Tech

Leading cancer experts at the University of Birmingham have solved a long-standing question of how various types of mutations in just one gene cause different types of diseases.

A team of scientists at the University's Institute of Cancer and Genomic Sciences, led by Professor Constanze Bonifer, studied a gene known as RUNX1, which is responsible for providing instructions for the development of all blood cells and is frequently mutated in blood cancers.

The results of their research has shown that the balance of cells types in the blood is affected much earlier than previously thought, which is particularly important for families that carry the mutant gene.

The research, published in Life Science Alliance, opens up the possibility of identifying early changes in cells of patients carrying the mutation even before any disease manifests itself - increasing their chances of survival.

The study, the culmination of four years of research, showed that whilst some types of RUNX1 mutations directly changed how other genes behaved in blood cells, not all did. In particular, the mutations that are inherited through families do not immediately affect the cells but instead change the roadmap they follow to become other cell types, such as platelets and white blood cells.

Lead author Professor Constanze Bonifer said: "The most important results we found came from studying mutations that run in families which predisposes their members to diseases such as Familial Platelet Disorder (FPD) and Acute Myeloid Leukaemia (AML).

"AML is an aggressive cancer of the white blood cells, whereas in FPD, the ability to produce blood clots which is required to stop bleeding is impaired. Prior to this study, it was completely unclear why changes in just one gene cause so many different diseases."

Co-corresponding author Dr Sophie Kellaway said: "We used a cell culture system capable of generating blood cells in vitro, then induced the mutant forms of RUNX1 in these cells and immediately examined the effect on cellular behaviour and gene activity.

"We found that every RUNX1 mutation changed cells in a different way and had a different impact on how genes responded.

"What we have been able to demonstrate is that different genetic alterations in RUNX1 can send cells towards alternate paths of malignancy."

This work was funded by grants from the Kay Kendall Leukaemia Fund, the Biotechnology and Biological Sciences Research Council, and Blood Cancer UK.

Rachel Kahn, Research Communications Manager at Blood Cancer UK said: "This detailed research shows that it's not only a mutation that's important in deciphering whether or not someone will develop a disease, but it's precisely where the mutation occurs that can alter how blood cells develop and lead to disease.

"Many blood cancers are difficult to treat and have a poor prognosis. This is particularly the case for AML, which was studied in this research. Understanding more about what specific changes lead to the disease will help us to tailor treatments in the future, giving everyone the best possible chance of survival."

The research results demonstrate that different classes of mutant RUNX1 proteins use unique multifactorial mechanisms to cause disease and so development of novel treatments will require an individual approach.

The team now plans to work with clinicians and families carrying mutant RUNX1 proteins, to examine patient blood cells to see whether their findings in cultured cells can also be seen in patient blood cells, in particular, before they develop any symptoms. They will then examine whether they can find ways to restore normal blood cell development.

Adaptability explains why insects spread so widely and why they are the most abundant animal group on earth. Insects exhibit resilient and flexible locomotion, even with drastic changes in their body structure such as losing a limb.

A research group now understands more about adaptive locomotion in insects and the mechanisms underpinning it. This knowledge not only reveals intriguing information about the biology of the insects, but it can also help to design more robust and resilient multi-legged robots that are able to adapt to similar physical damage.

The insect nervous system is comprised of approximately 105 to 106 neurons. Understanding the process behind this requires researchers to consider the role of the intrinsic neural circuits that influence the adaptions of insects under unfavorable circumstances and the sensory feedback mechanisms reflected in their body characteristics and physical interactions with the environment.

A research group comprising associate professor Dai Owaki from Tohoku University's Department of Robotics at the Graduate School of Engineering and associate professor Hitoshi Aonuma from the research institute of electronic science at Hokkaido University simultaneously recorded the leg movements and muscle activation of crickets, both before and after middle leg amputation.

Their findings showed that the walking manner of crickets shifted from a tetrapod/tripod gait to a four-legged trot after the middle leg had been removed.

Electromyogram (EMG) analysis of the muscles at the base of the middle leg revealed that the muscles were active in opposite phases when walking. Activation timing of the middle leg muscles synchronized in phase when both legs had been removed, whereas the activation timing showed anti-phase synchronization for crickets with all of their legs.

The findings demonstrated two things. First, an intrinsic contralateral connection exists within the mesothoracic ganglion, which generates in-phase synchronization of muscle activation. Second, mechanoreceptive informational feedback from the campaniform seensilla of the legs overrides the centrally generated patterns, resulting in the anti-phase leg movements of a normal gait.

"Our results will pave the way for the further understand of the leg coordination mechanism in insect locomotion," said professor Dai Owaki. "It may also aid design principles for a decentralized controller that enables flexible and adaptive walking in an insect-like-six-legged robot."

Both past and present-day scientists have suspected the intestines of playing a role in various diseases. Present-day studies focus on the intestinal flora's role in physical diseases such as diabetes and overweight, while others seek to establish a connection between the intestinal flora and e.g. autism, schizophrenia and depression. But even modern-day scientists have difficulties studying the around 500-1000 different species among the approx. 100 billion active bacteria in our intestines.

