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The X-ray crystal structure visualization technique has been known for over a hundred years. It keeps improving, but it is extremely difficult to focus the rays on the objects that are invisible with a naked eye, such as proteins. However, to get a clear image and effectively visualize the structure of a crystal, a sample should be positioned correctly. An international team of scientists suggested an optic system to help see a protein crystal in X-rays and place it in the center of a beam. The results of the study were published in the Structural Biology journal.

During crystallization atoms are arranged in a 3D lattice structured in a specific way. The distances between the atoms in that lattice are determined by the atoms themselves. The X-ray wavelength is comparable to interatomic distances, so the rays can be refracted on the planes. Due to this effect one can analyze crystal structure. The X-ray images show the distances between the planes. Based on this information it is possible to determine what atoms are in the lattice and how they interact with each other. In proteins studying, for example in the search of new drugs, their structure can be determined on the level of basic atom groups (amino acids).

The main issue of X-ray crystallography is that microscopic protein crystals are very difficult to be positioned in the center of an X-ray beam so that X-ray diffraction image may be blurry. Moreover, if the exact position of a crystal is unknown, one has to scan the whole sample. This increases the time of exposure to very intensive X-rays. Biological molecules start to denature under that exposure.

An international team of scientists developed an optic system allowing one to see a sample in X-rays and learn its position and orientation relative to the beam. Just like with a regular optical microscope it can move the sample, adjust rays intensity and focus the beam. Such a system can significantly reduce the time of analysis and thus preserve the integrity of the molecules. Scientists have demonstrated how the system works on the example of a crystal of antibacterial protein lysozyme. The quality of X-ray diffraction images turned out to be much higher after the positioning of the sample in the X-ray beam.

"Our system is now successfully used in the international research center by the DESY synchrotron in Hamburg, where the laboratories of the world's leading universities carry out their crystal structure studies. In the future, we plan to automate the crystal positioning process using neural networks," said Prof. Anatoly Snigirev, the head of the Science and Research Center "Coherent X-Ray Optics for Megascience Installations" at Kant Baltic Federal University.

Rapid progress in the field of metallic nanotechnology is sparking a science revolution that is likely to impact all areas of society, according to professor of physics Ventsislav Valev and his team at the University of Bath in the UK.

Metallic nanotechnology is an area that allows microscopic particles of metals, such as gold and silver, to be manipulated with heat and light. The potential applications are vast, ranging from optimising the way we harvest renewable energy to overhauling our treatment of cancerous tumours.

Writing in Advanced Optical Materials, Prof Valev's team reviews the current state of nanotechnology research and discusses its likely applications in the near and medium future.

PhD student Lukas Ohnoutek sees nanomedicine - a branch of medicine that uses nanotechnology to improve the diagnosis and treatment of disease - as a particularly buoyant area of research. On-command delivery of drugs has already proven successful in several animal trials, he says. Using this technology, medicines encapsulated in nanomaterials are directed to a specific site in the body before releasing their active ingredients in a highly controlled manner.

"It is crucial to increase the efficiency of drugs and to reduce side effects, and this is something that can be achieved with on-command drug delivery," said Mr Ohnoutek. "By illuminating metal nanoparticles, it is possible to control the location, time, and amount of drug released in a patient."

Research fellow Dr Kristina Rusimova says dramatic improvements are expected in the treatment of cancer, thanks both to on-command drug delivery and photothermal cancer therapy (PTT). PTT involves injecting nanoparticles into a patient's body, where they accumulate in the tumour. When the particles are then subjected to radiation, they heat up and destroy the tumour with very little damage to surrounding tissue. In animal trials, advanced tumours have completely disappeared following photothermal therapy.

"We have looked at animal trials conducted on mice, cats and dogs," said Dr Rusimova. "In each case, the treatment seemed successful, which is very encouraging for treatment in humans. We know that human trials have been approved and are currently ongoing, so we are cautiously optimistic."

Other research is focused on finding nanotechnology solutions to the climate crises. There is hope that non-radiative plasmonic decay will provide a new method for improving solar cells and for producing hydrogen fuel directly from water. This process is known as 'water splitting'. The result will be an efficient and economical low-carbon fuel, particularly suitable for heating homes and other spaces.

Other tantalising applications for metallic nanoparticles technology include advanced biomedical imaging, improved magnetic storage and nanorobotics, where robots are manufactured with components on the nanoscale.

Prof Valev said: "The tiniest metal pieces can now be formed, cut and joined with light. This allows us to integrate humanity's knowledge of metal working with our understanding of molecular self-assembly and nanoscale biotechnology. This research field offers some truly amazing perspectives for the future."

These prospects are all built around the ability of metallic nanoparticles to harvest and control light at the subwavelength scale.

ANN ARBOR, Mich. -- Eighty-six percent of parents agree that teens spend too much time gaming, but many may be mistaken about the extent of their own child's video game habits, a new national poll suggests.

Parents also report very different gaming patterns for teen boys than girls, according to the C.S. Mott Children's Hospital National Poll on Children's Health. Twice as many parents say their teen boy plays video games every day compared to parents of teen girls. Teen boys are also more likely to spend three or more hours gaming.

