Culture

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by excessive fat accumulation in the liver. It can cause serious complications, including nonalcoholic steatohepatitis, cirrhosis, and cancer. Although prevalent, there is a dearth of drugs to treat NAFLD, with current therapies revolving around lifestyle interventions.

In a recent study published in Journal of Medicinal Chemistry, scientists from Gwangju Institute of Science and Technology, Korea, led by Prof Jin Hee Ahn, aimed to find new therapeutic options for NAFLD. Prof Ahn says, "NAFLD is a serious public health problem worldwide. However, no pharmacological agents have been specifically approved for its treatment yet."

For their study, the scientists focused on a well-known neurotransmitter called serotonin. Serotonin is widely known as the "happy" neurotransmitter, and its deficiency in the central nervous system (CNS) can cause various brain disorders. But, not many know that it is also found in the gastrointestinal tract; here, it is called "peripheral" serotonin, which has different functions altogether, such as regulating lipid metabolism in the liver.

In a previous study published in Nature Communications, Prof Hail Kim, the co-corresponding author of this study, had investigated peripheral serotonin as a drug target with knockout mice models (mice lacking functional peripheral serotonin). This study reported that these mice showed reduction in liver weight, hepatic lipid accumulation, and hepatic triglyceride content and improved NAFLD activity.

These findings formed the basis of Prof Ahn's study and prompted the research group to identify new peripheral serotonin antagonists. The scientists selected a CNS drug approved for the treatment of Parkinson's, called pimavanserin. Pimavanserin acts as an "antagonist" to serotonin, mimicking its effect in the CNS. The scientists then structurally modified this drug such that it cannot permeate the blood-brain barrier, by adding different types of molecules to it. In this way, they generated an array of novel compounds. On testing these, the scientists found one compound in particular to show promising results: it showed very low blood-brain barrier permeation and thus had the potential to target peripheral serotonin systems.

The scientists tested this compound in obese mice with impaired liver function. Interestingly, the mice showed improvement in symptoms of fatty liver disease, such as improved glucose tolerance. Additionally, their body fat decreased while lean body mass increased. Prof Ahn says, "Through the chemical optimization of an existing drug, pimavanserin, we identified a new peripheral agent for the possible treatment of NAFLD."

Although this novel compound is yet to be tested in humans, these findings show that it has remarkable potential in treating fatty liver disease. Optimistic about these findings, Prof Ahn concludes, "We hope that our novel drug candidate will offer relief to patients bearing the brunt of NAFLD."

The people who lived in the area known as the Southern Levant--which is now recognized as Israel, the Palestinian Authority, Jordan, Lebanon, and parts of Syria--during the Bronze Age (circa 3500-1150 BCE) are referred to in ancient biblical texts as the Canaanites. Now, researchers reporting in the journal Cell on May 28 have new insight into the Canaanites' history based on a new genome-wide analysis of ancient DNA collected from 73 individuals.

"Populations in the Southern Levant during the Bronze Age were not static," says Liran Carmel of The Hebrew University of Jerusalem. "Rather, we observe evidence for the movement of people over long periods of time from the northeast of the Ancient Near East, including modern Georgia, Armenia, and Azerbaijan, into the Southern Levant region.

"The Canaanites, albeit living in different city-states, were culturally and genetically similar," he adds. "In addition, this region has witnessed many later population movements, with people coming from the northeast, from the south, and from the northwest."

Carmel and colleagues came to these conclusions based on an analysis of 73 new ancient DNA samples representing mainly Middle-to-Late Bronze Age individuals from five archaeological sites across the Southern Levant. To these new data, the researchers added previously reported data from 20 individuals from four sites to generate a dataset of 93 individuals. The genomic analysis showed that the Canaanites do represent a clear group.

"Individuals from all sites are highly genetically similar, albeit with subtle differences, showing that the archaeologically and historically defined 'Canaanites' corresponds to a demographically coherent group," Carmel says.

The data suggest that the Canaanites descended from a mixture of earlier local Neolithic populations and populations related to Chalcolithic Iran and/or the Bronze Age Caucasus. The researchers documented a significant increase in the proportion of Iranian/Caucasus-related ancestry over time, which is supported by three individuals who are descendants of recent arrivals from the Caucasus.

"The strength of the migration from the northeast of the Ancient Near East, and the fact that this migration continued for many centuries, may help to explain why rulers of city-states in Canaan in the Late Bronze Age carry non-Semitic, Hurrian names," says Shai Carmi of The Hebrew University of Jerusalem. "There were strong and active connections between these regions through movements of people that help to understand the shared elements of culture."

The researchers also studied the relationship of the Canaanites to modern-day populations. While the direct contribution of the Canaanites to modern populations cannot be accurately quantified, the data suggest that a broader Near Eastern component, including populations from the Caucasus and the Zagros Mountains, likely account for more than 50 percent of the ancestry of many Arabic-speaking and Jewish groups living in the region today.

Carmel reports that they are now working to extend their sampling, both geographically and over time. "We wish to analyze Iron Age samples from different areas of the southern Levant," Carmel says. "This may shed light on the composition of the populations in the biblically mentioned kingdoms of the region, among them Israel, Judah, Ammon, and Moab."

Using the very latest wide-bore magnetic resonance imaging (MRI) scanning equipment at the University of Nottingham experts found differences in blood flow to the placenta in healthy and pre-eclampsia pregnancies, a finding which could help understand why in pre-eclampsia the baby can be born small and pre-term.

The research published today in PLOS Biology also identified a completely new phenomenon which the researchers have termed the 'uteroplacental pump'. This involves contractions of placenta and the part of the uterine wall to which it is attached.

