Biology who conducted the study for her dissertation.

The other author of the Scientific Reports paper is U-M biologist Lacey Knowles, Auteri's faculty adviser.

While the study was small--involving tissue samples from 25 little brown bats killed by white-nose syndrome and nine bats that survived the disease--the authors say their sample size is large enough to detect genetic changes driven by natural selection. A larger follow-up study is underway, expanding both the number of bats and the areas affected by the disease, to develop a fuller picture of adaptive change that may be key to the species' survival.

The fungal pathogen that causes white-nose syndrome was inadvertently introduced in the northeastern United States in 2006 and is currently spreading across the continent.

Thirteen species of North American bats are currently affected, with some populations experiencing losses of 90-100%. The disease is named for a distinctive fungal growth around the muzzles and on the wings of hibernating bats.

The U-M team's study area is Michigan's northern Lower Peninsula and Upper Peninsula. White-nose syndrome fungus was first detected there in 2014, and its arrival allowed the researchers to study the pathogen's initial evolutionary impact.

For the study, the U-M researchers collected tissue samples from dead little brown bats found in or near hibernation sites during the winter. The hibernation sites were concentrated in the western Upper Peninsula and primarily consisted of abandoned iron and copper mines.

During the summer, they also collected small tissue samples from survivors that emerged successfully from hibernation despite exposure to the disease. Surviving bats had healing wing lesions or scars from the fungus.

In the laboratory, DNA was extracted from the tissues and sequenced, and the sequences were mapped to a previously generated reference genome for the species. A genome scan was conducted to test for evidence of evolutionary changes in response to white-nose syndrome.

The researchers found significant differences in three genes associated with arousal from hibernation (GABARB1), breakdown of fats (cGMP-PK1) and echolocation (FOXP2), as well as a fourth gene (PLA2G7) that regulates the release of histamines from mast cells.

"The function of one gene we identified hints that summer activities such as hunting via echolocation may be an important determinant of which individuals survive the winter infection period," Auteri said. "This suggests that conservation of summer foraging habitat--not just winter hibernation sites--may promote population recovery in bats affected by white-nose syndrome."

The observed genetic differences are suggestive of very rapid--though not unprecedented--evolutionary adaptation driven by natural selection, according to Auteri and Knowles.

"This apparent adaptation occurred very quickly, involves genes with a variety of functions which likely act across seasons in order to contribute to survivorship, and has taken place despite an observable reduction in genetic diversity associated with population declines," said Knowles, a professor in the Department of Ecology and Evolutionary Biology and a curator at the U-M Museum of Zoology.

Auteri and Knowles said it's too soon to say how the evolutionary changes they uncovered are likely to affect the little brown bat's prospects. After all, these bats have suffered dramatic population declines, and low population sizes inherently make a species more vulnerable to further perturbations.

"But we're finding the hint that there could be these genetic changes that are occurring that might provide some type of survival in the future," Knowles said. "So as these variants increase, there's some hope that these bats are not all going to die from the disease itself."

Because little brown bats only have one pup per year, recovery of the species would likely take a long time, according to Auteri and Knowles.

Due to population losses, little brown bats have been listed as endangered by the International Union for Conservation of Nature and by the federal government of Canada, with a similar decision by the U.S. government pending.

Researchers at the USC Viterbi School of Engineering have designed a new drug cocktail that kills some types of brain and soft tissue cancers by tricking the cancer cells to behave as if they were starving for their favorite food--glucose. The researchers' findings were recently published in the Journal of Biological Chemistry and may pave the way for targeted cancer treatments with greater efficacy and less harmful side effects.

To design their lethal drug combination, researchers James H. Joly, Alireza Delfarah, Philip S. Phung, Sydney Parrish and Nicholas A. Graham in the Mork Family Department of Chemical Engineering and Materials Science first studied how cell lines from glioblastoma (brain cancer) and sarcoma (soft tissue cancer) respond to glucose starvation. They noticed that cell lines that died following glucose starvation showed a toxic buildup of the amino acid L-cystine. This led the USC team to discover that L-cystine import was causing accumulation of reactive oxygen species, highly toxic molecules that can damage cells. When the team blocked L-cystine import with drugs targeting its transporter, a protein called xCT, the cancer cells survived glucose deprivation.