Overall, parents surveyed say gaming often gets in the way of other aspects of their teen's life, such as family activities and interactions (46%), sleep (44%), homework (34%), friendship with non-gaming peers (33%) and extracurricular activities (31%).

"Although many parents believe video games can be good for teens, they also report a number of negative impacts of prolonged gaming," says Mott Poll co-director and Mott pediatrician Gary Freed, MD, MPH.

"Parents should take a close look at their teen's gaming behavior and set reasonable limits to reduce harmful impacts on sleep, family and peer relationships and school performance."

But parents may not always have the most accurate perception of their teen's gaming tendencies. Among parents of daily gamers, 54% report their teen plays three or more hours a day (compared to only 13% of teens that do not play every day.) Just 13 percent of these parents believe their teen spends more time gaming than others, while 78% believe their teen's gaming is less than or about the same as their peers.

"Many parents of frequent gamers have a misconception that the amount of time their teenager spends playing video games is in line with their peers," Freed says.

While 71% of parents believe video games may have a positive impact on their teen, some (44%) try to restrict video game content. Parents of teens ages 13-15 (compared to those with older teens) are more likely to use rating systems to try to make sure games are appropriate (43% versus 18%), encourage their teen to play with friends in person rather than online and to ban gaming in their teen's bedroom.

Parents polled also use different strategies to limit the amount of time their teen spends gaming, including encouraging other activities (75%), setting time limits (54%), providing incentives to limit gaming (23%) and hiding gaming equipment (14%).

Freed notes that while gaming may be a fun activity in moderation, some teens -such as those with attention issues -- are especially susceptible to the constant positive feedback and the stimulus of video games. This may lead to prolonged play that is disruptive to other elements of a teen's life.

He recommends parents show interest by playing video games with their kids while also communicating healthy limits and ensuring that they have strong privacy settings. In some situations, he notes, games can help parents connect with older kids and may occasionally help open the door to other conversations and interactions.

But parents should also help teens understand that limits and rules around gaming are tied to safety, health, school and relationships.

"Parents can play an important role by setting clear rules about appropriate content and how much time is too much time spent on video games," Freed says.

"While many parents see benefits in gaming, the activity should not be at the expense of face-to-face time with family, friends, and teachers who play a pivotal role in promoting a teen's learning and healthy development."

Nagoya University scientists, in cooperation with Asahi Kasei Corporation, have succeeded in designing a laser diode that emits deep-ultraviolet light, according to research published in the journal Applied Physics Express.

"Our laser diode emits the world's shortest lasing wavelength, at 271.8 nanometers (nm), under pulsed [electric] current injection at room temperature," says Professor Chiaki Sasaoka of Nagoya University's Center for Integrated Research of Future Electronics.

Previous efforts in the development of ultraviolet laser diodes had only managed to achieve emissions down to 336 nm, Sasaoka explains.

Laser diodes that emit short-wavelength ultraviolet light, which is called UV-C and is in the wavelength region of 200 to 280 nm, could be used for disinfection in healthcare, for treating skin conditions such as psoriasis, and for analysing gases and DNA.

The Nagoya University deep-ultraviolet laser diode overcomes several issues encountered by scientists in their work towards the development of these semiconducting devices.

The team used a high quality aluminium nitride (AlN) substrate as their base for building up the layers of the laser diode. This, they say, is necessary, since lower quality AlN contains a large amount of defects, which ultimately impact the efficiency of a laser diode's active layer in converting electrical into light energy.

In laser diodes, a 'p-type' and 'n-type' layer are separated by a 'quantum well'. When an electric current is passed through a laser diode, positively charged holes in the p-type layer and negatively charged electrons in the n-type layer flow towards the center to combine, releasing energy in the form of light particles called photons.

The researchers designed the quantum well so that it would emit deep UV light. The p- and n-type layers were made from aluminium gallium nitride (AlGaN). Cladding layers, also made from AlGaN, were placed on either side of the p- and n-type layers. The cladding below the n-type layer included silicon impurities, a process called doping. Doping is used as a technique to modify a material's properties. The cladding above the p-type layer underwent distributed polarization doping, which dopes the layer without adding impurities. The aluminium content in the p-side cladding was designed so that it was highest at the bottom, decreasing towards the top. The researchers believe this aluminium gradient enhances the flow of positively charged holes. A top contact layer was finally added that was made from p-type AlGaN doped with magnesium.

The researchers found that the polarization doping of the p-side cladding layer meant that a pulsed electric current of "remarkably low operating voltage" of 13.8V was needed for the emission of "the shortest wavelength reported so far."

The team is now conducting advanced joint research with Asahi Kasei Corporation to achieve continuous room temperature deep-UV lasing for the development of UV-C semiconductor laser products.

DURHAM, N.C. -- Few singers reach their sunset years with the same voice they had in younger days. Singing sparrows are no different. Duke University-led research reveals that elderly swamp sparrows don't sound quite like they used to -- nor do they strike the same fear in other males who may be listening in.

Humans are remarkably good at guessing a person's age just by hearing their voice. But this is the first time the phenomenon has been demonstrated in wild animals, said Duke biology professor and study co-author Steve Nowicki.

The findings were published on January 7 in the journal Behavioral Ecology.

