Earth

Complete filling of batches of nanopipettes

image: Putting a batch of nanopipettes on a hot plate induces a thermal gradient, which enables complete filling of the pipettes with a solution. Adapted with permission from Linhao Sun, Kazuki Shigyou, Toshio Ando, and Shinji Watanabe. Thermally Driven Approach To Fill Sub-10-nm Pipettes with Batch Production, Anal. Chem. 91, 14080-14084 (2019). Copyright 2019 American Chemical Society.

Image: 
Kanazawa University

Nanopipettes, in which a nanoscale channel is filled with a solution, are used in all kinds of nanotechnology applications, including scanning-probe microscopy. Bringing a solution into a nanopipette with a pore diameter below 10 nanometer is challenging, however, since capillary forces prevent the complete filling of a sub-10-nm nanopipette pore with a liquid. Now, Shinji Watanabe and colleagues from Kanazawa University have found a simple but efficient way for filling nanopipettes. The researchers show that the 'air bubble' that typically remains near the pipette's pore end can be removed by applying a temperature gradient along the pipette.

The scientists investigated their 'thermally-driven method' to a batch of 94 pipettes, aligned length-wise next to each other, all with a pore diameter of around 10 nm. The pipettes were put on a metal plate kept at a temperature of 80 °C, with their tips protruding from the plate, resulting in a temperature gradient.

Time-lapsed optical microscopy images of the filling process of the nanopipettes showed that after 1200 seconds, the tips are completely filled with solution, and that air bubbles are driven out of the pipettes.

In order to double-check that the pipettes were indeed bubble-free, Watanabe and colleagues performed so-called I-V measurements. Every pipette was filled with a solution of potassium chloride (KCl), which is conducting. Both pipette ends were then contacted with electrodes. If an electrical current runs between the ends -- specifically, if the pipette has an electrical conductivity below a few GΩ-- then filling with the solution is complete. The resesarchers observed electrical currents and therefore filling for the whole batch of pipettes.

The scientists also performed transmission electron microscopy (TEM) measurments of pipettes with pore diameters below 10 nm. Although the thermally-driven method leads to good electrical contacts, particle-like structures were observed inside the tips of the nanopipettes, demonstrating that (quoting the researchers) "TEM observation without inducing pipette deformation is important for accurately determining the characteristics of sub-10-nm nanopipettes."

Watanabe and colleagues concluded that their method is very practical and easy to introduce in nanopipette frabrication and that their study "will provide a significant contribution to various fields of nanoscience using nanopipettes.

Credit: 
Kanazawa University

Human immune cells produced in a dish in world first

video: The bodies earliest immune cells were engineered to glow green when they arose from stem cells. These green cells can be seen migrating along blood vessels. Later, they populate the thymus - the so-called T-cell nursery.

Image: 
Murdoch Children's Research Institute

One day the advance could lead to a patient's own skin cells being used to produce new cells for cancer immunotherapy or to test autoimmune disease interventions.

The group, led by Professors Ed Stanley and Andrew Elefanty, from the Murdoch Children's Research Institute in Melbourne, Australia, said the work has added definitive evidence about how the body's earliest immune cells are formed.

These lymphocytes are produced by cells which form the embryo's first organs rather than the blood-producing stem cells that sit inside the body's bone marrow.

The research combined two powerful laboratory techniques, genetic engineering and a novel way of growing stem cells, to make the breakthrough, which has been published in the prestigious journal Nature Cell Biology.

First, the team engineered pluripotent stem cells to glow green when a specific protein marker of early immune cells, RAG1, was switched on. RAG1 is responsible for creating the immune response to infections and vaccines.

Next, the team isolated the glowing green RAG1-positive cells and showed that they could also form multiple immune cell types, including cells required for shaping the development of the whole immune system.

"We think these early cells might be important for the correct maturation of the thymus, the organ that acts as a nursery for T-cells" said Professor Stanley.

"These RAG1 cells are like the painters and decorators who set up that nursery, making it a safe and cosy environment for later-born immune cells," he said.

Professor Elefanty said, "Although a clinical application is likely still years away, we can use this new knowledge to test ideas about how diseases like childhood leukemia and type 1 diabetes develop. Understanding more about the steps these cells go through, and how we can more efficiently nudge them down a desired pathway, is going to be crucial to that process."

Credit: 
Murdoch Childrens Research Institute

Fish species benefit from marine protection to varying extents

image: Individual marine protected areas typically harbour more individual fish, particularly of large species targeted by fisheries.

Image: 
Maayan Tzuriel

Leipzig. Marine protected areas reduce fish mortality by limiting harvesting and reducing habitat destruction. They are often designed and implemented to promote biodiversity conservation and sustainable fisheries. New research shows these conservation efforts lead not only to an increase in the total number of fishes (individuals) in general. Protected areas in the northern Mediterranean Sea also harbour a higher number of common fish species, and significant positive network effects accumulate between individual reserves. This was found by a team of researchers from multiple institutions including the German Centre of Integrative Biodiversity Research (iDiv), Tel Aviv University, Martin Luther University Halle-Wittenberg (MLU) and the Helmholtz Centre for Environmental Research (UFZ). Their results have been published in the Journal of Applied Ecology and shed new light onto how fish communities respond to protection.

Coastal regions of the Mediterranean are home to more than one hundred million of people. For centuries, these regions have been impacted by multiple human stressors - such as nutrient pollution and harvesting of natural resources.

Currently, 6.5% of the Mediterranean Sea is designated with some level of protection, though less than 1% is fully protected from all extractive uses, including fishing. Such protection is known to increase the number of individuals and fish biomass inside protected areas, but the effect on the number of species (species richness) is more variable, and evidence for biodiversity gains through protection is mixed. The international team of researchers examined how fish biodiversity in the Mediterranean responded to protection by comparing the numbers of individuals, the relative abundance of species and how they are distributed in space, for fishes inside and outside of protected areas.

