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View into plant cells: A membrane protein is targeted to two locations

Metabolic processes are especially complex in plants due to their obligate sessile life style - which is why scientists discover more and more new and surprising connections that occur within their cells. An important metabolic route that has occupied plant scientists for decades is the so-called oxidative pentose-phosphate pathway by which carbohydrates are converted to reduction power. For this pathway, two membrane proteins play an important role - GPT1 and GPT2. They import activated glucose in the form of glucose-6-phosphate into plastids, special cell organelles of plants, to "feed" the oxidative pentose-phosphate pathway. This process is also important for plant reproduction, especially during pollen, ovule and seed development.

Since there were indications that the three oxidative steps of the pathway may also occur in other cell organelles, the peroxisomes, researchers from the University of Münster (Germany) pondered: are also membrane proteins directed simultaneously to two different sites within the same cell? Together with colleagues at the University of Düsseldorf (Germany) they now found an answer. Their results show that only GPT1 is distributed to two locations - and the alternative route of the membrane protein leads via the endoplasmic reticulum, another, net-like organelle of the cell. Thus, GPT1 enables at two sites simultaneously the formation of reduction power, i.e. the capability to transfer electrons.

"Our study shows that besides in plastids and the cytoplasm, the oxidative pentose-phosphate pathway is also a main source of the energy-rich coenzyme NADPH in peroxisomes," emphasizes head of the study Prof. Antje von Schaewen from Münster University. The researchers suppose that plants in which this pathway is blocked in peroxisomes may be less stress-resistant. The study was published in the journal The Plant Cell.

Background and Method:

The scientists investigated the processes in Arabidopsis thaliana, a genetic model plant. In previous studies they had already shown in this species, how other enzymes of the pathway are re-directed from plastids or the cytoplasm to peroxisomes under certain conditions. For this purpose, they employed fluorescent reporter fusion proteins. This method was also used in their current study to visualize GPT1 and GPT2 by life-cell imaging and modern light microscopic techniques.

They found that only GPT1 targets both plastids and the endoplasmic reticulum, from which new peroxisomes are formed in a particular region. The scientists observed that a still unknown factor initially prevents the transport of GPT1 to peroxisomes - until the membrane protein is needed there. "By experimentally enforcing interaction with peroxisomal import proteins at the endoplasmic reticulum we could show that GPT1 can be 'dragged' to its alternative location," explains first author Dr. Marie-Christin Baune.

After the researchers had discovered that GPT1 occurs at peroxisomal membranes, they investigated in an artificially reconstituted system from yeast which transport processes may occur. They found that GPT1 prefers to exchange glucose-6-phosphate for ribulose-5-phosphate, the product which again leaves the organelle. Ribulose-5-phosphate is an important precursor of nucleotides, the building blocks of nucleic acids.

So-called immunoblot analyses, by which proteins are visualised, additionally suggested that GPT1 is not only essential at plastids during fertilization but also at peroxisomes. Thus, GPT1 differs markedly from its "brother" GPT2 - a result that the scientists had not expected and which also became evident in genetically modified plants.

"Our results suggest that GPT1 and GPT2, despite their high similarity, fulfill only minimally overlapping tasks in plants. The loss of GPT2 is tolerated, at least under laboratory conditions. GPT1 however is indispensable, both at plastids and peroxisomes," says co-author Dr. Hannes Lansing.

"Since we now know that all reactions of the oxidative pentose-phosphate pathway that produce NADPH and ribulose-5-phosphate may occur in peroxisomes, we want to find out in future studies which other processes depend on them," says Antje von Schaewen.

Credit: 
University of Münster

NMDA receptors may link psychosis and sleep deficits

Sofya Kulikova, a researcher at HSE University in Perm, is part of an international research team that has discovered potential mechanisms that explain the sleep spindle deficit in electroencephalograms (EEG) of people with schizophrenia. The article was published in the Schizophrenia Research on June 5.

https://www.sciencedirect.com/science/article/abs/pii/S092099642030236X?via%3Dihub&fbclid=IwAR2VFGlKtqeYMsdtFidYS5yNpbarRGRA8Wts6TkIOCiWyDfkBot7z_yJs7w

Individuals with schizophrenia are often characterized by a deficit of sleep spindles--specific bursts in the brain's electrical activity that can be recorded by EEG while the patient is sleeping. Such a disorder is also observed in patients with other psychoses or predisposition to them.

Sleep spindles are generated by the thalamic reticular nucleus. Thalamus is a brain region that redistributes sensory information from sensory organs to other regions, and its reticular nucleus is involved in regulating the nervous system's activity. In particular, the reticular nucleus helps to filter the information exchanged by the thalamus and the cortex. Together thalamus and cortex form the 'thalamocortical system' of the brain. In people with psychosis, the normal activity of the thalamocortical system is disturbed, although not all mechanisms of these disorders have been studied.