During the early spring, a male swamp sparrow stakes out a breeding territory and threatens any male who dares to trespass on his turf. If a potential rival enters another male's territory and starts to sing, the resident male says "Get out!" by singing back with a rapid weet-weet-weet and flying toward the intruder. Eventually, if all else fails, he attacks.

Previous research by this team showed that male swamp sparrows reach their peak as vocalists at age two, and start to decline after that, singing less frequently and less consistently as they get older.

To find out if other males take note of such changes, the team set up a speaker in the territories of 35 male swamp sparrows in a Pennsylvania marsh and played them 5-minute audio clips of stranger males recorded at age two and again at age 10.

The team measured the birds' responses, noting how closely each male approached the speaker. They found that males approached seven feet closer when they heard a potential rival's song recorded at age two than at age 10. This suggests that males are more aggressive towards younger-sounding rivals.

Males in their prime pose an obvious threat: if a resident male isn't assertive, there's a good chance that the other guy could steal his mates, said first author Matthew Zipple, a doctoral student at Duke. But apparently the song of a 10-year-old -- a centenarian in bird years -- doesn't warrant getting as worked up over.

If decreases in song quality in later life reflect the inevitable consequences of physical decline, the researchers believe that such changes could indicate to other males that a once-formidable male is no longer a match.

Whether song changes after mid-life make males more or less attractive to females is still unknown. "One interesting question would be, is the equation a little different from the female's point of view?" Nowicki said.

Males accumulate genetic mutations in their sperm as they age that could make them less desirable mates. On the flip side, Nowicki said, "The mere fact that he's lived this long means he must be doing something right."

BIRMINGHAM, Ala. - The lungs and placentas of fetuses in the womb -- as young as 11 weeks after conception -- already show a bacterial microbiome signature, which suggests that bacteria may colonize the lungs well before birth. This first-time finding deepens the mystery of how the microbes or microbial products reach those organs before birth and what role they play in normal lung and immune system development.

A team led by University of Alabama at Birmingham researcher Charitharth Vivek Lal, M.D., found that a human fetal microbiome DNA signature is present in lungs as early as the first trimester. This fetal lung microbiome showed changes in diversity during fetal development, suggesting microbiome maturation with advancing gestational age. Finally, a placental microbiome was also present in human fetal tissue, and this microbiome signature showed some taxonomic overlap with the corresponding human fetal lung microbiome.

"We speculate that maternal-fetal microbial DNA transfer -- and perhaps of other microbial products and whole live or dead bacteria -- is a realistic possibility," said Lal, an associate professor in the UAB Pediatrics Division of Neonatology. "This may serve to 'prime' the developing innate immune system of the fetus and help in establishment of a normal host-commensal relationship."

Denise Al Alam, Ph.D., investigator in The Saban Research Institute of Children's Hospital Los Angeles and assistant professor of pediatrics at University of Southern California, is the first-author who spearheaded the concept of the study, which is published in the American Journal of Respiratory and Critical Care Medicine.

Study details

Researchers, including Lal and colleagues, have previously seen that the lungs of infants, sampled immediately after birth, are colonized with bacteria. Furthermore, similar microbiome profiles are found after either cesarean or vaginal delivery, which suggested that microbes somehow are able to reach the lungs before birth.

In the new study, 31 samples of lung, placenta and intestine tissue from fetuses between 11 and 20 weeks of gestation were collected. Duplicate, independent tests done in labs at Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, and at UAB detected bacterial DNA in all samples. The two labs used different DNA extraction kits and different microbiome analysis pipelines.

Bacterial DNA was detected through targeted analysis of the bacterial gene for 16S ribosomal RNA, which is a standard method to distinguish different microbial taxa. The initial 16S analysis in Singapore showed 48 unique taxa in the lung samples, 11 unique taxa in placenta samples and 24 shared taxa.

The 16S analysis of the same samples at UAB showed two separate human fetal lung microbiome groups, based on fetal age -- one group at 11 to 15 weeks' gestation, and the other at 16 to 20 weeks' gestation. Furthermore, the two gestational age groups showed a significant change in microbiome diversity with time.

"Overall, at both lab sites," Lal said, "analysis of the bacterial taxa distribution and diversity showed some overlap in microbiome signatures of fetal lungs and matched placentas."

Quantum physics is moving out of the laboratory and into our everyday lives. Despite the big headline results about quantum computers solving problems impossible for classical computers, technical challenges are standing in the way of getting quantum physics into the real world. New research published in Nature Communications from teams at Aalto University and Lund University hopes to provide an important tool in this quest.

One of the open questions in quantum research is how heat and thermodynamics coexist with quantum physics. This research field, "quantum thermodynamics", is one of the areas Professor Jukka Pekola, the leader of the QTF Centre of Excellence of the Academy of Finland, has worked on in his career. 'This field has up to now been dominated by theory, and only now important experiments are starting to emerge' says Professor Pekola. His research group has set about creating quantum thermodynamic nano-devices that can solve open questions experimentally.

