Earth

Tohoku University researchers have developed a strategy that could help cells get rid of disease-related debris. Further research could lead to treatments for neurodegenerative and metabolic diseases, Down syndrome, and maybe even aging-related diseases. The findings were published in the journal Molecular Cell.

Cells have a natural ability to routinely rid themselves of unnecessary or dysfunctional proteins and organelles. During this process of 'autophagy', debris are tagged with a compound called ubiquitin and then degraded within tiny cellular vacuoles. Autophagy is impaired in some cancers, and neurodegenerative and metabolic diseases, so scientists have been working to develop drugs that can regulate this process. However, little is known about the details of autophagy, such as how the cell knows which components to tag with ubiquitin.

In previous research, Hirokazu Arimoto, a chemical biologist at Tohoku University, and colleagues found that autophagy is initiated against invading streptococci bacteria when they are tagged with the nucleic acid guanine. The researchers wondered if guanine tagging could also initiate autophagy against other cellular components.

Their investigations led to the development of a molecule they called AUTAC, which stands for autophagy-targeting chimera. AUTAC is formed of guanine attached to a 'warhead', which can be changed to target specific intracellular components. Different AUTACs successfully targeted and tagged specific intracellular proteins for autophagy, the researchers report.

For example, they designed an AUTAC targeting a protein on the mitochondrial membrane. Mitochondrial dysfunction causes some symptoms frequently seen in Down syndrome, including heart disease, hearing loss and dementia. It also causes several diseases associated with aging.

The AUTAC successfully targeted fragmented mitochondria in cells taken from someone with Down syndrome. Not only did this accelerate their removal, it also fast-tracked the formation of new, normally functioning mitochondria.

"AUTAC degrades its target, making it a game-changing innovation for the drug industry," says Arimoto. "Current small molecule drugs bind to molecules, like proteins, and interfere with their functions, but do not degrade them. The degradation of biomolecules gets rid of all the functions and is a more powerful method."

Arimoto and his team are now working on developing second-generation AUTAC molecules that will be at least 100 times more effective, he says.

Not all neonicotinoid insecticides have negative effects on bees, according to researchers at Lund University and the Swedish University of Agricultural Sciences. Their new study indicates that the use of certain neonicotinoids could benefit bumblebees and pollination.

WATCH VIDEO STORY: https://www.youtube.com/watch?v=osL71KkyD94&feature=youtu.be

In a field study, the researchers Maj Rundlöf, Lund University, and Ola Lundin, the Swedish University of Agricultural Sciences, have found that the neonicotinoid thiacloprid does not have any detectable negative impact on bumblebees. When the insecticide was used on red clover fields, insect pests were successfully controlled while at the same time more bumblebees came to visit and pollinated the crop.

The study also showed that the bumblebee colonies close to the thiacloprid-treated red clover fields grew larger in comparison with bumblebee colonies in landscapes without red clover fields.

The research therefore indicates that certain neonicotinoids that are still permitted in the EU could actually benefit the bumblebees rather than harming them. The risk of direct impact on the bumblebees is low, while the thiacloprid protects the flowering fields where the bumblebees feed.

"Our study shows that neonicotinoids should not be treated as a homogenous group when evaluating the environmental risks of insecticides. There are pest management solutions that do not detectably harm bumblebees", says Maj Rundlöf.

Since 1 December 2013, there has been a ban within the EU on the use of three neonicotinoids on flowering crops. The ban concerns clothianidin, imidacloprid and thiamethoxam. The reason for the ban is that the substances have been identified as harmful to bees. In spring 2018, the EU tightened the ban, and now insecticides containing any of the three substances may only be used in permanent greenhouses.

If the recently studied neonicotinoid thiacloprid meets the same fate, it could lead to negative consequences for bumblebees, according to Maj Rundlöf.

"If this effective pest management solution was to disappear from the market without there being an adequate alternative, farmers would most likely grow less red clover seed and this would mean less food for the bumblebees", she say.

Thiacloprid is on the EU list of candidates for substitution, meaning it could be banned in the near future. This is because it has been found to have endocrine disruptive properties. However, Maj Rundlöf hopes future studies can build on the findings from this research.

"Our study nuances the view on neonicotinoids a little. The results open up to there being other alternatives within the neonicotinoid group that are not suspected to have endocrine disruptive properties. These could be alternatives for efficient pest regulation that are still acceptable for pollinators as well as humans", she concludes.

Engineers from Carnegie Mellon University's Scott Institute for Energy Innovation have compiled carbon emissions for the U.S. electric power sector for the second quarter (Q2) of 2019 as part of the CMU Power Sector Carbon Index. The index tracks carbon emissions and electricity generation over time and by energy source. Compared to Q2 of 2018, total U.S. power generation fell by 4% in Q2 of 2019, and the carbon intensity of the sector, measured in pounds of CO2 emissions per megawatt-hour, dropped by 9%.

"The U.S. electricity sector is continuing to get cleaner, and both carbon intensity and overall emissions are dropping," said Costa Samaras assistant professor of Civil and Environmental Engineering and Power Sector Carbon Index co-director.

Coal generation in 2019 Q2 is down 19% compared to just a year ago. After being the dominant source of power production in the U.S. for most of the electric age, coal has been on a steady decline for the past decade. In 2016, natural gas replaced coal as the largest source of electricity, a trend which has continued since. Burning natural gas produces only about half of the direct CO2 emissions that coal does, per unit of energy generated. In 2019 Q2, power generation from coal provided 21% of the nation's electricity, while natural gas provided 36%.