Therefore, researchers from the University of Copenhagen have developed a ground-breaking technique that can help us unravel some of the mysteries of the human intestinal bacteria. Aside from working together with the immune system in a vital cooperation, imbalance in the intestinal bacteria composition is the cause of chronic disease of the alimentary tract of which 50.000 Danes suffer.

'In recent years we have discovered that bacteria have a great impact on the body. A lot of research is being done within this field, but we still have not identified all the bacteria found in and on the human body. Knowledge of the bacteria is vital if we are to understand what is going on. That is where our technique can make a difference', says Associate Professor Simon Rasmussen, who together with his team of researchers at the Novo Nordisk Foundation Center for Protein Research is responsible for the new study, the results of which have just been published in Nature Biotechnology.

'The presence of bacteria is vital to the immune system, and this is true not least of intestinal bacteria. But the problem is that it is very difficult to study intestinal bacteria in their natural environment, which they often deeply depend on in order to survive. Now, we have developed a method that uses artificial intelligence to help us identify the bacteria found in and on the human body. This will give us an idea of how they work together and what happens when we fall ill', he explains.

Faeces are key to understanding

Instead of studying the bacteria inside the intestines, the researchers have analysed the intestines' ultimate by-product: faeces.

Faeces contain remains of the bacteria that have helped metabolise the food in the stomach and intestines and thus offer unique insight into an otherwise inaccessible environment. So far technology has only allowed researchers to read fragments of the bacteria's' DNA - which is equivalent to doing a puzzle with only a fraction of the pieces.

Therefore, Simon Rasmussen and his team of researchers have developed an algorithm that uses artificial intelligence to complete the DNA strings of bacteria in faeces. And now researchers from all over the world can help finish the puzzle.

'One gram of faeces contains around a billion bacteria of 500-1000 different kinds. If we are able to reconstruct their DNA, it will give us an idea of the types of bacteria we are dealing with, what they are capable of and what they actually do. It is not the complete picture, but it is a huge step forward. And our algorithm is available to other researcher and free to use', he says.

Identifies patterns in different types of data

But the method is not limited to intestinal bacteria, Simon Rasmussen explains. The ability of artificial intelligence to analyse the bacterial content of very small samples may also be used to study other substances than faeces.

For example, if you want to know how polluted soil has affected the microorganisms, you could use the new method to analyse a soil sample from the area in question. The same applies to lakes and watercourses located close to a factory or similar. Or, as Simon Rasmussen points out, if there are bacteria present, they can be now be identified.

'But the algorithm can not only be used to study bacteria. You could also use it to analyse health data, for example. Say that you are working on increasing our knowledge of specific diseases. To help us do so we can collect an amount of information about the patient group, such as knowledge of their genetics, protein composition, substances in the blood and data from electronic records. Our artificial intelligence can then analyse these very different sets of data and identify patterns and connections. It holds great potential', Simon Rasmussen explains.

Aside from the article on the algorithm, the team has several other studies in the pipeline demonstrating the use of their technology.

TAMPA, Fla. -- The hallmarks of cancer include rapid cell reproduction and metabolic activity. But these processes also lead to increased cellular stress and oxidation, and the risk of cell death. To circumvent these negative consequences of supercharged growth, cancer cells stimulate pathways to reduce oxidative stress and avoid cell death. In an article published in Cell Metabolism, Moffitt Cancer Center researchers report on a newly discovered biochemical pathway that protects cells from a type of cell death called ferroptosis.

Ferroptosis is a specialized type of cell death that is caused by imbalances in oxidation within cells. Ferroptosis results in changes to molecules in the cell membrane called lipids and can be caused by cysteine starvation. Cysteine is a type of amino acid that is one of the building blocks of proteins and is also used by the body for numerous important physiological processes, including cell survival, regulation of oxidative-reduction reactions and energy transfer. Because of its critical role in normal processes, cysteine is highly regulated to prevent excess or insufficient amounts of the amino acid.

Several different types of cancer overexpress molecules that play an important role in cysteine regulation. This suggests that reducing cysteine levels may negatively affect cancer growth. In fact, studies have shown that cancer cells can be induced to undergo cell death by either inhibiting cysteine uptake or starving cells of cysteine. However, the downstream processes that are stimulated by cysteine starvation are unclear. Moffitt researchers performed a series of laboratory investigations to learn what molecules become activated after cysteine deprivation and how this impacts cells.

The researchers discovered that cancer cells can activate signaling pathways to protect themselves against cell death due to cysteine starvation. When the team starved non-small cell lung carcinoma cells of cysteine, the cells began to undergo ferroptosis. However, cysteine starvation also resulted in an unexpected accumulation of small molecules called γ-glutamyl-peptides, which protected the cells against ferroptosis. The researchers found that the peptides were synthesized through the activity of the protein GCLC. Under normal conditions, GCLC is involved in the first step of the synthesis of the antioxidant glutathione from the amino acids cysteine and glutamate. However, this newly discovered activity of GCLC occurred in the absence of cysteine and was important to limit both glutamate accumulation and oxidant production.

The researchers further analyzed signaling mechanisms controlling GCLC-mediated peptide synthesis and discovered that GCLC was regulated by the protein NRF2. They found that under normal conditions, NRF2 regulated GCLC to produce glutathione, but under cysteine-starved conditions, NRF2 regulated GGLC to produce γ-glutamyl-peptides.