The placenta is vital in the transfer of the right amount of nutrition and oxygen from the mother to the baby. Any disturbance to the flow of blood could affect the delivery of vital nutrients restricting fetal growth. If the placenta is not working properly this can lead to pre-eclampsia.

In the placenta the fetal blood flows in tree-like villi which are bathed in a lake of the mother's blood, so that the two different blood supplies are kept separate. Changes in blood flow and oxygenation affects fetal growth and well-being.

Unprecedented insight

The research team scanned 34 women with healthy pregnancies and 13 women diagnosed with preeclampsia, gaining an unprecedented insight how the maternal blood percolates between the villi and how this affects placental oxygenation.

Dr Neele Dellschaft, from the University of Nottingham's School of Physics and Astronomy led the research, she explains: "I am part of a team of scientists who have used MRI to look at how blood flows through the placenta to deliver oxygen to the baby. We found that in healthy pregnancies the blood flows very slowly. This seems odd at first but our other measurements suggest that this is a way in which the placenta can function efficiently. We also found that the normal patterns of flow and oxygenation were much more variable in pre eclampsia, which can help explain why babies of pre-eclamptic pregnancies tend to be smaller and often have to be delivered before term.

Most excitingly, we also identified a completely new phenomenon which we called the 'uteroplacental pump'. This is a contraction of the placenta and the part of the uterine wall to which it is attached and it is not the same as the well-known Braxton Hicks contractions in which the entire uterus contracts in practice for labour. We now want to work out the purpose of these contractions but we think it might be to stop blood stagnating in parts of the placenta."

Professor Penny Gowland added: "At present we have no clinical tools to assess the function of the placenta directly, all we can do is assess the size and growth of the baby and blood flow in the umbilical cord using ultrasound. This research demonstrates that MRI is hugely effective in providing detailed information of exactly what is happening between the baby and the mother and what is changed in a pre-eclampsia pregnancy. It's also hugely exciting to have discovered a brand new physical phenomenon that takes place during pregnancy. We hope in the future this knowledge can be built upon by clinicians to better diagnose and manage conditions like preeclampsia."

The exchange of ideas and material culture in Western Asia is well established within archaeological research. Although distinct traditions and systems of social organization emerged across Western Asia, the region from the Southern Caucasus to Anatolia and Mesopotamia had been a hub for the exchange of ideas and material culture for millennia. The extent of these exchanges, however, and the processes that lead farming communities to organize into complex societies, is still poorly understood. Was this process primarily a movement of ideas and materials, or did it also include large-scale movement of populations?

To answer this question, scientists from research institutes and universities in Europe, Asia, and North America*, led by the Department of Archaeogenetics at the Max Planck Institute for the Science of Human History (MPI SHH), analyzed genome-wide data from 110 skeletons dated approximately 7500 to 3000 years ago from archaeological sites in Anatolia, Northern Levant, and the Southern Caucasus. Their analysis indicates two influential genetic events, as well as evidence for long-distance individual movement.

A large genetic cline and a sudden genetic shift

During the late Neolithic, approximately 8,500 years ago, populations across Anatolia and the Southern Caucasus began to genetically mix, resulting in a distinct admixture that gradually spread across the entire region. This gradual change of genetic profile over a geographic region, known as a cline in genetics, could be seen millennia later in Anatolian populations from Central-North to Eastern Anatolia. Rather than indicating stationary populations, as apparent genetic continuity often does, the authors argue the spread of genetic information from North and Central Anatolia to the Southern Caucasus and the Zagros mountains in today's Northern Iran indicates ongoing human mobility and the development of a regional genetic melting pot in Anatolia.

"This far-reaching vortex of homogenization shows that ancient people within Western Asia biologically mix before their increasing connectedness and emerging sociocultural developments became visible in the archaeological record," says Johannes Krause, director of the Department of Archaeogenetics at MPI SHH, co-director at Max Planck - Harvard Research Center for the Archaeoscience of the Ancient Mediterranean (MHAAM) and senior author of the study.

In contrast to the gradual changes taking place in Anatolia, the Northern Levant experienced an introduction of new populations. "We found that the genetic makeup of Bronze Age populations from the ancient cities of Alalakh and Ebla in today's southern Turkey and northern Syria differed from preceding populations from the same area," says Eirini Skourtanioti, lead author of the study. "We detected subtle genetic changes that point to influences from external groups."

This observation could contribute to debate on human mobility between the third and second millennium BC, as there are different interpretive constructs centering on either increasing inter-regional connectivity in these periods or migration connected with a mega-drought known as the "4.2k BP event." Regarding the latter, archaeological evidence indicates an abandonment of the Khabur river valley and texts record the migration of groups such as the 'Amorites' and 'Hurrians.' Ancient Mesopotamia was likely the source of the new genetic influence observed at Alalakh and Ebla, according to material evidence and geoarchaeological research currently under study by the Alalakh excavation team; however, to date no ancient genomes have been successfully retrieved from this region.

Curious burial taps a wellspring of questions

In addition to long-term transitions at the scale of entire populations, the team also found evidence of long-distance movements at the individual level. At the Alalakh site in southern Turkey, the team found an individual whose genetic profile is most similar to Bronze Age populations in Central Asia. In addition to being a genetic outlier, the individual, who was identified as female, was unearthed at the bottom of a well which was in use at the time of her consignment.

"I was fascinated by our results for the 'lady in the well,'" says Philipp Stockhammer, co-director of MHAAM and another senior author of the study. "She provides a unique insight into individual female mobility over large distances. We know from literary sources that women travelled in this time throughout Western Asia - very often as marriage partners. However, the story of this woman of Central Asian origin will remain an enigma."