The researchers looked at how NMDA glutamate receptors of the thalamocortical system contribute to the deficit of sleep spindles. They took sedated rats and injected them various medicines, such as ketamine--a substance that blocks NMDA receptors and causes a condition similar to acute psychosis. The changes in activity of certain brain neurons under the medications were registered by microelectrodes placed on various levels of the thalamocortical system. A deficit of sleep spindles was observed in rats, similar to the changes in brain activity in people with schizophrenia. The researchers also observed a considerable decrease in delta oscillations, which appear in the brain in the state of deep natural sleep.

These observations confirm the role of NMDA receptors in sleep disorders that accompany psychotic states. NMDA receptor blockade in rats was accompanied by changes in the strength of connection between the thalamus and the thalamic reticular nucleus, which led to changes in EEG oscillations. Similar changes in brain activity may also appear in patients with schizophrenia, but this assumption requires further confirmation.

The observed changes may be compensated by anti-psychotic medicines, such as clozapine - a medicine that is already used to decrease agitation in people with schizophrenia.

The new data emphasize the key role of NMDA receptors in disorders accompanying psychotic states and indicate the feasibly of developing and applying these receptor-targeted medicines to treat psychiatric disorders.

Credit: 
National Research University Higher School of Economics

American lobster, sea scallop habitat could shift off the northeast

Researchers have projected significant changes in the habitat of commercially important American lobster and sea scallops on the Northeast U.S. continental shelf. They used a suite of models to estimate how species will react as waters warm. The researchers suggest that American lobster will move further offshore and sea scallops will shift to the north in the coming decades.

Findings from the study were published recently in Diversity and Distributions. They pose fishery management challenges as the changes can move stocks into and out of fixed management areas. Habitats within current management areas will also experience changes -- some will show species increases, others decreases, and still others no change.

"Changes in stock distribution affect where fish and shellfish can be caught and who has access to them over time," said Vincent Saba, a fishery biologist in the Ecosystems Dynamics and Assessment Branch at the Northeast Fisheries Science Center and a co-author of the study. "American lobster and sea scallop are two of the most economically valuable single-species fisheries in the entire United States. They are also important to the economic and cultural well-being of coastal communities in the Northeast. Any changes to their distribution and abundance will have major impacts," he said.

Saba and study colleagues used a group of species distribution models and a high-resolution global climate model. They projected the possible impact of climate change on suitable habitat for the two species in the Northeast U.S. continental shelf large marine ecosystem. That ecosystem includes waters of the Gulf of Maine, Georges Bank, the Mid-Atlantic Bight, and Southern New England.

The high-resolution global climate model is, known as NOAA's CM2.6. It generated projections of future ocean bottom temperatures and salinity conditions across the ecosystem, and identified where suitable habitat would occur for the two species. The CM2.6 model was developed by the NOAA Geophysical Fluid Dynamics Laboratory in Princeton, New Jersey, where Saba is located.

To reduce bias and uncertainty in the model projections, the team used nearshore and offshore fisheries independent trawl survey data to train the habitat models. Those data were collected on multiple surveys over a wide geographic area from 1984 to 2016. The model combined this information with historical temperature and salinity data. It also incorporated 80 years of projected bottom temperature and salinity changes in response to a high greenhouse gas emissions scenario. That scenario has an annual 1 percent increase in atmospheric carbon dioxide.

American lobster are large, mobile animals that migrate to find optimal biological and physical conditions. Sea scallops are bivalve mollusks that are largely sedentary, especially during their adult phase. Both species are affected by changes in water temperature, salinity, ocean currents, and other oceanographic conditions.

Projected warming over the next 80 years showed deep areas in the Gulf of Maine becoming increasingly suitable lobster habitat. During the spring, western Long Island Sound and the area south of Rhode Island in the Southern New England region showed habitat suitability. That suitability decreased in the fall. Warmer water in these southern areas has led to a significant decline in the lobster fishery in recent decades.

Sea scallop distribution showed a clear northerly trend, with declining habitat suitability in the Mid-Atlantic Bight, Southern New England, and Georges Bank areas.

"This study suggests that ocean warming due to climate change will act as a likely stressor to the ecosystem's southern lobster and sea scallop fisheries and continues to drive further contraction of sea scallop and lobster habitats into the northern areas," Saba said. "Our study only looked at ocean temperature and salinity, but other factors such as ocean acidification and changes in predation can also impact these species."

"Ensemble modelling approaches like the one developed in this study can contribute to lobster and scallop assessments by improving the effectiveness of survey efforts and the precision of stock assessment models," Saba added. "It also provides a critical step toward establishing long-term adaptive management plans for these two valuable species."

Credit: 
NOAA Northeast Fisheries Science Center

New technique for engineering living materials and patterns

image: A bacterial biofilm patterned using MeniFluidics.