"NRF2 is known to play an important role in the protection against cellular oxidation and is often deregulated in lung cancer," said lead author Gina DeNicola, Ph.D., assistant member of the Cancer Physiology Department at Moffitt. "The ability of NRF2 to protect against ferroptosis has important implications for cancer, particularly lung cancers that commonly have NRF2 activation via mutations in KEAP1 and NRF2."

Many animal and insect species use Batesian mimicry - mimicking a poisonous species - as a defense against predators. The common palmfly, Elymnias hypermnestra (a species of satyrine butterfly), which is found throughout wide areas of tropical and subtropical Asia, adds a twist to this evolutionary strategy: the females evolved two distinct forms, either orange or dark brown, imitating two separate poisonous model species, Danaus or Euploea. The males are uniformly brown. A population group is either entirely brown (both males and females) or mixed (brown males and orange females).

City College of New York entomologist David Lohman and his collaborators studied the genome of 45 samples representing 18 subspecies across Asia to determine their evolutionary history and to establish what genes were responsible for the color variation in females. They found that neither the orange nor brown females had a common recent ancestor.

"The conventional wisdom is that once something evolves and you lose it, it's hard to re-evolve it," said Lohman. "That suggests something is acting like a switch, switching the gene on or off."

The researchers found two DNA nucleotides on the Elymnias hypermnestra genome that regulate WntA, a gene associated with color patterning in butterfly species.

The WntA gene can be switched on to recreate the phenotypic shift, even where it hasn't appeared for several generations. Reaching back into genetic history allows a species to create a variant without having to re-evolve the intermediate biochemical pathways.

"Evolution of a phenotype can be more plastic than we thought," said Shen-Horn Yen, one of Lohman's collaborators from the Department of Biological Sciences, National Sun Yat-Sen University, Taiwan.

The study appears in the journal Proceedings of the Royal Society B.

To Lohman, studying Elymnias hypermnestra encapsulates the study of biodiversity in its entirety. There's a universe of variety in color, form and size and genetic variability all found in a single genus of butterfly.

Decades after the industrialized world largely eliminated lead poisoning in children, the potent neurotoxin still lurks in one in three children globally. A new study in Bangladesh by researchers at Stanford University and other institutions finds that a relatively affordable remediation process can almost entirely remove lead left behind by unregulated battery recycling - an industry responsible for much of the lead soil contamination in poor and middle-income countries - and raises troubling questions about how to effectively eliminate the poison from children's bodies.

"Once the lead is in the environment, it stays there pretty much indefinitely without remediation," said study lead author Jenna Forsyth, a postdoctoral research fellow at the Stanford Woods Institute for the Environment. "Ultimately, we want to work toward a world in which battery recycling is done safely, and lead never makes it into the soil or people's bodies in the first place."

Among toxins, lead is a supervillain. There is no safe level of exposure to lead, which damages nearly every system in the body. Early childhood exposure leads to irreversible brain damage and permanently lowered IQ, among other severe symptoms. Worldwide, one in three children suffers from lead poisoning, according to a recent report by Unicef and international NGO Pure Earth that describes the problem as "a much greater threat to the health of children than previously understood." The annual cost of resulting lost productivity is estimated to be nearly $1 trillion dollars globally and $16 billion in Bangladesh alone.

A dangerous industry's legacy

Lead acid batteries, such as those used in many cars and backup power storage systems, account for at least 80% of global lead use. In poor and middle-income countries, informal or "backyard" recycling of leaded batteries often uses highly polluting techniques, such as open-pit smelting, that put approximately 16 million people at risk of lead poisoning. An earlier assessment in Bangladesh found nearly 300 such recycling sites with elevated soil lead concentrations and estimated that nearly 700,000 people across the country are living within the contaminated sites.

To better understand informal battery recycling's impact on children, study partners from the International Centre for Diarrheal Disease Research, Bangladesh, observed daily activities of people living adjacent to an abandoned battery recycling operation in rural Bangladesh and surveyed childcare givers. They noted, for instance, that women and children were regular visitors to the abandoned battery recycling site, spending hours a day there. The residents explored the area, scavenged battery scraps to use as household materials or toys, and even collected soil colored white by smelting ash to add visual appeal to their home exteriors, yards and earthen stoves. Children often played in the dirt, while women collected firewood and building materials or hung laundry out for drying in the area.

The researchers also tested children's blood before and after a multi-phased intervention that involved removing and burying contaminated soil, cleaning area households and educating residents about the dangers of soil lead exposure. Study partners from Dhaka University's Department of Geology and Pure Earth conducted the remediation work.

Challenges and solutions

Blood tests conducted prior to the remediation work showed many children had lead in their blood at levels up to 10 times higher than what the Centers for Disease Control and Prevention considers elevated. And while the remediation effort led to a 96% reduction in lead soil concentrations over 14 months, the researchers were surprised to find child blood lead levels decreased only 35% on average during the same period.

The discrepancy may lie in the children's chronic soil lead exposure over a long enough time that lead stored in their bones continued to leach into their blood more than a year after the soil had been cleaned. A likely contributing reason, according to the researchers: other sources of lead exposure, such as turmeric adulterated with lead chromate and lead soldered cans used for food storage.