The context of this finding raises many questions, many of whose answers are beyond the resolution of modern analytical tools. How did this woman and/or her recent ancestors move from Central Asia to Northern Levant? Was she forced to leave her homeland? What was her role in the society, and was this an accident or a murder? Despite these questions, this woman demonstrates the long distances humans travelled in the past and points to the existence of migrant communities in a globalized ancient world.

DURHAM, N.C. -- Duke University researchers have developed a synthetic molecule that selectively dampen the physiological rewards of cocaine in mice. It also may represent a new class of drugs that could be more specific with fewer side effects than current medications.

In mice that were treated with the stimulant cocaine or methamphetamine, the new molecule was found to calm their drug-induced hyperactivity and interfere with the dopamine system's ability to change metabolism in the brain's rewards center.

In mice that were allowed to self-administer cocaine, the treatment slowed down their drug use in 20 minutes to an hour, and reduced the amount of drug they used by more than 80 percent, compared to a control group of mice.

The molecule, SBI-553, activates cell surface chemical receptors called G protein-coupled receptors or GPCRs, which are the target of more than 35% of all FDA-approved drugs. (The discovery and characterization of GPCRs earned the team's Duke colleague, Robert Lefkowitz, the 2012 Nobel Prize in chemistry.)

When a GPCR is activated by a signaling molecule, it transmits that signal to the inner portion of the cell via interaction with two intracellular proteins: G protein and beta-arrestin. Most GPCR drugs in use today indiscriminately activate both G protein and beta-arrestin, and sometimes activating both molecules withthe same GPCR can produce dramatically different physiological effects.

Drug developers have been trying to identify compounds that selectively activate one or the other because they have the potential to be safer drugs with fewer side effects.

In a paper appearing online May 28 in the journal Cell, the Duke researchers report the development of a new class of small molecules that may allow for just that - thereby separating the good effects from the bad.

"This kind of idea has been kicking around for 20 years or so," said senior author Marc Caron, the James B. Duke professor of Cell Biology in the School of Medicine. His work has focused on GPCR signaling involved in disorders like addiction, schizophrenia, Parkinson's Disease and depression.

For decades, researchers working on drug abuse and addiction have pursued molecules that would activate one specific GPCR called neurotensin receptor 1 (NTSR1) as a way to interrupt the actions of stimulants and treat cocaine and methamphetamine addictions.

Neurotensin is known to be involved in drug-seeking behavior and food intake in mice. "It regulates the brain's reward system and motivated behavior," said senior post-doctoral fellow Lauren Slosky, who is the lead author on the paper.

But so far, the drugs that activate NTSR1 have severe side effects for blood pressure, body temperature and motor coordination, because those are also controlled by NTSR1. "This was known, but nobody could do anything about it," Caron said.

In collaboration with the Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California, the Duke team screened 400,000 small molecule drugs to see if any of them could stimulate the NTSR1 beta-arrestin response.

One small molecule called SBI-553 that emerged from the screen acts at a previously unknown site on the NTSR1 and selectively activates the beta-arrestin without activating the G protein. SBI-553 can bind the NTSR1 at the same time as this receptor's natural activator, a peptide known as neurotensin, and it promotes neurotensin's ability to activate beta-arrestin while blocking its ability to activate the G protein.

"This type of activity isn't something we've seen before," said study co-author Lawrence Barak, an associate research professor who has studied GPCRs for decades and initiated the NTSR1 research program at Duke as well as the collaborative, large-scale screening effort.

Like conventional NTSR1 activators, SBI-553 was found to reduce the amount of cocaine the animals consumed and their associated drug-craving. But it did so without the usual side effects of decreased blood pressure and body temperature and motor coordination problems.

"The current findings suggest that the selective activation of the NTSR1 beta-arrestin response is sufficient to produce some of the anti-addiction effects attributed to the NTSR1, but not its effects on blood pressure and body temperature," Slosky said.

Because NTSR1 is a prototypical GPCR, molecules of this class can now be pursued for other receptors, Slosky said. "This kind of modulator may allow for the fine-tuning of receptor signaling."

Detailed seafloor mapping of submerged glacial landforms finds that Antarctic ice sheets in the past retreated far faster than the most rapid pace of retreat observed today, exceeding even the most extreme modern rates by at least an order of magnitude, according to a new study. Using an autonomous underwater vehicle (AUV) to carefully measure the delicate sets of ridges left behind in seafloor sediments by retreating ice following the Last Glacial Maximum (LGM) roughly 14,000 years ago, the authors estimate deglaciation at a rate of more than 10 kilometers per year. The findings provide a clear indication of how quickly massive ice sheets can disappear into the ocean - events that, if repeated, would have significant implications for modern sea-level rise. Antarctica's ice shelves - the waterborne fringes of tidewater glaciers - form the boundaries between the Southern Ocean and the Antarctic Ice Sheet. At the grounding-line, the place where the ice sheet no longer rests directly on the sea floor and begins to float, warm air and ocean water conspire to melt ice from above and below. As a result, these regions are prone to rapid retreat. How the fastest rates of modern ice loss stack up against the maximum possible magnitude of retreat, however, is unknown. On the Larsen continental shelf off the east coast of the Antarctic Peninsula, Julian Dowdeswell and colleagues investigated a series of ridges in the soft seafloor sediment, which they interpret as artifacts left behind during the tidal rise and fall of the ice-shelf at the grounding line. Like glacial moraines on land, the grounding-zone wedges provided a record of glacier retreat and allowed Dowdeswell et al. to estimate that the rate of ice retreat at a resolution measured in days or weeks, revealing regional post-LGM deglaciation rates of 40-50 meters per day. "Perhaps most importantly, Dowdeswell et al. demonstrate the immense value of high-resolution seafloor mapping in unraveling the complex history of glacial dynamics. Only fractions of the seafloor in the hard-to-access ice-covered polar regions are mapped, and much is left to discover and learn," writes Martin Jakobsson in a related Perspective.