The researchers found that conservation has strong impacts on biodiversity. Most notable effects were found on the relative abundance of species in protected areas. Rare and common species were disproportionately affected by protection. In particular, there were more common species inside individual protected areas, as well as at the scale of all protected areas combined.

The researchers found that species most sensitive to exploitation responded more strongly to protection than species less sensitive to exploitation. Exploited species showed gains in the number of individuals inside protected areas, the number of common species, as well as of all species combined. Importantly, the increase in the number of common species with high sensitivity to exploitation was greater at regional than local scales. This reflects a tendency for different protected sites to have different exploited species. As a result, biodiversity benefits from a network of protected areas within an ecosystem.

"We found this network effect in reserves that were independently implemented, so they were not necessarily designed to combine as a network. It would be interesting to know whether similar patterns are found in networks of reserves designed with a particular focus, such as to maximize habitat diversity or promote connectivity among reserves", said first author Dr Shane Blowes from the German Centre for Integrative Biodiversity Research (iDiv) and Martin Luther University Halle-Wittenberg (MLU).

The research shows that examining multiple biodiversity components across scales gives new insights into how communities respond to protection. The findings of the team suggest that protection could help reverse taxonomic homogenisation that is possibly associated with harvesting, and that local biodiversity conservation initiatives can combine synergistically across a regional system of marine protected areas.

Credit: 
German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig

Kangaroo Island shows burn scars on one third of the land mass

image: This is a Terra satellite image of Kangaroo Island on Jan. 7, 2020.

Image: 
NASA Worldview

NASA's Terra satellite provided before and after imagery that showed the extent of the fires that have been ravaging Australia's Kangaroo Island. Kangaroo Island lies off the mainland of South Australia, southwest of Adelaide. About a third of the island is made up of protected nature reserves which are home to native wildlife which includes sea lions, koalas and diverse and endangered bird species, including glossy black-cockatoos which have been brought back from the brink of extinction over the last two decades.

The left image is from Dec. 16, 2019 and the right image was taken on Jan. 07, 2020. The devastation can clearly be seen as one-third of the island (155,000 hectares/383,013 acres) shows burn scars as well as areas that are still on fire. These images were captured by NASA's Terra satellite using its MODIS instrument. The MODIS (Moderate Resolution Imaging Spectroradiometer) instrument is able to overlay reflective bands of color to highlight areas burned and distinguish them from areas of regular vegetation.

Burned areas or fire-affected areas are characterized by deposits of charcoal and ash, removal of vegetation and/or the alteration of vegetation structure. When bare soil becomes exposed, the brightness in Band 1 may increase, but that may be offset by the presence of black carbon residue; the near infrared (Band 2) will become darker, and Band 7 becomes more reflective. When assigned to red in the image, Band 7 will show burn scars as deep or bright red, depending on the type of vegetation burned, the amount of residue, or the completeness of the burn. Vegetation is very reflective in the near infrared (Band 2), and absorbent in Band 1 and Band 7. Assigning that band to green means even the smallest hint of vegetation will appear bright green in the image.

NASA's satellite instruments are often the first to detect wildfires burning in remote regions, and the locations of new fires are sent directly to land managers worldwide within hours of the satellite overpass. Together, NASA instruments detect actively burning fires, track the transport of smoke from fires, provide information for fire management, and map the extent of changes to ecosystems, based on the extent and severity of burn scars. NASA has a fleet of Earth-observing instruments, many of which contribute to our understanding of fire in the Earth system. Satellites in orbit around the poles provide observations of the entire planet several times per day, whereas satellites in a geostationary orbit provide coarse-resolution imagery of fires, smoke and clouds every five to 15 minutes. For more information visit: https://www.nasa.gov/mission_pages/fires/main/missions/index.html

NASA's Earth Observing System Data and Information System (EOSDIS) Worldview application provides the capability to interactively browse over 700 global, full-resolution satellite imagery layers and then download the underlying data. Many of the available imagery layers are updated within three hours of observation, essentially showing the entire Earth as it looks "right now." Actively burning fires, detected by thermal bands, are shown as red points. Image Courtesy: NASA Worldview, Earth Observing System Data and Information System (EOSDIS).

In the western part of Kangaroo Island, specifically in Flinders Chase National Park, penguin colonies and famous coastal rock formations are found. Kangaroo Island is Australia's third largest island after Tasmania and Melville Island. In addition to it being a very popular tourist destination for both Australians and nature lovers, the island even boasts a colony of Ligurian honey bees which are the world's only pure-bred and disease-free population of this type of bee.

Which makes the devastating bushfires that have laid waste to almost one-third of the island not only just a major tragedy for the island but an ecological tragedy as well. The bushfires began as lightning strikes within Flinders Chase National Park. Ecologists within the park put estimates of the number of koalas that have perished in the fire at 25,000 which is half the island's population of the popular animals. NASA's fleet of satellites are able to monitor from their various satellites the extent of the damage and the areas continuing to burn which assist firefighters in fighting these major disasters. Below is a slider of two images that show Kangaroo Island both before and after the bushfires.

Credit: 
NASA/Goddard Space Flight Center

Federal data undercounts fatal overdose deaths caused by specific drugs

TAMPA, Fla. (January 7, 2020)- Fatal misuse of specific drugs is a bigger problem than federal statistics make them appear, especially in Florida. According to data collected by a researcher at the University of South Florida (USF), between 2008 and 2017, roughly one-in-three overdose deaths in Florida caused by opioids were not reported by the federal government. Likewise, nearly 3,000 deaths in the state caused by cocaine were not included in the total reported federal data. Those conclusions come following a comparison of data provided by the Florida Medical Examiners Commission (FMEC), which is based on state-mandated reporting, and the U.S. Centers for Disease Control and Prevention's Multiple Cause of Death (MCOD) database.

Troy Quast, PhD, associate professor at the USF College of Public Health found the MCOD data undercounted overdose deaths caused by benzodiazepines by 45 percent and amphetamines by 17 percent. According to the FMEC, more than 25,000 people died from opioids during that ten-year period. The study published in Drug and Alcohol Dependence also looked at several specific opioids. While heroin deaths ballooned during this time, fatal overdoses caused by methadone were less than half of what they were ten years prior. The percent of fatal overdoses not included in the MCOD data for these two drugs were approximately 25 percent and 45 percent, respectively.