Additionally, the research team's housecleaning efforts were unable to remove and wash mattresses and upholstered furniture, which could have continued to harbor lead-contaminated dust. Other potential ongoing sources of contamination could have been home foundations or earthen stoves that local women amended with soil from the site.

"We are gratified that focused efforts to clean up the environment can help," said study co-author Stephen Luby, a professor of infectious diseases at Stanford's School of Medicine. "But with the huge burden of lead toxicity on children globally, more radical efforts to remove lead from the economy are needed."

Since 2014, Forsyth, Luby and other Stanford researchers have worked in rural Bangladesh to assess lead exposure. With funding from the Stanford Woods Institute for the Environment's Environmental Venture Projects program, they first conducted a population assessment that found more than 30% of pregnant women had elevated blood lead levels.

Although the total cost of supplies and labor to implement the intervention - $40,300 - was relatively cheap by developed world standards, it's likely unfeasible in many regions of the developing world. The researchers suggest several ways to lower costs for such interventions, such as prioritizing house cleaning for children with the highest blood lead levels, but they emphasize the greater imperative to shift incentives away from informal battery recycling altogether.

Forsyth and Luby, together with researchers at Stanford's School of Earth, Energy & Environmental Sciences, Graduate School of Business, d.school and International Policy Studies Program; are part of an initiative aimed at eliminating lead from the value chain or otherwise find ways to ensure it does not contaminate the environment. The effort, funded by the Stanford King Center on Global Development, focuses on reducing lead exposure from batteries and turmeric in Bangladesh.

Superconductivity already has a variety of practical applications, such as medical imaging and levitating transportation like the ever-popular maglev systems. However, to ensure that the benefits of applied superconductors keep spreading further into other technological fields, we need to find ways of not only improving their performance, but also making them more accessible and simpler to fabricate.

In this regard, magnesium diboride (MgB2) has attracted the attention of researchers since its discovery as a superconductor with multiple advantages. It is a lightweight, easily processible material made from widely abundant precursors; these qualities combined, greatly lower the overall cost of working with MgB2.

However, a key practical property of a superconductor is its critical current density (Jc)--the maximum current density at which it can operate without dissipating energy like conventional conductors do. Increasing the Jc of MgB2 through affordable means has proven to be a notable challenge, which is usually tackled through materials engineering and by optimizing fabrication procedures and conditions.

In a recent study accepted for publication in Materials Science and Engineering: B, a team of scientists from Shibaura Institute of Technology, Japan, has developed a cost-effective technique to boost the Jc of bulk MgB2: ultrasonication. Their approach involves dissolving cheap commercial boron in hexane and using ultrasound to disperse the solute thoroughly. Once hexane is evaporated and removed, one obtains a very fine boron powder, which is then sintered with magnesium to produce MgB2. But why does using finer boron result in better superconducting properties?

The answer is magnetic flux pinning. Though superconductors generally repel external magnetic fields, some quantized amounts of magnetic flux sometimes penetrate the material under the right conditions, producing the strong force responsible for superconducting levitation. This penetration occurs only in pinning centers, which arise from various kinds of defects in the material; in the case of MgB2, the pinning centers are located at the grain boundaries. Professor Muralidhar Miryala, who led the study, explains: "To put it briefly, the refined boron powder obtained via ultrasonication results in a higher density of grain boundaries by reducing overall grain size. In turn, the increment in grain boundaries equals an increase in flux pinning centers, which are responsible for the higher Jc we observed in our samples."

The scientists' synthesis procedure produced high-quality bulk MgB2 mostly free of oxidation impurities. Compared with a non-ultrasonicated sample used as a reference, the Jc values increased by as much as 20%, depending on the ultrasonication time used. Moreover, the results of scanning electron microscopy and energy dispersive X-ray spectroscopy analyses revealed a secondary mechanism that could give rise to enhanced Jc. The team noted a layered structure of what seems to be Mg-B-O coating the walls of pores of boron deficiencies. This layered coating structure can not only act as a pinning center itself, but also have a restraining effect on the grain size.

Excited about the overall results, Miryala remarks: "Our study lays a foundation towards realizing affordable high-performance bulk MgB2 for superconducting magnets. This will help reduce the cost of magnet-based technologies and make them more accessible to the general population, especially in the medical field." Even though further studies will be needed to find the optimal solvent and ultrasonication parameters, the present findings are certainly promising and could promote the use of MgB2 superconducting magnets in other areas, including space applications, water cleaning, and electric motors. Hopefully, and given enough time, we shall all benefit from accessible superconductors in one way or another!

MEDFORD/SOMERVILLE, Mass. (Jan. 14, 2021)-- Exposure to discrimination plays a significant role in the risk of developing anxiety and related disorders, even - in a first - after accounting for potential genetic risks, according to a multidisciplinary team of health researchers led by Tufts University and the Harvard T.H. Chan School of Public Health.

Researchers determined that even after controlling for genetic risk for anxiety, depression, and neuroticism, greater reports of discrimination experiences remained associated with higher scores of anxiety and related disorders. The findings, recently published in Proceedings of the National Academy of Sciences, suggest that discrimination is a risk factor for anxiety and related disorders rather than solely a result of common genetic liability.

The study authors included researchers from Stony Brook University, University of Minnesota, in addition to Harvard's School of Public Health and Tufts.