Quantum states - like the qubits that power quantum computers - interact with their surrounding world, and these interactions are what quantum thermodynamics deals with. Measuring these systems requires detecting energy changes so exceptionally small they are hard to pick out from background fluctuations, like using only a thermometer to try and work out if someone has blown out a candle in the room you're in. Another problem is that quantum states can change when you measure them, simply because you've measured them. This would be like putting a thermometer in a cup of cold water making the water start to boil. The team had to make a thermometer able to measure very small changes without interfering with any of the quantum states they plan to measure.

Doctoral student Bayan Karimi works in QTF and Marie Curie training network QuESTech. Her device is a calorimeter, which measures the heat in a system. It uses a strip of copper about one thousand times thinner than a human hair. 'Our detector absorbs radiation from the quantum states. It is expected to determine how much energy they have and how they interact with their surroundings. There is a theoretical limit to how accurate a calorimeter can be, and our device is now reaching that limit', says Karimi.

A common and inexpensive drug may be used to counteract treatment resistance in patients with acute myeloid leukemia (AML), one of the most common forms of blood cancer. This is the conclusion of a study in mice and human blood cells performed at Karolinska Institutet and SciLifeLab and published in the medical journal EMBO Molecular Medicine. The researchers will now launch a clinical study to test the new combination treatment in patients.

Leukemia is a group of blood cancers that results in excess amounts of white blood cells. There are both chronic forms of leukemia that progress slowly over many years and acute types of leukemia that evolve rapidly. AML affects more than 20,000 people in the United States each year, and the mortality rate is high especially in older patients.

One of the most common drugs to treat AML is cytarabine (ara-C), a cytotoxic drug that interferes with DNA replication. However, many patients do not respond to the treatment because their leukemic cells express high levels of the enzyme SAMHD1, which breaks down the active metabolite of cytarabine, ara-CTP. These patients have a significantly worse survival rate than patients with low leukemic levels of SAMHD1. Therefore, one promising strategy to improve the treatment of AML is to inhibit the effects of this enzyme on cytarabine.

In this study, the researchers tested the impact of more than 33,000 different substances on SAMHD1's ability to break down ara-CTP in leukemia cells treated with cytarabine. The experiment led to the identification of three different substances, so-called ribonucleotide reductase inhibitors (RNRi), that all reduced SAMHD1's ability to deactivate ara-CTP: hydroxyurea, gemcitabine and triapine.

"Adding any of these three substances significantly improved the effect of the cytarabine-treatment in cell samples with high levels of SAMHD1," says Nikolas Herold, researcher at the Department of Women's and Children's Health at Karolinska Institutet in Sweden. "This was true for AML samples from both adults and children. In AML-mice, we also saw that the median survival was significantly prolonged when cytarabine was combined with an RNR-inhibitor."

Hydroxyurea is an inexpensive drug that is used to treat blood diseases such as AML. However, it has not systematically been used in combination with cytarabine. Gemcitabine is a potent drug that is used to treat many different types of cancers, but it can be toxic if given repeatedly. Triapine is a drug currently undergoing clinical studies for cancer treatment. In animal studies, the combination therapies did not exhibit any excess side-effects beyond those already established in cytarabine-treatments.

The research group is now planning to move forward with a clinical study that will evaluate the effect of combining standard AML-treatment with hydroxyurea in recently diagnosed patients. The study will be conducted in collaboration with the Swedish AML-group and will begin recruiting patients within a few weeks.

"Hydroxyurea is an approved drug that is already used to treat AML, so we think it has great potential," says Nikolas Herold. "If our research results can be confirmed in clinical trials, the treatment of AML could be significantly improved also in developing countries with limited resources since hydroxyurea is patent-free and doesn't cost more than ibuprofen."

The researchers were also able to show how the RNR-inhibitors affected the SAMHD1-levels mechanistically. These drugs change the intracellular composition of deoxynucleoside triphosphates (dNTP), which are building blocks for molecules. Since SAMHD1 needs dNTPs to activate its enzymatic activity, this effectively abrogates its ability to break down ara-CTP.

In 2017 a paper was published asserting that intravenous vitamin C given to patients with sepsis was literally a life saver. Despite the study only looking at 47 subjects the results garnered international coverage and was adopted in many ICUs worldwide.

The global burden of sepsis is estimated at up to 19 million cases annually killing 5 million mainly in low income countries. The infection affects 1.7 million Americans a year and kills more than 250,000, making it one of the top 10 causes of death. In Australia more than 5,000 die from sepsis each year and it contributes to up to a half of all hospital deaths.

A paper published today in the Journal of the American Medical Association by Monash researchers comprehensively quashes the idea that the vitamin C-based cocktail has any positive impact on patients with sepsis.

Sepsis is the body's overreaction to a severe infection, leading to multiple organ failure and, frequently, death.

Over the years, there has been indications that vitamin C might be effective against sepsis. For instance, people with sepsis tend to have surprisingly low levels of vitamin C in their blood. In 2014, Dr. Alpha Fowler published a paper involving just 24 patients, hinting that vitamin C was a benefit. In particular, Fowler noted that a measure of organ failure improved far more in the patients who had received vitamin C.

Dr. Paul Marik at the Eastern Virginia Medical School in the US, after reading the study, gave a seriously ill patient with sepsis high dose intravenous Vitamin C, together with thiamine and steroids (the traditional treatment for sepsis) and the patient recovered. Dr Marik started using it regularly in his intensive care unit, reporting that the mortality rate for sepsis in his ICU had plummeted after he switched to this treatment.