Florida medical examiners are required to wait for complete toxicology results before submitting an official cause of death to FMEC. It often takes weeks or even months to identify the exact drug or drugs that caused the deceased to overdose. By contrast, the MCOD data is based on death certificates filed by local authorities, which don't always include such detailed information. This causes significant underestimations to which drugs caused overdose deaths.

"The CDC data are widely reported in the news and referenced by politicians, which is problematic since those estimates significantly undercount the true scope of the epidemic for specific drugs," said Quast. "The rate of under-reporting for all overdose deaths in Florida is near the national average, so the problem is not to the state."

Quast also examined the data by gender, race and age and generally found similar rates of undercounting within each group. He found almost twice as many men died from opioid overdoses than women. For each drug studied, those between ages 45 and 54 and whites generally had the highest number of overdose deaths during the 2008 and 2017 period.

The federal government is working to improve the collection of data regarding fatal overdoses due to specific drugs. The CDC's Enhanced State Opioid Overdose Surveillance program recently awarded $13 million to help them more quickly conduct comprehensive toxicology reports. Quast believes efforts such as these will help enhance our understanding and improve the response to the drug misuse epidemic.

Credit: 
University of South Florida

Million Veteran Program study sheds light on genetic basis of anxiety

image: Numerous genetic studies are now underway using data from VA's landmark Million Veteran Program, which currently has upwards of 800,000 participants.

Image: 
Robert Lisak

In the largest genetic study on anxiety to date, VA researchers found new evidence on the underlying biological causes of the disorder. The study used VA Million Veteran Program (MVP) data to identify regions on the human genome related to anxiety risk. The findings could lead to new understanding and treatment of the condition, which affects 1 in 10 Americans.

According to Dr. Dan Levey of the VA Connecticut Healthcare Center and Yale University, one of the lead authors on the study, the findings are "an important step forward" in the understanding of anxiety disorders and how genes contribute to mental conditions.

The results appear Jan. 7, 2020, in the American Journal of Psychiatry.

Anxiety refers to anticipation of perceived future threats. In anxiety disorders, these concerns are out of proportion to the actual anticipated event, leading to distress and disability. Anxiety disorders often occur alongside other mental health disorders like depression.

Only a third of those with anxiety disorders receive treatment. Some forms of psychotherapy, such as cognitive behavioral therapy, have proved effective, as have medications such as selective serotonin reuptake inhibitors. In other fields of medicine, genetic studies have led to precision medicine approaches--tailoring drug treatment to patients' individual genetic and biochemical profiles--for a number of diseases. The researchers hope more genetic insight will lead to similar approaches for anxiety.

The researchers compared the genomes of nearly 200,000 MVP participants. They identified five locations on the human genome related to anxiety in Americans of European descent, and one in African Americans. Gene variants at these genome locations could increase anxiety risk, say the scientists.

The findings for the African American participants are especially important, says Levey. "Minorities are underrepresented in genetic studies, and the diversity of the Million Veteran Program was essential for this part of the project. The genetic variant we identified occurs only in individuals of African ancestry, and would have been completely missed in less diverse cohorts."

The study produced the first genome-wide significant findings on anxiety in African ancestry, notes Levey. About 18% of MVP participants are African American.

The anxiety-related genome locations also show overlap with other psychiatric conditions. One of the identified locations has previously been linked with risk for bipolar disorder and schizophrenia. The study also shows genetic overlap between anxiety symptoms and depression, PTSD (which is related to anxiety), and neuroticism--a personality trait that has been shown to increase risk for anxiety and related disorders. The results support the idea that overlap with these other traits is at least partially due to a significant genetic commonality, according to the researchers.

MVP is a national, voluntary research program funded by VA's Office of Research and Development. It is one of the world's largest databases of health and genomic information. MVP partners with veterans receiving care in VA to study how genes affect health. As of November 2019, MVP had enrolled more than 800,000 veterans.

"MVP has enormous potential for increasing our knowledge about the genetics underlying a huge range of traits, including psychiatric traits. It is one of the best samples in the world for this purpose," said Dr. Joel Gelernter, also of the VA Connecticut Healthcare Center and Yale University. Gelernter is one of the senior authors of the work, together with Dr. Murray Stein of the VA San Diego Healthcare System and University of California San Diego. For more information on MVP, visit http://www.research.va.gov/MVP.

Credit: 
Veterans Affairs Research Communications

Study of veterans details genetic basis for anxiety, links anxiety and depression

A massive genomewide analysis of approximately 200,000 military veterans has identified six genetic variants linked to anxiety, researchers from Yale and colleagues at other institutions report Jan. 7 in the American Journal of Psychiatry.

Some of the variants associated with anxiety had previously been implicated as risk factors for bipolar disorder, posttraumatic stress disorder, and schizophrenia.

The new study further contributes the first convincing molecular explanation for why anxiety and depression often coexist.

"This is the richest set of results for the genetic basis of anxiety to date," said co-lead author Joel Gelernter, the Foundations Fund Professor of Psychiatry, professor of genetics and of neuroscience at Yale. "There has been no explanation for the comorbidity of anxiety and depression and other mental health disorders, but here we have found specific, shared genetic risks."

Finding the genetic underpinnings of mental health disorders is the primary goal of the Million Veteran Program, a compilation of health and genetic data on U.S. military veterans run by the U.S. Veterans Administration. The research team analyzed the program's data and zeroed in on six variants linked to anxiety. Five were found in European Americans and one found only in African Americans.

"While there have been many studies on the genetic basis of depression, far fewer have looked for variants linked to anxiety, disorders of which afflict as many as 1 in 10 Americans," said senior author Murray Stein, San Diego VA staff psychiatrist and Distinguished Professor of Psychiatry and of family medicine and public health at UCSD.