Theoretically, this indicates that tumors with high xCT levels should die when starved of glucose. However, in a patient, starving cancer cells is not practical because it would mean starving their hosts (human beings). The USC researchers thus sought to kill these glucose- addicted cancer cells by designing a drug combination that mimicked the starvation-induced state. By simultaneously inhibiting a glucose transporter and an enzyme that metabolizes L-cystine, the authors found that they could set into motion metabolic processes imitating glucose deprivation, thereby forcing the cancer cells to die--even when glucose is present.

Current treatments for glioblastoma and sarcoma have limited efficacy due to acquired resistance, in which the cancer relapses by acquiring drug resistance. The use of drug combinations is thought to reduce the incidence of acquired resistance and might result in prolonged remission. In addition, the new combination of drugs might have fewer side effects since the drugs individually should have low toxicity towards non-cancerous cells. This differs from traditional chemotherapies that indiscriminately target rapidly growing cells, which results in death of many non-cancerous cells and causes side effects such as hair loss and nausea.

Moving forward, the USC Viterbi engineers are planning to partner with medical researchers from the Keck School of Medicine at USC to test this combination therapy in patient samples and mouse models of glioblastoma.

Cells are small factories that constantly produce protein and RNA molecules by decoding the genetic information stored in the DNA of their chromosomes. The first phase of this decoding, the transcription process, "transcribes" the DNA code into RNA molecules. In humans, and most other organisms, all cells of the body carry the full genetic information of the entire organism, with each individual cell requiring only a small subset of its DNA decoded. Even so, the first decoding phase (transcription) is pervasive and produces a large amount of surplus RNAs.

These extraneous RNAs do, however, not accumulate, as they are degraded shortly after their production. This prevents deleterious accumulation of non-functional transcripts that would otherwise be detrimental to cell health. Most of this RNA decay is carried out by the nuclear RNA exosome complex, an RNA 3'-5' exonuclease, which is recruited to RNA by specific adapters, like the so-called NEXT complex and the PAXT connection. The laboratory of Torben Heick Jensen previously found that NEXT and PAXT aid in decay of different kinds of nuclear RNAs, but how specificity is achieved remained enigmatic.

With their new publication, the research team now reveals that NEXT substrates contain 'naked' 3'ends, whereas PAXT substrates harbor so-called poly(A)-tailed 3'ends. Despite this clear division, the study also reveal that the decay systems can co-operate, which helps cells to degrade NEXT substrates, even in the potentially hazardous situation when NEXT activity is decreased. In this case, NEXT targets (which are normally produced without a poly(A) tail and swiftly removed) acquire poly(A) tails - a hallmark of PAXT targets - which subject them to PAXT-mediated decay. In conjunction, this provides a two-layered targeting mechanism for the efficient nuclear sorting of the human transcriptome. An important question now remaining to be answered is how this efficient sorting is coupled to the production (transcription) of RNA.

The findings result from a collaborative project spearheaded by postdoc Guifen Wu and team leader Manfred Schmid from the laboratory of Torben Heick Jensen at the Department of Molecular Biology and Genetics, Aarhus University, in collaboration with Leonor Rib and Albin Sandelin from the Department of Biology and Biotech Research and Innovation Centre, University of Copenhagen. The study was financed by the Novo Nordisk Foundation and the Lundbeck Foundation, and published in the international journal Cell Reports.

It's not easy to do pregnancy tests on whales. You can't just ask a wild ocean animal that's the size of a school bus to pee on a little stick. For decades, the only way scientists could count pregnant females was by sight and best guesses based on visual characteristics. For the last several years, researchers have relied on hormone tests of blubber collected via darts, but the results were often inconclusive (not negative or positive), and researchers couldn't confidently say if the animal was pregnant or just ovulating.

Research from the National Institute of Standards and Technology (NIST) and Australia's Griffith University points to a weakness of that testing and provides a new method for hormone testing that offers better results.

"Previous tests only looked at progesterone in blubber samples," said Ashley Boggs, a research biologist at NIST who helped to develop the new tests. "We found that androgens, and especially androstenedione in combination with progesterone, are much more likely to be a reliable marker of pregnancy."