What became known as the "Marik protocol" has been adopted by many units worldwide.

In today's JAMA publication a study led by Professor Rinaldo Bellomo, from Monash University and Co-Director of the Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), refutes the idea that the combination of high dose intravenous vitamin C, thiamine (vitamin B1) and hydrocortisone is beneficial in the treatment of sepsis.

The study (the VITAMINS trial) was set up by the ANZIC-RC across ten intensive care units in Australia, New Zealand and Brazil, looking at 216 patients in septic shock between May, 2018 and July, 2019.

216 patients were randomised to either the intervention group (thus receiving intravenous vitamin C, hydrocortisone and thiamine) or the control group (thus receiving hydrocortisone - a steroid - only).

The study found no improvement in the duration of support with blood pressure drugs for the treatment of shock or survival of those receiving vitamin C + thiamine + steroid therapy compared to steroid therapy alone.

According to Professor Bellomo, the study provides high quality evidence that, in patients with septic shock, the combination of high dose intravenous vitamin C, thiamine and hydrocortisone is not superior to usual care with hydrocortisone alone:

"The findings of the VITAMINS trials are clear: in patients with septic shock from Australia, New Zealand and Brazil there was no signal of benefit with the high dose vitamin C, thiamine and hydrocortisone cocktail. The search for treatments that might improve the outcome of these very sick patients must now focus on other interventions"

The U.N. and other international organizations agree that forest restoration is a critical part of the collective global effort to combat climate change, reduce extinctions, and improve the lives of people in rural communities. Dozens of nations have pledged to restore 230 million hectares of forest so far as part of projects such as the Bonn Challenge and REDD+. The Bonn Challenge goal is to restore 350 million hectares by 2030.

The leaders behind this work agree that ambitious goals are important if humanity is going to avoid the worst effects of climate change. However, a new paper in Conservation Letters has generated the first comprehensive data set that describes how countries are doing so far--and it's not looking good. The paper looked at 62 countries that have made restoration commitments, and reports that 54 percent of the Bonn Challenge's goal area for 2020 has not yet been pledged. It then digs into the data to understand why some countries are doing better than others, and what could help those that are struggling.

Aiming high

The authors found that most of the gap between goals and reality exists in the global South, a group of nations generally south of the equator previously referred to as developing countries. These are also the countries that pledged to restore the greatest amounts of land, the paper reports. For example, Rwanda pledged to restore 81 percent of its total land area, and Burundi pledged 79 percent. One-third of the countries pledged greater than 10 percent of their total area, which would require significant shifts in land use and food production.

The authors hypothesize multiple reasons for the large pledges from global South countries. "It could be that global South countries are more aware of the risks they face from climate change, and are therefore more interested in doing something about it," says Matthew Fagan, assistant professor of geography and environmental systems at UMBC and lead author on the paper. "They also generally have lower labor and land costs, making it easier for them to do restoration." On the other hand, they could be trying to access more dollars from international donor organizations to reach these aspirational goals, or could have underestimated the challenges of restoration at that scale.

The paper also attempted to predict which countries would have the greatest difficulty meeting their goals based on a dozen factors the team analyzed, such as population growth, government corruption, and previous deforestation rates.

Justin Drew '20, computer science, and a co-author on the paper, compiled the data for all 12 factors by writing computer code to pull quantitative information from public international databases. He also scoured the internet for information on individual countries' progress. Drew collected reliable information on the 12 factors for all 62 countries making restoration commitments, and progress information for 12 of them. "When we asked how they did based on these twelve factors, we found they did about as well as we expected," says Fagan. Countries with the lowest combined score considering all the implementation factors tended to be farther from meeting their goals.

Local engagement

But all is not lost. "We've identified countries that need help" to achieve their ambitious environmental goals, says Fagan. "It's clear that there's a whole set of countries that are facing headwinds, and if we expect them to be able to accomplish their goals, then the international community needs to support them."

Increased financial aid is important, but so are other means of support. That might mean providing technical tools and training to help governments and local communities make informed decisions about restoration efforts. Above all, it means listening to local communities' needs and working in collaboration to create solutions.

"Restoration efforts have a better chance of achieving sustained improvement when local communities have a voice early in the process, feel empowered to participate actively throughout, and can experience direct and long-term benefits from these efforts," says Maggie Holland. She is an associate professor of geography and environmental systems at UMBC and a co-author on the paper.

In one location, the best solution might be planting trees on agricultural land, such as shade-grown coffee. Other places, it might be tree plantations, reclaiming agricultural land for forest, or thinning existing forests to prevent fires.

"Different efforts will yield different benefits for mitigating climate change, for helping people, for restoring ecosystem health and conserving biodiversity," Holland says. She suggests that more social science research on the results of different strategies is needed to deploy them most effectively.

There are other, less direct, efforts that can also have a huge effect on forests. "Even if countries haven't necessarily made big strides in restoration, in some cases they're making big policy changes that will hopefully result in restoration in the longer term," Fagan says. For example, bringing electricity to more rural communities reduces the need for fuel wood and charcoal. That reduces forest loss while also improving human health by removing smoke from homes.