Some variants were linked to genes that help govern gene activity or, intriguingly, to a gene involved in the functioning of receptors for the sex hormone estrogen. While this finding might help explain why women are more than twice as likely as men to suffer from anxiety disorders, researchers stressed that the variant affecting estrogen receptors was identified in a veteran cohort made up mostly of men, and said further investigation is necessary.

Another of the newly discovered anxiety gene variants, MAD1L1, whose function is not fully understood, was also highly notable. Variants of this gene have already been linked to bipolar disorder, posttraumatic stress disorder, and schizophrenia.

"One of the goals of this research is to find important risk genes that are associated with risk for many psychiatric and behavioral traits for which we don't have a good explanation," said Yale's Daniel Levey, a postdoctoral associate and co-lead author of the study.

To do the study, Yale's researchers teamed up with colleagues at the Veteran Affairs Connecticut Healthcare System, VA San Diego Healthcare System, and the University of California San Diego.

Said Gelernter, "This is a rich vein we have just begun to tap."

Credit: 
Yale University

Binary star V Sagittae will explode as a very bright 'nova' by century's end

image: Professor Emeritus Bradley E. Schaefer, LSU Department of Physics & Astronomy

Image: 
LSU Physics & Astronomy

Currently, the faint star V Sagittae, V Sge, in the constellation Sagitta, is barely visible, even in mid-sized telescopes. However, around the year 2083, this innocent star will explode, becoming as bright as Sirius, the brightest star visible in the night sky. During this time of eruption, V Sge will be the most luminous star in the Milky Way galaxy.

This prediction was presented for the first time at the 235th American Astronomical Society meeting in Honolulu, by astronomers Bradley E. Schaefer, Juhan Frank and Manos Chatzopoulos, with the LSU Department of Physics & Astronomy.

"We now have a strong prediction for the future of V Sge," Schaefer said. "Over the next few decades, the star will brighten rapidly. Around the year 2083, its accretion rate will rise catastrophically, spilling mass at incredibly high rates onto the white dwarf, with this material blazing away. In the final days of this death-spiral, all of the mass from the companion star will fall onto the white dwarf, creating a super-massive wind from the merging star, appearing as bright as Sirius, possibly even as bright as Venus."

V Sge is a star system in a large and diverse class called Cataclysmic Variables, or CVs, consisting of an ordinary star in a binary orbit around a white dwarf star, where the normal star's mass is slowly falling onto the white dwarf. CVs include multiple types of binary stars, often with spectacular behavior. V Sge is the most extreme of all the CVs, approximately 100 times more luminous than all other known CVs, and is powering a massive stellar wind, equal to the winds of the most massive stars prior to their deaths. These two extreme properties are caused by the fact that the normal star is 3.9 times more massive than the white dwarf.

"In all other known CVs the white dwarf is more massive than the orbiting normal star, so V Sge is utterly unique," said Schaefer.

"Previously, astronomers have studied V Sge, realizing that it is an unusual system with extreme properties," said Frank. "However, no one had realized that the binary orbit was in-spiraling very fast."

This realization came from routine measures of V Sge's brightness on old sky photos now archived at the Harvard College Observatory, providing a detailed history going back to the year 1890.

Startlingly, V Sge has been systematically brightening by a factor of 10X, 2.5 magnitudes, from the early 1890s up until the last decade. This unprecedented behavior was confirmed with archival data collected from the database of the American Association of Variable Star Observers, AAVSO, showing V Sge brightening by nearly a factor of 10X, 2.4 magnitudes, from 1907 until the last few years.

"V Sge is exponentially gaining luminosity with a doubling time scale of 89 years," said Frank. "This brightening can only result with the rate of mass falling off the normal companion star increasing exponentially, ultimately because the binary orbit is in-spiraling rapidly."

Schaefer said, "In anticipation of this fast decaying of the orbit, the fate of V Sge is sealed. The critical and simple physics are derived from V Sge having the companion star being much more massive than the white dwarf star, so forcing the rate of mass transfer to rise exponentially. Anticipating the next few decades, V Sge will in-spiral at a rapid pace with increasing brightness. Inevitably, this in-spiral will climax with the majority of the gas in the normal star falling onto the white dwarf, all within the final weeks and days. This falling mass will release a tremendous amount of gravitational potential energy, driving a stellar wind as never before seen, and raise the system luminosity to just short of that of supernovae at peak."

This explosive event will have peak brightness over a month, with two stars merging into one star. The end result of the merger will produce a single star with a degenerate white dwarf core, a hydrogen-burning layer, surrounded by a vast gas envelope mostly of hydrogen.

"From this critical new input of the doubling time scale of 89 years, it becomes possible to directly calculate the future evolution of V Sge, all using standard equations describing the many physical mechanisms involved," said Schaefer.

The calculations give a robust answer to the brightness with the in-spiral merger happen for the final merge event will be around the year 2083.

"The uncertainty in this date is ±16 years, arising mostly from not having a perfect measure of the doubling time scale due to the large intrinsic jitter of the brightness in the historical record," said Frank. "Therefore, the merge will be approximately between 2067 and 2099, most likely near the middle of this range."

Schaefer said, "Thus, V Sge will appear startlingly bright in the night sky. This is substantially brighter than the all-time brightest known nova (at -0.5) just over a century ago, and the last time any 'guest star' appeared brighter was Kepler's Supernova in the year 1604.

"Now people the world over can know that they will see a wondrous guest star shining as the brightest in the sky for a month or so, being pointed at by the Arrow just below Cygnus, the Swan."

Credit: 
Louisiana State University

The growing pains of orphan chimpanzees

image: Chimpanzee mother resting with her young offspring (Taï Forest, Côte d'Ivoire).

Image: 
Liran Samuni

The prolonged periods of juvenility and nutritional dependence that are characteristic of human development are thought to facilitate brain and somatic growth in children, as well as provide opportunities to learn and accumulate skills required for a productive adult life. In chimpanzees, the benefits of continuing to associate with mothers after becoming nutritionally independent are less well understood.