Being able to determine whale pregnancy is important because it offers insight into the health of a population. Whales are sensitive to changes in their environment and can serve as early warning signals that something is amiss, including details about the health of the food web, the impact of ocean noise, and the levels of contaminant exposures. The Marine Mammal Protection Act was enacted in 1972 to protect whales, and since that time stock assessments and protections have been carried out by the National Oceanic and Atmospheric Administration (NOAA), including data on pregnancies. That's why NOAA came to NIST to try to advance hormone measurement technology for marine mammals.

In recent years, humpback whale numbers have increased dramatically in many places, although they are still considered endangered. The animals' large size makes it difficult to count or study them using traditional identification methods. Like most protected whales, this species cannot be held in captivity , and most of the information about them must be gained through observation in the wild. But humpbacks can serve as an indicator species for other, more endangered large whales, and by developing bioanalytical measurement techniques for these species that are doing well, scientists can confidently apply them to other, more protected species.

"Up to this point, most measurements had been conducted using immunoassays, which require a 'one at a time' approach to hormone measurements," Boggs said.

"We know that hormones act together in suites to cause large physiological changes. If you focus on only one hormone at a time, you might miss the major hormone of interest or simply run out of money or samples."

The research team studied female humpbacks along the east coast of Australia during two stages of migration. Fifty-two individuals were randomly sampled before reaching the calving grounds in June/July (austral winter) and again after departing the calving grounds in September/October (austral spring). Before reaching the calving grounds, only one had a high concentration of progesterone, the hormone that has previously been used as an indicator of pregnancy in this species. This number seemed too low to be reliable. The evidence indicated that the animals' hormone profiles change in late pregnancy, since multiple calves were seen later.

Finding chemical indicators for pregnancy in marine mammals is very different from finding them in humans, where a protein hormone called human chorionic gonadotropin (hCG) is detected right after the implantation of the embryo. Other protein hormones are difficult to use as a standard indicator for pregnancy because their levels vary from one species to the other.

Previous whale reproductive research had relied on the measurement of the hormone progesterone using a test known as enzyme-linked immunosorbent assay, or ELISA. ELISA has been the "go to" assay for years, but NIST scientists have determined that not all species rely on the same hormones during pregnancy, and in addition, some species' hormone levels exhibit significant shifts during different phases of the gestation process.

NIST researchers realized that a chemical analysis technique called mass spectrometry, which detects compounds based on their masses, would potentially allow the measurement of many hormones simultaneously and could help biologists to understand which hormones can be found at different stages of pregnancy.

The new analysis from NIST and Griffith University scientists allowed for gathering a simultaneous measurement of 11 steroid hormones in each sample of whale blubber using liquid chromatography tandem mass spectrometry. The technique identifies hormones based on molecular size and mass rather than attachment of the hormone to an antibody (as in the current method), ensuring higher accuracy and selectivity.

"By casting a wider net and looking for more hormones, we were able to get a better set of biomarkers," said Boggs. The same technique will also likely be applicable to other species including North Atlantic right whales, which are dying at alarming rates and considered to be a species in peril.

Boggs noted that correct timing could also improve the tests' accuracy rates.

"Criteria will change depending on how far along the pregnancy has progressed," she said. "In some species, progesterone drops off toward the end of pregnancy. And even closely related species can have very different hormonal profiles. Each test would need to be tailored to the species to be accurate, but the beauty of the mass spectrometry method means you don't have to know which hormone is dominant before you start looking. You can look at them all."

ITHACA, N.Y. - Cancer cells are a wily adversary. One reason the disease outfoxes many potential treatments is because of the diversity of the cancer cell population. Researchers have found this population difficult to characterize and quantify.

A Cornell-led team took a novel, interdisciplinary approach to analyzing the behavior of breast tumor cells by employing a statistical modeling technique more commonly used in physics and economics. The team was able to demonstrate how the diversity, or heterogeneity, of cancer cells can be influenced by their chemical environment - namely, by interactions with a specific protein, which leads to tumor growth.

A research team led by Mingming Wu worked with CNF to fabricate this microfluidic chip containing four identical three-channel devices. The team put breast tumor cells and the chemokine protein CCL19 into each device and then used open-source software to analyze the cancer cell behavior.

The researchers' paper, "Lymphoidal Chemokine CCL19 Promoted the Heterogeneity of the Breast Tumor Cell Motility Within a 3D Microenvironment Revealed by a Lévy Distribution Analysis," published Feb. 14 in Integrative Biology.

