Culture

Filial piety - the traditional value of caring for one's elders - is foundational to the Chinese concept of family and greatly influences intergenerational relationships. When older Chinese adults' expectations of care exceed receipt, however, it can lead to increased mortality risks, according to a new Rutgers study.

The study, published in Aging and Mental Health, assessed the discrepancy between older Chinese Americans' expectations versus receipt of the six domains of filial piety - care, respect, greet, make happy, obey, and financial support.

"Strong intergenerational relationships play a protective role in the health and well-being of the aging population," said lead author Mengting Li, a researcher at Rutgers University's Institute for Health, Health Care Policy and Aging Research. "Family solidarity is especially vital to the Chinese American immigrant population, who tend to rely more heavily on their families due to traditional filial piety values. Filial expectation and receipt are the belief and practice of filial piety, and discrepancies between the two have significant consequences to older Chinese adults' psychological well-being and mortality. More must be done to preserve filial piety and reduce discrepancy among the younger Chinese American generations."

For the study, researchers interviewed 3,021 older Chinese American immigrants whose mean age was 73 and who had at least one child. They compared the mortality risks among the six domains of filial piety across three groups - no filial discrepancy, filial expectation above receipt, and filial expectation below receipt. They found that higher expectations over receipt of respect - listening to and consulting with aging parents - and greet - expressing gratitude to aging parents - was associated with higher mortality risks. When receipt of care exceeded expectations, participants experienced a lower risk of mortality. The remaining domains - make happy, obey, and financial support - had no significant relationship with mortality risk.

"Although further qualitative study is necessary to understand the filial discrepancy experience comprehensively and to explore the mechanism through which filial discrepancy affects the mortality risk of older immigrants, the study has important practical implications for social and health care services and policies focused on older Chinese American adults," said Li.

The study recommends that social service organizations adopt a culturally relevant approach to providing services to older Chinese American immigrants. Action should be taken to reduce mortality risk by reducing filial discrepancies and improving awareness about expectations versus receipt in the areas of respect and greet. Program planners and service providers should take steps to create educational programs and services which focused on fostering children's filial beliefs and behavior in intergenerational interactions. Particular attention should be paid to greeting, listening, and seeking advice from parents to improve the protection role of family for older adults.

JUPITER, Fla.--Aug. 16, 2019--A team at Scripps Research in Florida has discovered a biological system that manages cells' response to opioid drug exposure. The unexpected discovery offers new ideas for improving the safety of the one of the most effective, and most abused, group of pain medications.

In a paper published as a "First Release," in the journal Science, lead authors Kirill Martemyanov, PhD, and Brock Grill, PhD, describe how they designed and implemented a new, unbiased approach for decoding the genetic network that controls actions of opioids in a nervous system.

They used a small soil dwelling animal, the nematode worm, to discover something surprising about one of the most-studied drug receptors.

"A study like this makes it clear that even though we may think we know everything there is to know about the opioid response, we're actually just scratching the surface," Martemyanov says.

Their system relies upon the nematode c. elegans, engineered to express the mammalian surface receptor for painkilling drugs, the μ (mu) opioid receptor (MOR). The receptor is not normally found in the worms' DNA, and adding it made the transgenic animals respond to opioids like morphine and fentanyl. The researchers then exposed the worms to mutagens and selected the ones with abnormal responses to opioids. Whole-genome sequencing and CRISPR engineering was then used to pinpoint the genes responsible for those aberrant responses.

"Forward genetics--unbiased genetic discovery--has never been applied to probing an opioid receptor like this," Grill says. "The opioid epidemic is a huge problem and we don't have good solutions. This type of approach can bring a whole new array of targets and a new way of thinking about and going after an old problem."

The work ultimately led the researchers to the worms' FRPR-13 receptor, conserved in all animals, and known as GPR139 in mammals. It is considered an "orphan" G-protein coupled receptor (GPCR) with poorly understood biology and unknown role in physiology. Further studies in mice showed that GPR139 was expressed on the same neurons as MOR and counteracted the effects of opioids on neuronal firing.

When researchers administered drugs that activate GPR139, mice dependent on opioid intake stopped taking the drug. Conversely, genetic elimination of GPR139 augmented the pain-killing effects of opioids. The genetically modified mice lacking GPR139 also showed something remarkable--they showed very minimal withdrawal symptoms following chronic exposure to opioids. Withdrawal syndrome, a set of extremely unpleasant symptoms, usually sets in upon the discontinuation of opioids following their prolonged use. This compels people to resume drug-taking, fueling the dependence, Martemyanov says. The discovery could point a way toward lessening the suffering associated with opioid withdrawal, Grill says.