As the intensity and frequency of the strongest cyclones east of Taiwan have increased, so has the strength of the Kuroshio current, a Pacific current responsible for redistributing heat throughout the western North Pacific Ocean. According to a new study, intensifying tropical cyclones have increased the amount of energy in the ocean eddies that feed into the Kuroshio, accelerating the current. The results reveal a positive feedback between tropical cyclones (TCs) and potentially significant increased warming at higher latitudes. Climate models that overlook this and similar mechanisms may misrepresent the magnitude and pattern of warming in future climate predictions, say the authors. Similar to the Atlantic's Gulf Stream, the Kuroshio current is responsible for transporting vast amounts of warm water from the tropics to higher latitudes, retributing tropical heat to cooler latitudes. The speed of the Kuroshio (and the rate of heat transfer) is largely controlled by the wind and the mesoscale ocean eddies that feed into the larger current. Here, Yu Zhang and colleagues show that the increasing frequency and intensity of TCs in the region - a product of Pacific warming - has had the overall effect of increasing the strength of cyclonic mesoscale ocean eddies that feed the Kuroshio. At the same time, it has decreased the strength of anticyclonic ones. The result is a northward acceleration of the current, resulting in the transfer of more heat energy into the mid- and high-latitude ocean water. The results illustrate how larger tropical cyclones related to increased climate warming can influence large-scale ocean circulation by modifying underlying eddy fields that feed currents - further enhancing climate warming in regions farther afield. "For a proper representation of eddies in climate models, more theoretical and modeling studies are needed to improve our understanding of the physical processes involved in the interactions among eddies, TCs and large-scale ocean circulation, write Zhang et al.

What The Study Did: Symptoms of posttraumatic stress disorder, depression, anxiety and insomnia among health care workers in Italy during the COVID-19 pandemic are reported in this observational study.

Authors: Rodolfo Rossi, M.D., of the University of Rome Tor Vergata in Italy, is the corresponding author.

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(doi:10.1001/jamanetworkopen.2020.10185)

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Many insects process visual information to make decisions about controlling their flying skills and movements- flies must decide whether to pursue prey, avoid a predator, maintain their flight trajectory or land based on their perceptions.

Why is understanding this process important? We move every day and perceive the world differently as a result.

For example, if you're driving on the freeway your visual system adapts to high speed, and after a while 50km/h feels very slow. In contrast, when running or walking you are able to maintain a more steady velocity.

New research published in journal Current Biology describes the firing of descending neurons in hoverflies to examine the important link between neural processing in the central brain and their normal behaviour in flight.

These neurons correspond to descending neurons in our human spinal cord.

"As the spinal cord is very inaccessible in humans, flies become an excellent comparison model," says Professor Karin Nordström, a neuroscientist at Flinders University who studies how insects perceive the world while moving.

"The responses of these descending neurons help explain how and where this discrepancy between adaptation to motion and the ability to maintain more constant movement takes place."

"We found that these descending neurons continue to respond to visual motion, which is fascinating, as sensory neurons typically adapt." says Professor Nordström.

The researchers investigated these significant observations in hoverflies by using test-adapt-test protocols, which are commonly used in visual science to quantify the effect adaptation has on responses to subsequent stimuli.

Flinders University Research Officer Sarah Nicholas says descending neurons haven't been studied enough and provide an important insight into the link between the brain and the resulting behaviour of hoverflies, and ultimately all vertebrates, including humans.

"These descending neurons show sensory properties (by adapting) as well as pre-motor properties (persistent firing), which is quite a unique integration of neuronal responses."

"As motion vision, and adaptation, in flies show many similarities to those described in vertebrate cortical areas, and as persistent firing has been shown in both invertebrate and vertebrate central pattern generators, our findings are broadly appealing."

Users of high-potency cannabis are four times more likely to report associated problems, and twice as likely to report anxiety disorder, than users of lower-potency strains, according to new research from the University of Bristol.

Published today on JAMA Psychiatry the research uses data from Children of the 90s, a long-term health study that recruited more than 14,000 pregnant women and their babies born in and around Bristol in the early 1990s and has been following their health and development ever since.

This is the first research of its kind to look at data from a general population sample, with previous research into the links between cannabis potency and mental health only looking at clinical and self-selecting samples of people who use drugs. Added to this, the nature of the data available from the Children of the 90s health study enabled the research team to take into account whether mental health symptoms were present before the individual started using cannabis.

Frequency of cannabis use, which is also often associated with increased mental health problems, was also taken into account in order to determine whether this would explain the relationship between higher-potency usage and mental health conditions.

Lead author Dr Lindsey Hines, Senior Research Associate from Bristol Medical School explained: "We know that people who use cannabis are more likely to report mental health problems than those who don't use cannabis, but we don't fully understand how recent increases in the strength and potency of cannabis affects this. This study gives us an estimate of the increased likelihood of mental health problems from use of high-potency cannabis, compared to use of lower-potency cannabis, and we are able to account for the effect that people's early adolescent mental health symptoms may have on this relationship."