"It's pretty tough to treat cancer. A lot of people in the field believe that is because of the diversity in the cancer population," said senior author Mingming Wu, professor of biological and environmental engineering in the College of Agriculture and Life Sciences. "While immune cells are rounded and kind of similar and move in the same way, cancer cells are different in shape and move at different speed. We know that fast movers are very lethal. How would you quantify that heterogeneity?"

Another challenge is that only a few cancer cells move fast and do the most damage, and they're difficult to find.

The effort to track these rare cells is similar to the search for elusive particles being conducted in the lab of co-author Anders Ryd, professor of physics in the College of Arts and Sciences. During a conversation over coffee, Ryd and Wu realized the cancer cell research could incorporate the same type of sophisticated statistical tools that have helped particle physicists understand rare energy phenomena, such as the much-sought Higgs boson.

"What we do in particle physics is really statistical data analysis, trying to figure out what functional forms describe our data," Ryd said. "And in this case here, the interest was to look at the outliers, the cells that migrated further, and characterize that. A lot of the tools that we are using in particle physics lend themselves very well to this analysis."

Wu's Biofluidics Lab worked with the Cornell NanoScale Science and Technology Facility (CNF) to fabricate a microfluidic device with three parallel channels, each roughly the width of a human hair. The team introduced breast tumor cells into the device, along with the chemokine protein CCL19, which is secreted by lymph nodes and is highly expressed in malignant tumor cells.

In order to model the cancer cell trajectories, the team used Root, an open-source software for performing statistical analysis in high-energy physics and in certain economics applications.

The researchers found that the presence of chemokine caused the targeted cancer cells to move faster, and heterogeneity increased.

"It is similar to how we as a society are trying to make the population more diverse, because we know that if the population is diverse, it's more robust, more healthy," Wu said. "I think that cancer is the same way. They are making their population more diverse, more indestructible."

A treatment that inhibits the receptor to CCL19 could potentially decrease the invasiveness of tumor cells, although that might also cause the cancer cells to adopt new, even stealthier strategies to survive, Wu said.

By analyzing how these cells respond to environmental cues - such as chemical gradients, temperature, light intensity and mechanical force - Wu's team hopes to elucidate the underlying principles of biology, which aren't as cut and dried as the fundamental laws of physics.

Her team may borrow a few techniques, too.

"There are a lot of tools in physical science already, because physical science has always been a very quantitative field," Wu said. "It's only recently that quantitative biology is starting to shape up. So I feel like this integration is powerful because you don't have to reinvent the wheel to do this modeling."

Enough water will come from the ground as a byproduct of oil production from unconventional reservoirs during the coming decades to theoretically counter the need to use fresh water for hydraulic fracturing operations in many of the nation's large oil-producing areas. But while other industries, such as agriculture, might want to recycle some of that water for their own needs, water quality issues and the potential costs involved mean it could be best to keep the water in the oil patch.

That is the takeaway from two new studies led by researchers at The University of Texas at Austin.

"We need to first maximize reuse of produced water for hydraulic fracturing," said Bridget Scanlon, lead author on both of the studies and a senior research scientist with the UT Bureau of Economic Geology. "That's really the message here."

The first study was published in Environmental Science and Technology on Feb. 16. It quantifies for the first time how much water is produced with oil and natural gas operations compared with how much is needed for hydraulic fracturing. The authors also projected water demand for hydraulic fracturing needs and produced water over the life of the oil and gas plays, which span decades. A play is a group of oil or natural gas fields controlled by the same geology.

The second study was published in Science of the Total Environment on Feb. 3. It assesses the potential for using the water produced with oil and natural gas in other sectors, such as agriculture. It included researchers from New Mexico State University, The University of Texas at El Paso and Penn State University. It shows that current volumes of produced water are relatively small compared with irrigation water demands and will not solve water scarcity issues.

Dealing with water issues has become increasingly challenging with oil and natural gas development in unconventional shale reservoirs. Operators need significant amounts of water to hydraulically fracture shales to produce oil and natural gas, which can be an issue in areas where water is scarce. And large quantities of water are brought up from the reservoirs as a byproduct of production, posing a whole new set of issues for how to manage the produced water, particularly as science has shown that pumping it back into the deep subsurface is linked to seismic activity in some regions.

The studies can help inform significant public policy debates about water management related to oil and natural gas production in Texas, Oklahoma, New Mexico and other parts of the country, Scanlon said.