"A lot of addicts know that if they stop using, they are going to deal with anxiety, nausea, tremor and they are going to be in a lot of pain. That probably has a very negative impact on people wanting to go into rehab," Grill says.

Opioids, a group of drugs that include fentanyl, Vicodin, OxyContin and morphine, are highly effective at blunting severe pain, however prolonged use can create tolerance and dependence. Excessive use can cause overdose.

MINNEAPOLIS, MN- August 16, 2019 - Approximately 1 in 5 adults in the United States experience mental illness in a given year. Severe mental illnesses cause the brain to have trouble dealing with cognitively effortful states, like focusing attention over long periods of time, discriminating between two things that are difficult to tell apart, and responding quickly to information that is coming in fast.

A new study, published in the Journal of Neural Engineering, could improve patients' abilities to manage symptoms of mental illness.

Previous research demonstrated that applying electrical stimulation at just the right time helps the brain of a patient with a severe mental illness work through difficult cognitive tasks. However, it was done in a laboratory setting, free from the complexities of real-world activities of daily living.

Senior author Alik Widge, MD, Ph.D, Assistant Professor of Psychiatry at the University of Minnesota Medical School, and investigators at Massachusetts General Hospital (MGH), consisting of researchers from Brown University and MGH, including co-senior author David Borton, PhD, Assistant Professor of Engineering at Brown University, were the first to analyze patients' brain activity to detect precisely when a patient is focused and their attention is fully devoted, compared to when he or she is 'at rest'. They studied patients who were undergoing surgery for severe epilepsy, who already had measurement electrodes in the relevant brain areas.

The study, which was part of DARPA's SUBNETS program, found that specific signatures and algorithms can be used to tell when someone is focused and really trying to do a task that is hard for them, indicating that they could benefit from an electrical stimulation to get an extra push.

The study also demonstrates that there is no single region of the brain that can tell when someone is in this focused, effortful state. In order to detect when the patient started to focus on a cognitive task, the researchers had to analyze the information at the network level. It was essential to look at how the activity of one region coordinated with the activity of another.

"Using the same neural signals that could drive adaptive deep brain stimulation, we have shown that it is possible to detect mental states that might be amenable to closed-loop control," said lead author Nicole Provenza, MS, PhD candidate, Brown University. "While further research is necessary to generalize our findings to real-world applications, we hope that this work will ultimately contribute to the development of more effective brain stimulation therapies for mental illness."

"We want to take a patient-centered approach to treating mental illness," explained Widge. "The job of a stimulator is not to take away the symptoms; its job is to help the patient manage his or her symptoms. It gives the power back to the individual and just gives them a little extra help when they need it."

There is still more work to be done, but Widge is excited to take the next step and eventually make these ideas into real products that will help people.

Bottom Line: Rates of marijuana exposure cases in children and teens reported to a poison control center increased after Massachusetts legalized medical marijuana in 2012. From 2009 to 2016, there were 218 cannabis-related calls (a small portion of the calls to the poison center) about exposure in children and teens to age 19, with most of the calls coming from health care facilities. Teens ages 15 to 19 were involved in the highest number of cases followed by children to age 4. Exposures among teenagers were mostly classified as intentional whereas exposures among young children were unintentional. There were statistically significant increases in the number of exposures to edible products in both of these age groups. The rate for all cases involving cannabis for the four years before and the four years after medical marijuana legalization increased from 1.3 to 2.2 per 100,000. Limitations of the study include the small number of calls and self-reported marijuana exposures that may not have been verified by laboratory testing.

Authors: Jennifer M. Whitehill, Ph.D., University of Massachusetts Amherst, and coauthors

(doi:10.1001/jamanetworkopen.2019.9456)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Bottom Line: Parents and teens find it difficult to talk about sex and alcohol, and this study finds that doctors can help. This randomized clinical trial evaluated whether interventions targeted at parents in primary care pediatric settings might improve communications between parents and their teens about sexual health and alcohol use. The interventions were selected because in previous research outside of clinic settings they have been shown to encourage teens to wait until they're older to have sex, use protection if they do have sex, and reduce alcohol use. The study included 118 parent-adolescent pairs, with 38 pairs in a sexual health intervention, 40 pairs in an alcohol prevention intervention, and 40 pairs in a control group for comparison who received usual care. Parents in the interventions received coaching on key messages regarding sexual health and alcohol and were encouraged to engage in parent-adolescent communication about it within two weeks, at which time there was a follow-up call to parents from health coaches. Participants were surveyed four months later and study authors report an increased frequency of parent-teen communications about sexual health and alcohol use in the intervention groups compared to the control group. Results suggest that doctors have an opportunity to help parents and teens communicate about sex and alcohol in ways that will help young people make healthier choices about sexual behaviors and alcohol use. Limitations of the study include that it was conducted at a single site and parent-teen communications were self-reported.