Investing in the foundation

Ultimately, the researchers argue that while it may sound good to pledge huge areas of land, that might not be the best strategy to reach the goals of combating climate change, improving people's lives, and protecting species from extinction. If countries feel pressured to meet their ambitious goals, they might employ the easiest restoration strategies, such as thinning forest. The U.S., for example, has already met its goal of 15 million hectares, and the vast majority of it was through this method. That may have some beneficial effects, like decreasing the chance of forest fires, but it's not the same as planting trees on agricultural land or shifting land use patterns.

In addition to supporting countries in need, "I think the wealthier countries need to get on this bandwagon and do more themselves as well," Fagan says. Ambitious, but realistic, and locally appropriate goals are the best way to succeed, Fagan and Holland agree.

Overall, Fagan is "guardedly optimistic." "There's a lot of potential and a lot of interesting policy work going on. I believe, though, that there's a time to build your castles in the air, and now it's time to put foundations under them. We're underinvesting in the foundations, and we need to spend more international aid money on helping countries figure out how to meet these commitments," he says.

"I'd like to hope that this article helps generate more support for that kind of work," Fagan shares, "because I think it is possible to make this kind of change."

Baltimore, MD-- A woman's supply of eggs is finite, so it is crucial that the quality of their genetic material is ensured. New work from Carnegie's Marla Tharp, Safia Malki, and Alex Bortvin elucidates a mechanism by which, even before birth, the body tries to eliminate egg cells of the poorest quality. Their findings describing this mechanism are published by Nature Communications.

"Some organisms produce a large number of offspring, many of which don't survive to adulthood; females in these species continually produce new egg cells throughout their reproductive lives," Bortvin explained. "But in mammals, females are born with a fixed supply of eggs and produce few progeny. Thus, each egg is a precious commodity necessitating quality control to ensure wellbeing of her children."

For 50 years, scientists have known that up to 80 percent of a female mammal's original pool of potential egg cells are eliminated during fetal development through a process called fetal oocyte attrition, or FOA. This phenomenon is conserved in all studied mammals, but despite its ancient origins, much about this process remains mysterious. Bortvin and his team say FOA targets those egg cells with reduced quality.

Previous work by Bortvin and Malki indicated that this elimination of potential egg cells during fetal development is related to a transposable element, or "jumping gene," called LINE-1.

Originally discovered by Carnegie biologist Barbara McClintock, jumping genes can move around in a cell's DNA, often breaking genes but sometimes also introducing genetic innovations that improve a species' survival.

Bortvin's group had previously demonstrated that jumping genes are quashed during sperm production, but not during egg development. They theorized that purging the cells with the greatest activity by the jumping gene LINE-1 allows for the selective survival of the immature eggs that have the lowest potential of succumbing to jumping genes.

Indeed, Malki and Bortvin previously discovered that AZT, a drug that blocks the multiplication of HIV and LINE-1, temporarily prevented death of immature egg cells. This observation indicated that that there was more than one mechanism to detect and eliminate egg cells with excessive LINE-1 activity.

Taking this idea to the next stage, the research team expanded their investigations by using AZT in mice lacking a protein called Chk2, which detects DNA damage and either repairs it or flags the cells where this genetic material is housed for death. When the LINE-1 jumping gene was inhibited by AZT, and the Chk2 protein was rendered ineffective by mutation, the reserve of egg cells increased.

"What's more, the shutting off the fetal egg cell elimination process in this way did not decrease fertility," Tharp explained. "This provides further evidence that this is a quality control process undertaken to try to maintain the caliber of the available egg supply."

More work is needed to determine whether these findings could help combat infertility due to premature ovarian failure by increasing a woman's total egg supply.

AI Therapeutics is a clinical-stage biopharmaceutical company that has created an artificial intelligence-driven drug development platform for matching drugs to new indications. The company has made significant recent progress with its four clinical assets and proprietary Guardian Angel™ algorithm.

LAM-002 is a first-in-class, PIKfyve kinase inhibitor that activates transcription factor EB (TFEB), the master regulator of lysosomal biogenesis [1]. TFEB activation clears toxic aggregates that drive neurodegenerative disorders [2-4]. Dr. Murat Gunel, Nixdorff-German Professor of Neurosurgery and Professor of Genetics and of Neuroscience at Yale University and a member of AI Therapeutics' Scientific Advisory Board indicated, "A wealth of new data points to the accumulation of toxic proteins as a common mechanism in neurodegenerative conditions disorders including amyotrophic lateral sclerosis (ALS), Parkinson's disease and Alzheimer's disease. We look forward to bringing the most advanced PIKfyve inhibitor into clinical development for patients suffering from ALS. We are pleased that our Guardian AngelTM platform made the connection of LAM-002 to ALS and that the finding was validated in our laboratories and with our collaborators, as well as in independent research published in Nature Medicine [5]."