"The water volumes that are quoted vary widely. That's why we did this study," she said. "This really provides a quantitative analysis of hydraulic fracturing water demand and produced water volumes."

The research looked at eight major plays across the U.S., including the Permian (Midland and Delaware), Bakken, Barnett, Eagle Ford, Fayetteville, Haynesville, Marcellus and Niobrara plays.

The scientists used historical data from 2009 to 2017 for all plays, and projections were developed for the life of the oil plays based on the technically recoverable oil using current technology. Oil plays produced much more water than natural gas plays, with the Permian Basin producing about 50 times as much water as the Marcellus in 2017. As far as recycling potential for hydraulic fracturing, the research shows that in many cases there's plenty of water that could be put to good use. For instance, in the Delaware Basin, which is part of the larger Permian Basin in Texas, scientists found that projected produced water volumes will be almost four times as great as the amount of water required for hydraulic fracturing.

Managing this produced water will pose a significant challenge in the Delaware, which accounts for about 50% of the country's projected oil production. Although the water could theoretically be used by other sectors, such as agriculture in arid West Texas, scientists said water quality issues and the cost to treat the briny water could be hurdles. In addition, if the water is highly treated to remove all the solids, large volumes of salt would be generated. The salt from the produced water in the Delaware Basin in 2017 alone could fill up to 3,000 Olympic swimming pools.

"The ability to beneficially reuse produced waters in arid and semi-arid regions, which can be water stressed, is not the panacea that we were hoping," said co-author Mark Engle, a professor at The University of Texas at El Paso. "There is definitely potential to do some good, but it will require cautious and smart approaches and policies."

In a first for quantum physics, University of Otago researchers have "held" individual atoms in place and observed previously unseen complex atomic interactions.

A myriad of equipment including lasers, mirrors, a vacuum chamber, and microscopes assembled in Otago's Department of Physics, plus a lot of time, energy, and expertise, have provided the ingredients to investigate this quantum process, which until now was only understood through statistical averaging from experiments involving large numbers of atoms.

The experiment improves on current knowledge by offering a previously unseen view into the microscopic world, surprising researchers with the results.

"Our method involves the individual trapping and cooling of three atoms to a temperature of about a millionth of a Kelvin using highly focused laser beams in a hyper-evacuated (vacuum) chamber, around the size of a toaster. We slowly combine the traps containing the atoms to produce controlled interactions that we measure," says Associate Professor Mikkel F. Andersen of Otago's Department of Physics.

When the three atoms approach each other, two form a molecule, and all receive a kick from the energy released in the process. A microscope camera allows the process to be magnified and viewed.

"Two atoms alone can't form a molecule, it takes at least three to do chemistry. Our work is the first time this basic process has been studied in isolation, and it turns out that it gave several surprising results that were not expected from previous measurement in large clouds of atoms," says Postdoctoral Researcher Marvin Weyland, who spearheaded the experiment.

For example, the researchers were able to see the exact outcome of individual processes, and observed a new process where two of the atoms leave the experiment together. Until now, this level of detail has been impossible to observe in experiments with many atoms.

"By working at this molecular level, we now know more about how atoms collide and react with one another. With development, this technique could provide a way to build and control single molecules of particular chemicals," Weyland adds.

Associate Professor Andersen admits the technique and level of detail can be difficult to comprehend to those outside the world of quantum physics, however he believes the applications of this science will be useful in development of future quantum technologies that might impact society as much as earlier quantum technologies that enabled modern computers and the Internet.

"Research on being able to build on a smaller and smaller scale has powered much of the technological development over the past decades. For example, it is the sole reason that todays cellphones have more computing power than the supercomputers of the 1980s. Our research tries to pave the way for being able to build at the very smallest scale possible, namely the atomic scale, and I am thrilled to see how our discoveries will influence technological advancements in the future" Associate Professor Andersen says.

The experiment findings showed that it took much longer than expected to form a molecule compared with other experiments and theoretical calculations, which currently are insufficient to explain this phenomenon. While the researchers suggest mechanisms which may explain the discrepancy, they highlight a need for further theoretical developments in this area of experimental quantum mechanics.

This completely New Zealand based research was primarily carried out by members of the University of Otago's Department of Physics, with assistance from theoretical physicists at Massey University.