The research looked at data collected from participants aged 24 years who had reported using cannabis in the previous year, of which 13 per cent reported use of high-potency cannabis. Participants were also asked about their usage, and those who self-reported two or more of the Cannabis Abuse Screening Test (CAST) items within the past year were classified as having recently experienced problems as a result of their cannabis use. Researchers were then able to compare this data to reported mental health symptoms at age 24 as well as early symptoms of mental health collected when participants were younger.

Dr Hines continued: "People who use cannabis are more likely to report mental health problems than those who don't use cannabis, but reducing the potency and regularity of their cannabis use may be effective for lessening likelihood of harms from use. In countries where cannabis is sold legally, limiting the availability of high-potency cannabis may reduce the number of individuals who develop cannabis use disorders, prevent cannabis use escalating to a regular behaviour, and reduce impacts on mental health. In countries like the UK, where we are not able to limit the availability of high-potency cannabis, we should make sure there is good treatment and support for those who develop problems from cannabis use."

The Near East was a crossroad for the ancient world's greatest civilizations, and invasions over centuries caused enormous changes in cultures, religions and languages. However, a new study of the DNA of ancient skeletons spanning 4,000 years has revealed that most of these changes had no lasting effect on the genetics of the local population of Beirut.

Whilst the invasions and conquests may have been revolutionary for the elite rulers, researchers at the Wellcome Sanger Institute, University of Birmingham, French Institute of the Near East in Lebanon and their collaborators found only three time periods that had any impact on the long-term genetics of the ordinary people. These were the beginning of the Iron Age, the arrival of Alexander the Great, and the domination of the Ottoman Empire.

Reported today (28 May) in the American Journal of Human Genetics, the study shows the value of using genetics alongside archaeology to help understand what could be happening in the lives of ordinary people throughout history.

Over the centuries, the Levant has had many different rulers, including the Egyptians, Babylonians, Assyrians, Persians, Greeks, Romans, Crusaders, Arabs, and Ottomans. Most of these had permanent cultural effects on the local population, including changes to religion and even languages, as shown by the historical records and archaeological findings.

However, despite this, previous research showed that present-day local people in Lebanon were mainly descended from local people in the Bronze Age (2100-1500 BCE)*, with 90 per cent of their genetic make-up coming from around 4,000 years ago, and very few lasting traces of even the Crusaders invasion around the 11th-13th Century**.

To understand this potential contradiction and build a picture of the genetic history of ordinary people in the region, the researchers studied the DNA of ancient skeletons through 4,000 years. The team sequenced the genomes of 19 ancient people who lived in Lebanon between 800BCE and 200CE, and by combining with previous ancient and modern data, created an 8-point time line across the millennia.

Scientists detected lasting genetic changes in the local people from just three time periods - during the beginning of the Iron Age (about 1,000 BCE), the arrival of Alexander the Great (beginning 330 BCE), and the domination of the Ottoman Empire (1516 CE) - but not from the other times.

Dr Marc Haber, first author from the University of Birmingham and previously from the Wellcome Sanger Institute, said: "We revealed a genetic history of the area across 4,000 years, with a time-point approximately every 500 years. This showed us that despite the huge cultural changes that were occurring during this period, there were only a few times that the genetics of the general population changed enough to affect the ordinary people."

The study revealed that some people did mix and form families with people from other cultures. One burial site was found to contain the remains of an Egyptian mother, and her son whose father had Egyptian and Lebanese ancestry. However, this cosmopolitan mixing did not seem to be widespread.

Historical evidence is based on archaeological findings and written records, but these are biased towards the elite rulers and people with money and influence, as they have far more resources and write the history. It can be difficult to understand the lives of the ordinary people.

Dr Joyce Nassar, an author on the paper and archaeologist from the French Institute of the Near East, Lebanon, said: "This study is really exciting, as the genetic evidence is helping us to interpret what we find. Some people might think that when a land was invaded, that the population would change. But this study shows it isn't that simple, and reveals there was only limited biological mixing, despite the cultural and political influence of the invasions."

The skeletons came from four archaeological excavation sites in Beirut, which were discovered during building projects in the Lebanese capital city and rescued by the Directorate General of Antiquities***. The archaeologists and researchers then worked together to transfer the bones to a laboratory in Estonia dedicated to ancient DNA, where the surviving ancient DNA was extracted from the temporal bone in the skulls. The DNA was then sequenced and analysed at the Sanger Institute. Recent advances in DNA extraction and sequencing technology made studying the ancient and damaged DNA possible.

Dr Chris Tyler Smith, senior author on the paper and previously from the Wellcome Sanger Institute, said: "We see that people like the Egyptians and the Crusaders came to Lebanon, lived, raised families and died there. Their DNA sequences reveal this, but a little while later, there may be no trace of their genetics in the local population. Our study shows the power of ancient DNA to give new information about the human past, that complements the available historical records, and reveals the benefits of archaeologists and geneticists working together to understand historical events."

CAMBRIDGE, MA -- Many proteins are useful as drugs for disorders such as diabetes, cancer, and arthritis. Synthesizing artificial versions of these proteins is a time-consuming process that requires genetically engineering microbes or other cells to produce the desired protein.

MIT chemists have devised a protocol to dramatically reduce the amount of time required to generate synthetic proteins. Their tabletop automated flow synthesis machine can string together hundreds of amino acids, the building blocks of proteins, within hours. The researchers believe their new technology could speed up the manufacturing of on-demand therapies and the development of new drugs, and allow scientists to design artificial proteins by incorporating amino acids that don't exist in cells.

"You could design new variants that have superior biological function, enabled by using non-natural amino acids or specialized modifications that aren't possible when you use nature's apparatus to make proteins," says Brad Pentelute, an associate professor of chemistry at MIT and the senior author of the study.