Authors: Carol A. Ford, M.D., Children's Hospital of Philadelphia, and coauthors

(doi:10.1001/jamanetworkopen.2019.9535)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

After medical marijuana became legal in Massachusetts, cannabis-related poison control calls involving the commonwealth's children and teenagers doubled, according to a public health investigation led by University of Massachusetts Amherst injury prevention researcher Jennifer Whitehill.

The increase in calls to the Regional Center for Poison Control and Prevention at Boston Children's Hospital occurred despite legislative mandates for childproof packaging and warning labels, and before the recreational use of marijuana was legalized for adults.

"As states across the country enact more permissive marijuana policies, we need to do more to promote safe storage in households with children," says Whitehill, assistant professor of health promotion and policy and lead author of the research published in JAMA Network Open.

Whitehill and former UMass Amherst graduate student Calla Harrington analyzed data from the poison control center in collaboration with staff from the center, including medical director Dr. Michele Burns and clinical fellow Dr. Michael Chary. The research team reviewed the center's data from 2009 through 2016 -- four years before and four years after medical marijuana was legalized in Massachusetts.

During the study period, the poison control center received 218 calls from Massachusetts involving cannabis exposure in children and teens, from infancy to age 19, including 98 single-substance calls and 120 polysubstance calls. Those calls represented 0.15 percent of all poison control calls during that time period for that age group.

"While we're pleased to see that the incidence is relatively low, we feel these cases are preventable, and the issue needs to be on the radar of policymakers and parents, particularly now that dispensaries are open for adult-use sales," Whitehill says.

Some highlights of the findings:

The incidence of calls for single-substance cannabis exposure increased 140 percent during the study period -- from 0.4 per 100,000 population before medical marijuana was legalized to 1.1 per 100,000 population after legalization.

Nearly 80 percent of the calls to the poison control center came from healthcare facilities, and, in terms of medical outcomes, most of the exposures resulted in moderate and minor effects. Four cases with major effects and no deaths were reported.

A little more than a quarter of the cases were reported as unintentional, with 19.4 percent of calls involving children from infancy through age 4.

Calls involving edible cannabis products increased for most age groups, including ages 15-19. Because other research has found that the proportion of teens using marijuana is remaining about the same even as marijuana laws are loosening, this finding suggests that teenagers may be caught off guard by the potentially potent effects of edibles and concentrated extracts, Whitehill says.

The paper concludes, "This study suggests that states liberalizing marijuana policies should consider strengthening regulations to prevent unintentional exposure among young children and enhancing efforts to prevent use by teenagers, with particular attention to edible cannabis products and concentrated extracts."

Whitehill says the next step is to study the impact of marijuana's legalization for adult use, which went into effect in late 2016. Two years later, in November 2018, marijuana retail stores began opening.

"Given what we've seen here," Whitehill says, "I would expect the calls to the poison control center to increase even more."

Homes are the front lines of military suicide prevention as nearly two-thirds of suicides occur at home using a firearm--nearly always a personal firearm. Because suicide risk decreases if a firearm is safely stored locked and unloaded researchers, led by Craig Bryan of the National Center for Veterans Studies at the University of Utah, surveyed military personnel to learn more about the relationship between safe firearm storage and thoughts of suicide or self-harm. Their results are published today in JAMA Network Open.

Only a third of the personnel surveyed kept a firearm in or around their home, Bryan and colleagues found, and only a third of those kept it stored locked up and unloaded. People who had thoughts of suicide or self-harm, though, (about ten percent of the survey group) were less likely to keep a firearm at home--but those who did keep a firearm were less likely to store it safely.

"Around 70% of military suicides involve a firearm, so the topic is of great importance for those of us wanting to prevent military suicides." Bryan said. "Safe storage practices can reduce firearms suicides by up to half, just like seatbelts can reduce traffic fatalities. Storing guns in a safe or using other locking devices is a simple way for families to protect their loved ones from unexpected and unpredictable tragedy."

The survey is based on self-reported responses, the authors write, but the results suggest that emphasizing safe gun storage practices may aid the ongoing effort to stem military suicides.