Otago scientists studying sperm whales off the coast of Kaik?ura have discovered earthquakes affect their ability to find food for at least a year.

The University of Otago-led research is the first to examine the impact of a large earthquake on a population of marine mammals, and offers new insight into how top predators such as sperm whales react and adapt to a large-scale natural disturbance.

Changes in habitat use by a deep-diving predator in response to a coastal earthquake, has recently been published in Deep Sea Research Part I.

Earthquakes and aftershocks can affect sperm whales in several ways, the study explains.

The whales depend on sound for communication, detection of prey and navigation and are also highly sensitive to noise.

Earthquakes produce among the loudest underwater sounds which can induce injuries, hearing damage, displacement and behavioural modifications.

While earthquakes and other extreme natural events are rare occurrences, they can really shift the state of ecosystems by wiping out animals and plants, lead author and Marine Sciences Teaching Fellow Dr Marta Guerra says.

"Understanding how wild populations respond to earthquakes helps us figure out their level of resilience, and whether we need to adjust management of these populations while they are more vulnerable."

The fatal 7.8 magnitude Kaik?ura earthquake on November 14, 2016 produced strong ground shaking which triggered widespread underwater mudslides in the underwater canyon off the coastline.

This caused what's known as 'canyon flushing', which in the case of the Kaik?ura earthquake, involved high-energy currents flushing 850 tonnes of sediment from the underwater canyon into the ocean.

The Kaik?ura canyon is an important year-round foraging ground for sperm whales, which have an important ecological role as top predators and are a key attraction for the local tourism industry - the main driver of the town's economy.

Just why the canyon is important to sperm whales is "a piece of the puzzle we are still trying to nut out", says Dr Guerra.

"But it's likely related to the immense productivity of the canyon's seabed, and a combination of how the currents interact with the steep topography of the submarine canyon."

Scientists examined data collected on the behaviour of 54 sperm whales between January 2014 and January 2018 - a timeframe which allowed an opportunity to determine any significant changes in pre and post-earthquake whale foraging behaviour.

"We really didn't know what to expect, as there is so little known about how marine animals react to earthquakes," Dr Guerra says.

The researchers found clear changes in the whales' behaviour in the year following the earthquake: most noticeably whales spent about 25 per cent more time at the surface - which potentially meant they needed to spend more effort searching for prey, either by diving deeper or for longer times

There are two main reasons the whales may have expanded their search effort, the study explains.

Firstly, benthic invertebrate communities which lived in the upper canyon may have been removed by the canyon flushing event, resulting in sparser prey and reduced foraging abilities.

Secondly, sediment deposition and erosion may have required sperm whales to 're-familiarise' with a modified habitat, increasing the effort to navigate and locate prey whose location may have changed.

"The flushing of almost 40,000 tonnes of biomass from the canyon's seabed probably meant that the animals that normally fed on the seabed had a short supply of food, possibly moving away," Dr Guerra says.

"This would have indirectly affected the prey of sperm whales (deep-water fish and squid), becoming scarce and making it harder for the whales to find food."

Scientists were particularly surprised by how clear the changes were, especially in terms of where the sperm whales were feeding.

"The head of the Kaik?ura canyon, where we used to frequently find sperm whales foraging, was quiet as a desert," Dr Guerra says.

Although earthquakes happen relatively frequently in areas where marine mammals live, this study was the first to document the impact on a population, thanks to a long-term monitoring programme which has been in place since 1990.

Globally, there have been punctual observations, such as a fin whale displaying an 'escape response' after an earthquake on the Gulf of California, or particularly low sightings of humpback whales coinciding with the months following an earthquake off Alaska, Dr Guerra says.

"Deep-sea systems are so out of sight that we rarely consider the consequences of them being disturbed, whether by natural of human impacts.

"I think our results emphasise how far-reaching the impacts to the sea bed can be, affecting even animals at the top of the food chain such as sperm whales."

The study found the whales' behavioural changes lasted about a year after the 2016 earthquake and returned to normal levels in the summer of 2017-18.

Dr Guerra believes this study also highlights the importance of long-term monitoring of marine wildlife and ecosystems, without which scientists wouldn't be able to detect changes that occur after marine mammals are exposed to disturbance.

New research from the UBC's Okanagan campus, Harvard Medical School and Michigan State University suggests that levitating human plasma may lead to faster, more reliable, portable and simpler disease detection.