"We're in the middle of an energy transition right now, and the biggest part of that story in the U.S. is how swiftly coal has been declining over the past decade," said Samaras. "The decline of coal can be attributed to the rise of natural gas, the continued improvement of renewables, and energy efficiency efforts."

Renewables saw considerable growth over the past year. Compared to 2018 Q2, generation from solar increased 10% and generation from wind increased by 7%. "Wind and solar power are getting more and more competitive in electricity markets," said Samaras, pointing to the falling production costs as a significant driver of renewable energy. The large majority of renewable generation currently comes from utility-scale projects, as opposed to distributed generation like residential roof-top solar or small wind turbines. Together, wind and solar accounted for 11% of U.S. power generation in 2019 Q2. Hydropower generation provided 8%.

Despite notable recent nuclear plant closures such as Three Mile Island Nuclear Generating Station, nuclear power remained the largest zero-carbon source of electricity in the U.S., accounting for 20% of total generation.

The Power Sector Carbon Index, supported by Mitsubishi Hitachi Power Systems, was created to give policy makers, academics, industries, think-tanks, and the public up-to-date information on trends in the carbon intensity of the U.S. power sector. Though it relies on publicly available data, the Power Sector Index compiles information from disparate datasets and standardizes the calculation of carbon intensity, providing a much-needed service for anyone wanting to track the performance of the sector.

Compared to 2005, a year commonly used to benchmark progress in reducing emissions, the carbon intensity of the U.S. power sector is down more than 38% in 2019 Q2. Much of this progress comes simply from displacing coal with natural gas, though high-efficiency natural gas plants do account for a small portion of this reduction. Renewable sources, which Samaras expects will continue to add capacity to the power sector, account for most of the rest of this reduction in carbon intensity.

In 2017, for the first time in decades, transportation supplanted power generation as the economic sector with the highest greenhouse gas emissions. Tracking carbon in the power sector, according to Samaras, remains the fundamental barometer of progress in decarbonization due to the promise of electrification reducing emissions from other sectors, like transportation (with electric vehicles), buildings (with electric space heating), and some industrial activities. The Power Sector Carbon Index will continue to track these trends in a useful, easy to understand, and reliable way for anyone interested in U.S. carbon emissions.

Sharks, penguins, turtles and other seagoing species could help humans monitor the oceans by transmitting oceanographic information from electronic tags.

Thousands of marine animals are tagged for a variety of research and conservation purposes, but at present the information gathered isn't widely used to track climate change and other shifts in the oceans.

Instead, monitoring is mostly done by research vessels, underwater drones and thousands of floating sensors that drift with the currents. However, large areas of the ocean still remain under-sampled - leaving gaps in our knowledge.

A team led by the University of Exeter says animals carrying sensors can fill many of these gaps through natural behaviour such as diving under ice, swimming in shallow water or moving against currents.

"We want to highlight the massive potential of animal-borne sensors to teach us about the oceans," said lead author Dr David March, of Centre for Ecology and Conservation on Exeter's Penryn Campus in Cornwall.

"This is already happening on a limited scale, but there's scope for much more.

"We looked at 183 species - including tuna, sharks, rays, whales and flying seabirds - and the areas they are known to inhabit.

"We have processed more than 1.5 million measurements from floating sensors to identify poorly sampled areas (18.6% of the global ocean surface)."

"By comparing this with gaps in current observations by drifting profiling sensors (known as Argo floats) we identified poorly sampled areas where data from animal sensors would help fill gaps," said Professor Brendan Godley, who leads Exeter Marine.

"These include seas near the poles (above 60º latitude) and shallow and coastal areas where Argo profilers are at risk of hitting the land.

"The Caribbean and seas around Indonesia, as well as other semi-enclosed seas, are good examples of places where Argo profilers struggle because of these problems."

Tagged seals in the poles have already complemented ocean observing systems because they can reach areas under ice that are inaccessible to other instruments.

The study suggests data collected by turtles or sharks could also enhance ocean monitoring in other remote and critical areas such as tropical regions, with large influence on global climate variability and weather.

The researchers say their work is a call for further collaboration between ecologists and oceanographers.

Professor Godley added: "It is important to note that animal welfare is paramount and we are only suggesting that animals that are already being tracked for ethically defensible and conservation-relevant ecological research be recruited as oceanographers. We do not advocate for animals being tracked solely for oceanography."

UCLA scientists have discovered a link between a protein and the ability of human blood stem cells to self-renew. In a study published today in the journal Nature, the team reports that activating the protein causes blood stem cells to self-renew at least twelvefold in laboratory conditions.

Multiplying blood stem cells in conditions outside the human body could greatly improve treatment options for blood cancers like leukemia and for many inherited blood diseases.

Dr. Hanna Mikkola, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and senior author of the study, has studied blood stem cells for more than 20 years.

"Although we've learned a lot about the biology of these cells over the years, one key challenge has remained: making human blood stem cells self-renew in the lab," she said. "We have to overcome this obstacle to move the field forward."

Blood stem cells, also known as hematopoietic stem cells, are found in the bone marrow, where they self-renew as well as differentiate to create all types of blood cells. Bone marrow transplants have been used for decades to treat people with some diseases of the blood or immune system. However, bone marrow transplants have significant limitations: Finding a compatible bone marrow donor is not always possible, the patient's immune system may reject the foreign cells, and the number of transplanted stem cells may not be enough to successfully treat the disease.