To address this, the researchers used a dataset comprising 18 years of research effort on three groups of wild chimpanzees at the Taï Forest, Côte d'Ivoire, to examine the effects of maternal loss and mothers' social status on offspring lean muscle mass development. "We assessed the muscle mass of 70 offspring from 41 mothers by means of urinary creatinine concentrations, a by-product of metabolic activity in muscles," explains Tobias Deschner, a researcher at the MPI for Evolutionary Anthropology. As expected, offspring muscle mass increased with age in both males and females. However, chimpanzee offspring that lost their mother after they were already weaned had less muscle mass than those with living mothers. Furthermore, mothers of high social status measured by dominance rank, produced offspring with higher muscle mass.

This study demonstrates how maternal presence and maternal social status can impact offspring phenotype in wild chimpanzees. Importantly, even once offspring are nutritionally independent, maternal loss has negative consequences on their growth. "Our results emphasize the crucial role of mothers and suggest that even in the absence of consistent direct provisioning from mothers to offspring, chimpanzee mothers still indirectly influence food consumption in their offspring", Liran Samuni, one of the two first authors on the study, points out.

"This may occur in similar ways to humans", suggests Patrick Tkaczynski, the other first author on the study. "Mothers may provide support to their offspring during competitive interactions with others, and increase their chance to 'win' conflicts, or soften reactions of offspring to challenging situations. Also, mothers may provide opportunities for offspring to learn how to find and access hard to extract or rare food items."

"Our study provides evidence that a mother-offspring association and dependence that lasts beyond the weaning age, although unique in its duration and level of investment in human societies, may be a trait with deep evolutionary origins that we share with one of our closest living relatives", declares Catherine Crockford, head of the ERC project group Ape Attachement and senior author of the study.

Credit: 
Max Planck Institute for Evolutionary Anthropology

Brain tumour research could help future precision medicine

New research on brain tumours could improve patient diagnosis and treatment options as part of a precision medicine approach. Brain tumours are the leading cause of cancer deaths in children and adults under the age of 40, with 16,000* people in the UK diagnosed with a brain tumour each year.

The study led by the Brain Tumour Research Centre at the University of Bristol in collaboration with the Cancer Research and Cell Biology (CCRCB) at Queen's University Belfast investigated the genetics of brain tumours. The research is published in the Journal of Oncology.

The DNA was extracted from the Brain tumours of 41 patients and presence of changes or mutations in the DNA were characterised. Results were described for different types of tumours before and after treatment.

The research outlines the mutations that are particular to different tumour types. This information is important to enable precision medicine, where a patient would receive therapies tailored to the specific DNA mutations in their tumour.

One of the challenges with brain cancer is getting drugs into the tumour beyond the blood-brain barrier. The new study also lists licensed drugs that are already available that could be used as combination therapies to target specific mutations in the future. These drugs can be taken orally and should be better tolerated with less side effects. To ensure patient safety, any new combination therapies would first need to be tested in clinical trials before they would become available to patients.

These findings could pave the way for developing new targeted treatments that are more effective. The research also followed the mutations that develop during brain cancer, which could identify new therapy options to be given as the cancer progresses and help to extend patient survival.

Dr Kathreena Kurian, Associate Professor in Brain Tumour Research at the University of Bristol, who led the research, said: "New treatments are urgently needed for this incurable and devastating disease. This approach should improve patient outcomes and save on prescribing medicines to patients that won't benefit from them, thereby reducing patient exposure to toxic chemicals from chemotherapy, as well as saving the NHS money."

Diagnoses and deaths from brain tumours are increasing (Office for National Statistics, 2019). Despite traditional chemotherapy and radiotherapy treatment, the five-year survival rate for brain cancer patients is 20 per cent, compared with 50 per cent as an average for all cancers*. Some patients who receive chemotherapy, which can have severe side-effects in some patients, do not respond to treatment and other patients respond initially but unfortunately in most cases the cancer grows back.

Professor Kevin Prise, Professor of Radiation Biology from the CCRCB at Queen's University Belfast and co-author, added: "With only five per cent of the national spend on cancer research allocated to brain cancer, there is a pressing need to build capacity and develop research programs for brain tumour research throughout the UK particularly to advance precision medicine. Precision medicine promises to offer more individualised treatments and better outcomes for brain tumour patients."

Credit: 
University of Bristol

Researchers develop universal flu vaccine that protects against 6 influenza viruses in mice

image: Ye Wang, first author of the study and a biology Ph.D. student working in Dr. Bao-Zhong Wang's lab in the Institute for Biomedical Sciences at Georgia State University.

Image: 
Georgia State University

ATLANTA--A novel nanoparticle vaccine that combines two major influenza proteins is effective in providing broad, long-lasting protection against influenza virus in mice, showing promise as a universal flu vaccine, according to a study by the Institute for Biomedical Sciences at Georgia State University.

The double-layered nanoparticle vaccine contains the influenza virus proteins matrix protein 2 ectodomain (M2e) and neuraminidase (NA). Mice were immunized with the nanoparticle vaccine before being exposed to influenza virus, and they were protected against six different strains of the virus.

The findings, which suggest this unique vaccine combination has potential as a universal influenza vaccine or component of such vaccines, are published in the journal Advanced Healthcare Materials.

"This nanoparticle antigen combination conferred mice with strong cross protection," said Ye Wang, first author of the study and a biology Ph.D. student working in Dr. Bao-Zhong Wang's lab in the Institute for Biomedical Sciences. "It can protect mice from different strains of influenza virus. Each season, we have different flu strains that affect us. By using this approach, we hope this nanoparticle vaccine can protect humans from different strains of influenza virus."

Influenza, a contagious respiratory illness caused by influenza viruses, is a leading cause of death by infection. Seasonal flu vaccines are insufficient to prevent influenza outbreaks, and developing a universal influenza vaccine is the ideal strategy for eliminating public health threats of influenza epidemics and pandemics. A universal influenza vaccine would eliminate the need for vaccinations each season and offers universal protection against all influenza strains.