A pair of University of Virginia School of Medicine scientists have revealed how E. coli seeks out the most oxygen-free crevices of your colon to cause the worst infection possible. The discovery could one day let doctors prevent the infection by allowing E. coli to pass harmlessly through the body.

The new discovery shows just how the foodborne pathogen knows where and when to begin colonizing the colon on its way to making you sick. By recognizing the low-oxygen environment of the large intestine, the dangerous bacterium gives itself the best odds of establishing a robust infection - one that is punishing for the host.

"Bacterial pathogens typically colonize a specific tissue in the host. Therefore, as part of their infection strategies, bacterial pathogens precisely time deployment of proteins and toxins to these specific colonization niches in the human host. This allows the pathogens to save energy and avoid detection by our immune systems and ultimately cause disease," said researcher Melissa Kendall, PhD, of UVA's Department of Microbiology, Immunology and Cancer Biology. "By knowing how bacterial pathogens sense where they are in the body, we may one day be able to prevent E. coli, as well as other pathogens, from knowing where it is inside a human host and allow it to pass through the body without causing an infection."

A Bacterial Goldilocks

E. coli naturally lives in our colons, and most strains do us no harm. But there are several strains that can cause cramps, diarrhea, vomiting, even kidney failure and death. Children are at particular risk. As such, E. coli outbreaks appear periodically in the news. In July, for example, people in several states were sickened by E. coli linked to ground bison meat.

Kendall and graduate student Elizabeth M. Melson have shed important light on how harmful E. coli infections establish themselves in the body. The researchers outlined a process the bacteria use to detect low oxygen levels in the large intestine and then produce proteins that allow E. coli to attach to host cells and establish infection.

Oxygen actually diffuses from the intestinal tissue into the gut, and there are comparably higher levels in the small intestine than the large. E. coli specifically waits until it has reached the-low oxygen large intestine before striking.

E. coli's vital asset is a small form of RNA that activates particular genes when oxygen levels are low enough, the researchers reveal. It's at this point that the infection really gets established. Thanks to this natural sensing process, the bacteria are able to establish infection and begin to manufacture harmful Shiga toxins.

The researchers believe that other bacterial pathogens, such as Shigella and Salmonella, likely employ a similar control mechanism, though more work needs to be done to establish that.

"If scientists can figure how to block oxygen sensing, we may be able to prevent E. coli from making proteins that allow it to stick to our guts," Kendall said. "This may be an effective strategy to limit infection, and because we are not targeting growth or survival, E. coli may not develop drug resistance - it just doesn't know where it is."

A microbiome is a community of microorganisms that inhabit an ecological niche. Microbiomes exist in both environmental biotopes, for example, a water body or forest soil - and in living multicellular host organisms - such as humans, animals or plants. A microbiome may be comprised of bacteria, archaea, and unicellular eukaryotes -protists and fungi.

For the last three years the scientists have been analysing the microbiomes of two ciliates: Paramecium and Stentor. The results of the study on Paramecium were published last winter. The new publication is the next step in the study of protistan microbiomes.

'The human and animal microbiome studies are at the cutting edge of biology, while only few studies investigated bacterial consortia associated with protists. Previously, the question whether protists host their own microbiomes -- that is, they harbour prokaryotic communities --had not been properly addressed. Therefore, the results of our study are setting a new direction for scientific research,' explained Alexey Potekhin, Professor at the Department of Microbiology of St Petersburg University.

The idea that ciliates might have their own microbiomes was not random. Microbiologists know that in sterile conditions these organisms die. Their viability depends strongly on the presence of bacteria in the environment. However, it was almost impossible to characterise their bacterial composition in detail, nor to separate the 'lodgers' of the ciliates from the inhabitants of their aquatic environment water source, -- there were no available methods. Metagenomic analysis, which had hardly ever been used for this purpose before, enabled to get closer to finding an answer.

'This approach enables to sequence complete set of certain genetic markers in the total DNA of a sample. Hence, all sequences are assigned to their hosts allowing to identify them. For bacteria and archaea, this is the 16S rRNA gene sequence. Metagenomics and high-throughput sequencing have expanded our understanding of the microbial diversity in natural environments tremendously over the last 10-15 years. In our study, we used metagenomic analysis to identify bacteria associated with the cells of two common freshwater ciliate genera - Stentor and Paramecium,' the scientist explains.

The researchers have discovered that the bacterial community of the environments -- be it a water of the stream or a laboratory culture medium --differs significantly from the microbial consortium associated with ciliates. The variety of microorganisms in natural reservoirs is always richer than in ciliates. However, the microbiologists were able to detect representatives of a few dozen of bacterial genera in Stentor cells. Each ciliate appeared to be an independent ecological microniche. 'Thus, ciliates indeed do have their own microbiome,' emphasises Alexey Potekhin.