In a paper appearing today in Science, the researchers showed that they could chemically produce several protein chains up to 164 amino acids in length, including enzymes and growth factors. For a handful of these synthetic proteins, they performed a detailed analysis showing their function is comparable to that of their naturally occurring counterparts.

The lead authors of the paper are former MIT postdoc Nina Hartrampf, who is now an assistant professor at the University of Zurich, MIT graduate student Azin Saebi, and former MIT technical associate Mackenzie Poskus.

Rapid production

The majority of proteins found in the human body are up to 400 amino acids long. Synthesizing large quantities of these proteins requires delivering genes for the desired proteins into cells that act as living factories. This process is used to program bacterial or yeast cells to produce insulin and other drugs such as growth hormones.

"This is a time-consuming process," says Thomas Nielsen, head of research chemistry at Novo Nordisk, who is also an author of the study. "First you need the gene available, and you need to know something about the cellular biology of the organism so you can engineer the expression of your protein."

An alternative approach for protein production, first proposed in the 1960s by Bruce Merrifield, who was later awarded the Nobel Prize in chemistry for his work on solid-phase peptide synthesis, is to chemically string amino acids together in a stepwise fashion. There are 20 amino acids that living cells use to build proteins, and using the techniques pioneered by Merrifield, it takes about an hour to perform the chemical reactions needed to add one amino acid to a peptide chain.

In recent years, Pentelute's lab has invented a more rapid method to perform these reactions, based on a technology known as flow chemistry. In their machine, chemicals are mixed using mechanical pumps and valves, and at every step of the overall synthesis they cycle through a heated reactor containing a resin bed. In the optimized protocol, forming each peptide bond takes on average 2.5 minutes, and peptides up to 25 amino acids long can be assembled in less than an hour.

Following the development of this technology, Novo Nordisk, which makes several protein drugs, became interested in working with Pentelute's lab to synthesize longer peptides and proteins. To achieve that, the researchers needed to improve the efficiency of the reactions that form peptide bonds between amino acids in the chain. For each reaction, their previous efficiency rate was between 95 and 98 percent, but for longer proteins, they needed it to be over 99 percent.

"The rationale was if we got really good at making peptides, we could expand the technology to make proteins," Pentelute says. "The idea is to have a machine that a user could walk up to and put in a protein sequence, and it would string together these amino acids in such an efficient manner that at the end of the day, you can get the protein you want. It's been very challenging because if the chemistry is not close to 100 percent for every single step, you will not get any of the desired material."

To boost their success rate and find the optimal recipe for each reaction, the researchers performed amino-acid-specific coupling reactions under many different conditions. In this study, they assembled a universal protocol that achieved an average efficiency greater than 99 percent for each reaction, which makes a significant difference when so many amino acids are being linked to form large proteins, the researchers say.

"If you want to make proteins, this extra 1 percent really makes all the difference, because byproducts accumulate and you need a high success rate for every single amino acid incorporated," Hartrampf says.

Using this approach, the researchers were able to synthesize a protein that contains 164 amino acids -- Sortase A, a bacterial protein. They also produced proinsulin, an insulin precursor with 86 amino acids, and an enzyme called lysozyme, which has 129 amino acids, as well as a few other proteins. The desired protein has to be purified and then folded into the correct shape, which adds a few more hours to the overall synthesis process. All of the purified synthesized proteins were obtained in milligram quantities, making up between 1 and 5 percent of the overall yield.

Medicinal chemistry

The researchers also tested the biological functions of five of their synthetic proteins and found that they were comparable to those of the biologically expressed variants.

The ability to rapidly generate any desired protein sequence should enable faster drug development and testing, the researchers say. The new technology also allows amino acids other than the 20 encoded by the DNA of living cells to be incorporated into proteins, greatly expanding the structural and functional diversity of potential protein drugs that could be created.

"This is paving the way for a new field of protein medicinal chemistry," Nielsen says. "This technology really complements what is available to the pharmaceutical industry, providing new opportunities for rapid discovery of peptide- and protein-based biopharmaceuticals."

The researchers are now working on further improving the technology so that it can assemble protein chains up to 300 amino acids long. They are also working on automating the entire manufacturing process, so that once the protein is synthesized, the cleavage, purification, and folding steps also occur without any human intervention required.

New research on one history's most important trading hubs provides some of the earliest genetic glimpses at the movement and interactions of populations that lived in parts of Western Asia between two major events in human history: the origins of agriculture and the rise of some of the world's first cities.

The work reveals how a high level of human movement in the region not only led to the spread of ideas and material culture but to a more genetically connected society well before the rise of cities, not the other way around, as previously thought.

The researchers, made up of an international team of scientists including Harvard anthropology professor Christina Warinner, looked at DNA data from 110 skeletal remains in West Asia dated 3,000 to 7,500 years ago. The remains came from archaeological sites in the Anatolia (present-day Turkey), the Northern Levant which includes countries on the Mediterranean coast such as Israel and Jordan, and countries in the Southern Caucasus which include present-day Armenia and Azerbaijan.

Based on their analysis, the scientists describe two genomic events that occurred around 8,500 years ago and 4,000 years ago that pointed to long-term genetic mixing in the region and subtle population movements within the area, shedding light on a long-standing question.