"The study results demonstrate that discriminatory experiences can potentially cause stress and mental health problems regardless of the genetic constitution of the individual," said Adolfo G. Cuevas, an assistant professor of community health and director of the Psychosocial Determinants of Health Lab at Tufts' School of Arts and Sciences, who is first author of the study. "From regular slights in public spaces to more significant incidents, such as being passed over for a promotion or a loan, these experiences can take a toll on your mental health."

Anxiety disorders, including generalized anxiety disorder, panic disorder or phobias, are the most common mental illness, affecting over 40 million people in the United States every year, according to the Anxiety and Depression Association of America. While exposure to discrimination has long been established as a risk factor in the development of these disorders, the relationship between discrimination and anxiety, when factoring in the role genetics play, has remained less clear.

To gain insight on the connection, the research team used data from a national probability sample of approximately 1,500 non-institutionalized, all English-speaking adults aged 25-74 and living in the mainland United States. Approximately 49 percent of the sample were women.

Three self-report scales were used to measure discrimination and other forms of social exclusion, including:

everyday discrimination, e.g. "being treated with less courtesy than other people" and "receiving poorer service than other people at restaurants or stores;"

major discrimination, e.g. "discouraged by a teacher or advisor from seeking higher education" and "being prevented from renting or buying a home in the neighborhood you wanted;" and

chronic job discrimination, e.g. "being unfairly given the jobs that no one else wanted to do" and "whether your supervisor or boss use ethnic, racial, or sexual slurs or jokes."

After accounting for increased genetic liability for anxiety, depression, neuroticism, and other potential genetic and sociodemographic factors, the researchers found a high degree of interdependence between discrimination and anxiety.

The team said the findings demonstrate that alleviating the impact of discrimination has the potential to improve mental health within the overall population. "Anxiety is one of the most significant issues in mental health today, and our study conclusions underscore the importance of reducing discrimination exposure and thereby improving the public's mental health overall," said the senior author of the study, Robert F. Krueger, Distinguished McKnight University Professor of Psychology at the University of Minnesota.

"These findings allow us to engage in conversations with political leaders, health officials, and community members to develop functional approaches to reduce exposure to discrimination and improve the mental health of all," David R. Williams, a study co-author and the Florence Sprague Norman and Laura Smart Norman Professor of Public Health at the Harvard T.H. Chan School of Public Health. Williams is also a professor in the department of African and African American Studies at Harvard.

The impact of anxiety disorders is significant. Symptoms are a common associated feature of depressive disorders and, generally, account for a substantial burden of morbidity and mortality as well as long-term work disability and absenteeism. For instance, anxiety disorders are associated with several chronic health conditions, including heart disease, hypertension, and diabetes.

The researchers identified key limitations of the study, including the use of a cohort of white-identifying respondents who were predominately of European ancestry. They noted while the effects of discrimination seem to be similar across racial/ethnic groups, racial/ethnic minorities experience more discrimination than their white counterparts, placing them at an increased risk for poor mental health. In addition, questions remain about the extent to which self-reported experiences of discrimination by whites are equivalent to those of more socially stigmatized groups.

The human body is like a construction site where hundreds of thousands of different molecular nanomachines, called proteins, are simultaneously at work. Each one of these biomolecules, which are chains of amino acids essential to living organisms, perform a different biological function, often in synergy with other proteins. During their formation (the folding process) or in the performance of their biological functions, proteins change their shape in a very specific way. In many cases it is possible to conduct experiments that provide images of proteins at near atomic resolution, but only when they are in the stable and biologically active form. The dynamic processes associated with changes in shape are still largely unknown. Understanding these mechanisms and predicting the behavior of proteins is a fundamental step, for example, to develop advanced medical treatments for old and new diseases, from the most studied (like cancer and degenerative diseases) to emerging ones (Covid-19), to rare diseases.

Great strides have been made in recent decades in the study of processes involving structural changes in proteins, using computer simulations. Now, quantum computers are a powerful tool for carrying out even more precise and complete observations, as demonstrated by the study conducted by a group of physicists of the University of Trento that appeared in Physical Review Letters, one of the most prestigious physics journals that has been published by the American Physical Society since 1958.

"For the first time, we demonstrate that quantum computers can be used to understand at near atomic detail the functioning of biomolecules", explains Pietro Faccioli, author of the scientific article together with colleague Philipp Hauke and student Giovanni Mattiotti. Using this technology, the researchers of the Physics Department of the University of Trento have developed a method to compute changes in protein shape and trajectory. A breakthrough that has implications for molecular biology, pharmacology and nanotechnologies.

The fields of application are many. Identifying the mechanisms behind neurodegenerative processes in some proteins, for example, can help limit their proliferation. Understanding how a protein takes on a certain shape can open the way to use the nanomachines that nature has designed to cut, edit or block damaged or defective genes.

"We reformulated the mathematical problem underlying the predictions of structure changes as an optimization problem", underlines Pietro Faccioli. "Quantum computers are particularly suitable for solving optimization problems because they exploit a fascinating phenomenon known as quantum delocalization, which is only found in the microscopic world," adds Philipp Hauke.