The influenza virus protein M2e is found in all influenza virus strains, with each strain having a very similar version, and the protein has mutated very slowly over time. The protein NA is found on the surface of influenza virus and has also mutated much slower than other influenza proteins. This double-layered nanoparticle vaccine uses M2e as its core, and NA is coated on the surface.

In the study, mice were exposed to one of six influenza virus strains after receiving the nanoparticle vaccine by intramuscular injection. The vaccine proved to have long-lasting immune protection, which was unchanged against viral challenges up to four months after immunizations.

"It's important to mention that a lot of flu vaccines haven't focused on NA before," said Gilbert Gonzalez, co-author of the study and lab manager in Dr. Bao-Zhong Wang's lab in the Institute for Biomedical Sciences. "NA is becoming a more important antigen for influenza vaccine research. Previously, it had been ignored or discounted because hemagglutinin (HA) is much more dominant. When you get a flu infection, your body reacts to the HA."

However, the HA protein mutates very quickly, which is why seasonal flu vaccines must be changed by scientists every year. Someone could get the flu this year and develop immunity against that particular HA protein, but by next flu season, the HA protein would have rapidly changed and they wouldn't be protected again.

Next, the researchers plan to load this double-layered nanoparticle vaccine onto microneedle patches for skin vaccination.

Credit: 
Georgia State University

Magnitude of Great Lisbon Earthquake may have been lower than previous estimates

The magnitude of the Great Lisbon Earthquake event, a historic and devastating earthquake and tsunami that struck Portugal on All Saints' Day in 1755, may not be as high as previously estimated.

In his study published in the Bulletin of the Seismological Society of America, Joao F. B. D. Fonseca at the Universidade de Lisboa used macroseismic data--contemporaneous reports of shaking and damage--from Portugal, Spain and Morocco to calculate the earthquake's magnitude at 7.7. Previous estimates placed the earthquake at magnitude 8.5 to 9.0.

Fonseca's analysis also locates the epicenter of the 1755 earthquake offshore of the southwestern Iberian Peninsula, and suggests the rupture was a complicated one that may have involved faulting onshore as well. This re-evaluation could have implications for the seismic hazard map of the region, he said.

The current maps are based on the assumption that most of the region's crustal deformation is contained in large offshore earthquakes, without a significant onshore component. "While the current official map assigns the highest level of hazard to the south of Portugal, gradually diminishing toward the north, the interpretation now put forward concentrates the hazard in the Greater Lisbon area," said Fonseca.

The 1755 Lisbon earthquake and tsunami event, along with the fires it caused that burned for hours in the city, is considered one of the deadliest earthquake events in history, leading to the deaths of about 12,000 people. The devastation had a significant impact on Portugal's economy and its political power within Europe, and its philosophical and theological implications were widely discussed by Enlightenment scholars from Voltaire to Immanuel Kant.

The widespread devastation led earlier seismologists to estimate a high magnitude for the earthquake. With modern modeling techniques and a better understanding of the region's tectonics, Fonseca thought it important to revisit the estimate. The 1755 earthquake is unusual in that it produced extreme damage hundreds of kilometers from its epicenter without any of the accompanying geological conditions--like amplification of seismic waves in a loose sedimentary basin, for instance--that normally cause such severe site effects.

"Explanations put forward for the extreme damage in Lisbon tend to invoke abnormally low attenuation of seismic energy as the waves move away from the epicenter, something that is not to be observed anywhere else in the globe," Fonseca explained. "Current attempts to harmonize seismic hazard assessment across Europe are faced with large discrepancies in this region, which need to be investigated and resolved for a better mitigation and management of the risk through building codes and land use planning."

Fonseca used 1206 points of macroseismic data to reassess the 1755 earthquake's magnitude and epicenter. The analysis and modeling also indicate that some of the very high earthquake intensities reported in the region's nearby Lower Tagus Valley and the Algarve may have been due to two separate onshore earthquakes in these locations. These earthquakes, which took place a few minutes after the offshore rupture, may have been triggered by the first earthquake, Fonseca suggests.

The new magnitude estimate for the 1755 earthquake is similar to that of another large regional earthquake, the 1969 magnitude 7.8 Gorringe Bank quake. However, the damage from the Gorringe Bank earthquake was much less severe, possibly in part because the onshore faults had not accumulated enough stress to make them "ripe to rupture," Fonseca says. "The Lower Tagus Fault, near Lisbon, ruptured in 1909, in 1531 and likely in 1344. It is plausible that it was good to go in 1755, but still halfway through the process of accumulating stress in 1969."

Fonseca also suggests that the destructive size of the 1755 accompanying tsunami might be due more to the presence of a large sedimentary body produced by past subduction, called an accretionary wedge, on the ocean bottom in the Gulf of Cadiz. When a fault rupture moves through this wedge, it can generate a tsunami even without an extreme magnitude rupture, he said.

Credit: 
Seismological Society of America

Research team traces evolution of the domesticated tomato

image: Evolutionary biologists and geneticists at UMass Amherst report that they have identified missing links in the tomato's evolution from a wild blueberry-sized fruit in South America to the larger modern tomato of today.

Image: 
University of Georgia/Alexis Ramos

AMHERST, Mass. - In a new paper, a team of evolutionary biologists and geneticists led by senior author associate professor Ana Caicedo, with first author Hamid Razifard at the University of Massachusetts Amherst, and others, report that they have identified missing links in the tomato's evolution from a wild blueberry-sized fruit in South America to the larger modern tomato of today.

The missing link that deserves more attention than it has gotten to date, they say, is one of a number of intermediate variants between the fully wild and fully domesticated tomato. Results of their genetic studies indicate that the modern cultivated tomato is most closely related to a weed-like tomato group still found in Mexico rather than to semi-domesticated intermediate types found in South America.