When blood stem cells are removed from the bone marrow and placed in laboratory dishes, they quickly lose their ability to self-renew, and they either die or differentiate into other blood cell types. Mikkola's goal, making blood stem cells self-renew in controlled laboratory conditions, would open up a host of new possibilities for treating many blood disorders -- among them safer genetic engineering of patients' own blood stem cells. It could also enable scientists to produce blood stem cells from pluripotent stem cells, which have the potential to create any cell type in the body.

To uncover what makes blood stem cells self-renew in a lab, the researchers analyzed the genes that turn off as human blood stem cells lose their ability to self-renew, noting which genes turned off when blood stem cells differentiate into specific blood cells such as white or red cells. They then put the blood stem cells into laboratory dishes and observed which genes shut down. Using pluripotent stem cells, they made blood stem cell-like cells that lacked the ability to self-renew and monitored which genes were not activated.

They found that the expression of a gene called MLLT3 was closely correlated with blood stem cells' potential to self-renew and that the protein generated by the MLLT3 gene provides blood stem cells with the instructions necessary to maintain its ability to self-renew. It does this by working with other regulatory proteins to keep important parts of the blood stem cell's machinery operational as the cells divide.

The researchers wondered if maintaining the level of the MLLT3 protein in blood stem cells in lab dishes would be sufficient to improve their self-renewing abilities. Using a viral vector -- a specially modified virus that can carry genetic information to a cell's nucleus without causing a disease -- the team inserted an active MLLT3 gene into blood stem cells and observed that functional blood stem cells were able to multiply in number at least twelvefold in lab dishes.

"If we think about the amount of blood stem cells needed to treat a patient, that's a significant number," said Mikkola, who is also a professor of molecular, cell and developmental biology in the UCLA College and a member of the UCLA Jonsson Comprehensive Cancer Center. "But we're not just focusing on quantity; we also need to ensure that the lab-created blood stem cells can continue to function properly by making all blood cell types when transplanted."

Other recent studies have identified small molecules -- organic compounds that are often used to create pharmaceutical drugs -- that help to multiply human blood stem cells in the laboratory. When Mikkola's team used the small molecules, they observed that blood stem cell self-renewal improved in general, but the cells could not maintain proper MLLT3 levels, and they also did not function as well when transplanted into mice.

"The previous discoveries with the small molecules are very important, and we're building on them," said Vincenzo Calvanese, a UCLA project scientist and the study's co-corresponding author. "Our method, which exposes blood stem cells to the small molecules and also inserts an active MLLT3 gene, created blood stem cells that integrated well into mouse bone marrow, efficiently produced all blood cell types and maintained their self-renewing ability."

Importantly, MLLT3 made the blood stem cells self-renew at a safe rate; they didn't acquire any dangerous characteristics such as multiplying too much or mutating and producing abnormal cells that could lead to leukemia.

The next steps for the researchers include determining what proteins and elements within blood stem cell DNA influence the on-off switch for MLLT3, and how this could be controlled using ingredients in the lab dishes. With that information, they could potentially find ways to switch MLLT3 on and off without the use of a viral vector, which would be safer for use in a clinical setting.

LA JOLLA, CA - The brain mechanism that enables us to maintain a constant body temperature may also be the key to rapid weight loss, a new study finds. In experiments involving mice that were given a calorie-restricted diet, scientists at Scripps Research discovered that blocking a brain receptor that normally regulates body heat resulted in significant weight reductions.

The findings will be further explored as a potential treatment approach for obesity, which the World Health Organization has called a global epidemic. Obesity affects virtually all age and socioeconomic groups--increasing risk for heart disease, stroke, diabetes, cancer and many other serious health conditions.

The new study, led by Scripps Research Professor Bruno Conti, PhD, appears in Current Biology.

"Up to 50 percent of what we eat every day is used as energy to maintain body temperature," Conti says. "But when food is scarce, mammals adapt by lowering their temperature, limiting energy expenditure and the loss of body weight."

Some species, he notes, can go into complete hibernation. Of course, humans don't hibernate when they're on a calorie-restricted diet, but they do naturally experience a lower body temperature just like other mammals. And that makes it harder to lose weight when on a diet.

"It's a basic survival mechanism," Conti says. "The body is saying: Let's save energy today and maybe we will find food tomorrow."

In a continuation of their earlier research on lifespan and aging, Conti and his team investigated the cellular mechanisms that regulate the body's cooling response to calorie restriction. Biological data obtained in collaboration with the Scripps Research lab of Gary Siuzdak, PhD, suggested the possibility that opioid compounds that naturally occur within the body could be mediating these effects.

Next, the team tested whether blocking the activity of opioid receptors would affect body temperature during calorie restriction. It did. They also determined that this mechanism was uniquely regulated by one of the three known opioid receptor types: the kappa opioid receptor. The finding made sense, as the kappa receptor is the most abundant opioid receptor in the hypothalamus, the part of the brain already known to play a role in regulating both body temperature and feeding.

Conti's team then wondered if by blocking the kappa receptor, the body would continue to burn up calories to regulate heat even when food was restricted. "We developed an experimental protocol that would allow us to determine what changes were happening as a result of body heat regulation, not diet," says Rigo Cintron-Colon, PhD, first author of the study.

In one set of experiments, the scientists observed two groups of lean mice that had already been on calorie-restricted diets for six weeks. One group was then treated with a drug to block the kappa receptor. The control group had adapted to the new diet and weight loss plateaued, while the experimental group showed greater energy expenditure and lost an additional 6 percent of body weight.

"When we blocked the kappa receptor, the animals did not lower their temperature during calorie restriction and lost more body weight," Conti says.