Researchers at the UC Davis Violence Prevention Research Program (VPRP) assessed the prevalence of exposure to violence, such as robbery or assault, and its impacts on the mental health and social functioning of California adults. Their study, published in the Journal of Interpersonal Violence, shows the far-reaching psychological effects an incident of gun violence can have on victims and those close to them.

The study's findings are based on data from 2,558 adults who responded to the 2018 California Safety and Wellbeing Survey (CSaWS). CSaWS is an ongoing survey research project on firearm ownership and the consequences of exposure to violence in California. Responses were weighted to be statistically representative of the state's adult population.

These findings come as many localities across the country, including in California, have experienced a historic increase in firearm acquisition and gun-related deaths and injuries over the past year.

"Our study highlights the pervasive socioemotional impacts of violence exposure," said Amanda Aubel, first author on the study and a research data analyst at VPRP. "It points to the urgent need to address not only the physical but also the psychological consequences of violence exposure and the unique, exacerbating influence of firearms."

Prevalence and impact of exposure to violence

According to the study, around 4% of respondents--an estimated 1.2 million California adults--said they or a household member had experienced violence while living in their current neighborhood. Half of these respondents stated that the most recent incident of violence had happened to them directly. Violent events included robbery, physical assault and rape or sexual assault.

The study also found that half of the people exposed to violence reported that the event was "severely" distressing. For 47% of exposed respondents, the event led them to experience significant problems with family members or friends, with their job or schoolwork, or both. For comparison, only 12% of unexposed adults reported having such social functioning problems in the past 12 months.

Weapon involvement in violent events

More than one-third of exposed respondents indicated that a weapon or something that could be used as a weapon was present during the violent event. In 40% of these cases, the weapon was a firearm.

The study explored whether firearm involvement was associated with socioemotional consequences.

"Violence involving firearms may be particularly detrimental for mental health and social functioning," Aubel said. "The mere presence of a firearm during an act of violence can increase the perceived level of threat to one's life."

While the presence of a weapon was not associated with distress levels, when a weapon was present, events considered severely distressing were significantly more likely to involve firearms and less likely to involve other types of weapons. This is consistent with prior studies that have found violence involving firearms has unique negative effects on mental health compared to violence involving other or no weapons.

Exposure to violence and gun ownership

The study is one of few to examine exposure to violence among gun owners and gun purchasing intentions following such exposure.

Compared to unexposed individuals, respondents with exposure to violence were significantly more likely to live in households with guns but not to own guns themselves. The authors note that this finding warrants further investigation, given substantial evidence that household firearm ownership is associated with an elevated risk of firearm death and injury for everyone living in the home.

One-third of exposed respondents said the violent event led them to consider buying a gun. Of that group, only 1% reported personally owning guns at the time of the survey. For comparison, 17% of unexposed respondents considered buying a gun in the past 12 months; 35% were gun owners already.

These findings suggest that experiencing violence may motivate people to buy a firearm who would not have considered doing so otherwise. Yet, these new gun owners could be increasing their risk of harm by bringing a firearm into their home.

"State-level data such as these may be important for designing effective violence prevention programs and policies," said Nicole Kravitz-Wirtz, assistant professor with VPRP and senior author on the study. "Interventions must include trauma-informed services and sustained financial investments in the communities most highly impacted by firearm violence."

New York, NY (January 14, 2020) -- Girls who are emotionally neglected or severely sexually abused early in their lives report riskier sexual behaviors during adolescence, Mount Sinai researchers report. The findings highlight the need--and suggest the potential for tailored approaches--to promote healthy sexual development in vulnerable populations.

The researchers identified four distinct patterns of neglect and sexual abuse in low-income, predominantly Black and/or Latina girls and young women that led to distinct trajectories of risky sexual behavior during adolescence. Their findings were published in Child Development in January.

The study was the first of its kind to identify categories of maltreatment among adolescent girls of color in an urban setting that correspond with measurable changes in sexual behavior as they get older. The four categories are low maltreatment, moderate emotional neglect only, severe physical and emotional abuse, and severe sexual abuse.

The study examined how different categories of maltreatment were related to changes in risky sexual behaviors between ages 13 and 23. Risky sexual behaviors included not using condoms, having five or more lifetime partners, having sex in return for money, having sex with someone known to be infected with a sexually transmitted disease, having a partner at least five years older than themselves, and having sex while under the influence of drugs or alcohol.

A noteworthy finding was that adolescents categorized as having had moderate emotional neglect without abuse, as well as those categorized as having experienced severe sexual abuse, reported more sexual risk behaviors than peers who reported low maltreatment. Those with severe sexual abuse also reported the fastest increase of sexually risky behaviors over time.

The girls who experienced moderate emotional neglect, which is the most common form of child maltreatment, may develop riskier behaviors than their peers who were not neglected because emotional neglect may interfere with the development of a secure bond with a parent and the self-esteem that bond produces; the lack of these may precipitate the onset and risky patterns of sexual behavior during middle adolescence, according to the study. Contrary to other research, the study did not find different sexual behaviors between girls and young women who reported severe physical and emotional abuse and those in the low-maltreatment group.

Given that sexually risky behavior often increases in adolescence and decelerates in young adulthood, effective sexual health intervention programs must be designed and implemented earlier in adolescence, particularly among youth with a history of maltreatment, the researchers say. The results from this longitudinal study can inform tailored prevention and intervention efforts, and clinical diagnostic tools, that recognize the different types of neglect and abuse in adolescents and young adults to meet their individual needs in a developmentally appropriate manner.