The second important conclusion is that Stentor microbiome is different from Paramecium microbiome. In other words, different ciliates, even from the same water source, coexist with different bacteria. However, scientists have yet to determine the species-specific traits of ciliate microbiomes, their stability and specificity, which will require further study.

The last but not the least discovery is that the microbiomes of ciliates, especially of Stentor, comprise representatives of bacterial genera which include a number of species known as opportunists, commensals and even potential human pathogens, such as Mycobacterium, Streptococcus, and Neisseria. The research method does not allow identification of individual species (only the genus). Therefore, at present, it cannot be claimed that ciliates are natural carriers of pathogenic bacteria. 'In any case, it is evident that it is mainly bacteria adapted to form symbiotic associations with host organisms that cohabit with ciliates. Apparently, once outside the host, in a water body, these bacteria colonise protists, for lack of better alternatives. After all, protists are large eukaryotic cells, which are not so dissimilar to those of multicellular organisms. So, depending on the tactics of a particular bacterium, it can survive for some time either outside or inside the host cell. The associated bacteria, however, rarely thrive in association with protists to be able to propagate rapidly. Their numbers, as our analyses have shown, are always small, but they are comfortable enough to survive the challenging times. Thus, ciliates (and, most likely, other protists) may play the role of transient reservoirs for bacteria outside their preferred multicellular host,' concludes the scientist.

The largest and most comprehensive mental health survey of college students in the US reveals that students who identify as transgender, gender nonconforming, genderqueer, and nonbinary face enormous mental health disparities relative to their peers. In a first-of-its-kind study published on Friday, August 16, in the American Journal of Preventive Medicine, Boston University researchers and collaborators found that gender minority students, whose gender identity differs from the sex assigned them at birth, are between two and four times more likely to experience mental health problems than the rest of their peers.

"There has never been a more important time for colleges and universities to take action to protect and support trans, genderqueer, and nonbinary students on campus," says study lead author Sarah Ketchen Lipson, a Boston University School of Public Health assistant professor of health law, policy & management.

The research team--which also included Julia Raifman, BU School of Public Health assistant professor of health law, policy & management, Sari Reisner of Harvard Medical School and The Fenway Institute, and Sara Abelson of the University of Michigan School of Public Health--looked at rates of depression, anxiety, eating disorders, self-injury, and suicidality in a sample of over 1,200 gender minority students from 71 colleges and universities. About 78 percent of the gender minority students included in the study met the criteria for one or more mental health problems, with nearly 60 percent of gender minority students screening positive for clinically significant depression, compared to 28 percent of cisgender students, whose sex assigned at birth aligns with their current gender identity.

Those findings stemmed from analysis of two waves of data collected between fall 2015 and spring 2017 through the Healthy Minds Study, a national, annual survey about campus mental health that Lipson co-leads with University of Michigan colleague Daniel Eisenberg.

The Healthy Minds Study, which more than 300,000 US college students have voluntarily taken since its launch in 2007, uses clinically validated methods of screening for symptoms of depression, anxiety, eating disorders, and other mental health concerns. The survey includes space for participants to fill in their assigned gender at birth as well as their current gender identity, which allowed the researchers to filter their analysis and focus on the collective mental health of gender minority students. The Healthy Minds Study is part of the Healthy Minds Network, a larger effort dedicated to improving the mental well-being of young adults, based out of the University of Michigan and Boston University.

"Reports that more than 40 percent of transgender people have attempted suicide in their lifetimes suggested, to me, that there is a large and disproportionate burden of disease among [people in the gender minority] that public health research can contribute to addressing," says Raifman.

The Healthy Minds Study results reinforce the disparities facing gender minority students revealed by other research, which has shown that college dropout rates are higher among transgender students, and that they experience near-constant discrimination and harassment. Bathrooms and housing are some of the most stressful areas on college campuses for transgender students, with research showing that transgender college students are at significantly higher risk for suicide and attempted suicide when denied access to gender-appropriate bathrooms and housing on college campuses.

Along with a significantly higher prevalence of self-reported mental health issues among the gender minority community, the researchers also found that transgender men and genderqueer students are particularly vulnerable groups, a statistic that warrants further research, Lipson says.

"Mental health outcomes, as well as negative educational outcomes like dropping out, are preventable," says Lipson. "The most effective way to prevent them would be, from my perspective, through policy changes. Inclusive policies are necessary to advance equity. And that's what I really want these data to speak to."