Similar results were obtained with mice that had developed diet-induced obesity. Blocking the kappa opioid receptor during calorie restriction nearly doubled the body weight loss that the obese animals would normally undergo if their receptor was functional. However, when animals were allowed to eat freely, blocking the kappa opioid receptor had no effects on body temperature and did not alter the normal rate of body weight loss.

This is important, Conti says, as it tells us that kappa opioid blockers are effective in both lean mice and obese mice, but that the medicine is able to affect body weight only in animals that are dieting.

The findings suggest a possibility that by translating these findings into humans, a pharmaceutical product may be able to help those who are struggling to lose weight, despite their adherence to a calorie-restricted diet. As a next step, Conti would like to explore whether existing medicines that are known to block the kappa receptor could be repurposed and refined to safely treat obesity.

"The tools to interact with this mechanism may already be available, and if they are, they may be able to translate quickly into a medicine," he says. "Unfortunately, for many people who are obese, losing weight isn't as simple as eating less."

Once a bully, always a bully?

It's not that simple, according to a new University of Guelph study of aggression in fruit flies that underlines the often unpredictable nature of behaviour from insects to humans.

The study is the first to show that effects of an earlier aggressive encounter carry over in time and across different social groups but not necessarily in expected ways, said Julia Kilgour, lead author and a PhD student in the Department of Integrative Biology.

The study was published recently in the journal Behavioral Ecology.

"This study shows that aggression doesn't just depend on who you are and who you're interacting with but also depends on your previous interactions. That's the unique part," Kilgour said.

In different settings and from one encounter to the next, the schoolyard bully might turn passive or the mild-mannered office worker might unexpectedly lash out at a colleague.

"Aggression is a plastic trait," said Prof. Andrew McAdam, who co-advised Kilgour along with integrative biology professor Ryan Norris. "Someone may be aggressive with one partner and not another."

For this study, Kilgour worked with two strains of fruit flies specially bred for aggressive or non-aggressive behaviour.

She sorted the flies into five social groups, including two homogeneous groups: one with all aggressive insects and another with all non-aggressive flies.

For the three other groups, she mixed flies with those opposing traits: 75-percent aggressive; 50-50 aggressive and less aggressive; and 75-percent less aggressive.

From each of the five social groups, half were placed in clusters of only 30 insects and the other half in swarms of 300 flies. Each of the resulting 10 clusters received the same amount of food for four days, forcing the insects into less or more competition for the fixed resource.

Kilgour also separated males and females to see whether sex affected behaviour.

After four days, she measured aggression in all the groups. To do that, she paired an individual fly from each group with a new fly and looked for characteristic head-butting in females and lunges in males.

Describing pugilism Drosophila-style, Kilgour said, "One fly will rear up and snap down on the other fly. It gets pretty aggressive."

The team found that males in homogeneous groups - whether in high- or low-density clusters of flies - became more aggressive in later one-on-one encounters.

Among mixed groups, male flies that made up a minority also became more aggressive. But males from groups of equally mixed strains and males that made up a majority showed no more aggression in subsequent one-on-ones.

In all cases, the effects lasted for up to three days.

Researchers found no behavioural change among female flies, although Kilgour said further tests might uncover more subtle differences.

Although she can't explain the varied responses among groups, she said the study underlines the unpredictable nature of behaviour. "We thought that aggression was always going to be beneficial to get what you want. But it's not so clear cut. This shows how complicated behaviour is, even in fruit flies."

As for people, she added: "Our behaviour is heavily influenced by past social experiences. We may not always behave in a way that is optimal - being angry when we shouldn't or being passive when we shouldn't. Part of the reason is our social experiences."

McAdam said behaviour in one place may not always predict what happens later in other settings.

Referring to day-to-day stresses, he said, "We all hope to leave work at work and not bring it home, but inevitably you carry some of your previous social interactions back home, and these influence how you interact with your loved ones.

"Or a child in school acting in one way: that behaviour might not necessarily be explained only by what happens in the classroom. Children bring previous experiences from home or other places with them to school each day."

Researchers at the Tokyo Medical and Dental University (TMDU) discover a new method for synthesizing γ-aryl-β-ketoesters, an important class of molecules for the pharmaceutical industry

Tokyo, Japan - Researchers at the Tokyo Medical and Dental University (TMDU) have introduced a new synthetic process for producing an important family of carbon-based molecules known as γ-aryl-β-ketoesters. These molecules are used in the production of many vital pharmaceuticals, including alectinib, which is administered to treat non-small-cell lung cancer, and Januvia, a diabetes drug. This chemical approach may help in the preparation of a diverse range of their analogs and many other medication candidates more quickly.

Organic chemistry, which studies reactions involving carbon-based molecules, is central to the pharmaceutical industry. Certain reactions, such as the formation of multi-substituted aromatic compounds, are essential to the production of a variety of drugs. One important class of molecules that can be utilized as versatile intermediates are the γ-aryl-β-ketoesters. However, it was difficult to synthesize a variety of these critical molecules. In a study published in Organic Letters at October 24, researchers from Tokyo Medical and Dental University (TMDU) report a new reaction pathway to easily produce γ-aryl-β-ketoesters. To do this, they utilized aryne chemistry, which involves the removal of two substituents from a benzene ring, yielding a very reactive chemical species. "To successfully synthesize the γ-aryl-β-ketoesters, we decided to use a pathway that involves γ-aryl-β-ketoester-type arynes, because they are useful intermediates for creating multi-substituted aromatic derivatives," says first author Keisuke Uchida.