Razifard, a postdoctoral researcher in the Caicedo lab, says, "What's new is that we propose that about 7,000 years ago, these weedy tomatoes may have been re-domesticated into the cultivated tomato." The common cultivated tomato is the world's highest value and most widely grown vegetable crop and an important model for studying fruit development, Caicedo and colleagues point out.

In this work, part of a larger research effort supported by the National Science Foundation and led by Esther van der Knaap at the University of Georgia, the researchers say that for many years an oversimplified view of tomato domestication was thought to involve two major transitions, the first from small, wild Solanum pimpinellifolium L. (SP) to a semi-domesticated intermediate, S. lycoperiscum L. var. cerasiforme (SLC). The second was a transition from an intermediate group (SLC) to fully domesticated cultivated tomato (S. lycopersicum L. var. lycopersicum (SLL)).

Their genetic studies address the role of what they call a "historically contentious" and complex intermediate stage of tomato domestication, an essential chapter that should not be overlooked in the tomato's long journey from wildness to domestication. Details appear in an Advanced Access edition of Molecular Biology and Evolution.

Razifard and colleagues, who created a public genomic variants dataset for this study, used whole-genome sequencing of wild, intermediate and domesticated (SP, SLC, and SLL) varieties, plus population genomic analyses to reconstruct tomato domestication, focusing on evolutionary changes especially in the intermediate stages (SLC). They generated new whole-genome sequences for 166 samples, with particular attention to intermediate variants from its native range and cultivated fruit from Mexico, previously under-represented in studies.

Razifard says, "We found that SLC may have originated in Ecuador around 80,000 years ago as a wild species rather than a domesticate. It was cultivated in Peru and Ecuador by native people later to create medium-size tomato fruits. We also found that two subgroups from the intermediate group may have spread northward to Central America and Mexico possibly as a weedy companion to other crops."

"Remarkably, these northward extensions of SLC seem to have lost some of the domestication-related phenotypes present in South America. They still grow in milpas of Mexico, where people use them as food although not cultivating them intentionally," he adds. Milpas are fields where farmers plant many different crops in the same area.

He and Caicedo note that an origin of the domestic tomato from weed-like ancestors was proposed in 1948 based on the many native names that exist for the weed-like tomato, in contrast to fewer names for the common cultivated tomato. This hypothesis was challenged by others who argued against Mexico as a center of tomato domestication due to the absence of completely wild tomatoes there.

Razifard says, "It's still a mystery how tomatoes have moved northward. All we have is genetic evidence and no archaeological evidence because tomato seeds don't preserve well in the archeological records."

The researchers point out that exploring intermediate stages of tomato domestication has "direct implications for crop improvement." For example, they observed some signals of selection in certain intermediate populations for alleles involved in disease resistance and drought tolerance, important, Razifard says, "Such evidence is useful for finding candidate alleles that can be used for creating disease-resistant and/or drought-tolerant tomatoes." Other intermediate populations had higher beta-carotene or sugar content, attractive traits to consumers.

The evolutionary biologist says, "This is the kind of paper that Darwin would have enjoyed reading. He drew many of his insights on evolution from studying plants, especially crops. He corresponded extensively with botanists before he finalized his theory of evolution through natural selection."

A postdoctoral researcher who did much of the population genomic analyses for this project, Razifard adds that he wants to support the movement in biology against "plant blindness," the tendency to ignore the importance of plants in studying evolution as well as other subfields of biology. Also, he is from a minority Azerbaijani-speaking area of Iran and says, "This paper is special to me because it's my first one with a female-majority author list. I feel lucky to be part of a generation that is changing science, and I hope this paper serves as a model for gender equity in STEM fields."

Credit: 
University of Massachusetts Amherst

A new link between fear, imitation, and antisocial behavior in children

Why do some children have more difficulties understanding others' emotions or feeling sorry after misbehaving? Why do some act out in certain situations and behave in others? How should adults respond in these circumstances?

For parents, such puzzles can seem unsolvable yet having insight into the inner workings of these situations becomes increasingly important when the behaviors start to interfere with daily functioning and healthy development.

Two papers from psychologists Rebecca Waller of the University of Pennsylvania and Nicholas Wagner of Boston University, one published in The Journal of Child Psychology and Psychiatry, the other in Psychological Medicine, may provide new insight into a set of behaviors known as callous-unemotional (CU) traits. The researchers found that young children who exhibited less fear and desire for social connection and who engaged less frequently in a copycat behavior called arbitrary imitation developed more CU traits, which are known to lead to antisocial behavior later.

A link between antisocial or aggressive behavior and CU traits--characterized by lack of empathy, guilt, and reduced sensitivity to others' emotions--is already well known. Previous research has revealed that children with these characteristics are more likely to develop severe, persistent antisocial behavior, often expressed through violence and hostility.

Practically speaking, this translates to a child who is "less compassionate, doesn't care about breaking the rules, doesn't change a behavior when they're told, 'If you do X, this bad thing will happen,'" says Waller, an assistant professor in Penn's Department of Psychology and director of the EDEN Lab. "They're also more likely to be aggressive to get what they want because they don't fear the consequences."

What's less understood are the mechanisms and processes that give rise to CU traits, knowledge with important implications for the development and implementation of effective interventions. Waller and Wagner looked at two ideas: The first focuses on fear and social belonging, also known as affiliation; the second is related to imitation.

Fearlessness and social connections

To test their first theory, the researchers used data from the Boston University Twin Project, led by BU professor Kimberly Saudino. During two two-hour lab visits, at age 3 and again at age 5, children played out several scenarios, like offering a parent "candy" from a canister that actually contained a stuffed snake, popping bubbles, or separating different-colored beads into piles.

Analysis of the children's behaviors showed that less fearful children who cared less about social connections at the first visit were more likely to develop callous-unemotional traits by the second. "Fearlessness on its own is not the only ingredient," Waller says. "These children also don't feel, to the same degree, that inherent motivation and reward from having positive social bonding with others."

The researchers also found that harsh parenting--which includes tactics like yelling and spanking--intensified the fearlessness and strengthened the link with later CU traits.