Slowly, gender-neutral bathrooms and housing options are becoming the norm. The researchers hope that leaders in higher education will use these results as a springboard for much more urgent action, such as addressing gender minority needs in housing policies, creating or revising policies that allow students to change their name in campus records, improving mental health resources on campuses, and raising awareness of gender minority issues.

"As a cisgender woman working on this topic, I think a lot about allyship and how I can conduct and disseminate research to advance advocacy efforts. First and foremost, allies on campus need to listen to and make space for the voices of trans people," Lipson says. Peers, friends, and colleagues on college campuses should be "upstanders," speaking up to call out hateful rhetoric, discrimination, microaggressions, and transphobic policies, she adds.

The researchers plan to continue using data from the Healthy Minds Study with the eventual goal of recording longitudinal data that follows gender minority students throughout their college experience, examining mental health alongside individual, institutional, and societal factors. They say additional research is also needed to explore the intersectionality of gender identities with other identities, such as race or religious beliefs.

"We are in a time when transgender people are being denied equal rights--to jobs, to housing, to healthcare, and to participation in the military. These data suggest that new policies eliminating equal rights for transgender people are affecting a population that already experiences a disproportionate burden of disease," says Raifman, referring to recent actions initiated by the Trump administration, such as banning transgender individuals from serving in the military and rolling back Obama-era rules intended to protect transgender individuals from discrimination. "As next steps, it will be important to evaluate whether equal rights or the elimination of equal rights for transgender people affects mental health disparities," she says.

A new chip-based platform developed by researchers at UC Santa Cruz integrates nanopores and optofluidic technology with a feedback-control circuit to enable an unprecedented level of control over individual molecules and particles on a chip for high-throughput analysis.

In a paper published August 16 in Nature Communications, the researchers reported using the device to control the delivery of individual biomolecules--including ribosomes, DNA, and proteins--into a fluid-filled channel on the chip. They also showed that the device can be used to sort different types of molecules, enabling selective analysis of target molecules from a mixture.

The capabilities of the programmable nanopore-optofluidic device point the way toward a novel research tool for high-throughput single-molecule analysis on a chip, said Holger Schmidt, the Kapany Professor of Optoelectronics at UC Santa Cruz and corresponding author of the paper.

"We can bring a single molecule into a fluidic channel where it can then be analyzed using integrated optical waveguides or other techniques," Schmidt said. "The idea is to introduce a particle or molecule, hold it in the channel for analysis, then discard the particle, and easily and rapidly repeat the process to develop robust statistics of many single-molecule experiments."

The new device builds on previous work by Schmidt's lab and his collaborator Aaron Hawkins' group at Brigham Young University to develop optofluidic chip technology combining microfluidics (tiny channels for handling liquid samples on a chip) with integrated optics for optical analysis of single molecules. The addition of nanopores allows controlled delivery of molecules into the channel, as well as the opportunity to analyze the electrical signal produced as a molecule passes through the pore. This latest work was led by first author Mahmudur Rahman, a graduate student in Schmidt's lab at UC Santa Cruz.

Nanopore technology has been successfully used in DNA sequencing applications, and Schmidt and other researchers have been exploring new ways to exploit the information in the signals produced as molecules or particles translocate through a nanopore.

With the feedback control system (a microcontroller and solid-state relay) in the new device, real-time analysis of the current turns the nanopore into a "smart gate" that can be programmed by the user to deliver molecules into the channel in a predetermined manner. The gate can be closed as soon as a single molecule (or any number set by the user) has passed through, and opened again after a set time.

"The use of nanopores as 'smart gates' is a key step toward a single-molecule analysis system that is user-friendly and can work at high throughput," Schmidt said. "It allows user-programmable control over the number of molecules that are being delivered to a fluidic channel for further analysis or processing, selective gating of different types of single molecules, and the ability to deliver single molecules into a chip at record rates of many hundreds per minute."

Using bacterial (70S) ribosomes, the researchers demonstrated controlled delivery of more than 500 ribosomes per minute. Coauthor Harry Noller, the Sinsheimer Professor of Molecular Biology at UC Santa Cruz, has done pioneering research on the structure and function of ribosomes, the molecular machines that synthesize proteins in all living cells, and has been collaborating with Schmidt's group since 2006.

The researchers also used a mixture of DNA and ribosomes to show the device's capacity to selectively activate the gating function for a target molecule (in this case, DNA). This can enable, for example, fluorescence experiments on a controlled number of target molecules, while unlabeled particles are ignored and discarded. Selective gating could also be used for purification or sorting of different particles downstream from the nanopore, based on the signals as the particles pass through the nanopore, Schmidt said.