As a demonstration of the value of producing γ-aryl-β-ketoester using this novel method, the research team synthesized an analog of alectinib, which is an important inhibitor of certain lung cancers. As a complex molecule, the synthesis of various analogs by the conventional method takes considerable time and efforts, so the new approach that renders various γ-aryl-β-ketoesters easily available can improve the accessibility to them. This is true for many other organic compounds as well. "By virtue of the flexibility of aryne intermediates, our new synthetic approach may assist in the preparation of many important bioactive compounds, both for the pharmaceutical sector as well as for agrochemical sciences," senior author Takamitsu Hosoya says. The research group plans to expand the scope of their method to other molecules which may lead to faster and more cost-effective drug discovery in the future.

PHILADELPHIA - Soft tissue sarcoma cells stop a key metabolic process which allows them to multiply and spread, and so restarting that process could leave these cancers vulnerable to a variety of treatments. The enzyme that controls the process is called FBP2, and researchers from the Abramson Cancer Center of the University of Pennsylvania, who detailed their findings in Cell Metabolism, also showed that manipulating sarcoma cells to ramp up FBP2 expression slows or even stops their growth entirely. This ultimately leaves them susceptible to targeted therapies and potentially takes away their ability to develop treatment resistance.

Soft tissue sarcoma is actually a collection of distinct, rare cancer types affecting tissues that connect and surround other parts of the body, including muscle, fat, tendons, nerves, and blood vessels. While they can grow anywhere, the arms, legs, chest, and stomach are the most common sites. Because these cancers appear in so many different places in the body, their biology is incredibly diverse, making it difficult to develop one targeted treatment that can be broadly effective for all patients. Currently, the best options for treatment are surgery - which may involve amputation - chemotherapy, and radiation.

"While other cancer types associated with high mutational burden have benefitted from the development of immunotherapies, the diversity and low frequency of genetic mutations in soft tissue sarcomas have made them more difficult to treat, which is why our identification of a broadly expressed metabolic approach is potentially so exciting," said the study's senior author M. Celeste Simon, PhD, the Arthur H. Rubenstein, MBBCh Professor of Cell and Developmental Biology in Penn's Perelman School of Medicine and scientific director of the Abramson Family Cancer Research Institute. The study's lead author is Peiwei Huangyang, who performed the work while obtaining her PhD in Simon's lab.

While FBP2 is broadly expressed in normal cells, soft tissue sarcomas have a way of dramatically suppressing it. Building on their previous work - published in Nature - showing a related pathway controlled by FBP1 serves a similar function in renal and liver cancer, Simon and her team used mouse models to show that causing soft tissue sarcoma cells to re-express FBP2 the way healthy cells do stops the cancer from growing, potentially making it more vulnerable to both targeted and immune-based therapies.

"Essentially, once they start acting like normal cells, they don't hide and grow the way cancer normally does," Simon said.

The team also found that the enzymes involved in this process are located in the cell's nucleus, meaning this pathway could stop cancer cells from adapting to their natural environment and becoming resistant to cytotoxic drugs. It's tied to the understanding of how cells respond to environmental stresses to alter their metabolism and survive, which is the work that received the 2019 Nobel Prize in Physiology or Medicine.

While this study shows the importance of FBP2, further research is needed to show that using drugs to manipulate cells to re-express FB2 will have the expected effect. Simon points out that these drugs already exist in other cancer treatments - specifically blood cancers - meaning the pipeline to translate this approach to patients should be relatively rapid if research proves it is effective.

MADISON, Wis. -- Last year, scientists announced that a human jawbone and prehistoric tools found in 2002 in Misliya Cave, on the western edge of Israel, were between 177,000 and 194,000 years old.

The finding suggested that modern humans, who originated in Africa, began migrating out of the continent at least 40,000 years earlier than scientists previously thought.

But the story of how and when modern humans originated and spread throughout the world is still in draft form. That's because science hasn't settled how many times modern humans left Africa, or just how many routes they may have taken.

A new study published this week [Nov. 25, 2019] in the Proceedings of the National Academy of Sciences by American and Israeli geoscientists and climatologists provides evidence that summer monsoons from Asia and Africa may have reached into the Middle East for periods of time going back at least 125,000 years, providing suitable corridors for human migration.

The likely timing of these northward monsoon expansions corresponds with cyclical changes in Earth's orbit that would have brought the Northern Hemisphere closer to the sun and led to increased summer precipitation. With increased summer precipitation there may have been increased vegetation, supporting animal and human migration into the region.

"It could be important context for experts studying how, why, and when early modern humans were migrating out of Africa," says lead author Ian Orland, a University of Wisconsin-Madison geoscientist now at the Wisconsin Geological and Natural History Survey, in the Division of Extension. "The Eastern Mediterranean was a critical bottleneck for that route out of Africa and if our suggestion is right, at 125,000 years ago and potentially at other periods, there may have been more consistent rainfall on a year-round basis that might enhance the ability of humans to migrate."

For as long as humans have kept records, winters have been wet and summers have been hot and dry in the Levant, a region that includes Israel, Syria, Lebanon, Jordan and Palestine. Before modern times, those hot, dry summers would have presented a significant barrier to people trying to move across the landscape.

Scientists, though, have found it difficult to determine what kinds of precipitation patterns might have existed in the prehistoric Levant. Some studies examining a variety of evidence, including pollen records, ancient lake beds, and Dead Sea sediments, along with some climate modeling studies, indicate summers in the region may have, on occasion, been wet.