"Within this geographic scope, you have a number of distinct populations, distinct ideological groups that are interacting quite a lot and it hasn't really been clear to what degree people are actually moving or if this is simply just a high contact area from trade," said Warinner, assistant professor of anthropology at the Faculty of Arts and Sciences and the Sally Starling Seaver Assistant Professor at the Radcliffe Institute for Advanced Study. "What we can see is that rather than this period being characterized by dramatic migrations or conquest, what we see is the slow mixing of different populations, the slow mixing of ideas, and it's percolating out of this melting pot that we see the rise of urbanism -- the rise of cities,"

The study was led by the Max Planck-Harvard Research center for the Archaeoscience of the Ancient Mediterranean and published in the journal Cell. Warinner was a senior author on the paper.

Historically, Western Asia, which includes the modern-day Middle East, is one of the world's most important geographical locations. Early on it not only created some of humanity's earliest cities but its early trade routes laid the foundation for what would become the Silk Road, a route that commercially linked Asia, Africa, and Europe.

Even prior to being connected with other regions, however, populations across Western Asia had already developed their own distinct traditions and systems of social organization and complexity. The areas studied in this paper played major roles in this development from early farming to pastoral communities to early state-level societies.

With the study, the researchers wanted to fill in some of the anthropological gaps between the origins of agriculture and of cities to better understand these different communities came together to eventually form cities.

"What we see in archeology is that the interconnectivity within Western Asia increased and areas such as Anatolia, the Northern Levant, and the Caucasus became a hub for [the] exchange of ideas and material culture," said Eirini Skourtanioti, a Ph.D. student at the Max Plank Institute and the lead author of the study, in a video accompanying the release of the paper. "The goal of our study was to understand the role of human mobility throughout this process."

The researchers included an international team of authors from many disciplines and countries, including Australia, Azerbaijan, France, Italy, Germany, South Korea, Turkey, and the United States. They gathered the 110 ancient remains and took samples from their teeth and part of the temporal bone called the petrous, which is part of the inner ear. The samples from the skeletons were all previously excavated and were housed in different museums and labs around the world. The genetic analysis was all conducted by scientists at the Max Planck Institute, including Warinner.

In the paper, the authors outline how approximately 8,500 years ago, populations across Anatolia and the Southern Caucasus began genetically mixing. It resulted in a gradual change in genetic profile that over a thousand years slowly spread across the both areas and entered into what is now Northern Iraq. Known as a cline in genetics, this mixture indicated to the researchers ongoing human mobility in the area and the development of a regional genetic melting pot in Anatolia and its surrounding areas.

The other shift researchers detected wasn't as gradual. They looked at samples from the ancient cities of Alalakh and Ebla in what is today southern Turkey and northern Syria and saw that around 4,000 years ago the Northern Levant experienced a relatively sudden introduction of new people.

The subtle genetic shifts points to a mass migration event. The timing of this migration corresponds with a massive drought in Northern Mesopotamia. It is likely where the migrants that entered the Northern Levant area originated from. The scientists can't be sure because there are currently no well preserved genomes for Mesopotamia.

Along with findings on interconnectivity in the region, the paper presents new information about long distance migration during the late Bronze age about 4,000 years ago. Researchers determined that a lone corpse, found buried in a well, genetically belonged in Central Asia at the time, not at a site that is part of present-day Turkey.

"We can't exactly know her story, but we can piece together a lot of information that suggests that either she or her ancestors were fairly recent migrants from Central Asia," said Warinner, who is also a group leader in the Department of Archaeogenetics at the Max Planck Institute. "We don't know the context in which they arrived in the Eastern Mediterranean but this is a period of increasing connectivity in this part of the world."

The corpse had many injuries and the way she was buried indicates a violent death. Warinner hopes more genomic analysis can play some type of role in unraveling the ancient woman's story.

For Warinner, who earned her master's in 2008 and her Ph.D. in 2010 from the Graduate School of Arts and Sciences, these types of studies are proof of the insights DNA analysis can provide when more traditional clues don't tell the full story.

"What's really interesting is that we see these populations are mixing genetically long before we see clear material culture evidence of this -- so, long before we see direct evidence in pottery or tools or any of these more conventional archaeological evidence artifacts," Warinner said. "That's important because sometimes we're limited in how we see the past. We see the past through artifacts, through the evidence people leave behind. But sometimes events are happening that don't leave traces in conventional ways, so by using genetics, we were able to access this much earlier mixing of populations that wasn't apparent before."

The existence of a planet the size of Earth around the closest star in the solar system, Proxima Centauri, has been confirmed by an international team of scientists including researchers from the University of Geneva (UNIGE). The results, which you can read all about in the journal Astronomy & Astrophysics, reveal that the planet in question, Proxima b, has a mass of 1.17 earth masses and is located in the habitable zone of its star, which it orbits in 11.2 days. This breakthrough has been possible thanks to radial velocity measurements of unprecedented precision using ESPRESSO, the Swiss-manufactured spectrograph - the most accurate currently in operation - which is installed on the Very Large Telescope in Chile. Proxima b was first detected four years ago by means of an older spectrograph, HARPS - also developed by the Geneva-based team - which measured a low disturbance in the star's speed, suggesting the presence of a companion.

The ESPRESSO spectrograph has performed radial velocity measurements on the star Proxima Centauri, which is only 4.2 light-years from the Sun, with an accuracy of 30 centimetres a second (cm/s) or about three times more precise than that obtained with HARPS, the same type of instrument but from the previous generation.

"We were already very happy with the performance of HARPS, which has been responsible for discovering hundreds of exoplanets over the last 17 years", begins Francesco Pepe, a professor in the Astronomy Department in UNIGE's Faculty of Science and the man in charge of ESPRESSO. "We're really pleased that ESPRESSO can produce even better measurements, and it's gratifying and just reward for the teamwork lasting nearly 10 years."