Through its action on the lysosome, LAM-002 also selectively kills tumor cells. AI Therapeutics has recently completed enrollment in a clinical trial with patients previously treated for follicular lymphoma. Efficacy has been observed with LAM-002 as a single agent and when combined with rituximab or atezolizumab. LAM-002 appears to be well-tolerated with patients on continuous treatment for well over a year. Dr. Sarah Rutherford, Assistant Professor at Weill Cornell Medicine noted "LAM-002 represents a novel targeted approach to treat patients with follicular lymphoma. Our patients have shown durable objective responses while on LAM-002 therapy without the adverse effects often associated with other drugs."

AI Therapeutics is also pleased to announce that it had a Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss the registrational program for LAM-002 in patients with previously treated follicular lymphoma. At this meeting, AI Therapeutics reached concurrence on the design of a pivotal trial that could support accelerated approval. The clinical data to support full approval in patients with previously treated follicular lymphoma was also discussed and a path forward was detailed.

LAM-002 has received Fast Track status and Orphan Drug Designation from the FDA for the therapy of follicular lymphoma. The safety and clinical data for LAM-002 are expected to be presented at the American Society of Clinical Oncology (ASCO) conference in 2020.

Older adults from ethnic minority groups report having fewer close friends and fewer friends who live locally than older white people, according a new UCL study.

The research, published in Ageing & Society, found that Black and Asian adults over the age of 65 years are almost twice as likely to report having no close friends (9% and 7% respectively) compared to White and mixed or 'other' ethnicity adults of the same age (both 4%).

"Despite the high rates of loneliness found in older ethnic minority adults, it is often assumed that they are protected from social isolation and loneliness because they are perceived as being likely to live in multigenerational households with traditional family practices. These stereotypes are damaging because they fail to acknowledge the diverse experiences and needs of different minority adults," said lead author Brenda Hayanga, PhD candidate (UCL Institute of Education).

Of all the black people surveyed, half (50%) reported that none of their friends were family members compared to a third of respondents with mixed or 'other' ethnicity (33%) and Asian respondents (32%) and just a quarter of White respondents (26%).

A higher proportion of Black (13%) and Asian (11%) people reported that none of their friends lived locally compared to White people (6%) and those of mixed or 'other' ethnicity (8%). After controlling for age, gender, marital status, household size, current financial situation, rurality, long-standing illness, and life satisfaction, older ethnic minority adults are more likely to report having only two close friends or fewer compared to older white adults. They also remain more likely to report that half or less than half of their friends live locally compared to older white adults.

"Having close friends and peers plays a role in reducing social isolation and loneliness. Therefore, our findings suggest that older ethnic minority adults may be more vulnerable to social isolation and loneliness than older white people," said Dr Dylan Kneale (UCL Institute of Education).

The study draws on data from Understanding Society: The UK Household Longitudinal Study, and utilises data from 2014 and 2015, when there was a notable boost in representation of ethnic minority groups.

The researchers analysed a sample of 7,499 participants aged 65 years and above, 329 (4.3%) of whom identified as belonging to a minoritised ethnic group. Some supplementary analyses exploring trends for older people aged 50 and over are also included.

The number of ethnic minority adults aged 65 and over in England and Wales is estimated to increase from 0.4 million in 2011 to 2.7 million by 2051, and the findings have important implications for policymakers.

The UK Government's vision, as stated in the new loneliness strategy, is for the country to be a place where families, friends and communities can support each other and build strong social relationships especially at vulnerable points where individuals are at an increased risk of loneliness. However, much of the evidence included in this and other strategies is based predominantly on the experiences of older white adults.

Professor Ann Phoenix (UCL Institute of Education) said: "From a policy and practice perspective, the findings of this study suggest that older ethnic minority adults have different needs to older white people."

"Interventions for older people need to move away from a 'one size fits all' approach, towards interventions that are targeted, evidence-based and are reflective of the diverse experiences of older people."

WEST LAFAYETTE, Ind. -- Manufacturing prescription drugs with distinct markings, colors, shapes or packaging isn't enough to protect them from counterfeiting, U.S. Drug Enforcement Administration reports have shown.

Purdue University researchers are aiming to stump counterfeiters with an edible "security tag" embedded into medicine. To imitate the drug, a counterfeiter would have to uncrack a complicated puzzle of patterns not fully visible to the naked eye.

The work is published in the journal Nature Communications. A YouTube video is available at https://youtu.be/0bN1qODhRPU.

Fake medicine is a thriving business, making up at least 10% of global pharmaceutical commerce while also claiming thousands of lives each year.

In the U.S., counterfeit drugs range from cancer and diabetes treatment to erectile dysfunction medication. Counterfeit opioids have caused deaths in 46 states.

Tagging drugs would not only guard against fakery, but also help pharmacies better verify the legitimacy of a drug before selling to consumers.

"Every single tag is unique, offering a much higher level of security," said Young Kim, an associate professor in Purdue's Weldon School of Biomedical Engineering.

The tag acts as a digital fingerprint for each drug capsule or tablet, using an authentication technique called "physical unclonable functions," or PUF, that was originally developed for information and hardware security.

PUFs have the ability to generate a different response each time that they are stimulated, rendering them unpredictable and extremely difficult to duplicate. Even the manufacturer wouldn't be able to re-create an identical PUF tag.

Kim's group is the first to create an edible PUF - a thin, transparent film made of silk proteins and fluorescent proteins genetically fused together. Because the tag is easily digestible and made entirely of proteins, it can be consumed as part of a pill or tablet.