To try to better understand this seasonality, Orland and colleagues looked at cave formations called speleothems in Israel's Soreq Cave. Speleothems, such as stalactites and stalagmites, form when water drips into a cave and deposits a hard mineral called calcite. The water contains chemical fingerprints called isotopes that keep a record, like an archive, of the timing and environmental conditions under which speleothems have grown.

Among these isotopes are different forms of oxygen molecules -- a light form called O16 and a heavy form called O18. Today, the water contributing to speleothem growth throughout much of the year has both heavy and light oxygen, with the light oxygen predominantly delivered by rainstorms during the winter wet season.

Orland and his colleagues hypothesized they might be able to discern from speleothems whether two rainy seasons had contributed to their growth at times in the past because they might show a similar signature of light oxygen in both winter and summer growth.

But to make this comparison, the scientists had to make isotope measurements across single growth bands, which are narrower than a human hair. Using a sensitive instrument in the UW-Madison Department of Geoscience called an ion microprobe, the team measured the relative amounts of light and heavy oxygen at seasonal increments across the growth bands of two 125,000-year-old speleothems from Soreq Cave.

This was the first time that seasonal changes were directly measured in a speleothem this old.

At the same time that Orland was in pursuit of geologic answers, his UW-Madison colleague in the Nelson Institute for Environmental Studies Center for Climatic Research, Feng He, was independently using climate models to examine how vegetation on the planet has changed with seasonal fluctuations over the last 800,000 years. Colleagues since graduate school, He and Orland teamed up to combine their respective approaches after learning their studies were complementary.

A previous study in 2014 from UW-Madison climatologist and Professor Emeritus John Kutzbach showed that the Middle East may have been warmer and wetter than usual during two periods of time corresponding roughly to 125,000 years ago and 105,000 years ago. Meanwhile, at a point in between, 115,000 years ago, conditions there were more similar to today.

The wetter time periods corresponded to peak summer insolation in the Northern Hemisphere, when Earth passes closer to the sun due to subtle changes in its orbit. The drier time period corresponded to one of its farthest orbits from the sun. Monsoon seasons tend to be stronger during peak insolation.

This provided He an opportunity to study high and low insolation rainfall during summer seasons in the Middle East and to study its isotopic signatures.

The climate model "fueled the summer monsoon hypothesis" because it suggested that "under these conditions, the monsoons could have reached the Middle East and would have a low O18 signature," He, a study co-author, says. "It's a very intriguing period in terms of climate and human evolution."

His model showed that northward expansion of the African and Asian summer monsoons was possible during this time period, would have brought significant rainfall to the Levant in the summer months, would have nearly doubled annual precipitation in the region, and would have left an oxygen isotope signature similar to winter rains.

At the same time, Orland's speleothem isotype analysis also suggested summers were rainier during peak insolation at 125,000 and 105,000 years ago.

For similar reasons, the Middle East may have also been warm and humid around 176,000 years ago, the researchers say -- about when the jawbone made its way to Misliya Cave. And before the jawbone, the previous oldest modern human fossils found outside of Africa were at Israel's Skh?l Cave, dating back between 80,000 and 120,000 years ago.

Overall, the study suggests that during a period of time when humans and their ancestors were exploring beyond the African continent, conditions may have been favorable for them to traverse the Levant.

"Human migration out of Africa occurred in pulses, which is definitely consistent with our idea that every time the Earth is closer to the sun, the summer monsoon is stronger and that's the climatic window that opened and provided opportunities for human migration out of Africa," says He.

Staphylococcus aureus is a major human pathogen prone to developing antibiotic resistance, causing 120,000 cases of bloodstream infections every year in the United States and over 5000 in Australia; the mortality rate is around 25 per cent from each case.

The Bengal Bay clone was first described in the 1990s with reports of it causing severe disease in India.

Researchers from the Peter Doherty Institute for Infection and Immunity (Doherty Institute), the Australian Institute of Tropical Health and Medicine and the Wellcome Sanger Institute in the UK found the Bengal Bay clone combines the high virulence potential of community clones with the multi-drug resistance of health care-associated S. aureus lineages.

Published today in the journal mBio, researchers were able to show step-by-step mutations of the Bengal Bay clone, narrowing down the timeline of increasing resistance to different antibiotics and when it was exported across international borders.

Senior author, Royal Melbourne Hospital Clinician Researcher, Associate Professor Steven Tong from the Doherty Institute, said the team sequenced 340 isolates from 14 countries, including the first isolates from Bangladesh and India from the 1990s.

"By being able to map the Bengal Bay clone over many years, we were able to see it progressively acquire specific antibiotic resistance mechanisms, following which it achieved global transmission through family contacts or travel. Several small-scale community and health care outbreaks were evident after importation to countries outside the Indian subcontinent," Associate Professor Tong said.

"We have already seen two documented cases of the Bengal Bay clone in neonatal intensive care units.

"This study highlights how antibiotic resistant pathogens can arise from areas of the world with limited public health infrastructure and control of antibiotic use, and then spread globally. Ultimately, rising rates of antibiotic resistance is a global issue."

Associate Professor Tong said previously, antibiotic resistant forms of S. aureus (MRSA) were mainly found in hospitals and were difficult to treat due to resistance to multiple antibiotics.

"More recently, MRSA clones have been causing major problems in the community setting in patients who have never been to hospital," he said.

"These community clones tended to be more virulent with the ability to cause severe disease in otherwise young, healthy individuals. But thankfully, the community clones have typically been resistant to fewer antibiotics. The Bengal Bay clone combines a high level of both antibiotic resistance and virulence."