The researchers used a stream of electricity that acted like a magnet and separated protein from blood plasma. Plasma is the clear, liquid portion of blood that remains after red blood cells, white blood cells, platelets and other cellular components are removed.

"Human plasma proteins contain information on the occurrence and development of addiction and diseases," says Sepideh Pakpour, an assistant professor with UBCO's School of Engineering and one of the authors of the research.

Pakpour is using the proteins to predict opioid dependencies and addictions, but the findings could one day lead to medical diagnoses using the technology.

As plasma proteins are different densities, when separated the proteins levitate at different heights, and therefore become identifiable. An evaluation of these types of proteins and how they group together can paint a picture that identifies whether a patient has the possibility of getting a disease or becoming addicted to drugs like opioids.

"We compared the differences between healthy proteins and diseased proteins to set benchmarks," says Pakpour. "With this information and the plasma levitation, we were able to accurately detect rare proteins that are only found in individuals with opioid addictions."

According to Pakpour, the researchers are particularly excited about the possibility of developing a portable and accurate new diagnostic tool for health care practitioners.

"More investigation is required, but our findings are certainly a step forward towards an optical imaging disease detection tool," she adds.

The five-minute test, uses machine-learning and predictive models, may one day lead to tools that can not only diagnose diseases but also help practitioners prescribe medications that won't lead to drug dependencies.

The researchers are now evaluating other dependencies and diseases to establish roadmaps for detection.

Scientists from the Hubrecht Institute (KNAW) and the University of Cambridge (UK) have managed to generate complex embryo-like structures from mouse embryonic stem cells. These structures, called gastruloids, can now for the first time grow somites, the blocks of tissue that later develop into the vertebrae and muscles of the embryo. It is the first time that scientists managed to generate such advanced embryo-like structures that represent this stage of embryonic development, which occurs after implantation in the uterus. This model system allows these later stages of embryonic development to be studied in a dish. The results of their study were published in Nature on the 19th of February.

During embryogenesis, a fertilized egg develops into a complete organism. However, much is still unknown about the processes that direct embryonic development in mammals. For example, how do mammals regulate the number of vertebrae that make up their spines, or on which side of the body the heart should develop? Every now and then, something goes wrong in these processes. How does this happen? And can we prevent this from happening? Which compounds are beneficial for embryonic development, and which ones are bad? Studies that address such questions often require the use of mouse embryos. These embryos however develop within the uterus and it is difficult to obtain them in large numbers. Scientists from the laboratories of Alexander van Oudenaarden and Katharina Sonnen (Hubrecht Institute) and the laboratory of Alfonso Martinez Arias (University of Cambridge) are therefore developing an alternative: gastruloids, embryo-like structures generated from stem cells in the lab.

Somites

In 2014, these scientists for the first time grew embryo-like structures, called gastruloids, from mouse stem cells. Now, they have further improved the culture conditions to increase the similarities between gastruloids and embryos, which has resulted in gastruloids that grow somites. Somites are small "blocks" of tissue that line the back of the embryo, and will later form the vertebrae and skeletal muscles. The current gastruloids are thus more complex and resemble mouse embryos in more detail than previous models. Susanne van den Brink (Hubrecht Institute): "This is the first time we have managed to generate such complex embryo-like structures that recapitulate the embryonic stages of development that normally happen after implantation in the uterus." Vincent van Batenburg (Hubrecht Institute) adds: "It is fascinating to see that a homogenous group of cells can organize itself into an embryo-like structure that generates somites in a dish."

Gastruloids and embryos

The scientists made a detailed comparison between gastruloids and embryos by investigating what cell types and tissues are present in these structures. In addition, they investigated where these cell types and tissues are located along the head-to-tail body axis, in both gastruloids and embryos. As the combination of active genes determines the cell type, they could investigate these cell types by measuring which genes are active in which location, in both embryos and gastruloids.

State-of-the-art

To this end, the scientists used state-of-the art technologies, such as single-cell sequencing and tomo-sequencing. Single-cell sequencing can be used to measure the total set of active genes in each individual cell, but it does not provide information about the location of these cells. In contrast, tomo-sequencing is a method in which the embryo or gastruloid is sectioned into thin slices, in this case from head to tail, after which the activity of genes is measured in each of these sections.