The programmable system allows flexibility for a wide range of potential applications, he said.

New research led by academics at the University of Bristol Veterinary and Medical Schools used the 'One Health' approach to study three bacterial species in the noses of young cattle and found the carriage of the bacteria was surprisingly different. The findings which combined ideas and methods from both animal and human health research could help prevent and control respiratory diseases.

Cattle, like humans, harbour a wide range of bacteria in their noses, microbes which are normally present and probably necessary for health like those that live in the gut. However, some species of these bacteria do cause serious illness at times, particularly when infection becomes established in the lower respiratory tract within the lungs.

In an open access paper published in Scientific Reports today [Friday 16 August], the researchers investigated the patterns of acquiring and clearing these microbes in healthy young cattle, which have not previously been studied in detail.

The research team took nasal swabs at intervals during the first year of life, to detect their presence and measure their abundance using a DNA-detection technique called quantitative polymerase chain reaction (qPCR) that targeted genes found in three bacterial species well-known for their ability to cause respiratory disease in cattle: Histophilus somni, Mannheimia haemolytica and Pasteurella multocida.

The researchers found the carriage patterns of the three bacteria differed remarkably. Pasteurella was found in most of the animals, large numbers of bacteria were usually present, and the bacteria stayed in the nose for weeks or months. Histophilus was present in up to half the animals, usually in smaller numbers and the periods it was present were shorter. Mannheimia was rarely found although the numbers detected, when present, varied widely.

These differences are of interest because the numbers of bacteria and their duration of carriage are likely to influence their spread among healthy cattle and the likelihood of causing severe respiratory disease.

Amy Thomas, lead author who carried out the research as part of her PhD studies in Clinical Veterinary Science, said: "These techniques and results offer a way forward in understanding why and how apparently healthy cattle harbouring these bacteria may go on to develop respiratory illness and should help in finding new ways to prevent it."

Professor Mark Eisler, co-author and Chair in Global Farm Animal Health at the Bristol Vet School, added: "These studies are particularly important because cattle are known to contribute to greenhouse gas emissions and improving how their diseases are controlled will help mitigate climate change. Also, reducing the use of antimicrobials that treat respiratory diseases in cattle should help reduce the increasing global threat of antimicrobial resistance in animals and humans."

The ability to observe how life works at a nanoscale level is a grand challenge of our time.

Standard optical microscopes can image cells and bacteria but not their nanoscale features which are blurred by a physical effect called diffraction.

Optical microscopes have evolved over the last two decades to overcome this diffraction limit; however, these so-called super-resolution techniques typically require expensive and elaborated instrumentation or imaging procedures.

Now, Australian researchers from the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) report in Nature Communications a simple way to bypass diffraction limitations using standard optical imaging tools.

Lead authors Dr Denitza Denkova, and Dr Martin Ploschner from the CNBP node at Macquarie University say, "Working closely with biologists has inspired us to look for a solution that can transform super-resolution from a complex and expensive imaging method into an everyday bio-imaging technique."

Dr Ploschner explains how the technique works: "We have identified a particular type of fluorescent markers, so-called upconversion nanoparticles, that can enter into a regime in which light emitted from the particles grows abruptly ¬- in a super-linear fashion - when increasing the excitation light intensity. Our key discovery is that if this effect is exploited under the right imaging conditions, any standard scanning optical microscope can spontaneously image with super-resolution."

"While we have chosen to demonstrate this upconversion super-linear excitation-emission (uSEE) on one of the most commonly used types of optical microscopes - a confocal microscope - practically any type of scanning microscope or microscope involving variations in the illumination intensity can benefit from this spontaneous improvement of the resolution."

Dr Denitza Denkova says the uSEE approach improves the resolution beyond the diffraction limit simply by reducing the illumination intensity.

"Our approach works in the opposite direction to all other existing super-resolution methods; the lower the laser power, the better the resolution and the lower the risk of photo-damage to the bio-samples," she says.

"Best of all, super-resolution can be achieved without setup modifications and image processing. Thus, this method has the potential to enter any biological lab, at practically no extra cost."

"The value of our work is in realising the technique, for the first time, in a 3D biological setting, using biologically convenient particles. We suggest a modification of the composition of the nanoparticles and the imaging conditions, which triggers the spontaneous super-resolution to occur under a practically relevant microscopy configuration. We also develop a theoretical framework which allows end-users to adjust the particle composition and the imaging conditions and achieve super-resolution in their own laboratory setting."