The near-infrared light is a light source with the shortest wavelength, indicated outside of the red color in the light spectrum. The near-infrared light has been widely used in optical communications, medical lasers, LiDAR of self-driving vehicles, and security and surveillance instruments, ranging from private to defense industry. To utilize this near-infrared light, the technology that converts light into an electrical energy through a photodetector is crucial. The research team from POSTECH successfully developed a photodiode with increased absorption of the near-infrared light by using the hourglass principle.

The research team was led by Professor Chang-Ki Baek and consisted of a research professor, Kihyun Kim, Myunghae Seo of Creative IT Engineering and Sol Yoon of Electronic and Electrical Engineering. The team developed hourglass-shaped silicon nanowires to enhance photoresponse while using the conventional semiconductor process. Their establishment was published in the world's most renowned respected journal of electronics engineering, Nature Electronics on November 5.

Before their finding, the near-infrared photodiodes were made of chemical materials. For this reason, it required a separate cooling device due to the noise and high production cost when making into a large area. It was also very difficult to integrate. To overcome these difficulties of chemical materials, the team used silicon instead. Furthermore, they suggested to use hourglass-shaped silicon nanowires to increase silicon's absorptance of the near-infrared light.

As low sound can be heard loudly in the upper part of the nanowires, the light causes whispering-gallery-mode resonance*. So, the near-infrared light rotates along the diameter of nanowires and is absorbed. Thus, it is effective in extending wavelength of light. Also, the lower part of the nanowires has its diameter size gradually enlarged in the vertical direction where the difference of reflectance between air and silicon is progressively increased. This makes it effectively reabsorb the light source reflected and/or penetrated from the upper part of the nanowires.

The research team proved that the hourglass-shaped nanowires illustrated 29% increased near-infrared photoreseponse at wavelength of 1,000nm in comparison to the existing silicon photodiode with flat-panel. In addition, this newly developed photodiode was applied to a mobile heart-rate measurement system for demonstration. By doing this, they verified and confirmed of its commercialization when it demonstrated larger wave of heart rate and less than 1% of error rate than the existing photodiodes.

Professor Chang-Ki Baek who led this research said in his comment, "this study used the existing silicon that can be produced in mass at low cost and 100% compatible to the semiconductor production. It is very meaningful in that we were able to demonstrate increased photoresponsivity of the near-infrared light at the wavelength where the existing silicon cannot detect. It is possible that the developed device can optimize the absorption of the near infrared wavelength desired according to the structure of nanowires. It is expected to provide optical solutions to various fields such as LiDAR of a vehicle, medical laser, military night vision goggles, image sensors and more.

The Bulwer's petrel reaches more than 1,800 kilometers from the Canary archipelago up to the Azores on its route in search of food, according to data from a new scientific monograph based on the studies carried out from 2010 to 2018 by the Research Group of Ecology of Marine Birds of the Faculty of Biology and the Biodiversity Research Institute of the University of Barcelona (IRBio), under the supervision of Professor Jacob González-Solís.

The new study, carried out in the breeding colony in the Canary Island Montaña Clara, at the north of Lanzarote, shows the migratory routes as well as wintering areas of the Bulwer's petrel. With the data researchers obtained from 105 birds with geolocation devices (GPS and GLS), 59 complete routes to find food and 48,597 geographical positions, this is the most comprehensive scientific studied ever published so far on the space ecology, diet and daily and annual pattern of movements of the Bulwer's petrel, a threatened species.

The new volume is the fourth monograph of the Migra program, promoted by SEO/BirdLife, with the collaboration of Iberdrola Spain Foundation. This monography, whose first author is Marta Cruz Flores, researcher at UB-IRBIO and coordinator of the SEO/BirdLife Iberian Group for Marine Birds (GIAM), also counts on the participation of Raül Ramos, Mariona Sardà-Serra, Sofía López and Teresa Militão (UB-IRBio).

Featured on the red list of threatened birds in Spain

Most part of the global population of the Bulwer's petrel (Bulweria bulwerii) lives in the Pacific Ocean. In the Atlantic, this marine bird breeds regularly in the archipelagos of the Canary Islands, Azores, Madeira and Cape Verde. This species, which spends most of the time at the open sea, gets closer to the land -mainly cliffs and stone quarries- during its mating season.

At the moment, predation by introduced mammals (rats and cats), loss of natural habitat due coastal urbanizations and marine and light pollution -which confuses birds when flying- are the main threats for this species, listed as endangered according to the Red Book of Birds of Spain. There are about 1,000 bird couples in Spain.

Where are the petrels during the year?

The new study notes the two big migratory strategies described for the Bulwer's petrel populations during wintering seasons: one towards the Central Atlantic and the other to Southern Atlantic, and these are always on ocean waters which are far from continental platforms.

From November to February, petrels are exclusively in these wintering areas, to which they come back to every year. In general, birds that winter in the Central Atlantic show a two-way migration to an only wintering area (between 20º N and 10º S latitude). Regarding the population that winters in the Southern Atlantic, those birds combine migratory periods with up to five migratory stops (over 15º S and sometimes 30º S).

Males and females take turns to incubate the only laid egg

During the breeding season -between May and August- the petrel flies around the Canary Islands and reaches the Azores in order to find food. These journeys take place over the ocean waters -where preys live- and are two-way journeys coming back to the breeding colony. Both males and females take turns up to 15 days to incubate the only laid egg, a strategy that enables them to reach large distances, up to 2,0

After the hatching of the egg -after 45 days of incubation- the bird has to be fed frequently and these routes are reduced to a half of their usual extension. In both phases (incubation and breeding), petrels fly during a similar period of time during day and night, and there are no differences in time, distribution areas, and distances made by both genders.