Alejandro Suarez Mascareño, the article's main author, adds: "Confirming the existence of Proxima b was an important task, and it's one of the most interesting planets known in the solar neighbourhood."

The measurements performed by ESPRESSO have clarified that the minimum mass of Proxima b is 1.17 earth masses (the previous estimate was 1.3) and that it orbits around its star in only 11.2 days.

"ESPRESSO has made it possible to measure the mass of the planet with a precision of over one-tenth of the mass of Earth", says Michel Mayor, winner of the Nobel Prize for Physics in 2019, honorary professor in the Faculty of Science and the 'architect' of all ESPRESSO-type instruments. "It's completely unheard of."

And what about life in all this?

Although Proxima b is about 20 times closer to its star than the Earth is to the Sun, it receives comparable energy, so that its surface temperature could mean that water (if there is any) is in liquid form in places and might, therefore, harbour life.

Having said that, although Proxima b is an ideal candidate for biomarker research, there is still a long way to go before we can suggest that life has been able to develop on its surface. In fact, the Proxima star is an active red dwarf that bombards its planet with X rays, receiving about 400 times more than the Earth.

"Is there an atmosphere that protects the planet from these deadly rays?" asks Christophe Lovis, a researcher in UNIGE's Astronomy Department and responsible for ESPRESSO's scientific performance and data processing. "And if this atmosphere exists, does it contain the chemical elements that promote the development of life (oxygen, for example)? How long have these favourable conditions existed? We're going to tackle all these questions, especially with the help of future instruments like the RISTRETTO spectrometer, which we're going to build specially to detect the light emitted by Proxima b, and HIRES, which will be installed on the future ELT 39 m giant telescope that the European Southern Observatory (ESO) is building in Chile."

Surprise: is there a second planet?

In the meantime, the precision of the measurements made by ESPRESSO could result in another surprise. The team has found evidence of a second signal in the data, without being able to establish the definitive cause behind it. "If the signal was planetary in origin, this potential other planet accompanying Proxima b would have a mass less than one third of the mass of the Earth. It would then be the smallest planet ever measured using the radial velocity method", adds Professor Pepe.

It should be noted that ESPRESSO, which became operational in 2017, is in its infancy and these initial results are already opening up undreamt of opportunities. The road has been travelled at breakneck pace since the first extrasolar planet was discovered by Michel Mayor and Didier Queloz, both from UNIGE's Astronomy Department. In 1995, the 51Peg b gas giant planet was detected using the ELODIE spectrograph with an accuracy of 10 meters per second (m/s). Today ESPRESSO, with its 30 cm/s (and soon 10 after the latest adjustments) will perhaps make it possible to explore worlds that remind us of the Earth.

Major life events such as marriage, death of a loved one or bankruptcy all affect our wellbeing. Now, for the first time, researchers have compared the differing impact of these events on the happiness and life satisfaction and how long that impact lasts.

The study examined 18 major life events, and how they affected a sample of 14,000 Australians between 2002 and 2016. The data was taken from the HILDA survey, which examines the social, health and economic conditions of Australian households using face-to-face interviews and self-completion questionnaires.

The study: The differential impact of major life events on cognitive and affective wellbeing, was recently published in the journal 'SSM - Population Health' with co-authors from the University of Technology Sydney (UTS) and the University of Sydney.

The results show that some events, such as moving house, getting fired or getting a promotion, had little impact on wellbeing, while others, such as the death of a partner or a large financial loss, had profound impacts.

"Marriage, childbirth and a major financial gain produced the greatest elevation to wellbeing, however they did not lead to long-lasting happiness - the positive effect generally wore off after two years. However, there was also an anticipatory effect for marriage and childbirth, with wellbeing increasing prior to these events," says lead researcher, UTS economist Dr Nathan Kettlewell.

"The life events that saw the deepest plunge in wellbeing were the death of a partner or child, separation, a large financial loss or a health shock. But even for these negative experiences, on average people recovered to their pre-shock level of wellbeing by around four years," he says.

A greater understanding how life events impact wellbeing, and how long it takes to adapt, can help government and policy makers better target resources to improve the happiness and welfare of society.

"A growing number of countries, including the UK, Iceland and New Zealand, as well as the OECD, are measuring wellbeing, alongside economic growth, as a way to gauge success in improving the lives of citizens," Dr Kettlewell says.

"Information on wellbeing also helps clinicians and healthcare professionals better understand the repercussions of major life crises such as the death of a loved one, a health shock or job loss."

The researchers examined two different types of wellbeing.

The first was 'affective' wellbeing, which reflected 'happiness' or the frequency and intensity of positive or negative emotions. The second was 'cognitive' wellbeing, which refers to a more deliberate, goal-directed evaluation of 'life satisfaction'.

While some life events such as marriage and retirement had positive effects on 'cognitive' wellbeing, the net effect of positive events on 'affective' wellbeing was close to zero.

Pregnancy and childbirth in particular saw the largest gap between the two domains. Measures of 'life satisfaction' were quite positive in the first year after the birth of a child, while happiness or emotional wellbeing actually declined during this time.

The researchers also accounted for how life events often occur together, for example divorce and financial loss, to tease out the differing impacts.

The four most common life events were moving house, finding a new job, a serious injury or illness in a close family member and pregnancy. The least frequent were becoming widowed and getting married.

"While chasing after happiness may be misplaced, the results suggest that the best chances for enhancing wellbeing may lie in protecting against negative shocks, for example by establishing strong relationships, investing in good health and managing financial risks," says Dr Kettlewell.

"And we can take consolation from the fact that, although it takes time, wellbeing can recover from even the worst circumstances."