"Our findings among an underrepresented sample of Latina and Black adolescent girls and young women contribute to the understanding of sexual risk trajectories among girls of color," said Li Niu, PhD, postdoctoral fellow in Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai. "This study provides unique information about patterns of abuse and neglect and underscores the need for better and more comprehensive tools in clinical and research settings. In addition, the larger society needs to recognize crucial social forces, such as stigma and victim-blaming, that affect girls' sexual development, and work together to address factors such as gender inequalities and stereotypes."

This study measured self-reported childhood maltreatment among 882 sexually active adolescents and young adults every six months between the ages of 13 and 25. The participants were enrolled in an ongoing human papillomavirus surveillance study at the Mount Sinai Adolescent Health Center and were recruited on a rolling basis from 2007 to 2016.

The researchers believe that one outcome from the study could be that primary care physicians conduct interviews with girls about neglect and abuse to identify possible interventions. In addition, the study points to a need for further research into how details such as the relationship of a perpetrator of abuse or the chronicity of the maltreatment, might play in sexually risky behavior.

DURHAM, N.H.-- Waldenström macroglobulinemia (WM), a rare form of lymphoma, does not have any known cure and only one FDA-approved treatment making it challenging to treat patients. Researchers at the University of New Hampshire took the novel approach of targeting specific cell proteins that control DNA information using inhibitors, or drugs, that were effective in reducing the growth of the cancer cells and when combined with a third drug were even more successful in killing the WM cancer cells which could lead to more treatment options.

"This is the first study to report the promising results of BET inhibitors in Waldenström macroglobulinemia which could open the door to new clinical possibilities," said Sherine Elsawa, associate professor of molecular, cellular and biomedical sciences. "We know that targeting these types of proteins with inhibitors can increase high therapeutic results in many other kinds of cancer but desired results in WM cells has been lacking."

In their study, just published in the journal Epigenomics, Elsawa and her team focused on the epigenetic regulation of WM cancer cells. Epigenetics is the study of how DNA is opened and closed to allow certain genes to be expressed or encoded. Each protein has a different function--some write the genetic code, some read or interpret it and others can erase the code. The researchers focused on two proteins, bromodomain and extraterminal (BET), which are epigenetic readers. BET proteins have been shown to be involved in pathological conditions including cancer. Drugs that inhibit these proteins can block gene expression that regulate cancer cells by slowing and stopping their growth.

The WM cancer cells were treated with the BET inhibitors JQ-1 and I-BET-762 which reduced the growth of the WM cells in the lab. While the dose dependent effect was significant for both drugs, JQ-1 showed the strongest inhibitory effect with 70% reduction in cell proliferation at the highest dose. However, neither inhibitor was effective in inducing cell death.

Researchers tried adding three different drugs, venetoclax, panabinostat and ibrutinib (the only FDA approved therapy specifically for WM patients), one at a time in combination with the BET inhibitors ((JQ-1 and I-BET-762). After studying each separate drug combination, they found that adding venetoclax or panabinostat to the inhibitors was more effective than adding ibrutinib--with panobinostat offering the greatest combination therapy. Although ibrutinib alone has shown efficacy in WM patients, the study suggests epigenetic targeting is likely to provide a better therapeutic outcome and WM patients undergoing ibrutinib therapy may benefit from the addition of JQ1 which may enhance the efficacy of ibrutinib.

A refractive index of zero induces a wave vector with zero amplitude and undefined direction. Therefore, light propagating inside a zero-index medium does not accumulate any spatial phase advance, resulting in perfect spatial coherence. Such coherence brings several potential applications, including arbitrarily shaped waveguides, phase-mismatch-free nonlinear propagation, large-area single-mode lasers, and extended super radiance. A promising platform to achieve these applications is an integrated Dirac-cone material that features an impedance-matched zero index. However, although this platform eliminates ohmic losses via its purely dielectric structure, it still entails out-of-plane radiation loss (about 1 dB/μm), restricting the applications to a small scale.

In 2018, Professor Shanhui Fan's research group at Stanford University designed a low-loss Dirac-cone zero-index material based on symmetry-protected bound states in the continuum (BICs). However, this Dirac cone is consisted of high-order modes, thus it is challenging to homogenize the photonic crystal slab as a bulk zero-index medium.

In a new paper published in Light Science & Application, a team of scientists, led by Professor Yang Li from the Department of Precision Instrument at Tsinghua University, China, Professor Eric Mazur from the John A. Paulson School of Engineering and Applied Sciences at Harvard University, the US, Professor Weiguo Chu from Nanofabrication Laboratory at the National Center for Nanoscience and Technology, China, and co-workers achieved a zero-index design based on a purely dielectric photonic crystal slab (PhC slab). This design supports an accidental Dirac-cone degeneracy of an electric monopole mode and a magnetic dipole mode at the centre of the Brillouin zone. Such low-order mode-based design can be better treated as a homogeneous zero-index medium.