"Parents have a set of tools," says Wagner, an assistant professor at BU and director of the Biobehavioral and Social-Emotional Development Lab. "If kids are fearless, including toward the potential for punishment, the likelihood that harsh parenting will exacerbate risk increases. That fits into the model that clinicians understand already. It takes two to tango; what kids bring to the table mixes with what they're experiencing in the environment."

They published these findings in Psychological Medicine.

Arbitrary vs. functional imitation

The Journal of Child Psychology and Psychiatry work, conducted with a different set of two- and three-year-old BU Twin Study participants, compared instrumental and arbitrary imitation. The former means copying behaviors that serve a function, often done to learn a skill. The latter means following another's actions for no purpose than to exhibit the desire for a social connection.

"Arbitrary imitation is intended to build bonds," Wagner says, "to show another person that you're in their group, that you accept their ways, that you can and will do what they're doing."

For this work, the team built a pair of experiments. In the first, children had to free a stuffed bird from a hard-to-open cage. An adult showed them how, interspersing necessary instruction with unneeded vocalizations like "Look, it's a birdy!" During a second task, children had to use a stick to liberate a cracker stuck in the middle of a clear tube. Again, an adult modeled the steps, mixing essential and arbitrary directions.

In both cases, researchers watched and coded which behaviors the children repeated and which they ignored.

They found that the two-year-olds who engaged in less arbitrary imitation overall--in other words, those who ignored more of the unneeded actions--were at greater risk for developing CU traits later. "This says to us that these children are less motivated to make connections with other kids or adults," Wagner says. "The same was not true for instrumental imitation."

Waller takes it a step further. "It's not that they're not capable of seeing and watching someone doing something," she adds. "They simply don't do the social-bonding thing, the funny, quirky behavior after that would create a nice social moment."

Advising parents

Though these findings offer important clues to why CU traits can lead to antisocial behavior, the researchers want to make clear that they're looking at overall patterns, not one-off instances. "We don't want to scare parents," Waller says. "It's not like if you notice these behaviors once, you're in trouble. It's part of an overarching dimension."

Parents, they suggest, can positively support these aspects of social and emotional development by artificially creating situations, like one in which arbitrary imitation happens, for example. "Encourage the child to make the silly noise or movement you did, then laugh about it," Waller says. "You more explicitly scaffold the situation than if it were to happen naturally, but the children still get the positive reinforcement and it can become a bonding moment."

In regard to fearlessness and social affiliation, Wagner suggests veering away from harshness, toward warmth. "Changing kids' experiences," he says, "that's where we can intervene."

Credit: 
University of Pennsylvania

Illegal hunting and bushmeat trade threatens biodiversity and wildlife of Angola

image: Map of Africa showing the location of Angola (left) and the provinces covered by the study along the main road from Lubango (Huíla province) to Uíge (right).

Image: 
Francisco Maiato P. Gonçalves

Hunting wild animals has been practised by humans for millions of years; however, the extraction of wildlife for subsistence and commercialisation has become a major biodiversity threat in recent decades. Meanwhile, over-exploitation is reported to be the second most important driver of change and biodiversity loss globally.

To assess the state of affairs, an international group of scientists, led by Dr. Francisco M. P. Gonçalves of the University of Hamburg in Germany, went on a roundtrip along the roads between five main Angolan cities. Their observations made it possible to conclude that, despite the existing legislation, as well as government efforts to handle poaching and bushmeat trade, currently there is no effective law enforcement mechanism to help dealing with the situation.

In their study, the team also states that Angola is one of the richest and most biodiverse countries in Africa with an estimated 6,850 native and 226 non-native plant species, 940 bird species (including many endemic species), 117 amphibians species, 278 reptile species, 358 freshwater fishes (22% of them endemic) and 275 species of mammals.

The long-lasting civil war in Angola has contributed to the dramatic loss of wildlife and led to the near extinction of many species, as a result of the increase in illegal poaching. A variety of fresh, smoked or dried bushmeat, as well as live animals, are being sold along the roads, mostly to urban dwellers travelling between the main cities of Angola.

Despite the recent outbreaks of diseases (i.e. Ebola in the neighbouring Democratic Republic of Congo), animals still appear to be obtained directly from hunters and slaughtered with no sanitary measures, while the consumption of wildlife in Africa is frequently associated with an increased risk of acquiring zoonotic diseases.

The major trade road runs between the provinces of Bengo and Uíge, where the animals sold include many species of antelopes, monkeys, snakes and a globally protected species of pangolin (Manis tricuspis). Multiple species of wading birds and parrots are often sold in pet shops, as well as along the streets. At fairs and entry points to the main cities, these can be found offered by young boys.

Although there is no evidence of cross-border trade, there might, however, be cases of bushmeat trade in the informal markets at the principal border posts. Commercial activities between the countries are not regulated and stay intense, note the scientists.

"We witnessed a Chinese customer looking for pangolins in one of the villages; pangolin scales, when soaked, are trusted for having medicinal properties for a large variety of human illnesses mostly in Asia. It is currently estimated there are 0.4-0.7 million pangolins hunted annually, representing an increase of around 150% only for medicinal purposes over the past four decades," share the researchers.

Trying to find a solution, the Angolan government has undertaken a number of measures, including: a list of species prohibited for hunting and trade (five of those species were found on the markets during the survey); banning hunting of certain species outside the hunting season; introducing compensation fees.

However, despite the legal basis, local authorities (i.e. police checkpoints close to the road markets) do not take the necessary measures to discourage hunting and bushmeat trade practices in the region. Due to lack of clear definition and responsibility arrangements, the hunting and trade of wild animals remain uncontrolled.

All these recent observations bring us to the necessity for a re-assessment of the wildlife in Angola and the need to produce appropriate legislation to be efficiently enforced across the whole territory of the country. This can be achieved through better-educated police officials and alternative sources of meat supply in rural areas. These actions should bring down the demand for bushmeat and reduce the overharvesting of wildlife, suggest the scientists.

Credit: 
Pensoft Publishers