"Our work enables microscopists to look in a new way with their existing tools."

CNBP node leader at Macquarie University, Professor James Piper AM, who is also an author on the paper, says the concept has been around for a while, but its practical realisation was elusive due to the need to combine the distinct research fields of biology, material science, optical engineering and physics.

"CNBP offered an ideal meeting platform for scientists with diverse expertise to join forces and take the idea from the drawing board to a practical imaging tool," Professor Piper says.

Stone tools uncovered in Mongolia by an international team of archaeologists indicate that modern humans traveled across the Eurasian steppe about 45,000 years ago, according to a new University of California, Davis, study. The date is about 10,000 years earlier than archaeologists previously believed.

The site also points to a new location for where modern humans may have first encountered their mysterious cousins, the now extinct Denisovans, said Nicolas Zwyns, an associate professor of anthropology and lead author of the study.

Zwyns led excavations from 2011 to 2016 at the Tolbor-16 site along the Tolbor River in the Northern Hangai Mountains between Siberia and northern Mongolia.

The excavations yielded thousands of stone artifacts, with 826 stone artifacts associated with the oldest human occupation at the site. With long and regular blades, the tools resemble those found at other sites in Siberia and Northwest China -- indicating a large-scale dispersal of humans across the region, Zwyns said.

"These objects existed before, in Siberia, but not to such a degree of standardization," Zwyns said. "The most intriguing (aspect) is that they are produced in a complicated yet systematic way -- and that seems to be the signature of a human group that shares a common technical and cultural background."

That technology, known in the region as the Initial Upper Palaeolithic, led the researchers to rule out Neanderthals or Denisovans as the site's occupants. "Although we found no human remains at the site, the dates we obtained match the age of the earliest Homo sapiens found in Siberia," Zwyns said. "After carefully considering other options, we suggest that this change in technology illustrates movements of Homo sapiens in the region."

Their findings were published online in an article in

Scientific Reports.

The age of the site -- determined by luminescence dating on the sediment and radiocarbon dating of animal bones found near the tools -- is about 10,000 years earlier than the fossil of a human skullcap from Mongolia, and roughly 15,000 years after modern humans left Africa.

Evidence of soil development (grass and other organic matter) associated with the stone tools suggests that the climate for a period became warmer and wetter, making the normally cold and dry region more hospitable to grazing animals and humans.

Preliminary analysis identifies bone fragments at the site as large (wild cattle or bison) and medium size bovids (wild sheep, goat) and horses, which frequented the open steppe, forests and tundra during the Pleistocene -- another sign of human occupation at the site.

The dates for the stone tools also match the age estimates obtained from genetic data for the earliest encounter between Homo sapiens and the Denisovans.

"Although we don't know yet where the meeting happened, it seems that the Denisovans passed along genes that will later help Homo sapiens settling down in high altitude and to survive hypoxia on the Tibetan Plateau," Zwyns said. "From this point of view, the site of Tolbor-16 is an important archaeological link connecting Siberia with Northwest China on a route where Homo sapiens had multiple possibilities to meet local populations such as the Denisovans."

Enteroviruses are one of the most common human pathogens leading to high number of acute and chronic infections worldwide. The physiological events leading to successful enterovirus infection are still poorly understood. Researchers at the Nanoscience Center at the University of Jyväskylä and at the University of Helsinki have found significant new information concerning the role of Albumin and ions in host cell vesicles that promote genome release and efficient infection. The results may yield targets for therapeutic development. The research was published in the Journal of Virology in August.

Especially the molecular factors that help enteroviruses to open up and release its genome in human cells are not well understood.

Using real-time uncoating measurements and high-resolution structures, a research team comprised of docent Varpu Marjomäki´s group (Nanoscience Center at the University of Jyväskylä) and professor Sarah Butcher´s group (University of Helsinki) found that the common molecule in serum and interstitial fluids, albumin, and an ion composition that is typically developed in cellular vesicles, trigger expansion of the virion.

This expanded and fenestrated virus then allows more small molecules such as ions to enter the virus. The results of this study suggest that before entering cells, albumin primes the virus to form a metastable yet infectious intermediate particle. Then, ionic changes that are likely to occur in cellular vesicles further contribute to opening and promote release of the genome.

"The successful release of the genome is one of the rate-limiting steps in virus infection. It needs to occur in the right place in the right time to ensure efficient infection. This work provides new insight into understanding this fundamental aspect of enterovirus life cycle and may yield targets for therapeutic development", says docent Varpu Marjomäki from the Nanoscience Center at the University of jyväskylä.