Their design consists of a square array of silicon pillars embedded in silicon dioxide background matrix, featuring an easy fabrication using standard planar processes. To reduce the radiation loss, they model the top and bottom interfaces of a zero-index PhC slab as two partially reflective mirrors to form a Fabry-Pérot (FP) cavity. Then, they adjust the thickness of this FP cavity to induce destructive interference of upward (downward) radiations in the far field. Inside each pillar, there are axially propagating mode(s) with dipole symmetry showing a round-trip phase of an integer multiple of 2π, therefore becoming resonance-trapped modes. The monopole mode does not radiate in the out-of-plane direction because of its intrinsic mode symmetry.

"Our design exhibits an in-plane propagation loss as low as 0.15 dB/mm at the zero-index wavelength. Furthermore, the refractive index is near zero (|neff|

For applications, Yueyang Liu predict: "our on-chip BIC Dirac-cone zero-index PhC slabs provide an infinite coherence length with low propagation loss. This opens the door to applications of large-area zero-index materials in linear and nonlinear optics as well as lasers. For examples, electromagnetic energy tunnelling through a zero-index waveguide with an arbitrary shape, nonlinear light generation without phase mismatch over a long interaction length, and lasing over a large area in a single mode."

"This work can also serve as an on-chip lab to explore fundamental quantum optics such as efficient generation of entangled photon pairs and collective emission of many emitters. Particularly, because the spatial distribution of Ez in each silicon pillar oscillates between a monopole mode and a dipole mode as time elapses, all the quantum emitters within the pillars will experience the same spatial phase in the monopole half cycle. This significantly alleviates the challenge of precise positioning of quantum emitters in a photonic cavity." Yueyang Liu added.

The development of ultrafast all-optical switches has long been a popular topic in photonics, while the speed of magnetization reversal triggered by means other than magnetic fields has recently attracted intense interest in spintronics. The discovery of all-optical helicity-dependent switching in metallic GdFeCo has promised a merger of the fields of photonics and spintronics, paving the way for faster and more energy-efficient information processing technologies. However, the real potential of all-optical switching is still poorly understood because it is still unclear whether magnetic switching by light can keep up with the GHz frequencies required by photonics technologies. Another serious obstacle is the skepticism regarding the scalability of all-optical magnetic switching down to the sizes of spintronic devices, which are well below the diffraction limit.

In a new paper published in Light: Science & Applications, a team of scientists, led by Professor Xiangping Li at Jinan University in China and Professor Alexey V. Kimel at Radboud University in The Netherlands have proposed a dual-shot opto-magnetic switching method and studied its dynamics through a time-resolved magneto-optical imaging system. They experimentally unveiled the ultimate frequency of repetitive all-optical magnetization reversal through time-resolved studies of the dual-shot magnetization dynamics in Gd27Fe63.87Co9.13. Varying the intensities of the shots and the shot-to-shot separation, they revealed the conditions for ultrafast writing and the fastest possible restoration of magnetic bits. It is shown that although magnetic writing launched by the first shot is completed after 100 ps, a reliable rewriting of the bit by the second shot requires separating the shots by at least 300 ps. Using two shots partially overlapping in space and minimally separated by 300 ps, they demonstrated an approach for GHz magnetic writing that can be scaled down to sizes below the diffraction limit.

These scientists forecast: "Our findings demonstrate the potential of all-optical magnetic writing with a repetition rate of up to 3 GHz and a spatial resolution below the diffraction limit, which fills a knowledge gap and completes missing technology to promote its widespread applicability in the next revolution of information processing. The advanced features observed in this work may favour the realization of spatially and temporally confined magnetization control through light and greatly promote the development of ultrafast and highly compact devices at the intersection of photonics and spintronics."

University of Otago researchers have added another piece to the puzzle about how best to translocate New Zealand lizards for conservation purposes - confine them.

In a paper just published in the New Zealand Journal of Ecology, the Department of Zoology researchers outlined how they translocated 19 barking geckos to Mana Island, using the method of penned release - enclosing them in a 100m² pen for three months so they get used to the site and hopefully establish a breeding population.

It was the first time such a method had been used with the species and the researchers found it worked well. The geckos' area use decreased over time, indicating territory establishment.

Co-author Dr Jo Monks, Otago Honorary Research Fellow and Department of Conservation Science Advisor, says translocations of reptiles and amphibians has, historically and globally, been notoriously unsuccessful. However, recent penned release success of jewelled geckos prompted them to try with a different species.

"By understanding the behavioural response of barking geckos to a penned release, this research is helping us to understand which techniques best help a new population of geckos establish following translocation to a new site," she says.

Barking geckos are one of nine green gecko, moko-kākāriki, species that only live in Aotearoa New Zealand. They are considered 'At Risk - Declining' under New Zealand's Threat Classification System due to ongoing predicted declines from habitat destruction and predation by introduced mammals.

Many green gecko populations have undergone decline in numbers and locations due to predators, habitat modification, and poaching for illegal trade, but little research on their ecology exists.

"Protecting barking geckos and other reptiles of Aotearoa is important in its own right and for the mauri of ecosystems in which they have important roles as pollinators and seed dispersers as well as being predators of invertebrates and prey of larger animals," Dr Monks says.

There is potential for penned release to work for a wide range of fauna where initial dispersal following translocation could be detrimental to species establishment. It has been done for birds and lizards in Aotearoa.