The geolocation techniques also allowed researchers to know the daily activity of these birds over the year. Bulwer's petrels rest in the surface waters during the day and show eating habits during the night. In particular, they feed from preys -fish, small cephalopods and some crustaceans- that move to the surface to eat at night.

Challenge: improving the environmental management in marine ecosystems

Bulwer's petrels' threats in the open sea are not clear yet but there is no doubt the effect of climate change on the ocean is one of them. In order to shape the future impact of global warming on this species -its tropical populations will be the first affected ones- is essential to know the current distribution of the Bulwer's petrel populations. Therefore, having a good environmental management of ocean waters where Bulwer's petrels live during the year will be a determining element to improve the future preservation of these endangered species.

The monograph Migración y ecología especial de la población española de petrel de Bulwer will be presented on Friday, November 15, within the frame of the XXIV Spanish Conference and VII Iberian Ornithology Conference held in Cadiz from November 13 to 17. Asunción Ruiz, assistant director of SEO/BirdLife, Professor Jacob González-Solís and the expert Marta Cruz Flores, members of the Research Group of Ecology of Marine Birds (UB-IRBio) take part in the presentation.

If your DNA is a cookbook, a single gene is a recipe. But it's a flexible recipe that if edited one way can make a pie; edited another way can make a cake. And that difference can mean cancer, as a team of researchers who looked at those gene editors writes in the 26 November issue of Cell Reports.

Those gene editors are known as splicing factors. When a gene is read out and copied, splicing factors choose where to cut and past the text so that it will give the right recipe to the cell for that moment in time.

"A gene can code for a protein that causes cell death, or a protein that prevents it, depending on the editing," says breast cancer researcher Olga Anczukow, a molecular biologist who holds joint affiliations at the Jackson Laboratory for Genomic Medicine (JAX) and UConn Health .

Anczukow and colleagues at UConn Health, JAX, and Cold Spring Harbor Laboratory were curious whether splicing factors could be responsible for the way some breast cancers grow and spread through the body. If a splicing factor was giving the cell the wrong recipe, it could cause the cell to behave badly, growing out of control or migrating through the body to cause cancers elsewhere, in what's called metastasis.

They looked at cells from breast cancers, and found that only a few splicing factors seemed connected to the cell's cancerous behavior. In particular, three splicing factors gave the cells the same wrong recipe, enhancing the cell's ability to grow and to migrate. Among these, a splicing factor called TRA2B seemed particularly enriched in triple negative breast cancers. Triple negatives are the worst breast cancers: they have the highest rates of metastasis, worst prognosis, and no targeted treatments. 

The researchers blocked TRA2B expression in cells, in tiny tumors in a petri dish, and in mice. In all three situations, cells lacking TRA2B were unable to metastasize.

Identifying TRA2B was exciting. Finding a way to block it could provide a treatment for this most dreaded form of breast cancer. The researchers hope to learn more about how the splicing factors become dysregulated, and eventually develop a drug to target them.

Targeting splicing defects has become a reality with the approval of Spinraza, a first of its kind drug that corrects abnormal splicing. Spinraza was developed by Adrian Krainer from Cold Spring Harbor Laboratory, co-author on this study, and is the first FDA-approved drug to treat children with spinal muscular atrophy. Researchers hope that in the future this type of drug can be used to treat other diseases with splicing defects, including cancer.

Many chemical processes depend on catalysts to facilitate reactions that would otherwise proceed very slowly, or not at all. An innovative procedure for visually representing the structure of catalysts via computer-assisted design, developed at KAUST, is helping researchers build better catalysts.

The software generates topographic steric maps and has been developed by Luigi Cavallo's research group at the KAUST Catalysis Research Center. The source code required is now freely available online.

Scientists from 65 countries have already used the interfaced web application, reports postdoctoral fellow Laura Falivene, and they often call on the KAUST researchers for more information. The team has now published a perspective article explaining in detail the creation and use of the topographic steric maps.

"The power of visualization is of great value in chemistry where much time is spent imagining things that we cannot see," Falivene says.

Each map uses color-coding to convey the three-dimensional geometry of the chemical groups forming the functional heart of a catalyst, known as the catalytic pocket (see images). The data to build a map can come from several techniques, such as x-ray crystallography and quantum mechanics calculations, which indicate the identity and position of each atom in the catalytic pocket.

This helps researchers better understand how known catalysts function, while also guiding exploration of chemical modifications that could adjust the structures to make better catalysts.

"We are building an important bridge between the experimental and computational approaches," Falivene explains. She adds that the growing popularity of the topographic steric maps helps other chemists to appreciate the significance of the work done by theoretical chemists like herself.

"Using the maps explains the importance of combining experimental and theoretical approaches better than my words have been able to do," she observes. "They can be used with any class of catalysts, from reactivity promoted by simple organic molecules, to that promoted by transition metal complexes, and large metalloenzymes, where a metal is hosted inside a protein." Metalloenzymes catalyze some of the most crucial reactions of life.

Work at KAUST continues to enhance the method including developing machine learning approaches to rapidly screen the potential of possible new catalysts.

"This perspective article is important because it officially states the validity and value of the topic," says Falivene. She describes it as a new starting point that brings together the early, less formal achievements to promote wider use and further development of the maps.