Shining various LED light sources on the tag excites the fluorescent silk microparticles, causing them to generate a different random pattern each time. The microparticles emit cyan, green, yellow or red fluorescent colors.

Digital bits can then be extracted from an image of those patterns to produce a security key, which a pharmacy or patient would use to confirm that a drug is authentic.

The researchers are currently converting this process to a smartphone app for both pharmacies and consumers.

"Our concept is to use a smartphone to shine an LED light on the tag and take a picture of it. The app then identifies if the medicine is genuine or fake," said Jung Woo Leem, a postdoctoral associate in biomedical engineering at Purdue.

The tag also has the potential to hold much more information than simply a confirmation of what the drug is, Leem said, such as the dose and expiration date.

Leem found that the tag works for at least a two-month period without the proteins degrading. Next, the team will need to confirm that the tag could last as long as a drug does and that it doesn't affect a medicine's key ingredients or potency.

DALLAS - Jan. 16, 2020 - A UT Southwestern researcher led a team that identified a new vulnerability in kidney tumors, the 10th most common cause of cancer death in men and women.

In their investigation of the most common type of kidney cancer, called clear cell renal cell carcinoma (ccRCC), Qing Zhang, Ph.D., and his colleagues identified a possible way to treat tumors while sparing nearby healthy tissue.

Their study uncovers a mechanism by which either the loss of a protein that protects against cancer or an oxygen-poor (hypoxic) environment can promote tumor growth via the cancer cell's oxygen-sensing pathway, he explains. Their work points to inhibiting an enzyme called TBK1, which becomes more active once the protein is lost, as a potential cancer-fighting strategy.

Because kidney cancer is often resistant to the most advanced treatments, new therapies are critically needed, says Zhang, associate professor of pathology and a corresponding author of the study published online recently by Cancer Discovery.

The American Cancer Society estimates that in 2019, kidney cell and renal pelvic cancers affected about 74,000 people in the U.S., resulting in nearly 15,000 deaths. Recently, it has been shown that treatment with one member of a drug class called hypoxia-inducible factor 2 alpha (HIF2α) inhibitors can block tumor growth in some kidney cancers. However, only a subset of tumors respond to that therapy and a significant number of patients develop resistance to it. "We need to identify additional strategies that would work alone or in combination with the HIF2α inhibitors," Zhang says.

Previous studies had found that 70 to 80 percent of kidney cancers show a loss of function of a critical tumor suppressor gene called von Hippel Lindau (VHL). "It had previously been shown that loss of the protein product of that gene mimics the hypoxic conditions under which many solid tumors seem to thrive," Zhang says.

Based on that knowledge, the researchers aimed to identify enzymes with potential therapeutic action against kidney cancer with VHL protein loss.

"We identified one particular enzyme, called TBK1 (TANK-binding kinase 1), that is highly activated in kidney cancer patients with VHL loss," says Zhang of the study that began while he was at the University of North Carolina at Chapel Hill and continued after his arrival at UT Southwestern last year.

TBK1 is an enzyme best known for its role in innate immunity, where it is important in the STING cellular sensing pathway that detects viral invaders. To study the enzyme's activity in the context of cancer, the scientists conducted a series of experiments on several VHL protein-deficient ccRCC cell lines to see what would happen when TBK1 activity was reduced. Specifically, they used CRISPR gene-editing technology to remove the gene that makes TBK1, pharmacologically reduced the enzyme's activity, and used small molecules to degrade TBK1 protein.

"We found that inhibiting TBK1 activity slowed or blocked cancer cell growth," Zhang says.

In comparison experiments of cancerous and healthy cells that used small molecules to block TBK1 activity, the researchers found the strategy inhibited tumor growth in VHL-deficient ccRCC cells while leaving healthy cells with normal VHL protein levels unaffected. "That indicates this strategy holds the potential for selective lethality, killing the cancer cells without harming the healthy ones," says Zhang, a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar.

Because hypoxia is thought to occur in most tumors, the study may have broader implications. The researchers found that hypoxia can increase TBK1 activity through the same mechanism as VHL loss, i.e., through the cell's oxygen-sensing pathway, he says. "We believe targeting and manipulating TBK1 activity - possibly with drugs already under investigation for other cancers - may benefit patients with other forms of cancer," he says.

TBK1 is central to cell signaling in the innate immune system's antiviral response, so the researchers wanted to learn whether the protein's immune system activity was connected to the effects they observed in kidney cancer. To do that, they studied TBK1-depleted cancer cells to see if the proteins created by genes governing the cell's innate immune response pathway were affected. They were not. That finding indicated that TBK1's novel role in cancer is distinct from the enzyme's function in the immune system.

Next steps include trying to optimize the efficiency of the small molecules used in this study and testing them in ccRCC tumor cells grown in mice, Zhang says. Additionally, recent studies from other laboratories indicated depletion of TBK1 can boost the effectiveness of a class of anti-cancer drugs called immune checkpoint inhibitors. So that is another area of interest for future studies, he adds.

"We propose that TBK1 is a promising potential therapeutic target for kidney cancer," Zhang says.