A suitable model system

The combination of single-cell sequencing and tomo-sequencing enabled the scientists to measure exactly which cell types are present in gastruloids, and where these cell types were positioned along the head-to-tail axis of gastruloids and embryos. Susanne van den Brink (Hubrecht Institute): "We discovered that gastruloids are very similar to embryos, which makes them a very suitable model system to study embryonic development." Anna Alemany: "An important difference between embryos and gastruloids however, is that gastruloids do not have a brain or placenta. Therefore, these structures are not viable."

Studying developmental processes

With this study, the scientists show that gastruloids can now be used to study more complex processes that happen in embryos, such as the processes that regulate somite formation. Alexander van Oudenaarden: "A main advantage of this model system is that gastruloids can be grown in large numbers. This means that we may be able to use them to test new drugs for developmental defects, or to test which compounds are toxic for developing embryos." Scientists can also use gastruloids to study how embryonic defects appear, such as defects during the formation of the heart and muscles.

ALBANY, CALIFORNIA, February 19, 2020--A simple, portable test that can detect the deadliest of the mushroom poisons in minutes has been developed by Agricultural Research Service (ARS) scientists and their colleagues.

Eating toxic mushrooms causes more than 100 deaths a year, globally, and leaves thousands of people in need of urgent medical assistance. Amanitin is the class of mushroom toxins that cause the most serious issues.

The new test can identify the presence of as little as 10 parts per billion (equivalent to 10 cents out of $10 million) of amanitin in about 10 minutes from a rice grain size sample of a mushroom or in the urine of someone who has eaten a poisonous amanitin-containing mushroom. The test also works with dog urine, as dogs are known to indiscriminately eat mushrooms.

"We developed the test primarily for mushrooms as food products. Serendipitously, it was sensitive enough to also detect the toxin in urine," said ARS microbiologist Candace Bever, who worked on the development. Bever is with the Foodborne Toxin Detection and Prevention Research Unit in Albany, California.

No definitive point-of-care clinical diagnostic test currently exists for amatoxin poisoning. Early detection of amanitin in a patient's urine would help doctors trying to make a diagnosis.

"Our hope is that doctors and veterinarians will be able to quickly and confidently identify amatoxin poisoning rather than having to clinically eliminate other suspected gastrointestinal diseases first," she added. "We also hope that will give patients a better chance at recovery, even though there are no clearly effective, specific treatments right now."

The test also could be a practical and definitive way for mushroom foragers to identify and avoid eating mushrooms with amanitin toxin if a commercial partner can be found to produce and market a test kit. This test is the most sensitive and reliable field method available to chemically identify amanitin-containing mushrooms. Although mushroom experts can identify deadly mushrooms just by looking at their appearance, experts cannot see the toxin chemicals that lurk inside.

Still this test only identifies the presence or absence of this specific class of toxin; it does not detect other compounds such as hallucinogens or toxins that cause other gastrointestinal or neurological symptoms. So, it cannot determine if a mushroom is edible.

Mushroom hunting has gained in popularity in the last several decades. A single mushroom identification group on Facebook, among many, has more than 166,000 members. Foraging for mushrooms is popular throughout most of Europe, Australia, Japan, Korea, parts of the Middle East, and the Indian subcontinent, as well as in Canada and the United States. Distinguishing toxic from nontoxic mushroom species is based on first correctly identifying the mushroom and then referencing a mushroom field guide to determine if it is known to contain toxins or not. But mushrooms of the same species can vary in appearance, especially at different life stages and habitats, making them very difficult to identify.

Many poisonous mushrooms closely resemble edible wild mushrooms. For instance, the Springtime Amanita (Amanita velosa) is a highly desirable edible wild mushroom in the Pacific coastal United States. But to the untrained eye, it can appear similar to the Death cap mushroom A. phalloides. The Death Cap accounts for more than 90 percent of fungus-related poisoning deaths in Europe.

"This test can provide more information about a wild mushroom beyond physical appearance and characteristics, and detect something we cannot even see--the presence of amanitins," said Bever. If an affordable product like this was available, foraging could become even more popular and possibly safer.

The new test is an immuno-assay and depends on a very specifically reactive monoclonal antibody--a lab-produced protein that detects and binds only with a specific target. Scientists from the University of California-Davis, Pet Emergency and Specialty Center of Marin and Centers for Disease Control and Prevention also contributed to this project.