Image: 
University of Warwick

Engineered living materials (ELMs) is a new class of materials that exploit the properties of living organisms

· While various techniques such as 3D printers have been utilized for developing ELMs, these techniques are typically limited for static patterns and suffer for technical complications

· Researchers at the Departments of Physics and the School of Life Sciences, University of Warwick used fluidic channels to make patterns using bacterial cells

· The method, named MeniFluidics, opens the door for further innovations and creation of arts, from ELMs, fundamental research into cellular interactions, to bio-art and tissue engineering

A new method for engineering living materials called 'MeniFluidics', made by researchers at the University of Warwick could see a transformation in tissue engineering and bio-art, as well as new ways to research cellular interactions.A bacterial biofilm patterned using MeniFluidics.

Living cells have many properties that non-living materials simply don't. The ability of controlling the emergent behaviours of cells and organising them into arbitrary patterns is a key step forward towards utilizing living materials, for uses such as organs on a chip. This is why new technologies are being developed to obtain such an ability.

Physicists and biologists at the University of Warwick have teamed up to develop a new method for controlling cellular patterns, published in the journal ACS Synthetic Biology, titled 'Pattern engineering of living bacterial colonies using meniscus-driven fluidic channels', their new technique is called MeniFluidics.

Grounded on the physics of meniscus generation, the researchers implemented structures into gel surfaces. Evaporation of water from gel materials lead to formation of open channels which can be used for guiding the direction and speed of cellular expansion.

Dr Vasily Kantsler, from Department of Physics at the University of Warwick comments;

"I believe that our catchy named (Menifluidics) technique will enable new opportunities in biophysical and biomedical research and applications such as antibiotic resistance and biofouling"

Dr Munehiro Asally, from School of Life Science at the University of Warwick adds;

"We hope MeniFluidics will be used widely by biophysics, microbiologists, engineers and also artists! As it is a simple and versatile method."

Credit: 
University of Warwick

Cord blood for stem cell transplant may outperform matched sibling donor

image: Jonathan Gutman, MD, and colleagues show that cord blood as a source for bone marrow transplant may outperform even the accepted "gold standard" of matched sibling donor

Image: 
University of Colorado Cancer Center

When a cancer patient needs a bone marrow transplant, there are four common donor sources: A matched related donor (sibling), a matched unrelated donor (from a donor database), a half-matched donor, or umbilical cord blood. Of course, there are plusses and minuses to each approach, but consensus has generally ranked a matched sibling first, followed by a matched unrelated donor, with cord blood and half-matched donors reserved for patients without either of the first two options. Now a University of Colorado Cancer Center study based on a decade of research and treatment may reshuffle this list. In fact, the comparison of 190 patients receiving cord-blood transplants with 123 patients receiving transplants from the "gold standard" of matched sibling donors showed no difference in survival outcomes between these two approaches, with significantly fewer complications due to chronic graft-versus-host disease in patients receiving transplants from cord blood.

"Our cord blood patients were doing as well as patients receiving transplants from matched siblings, and in selected populations cord blood patients were doing even better. Our program at CU Cancer Center is somewhat unique in its emphasis on cord blood as a donor source for stem cell transplants and this study is an affirmation of why we do what we do here," says Jonathan Gutman, MD, CU Cancer Center investigator and director of the allogeneic stem cell transplantation program at UCHealth University of Colorado Hospital.

In addition to showing a decrease in the chance of graft-versus-host disease, which develops when a transplanted blood system attacks a patient's tissues, the study shows a slightly lower rate of relapse in these patients undergoing transplant with cord blood.

"Especially with younger, fitter patients who we can hit harder in the transplant process, we have strong hints here that cord blood may be actively better in terms of reducing both graft-versus-host disease and relapse," Gutman says.

Umbilical cord blood, which is banked for public use at designated centers around the world, is rich in stem cells, which can repopulate a patient's blood system. Because these umbilical cord stem cells are more "basic" than adult blood cells, they require a lower degree of match than blood cells from an adult donor. However, one challenge has been obtaining enough of these cells to perform a successful transplant.

"It turns out that for adults, it's very hard to find a single cord blood unit that meets the parameters we know need to be met in terms of size. To overcome this barrier, we often use two units from different sources," Gutmans says. Also, research at CU Cancer Center and elsewhere is developing techniques to expand small samples of banked cord blood to the volume needed for transplant.

"We think there are important advantages of cord blood, especially with respect to graft-versus-host disease," Gutman says. "Previously, we've taken a position recommending cord blood over matched unrelated donors, and now we show that cord blood may even out-compete the gold standard of matched sibling donors."

Credit: 
University of Colorado Anschutz Medical Campus

PFAS present throughout the Yadkin-Pee Dee river food chain

Researchers from North Carolina State University have found per- and polyfluoroalkyl substances (PFAS) in every step of the Yadkin-Pee Dee River food chain, even though the river does not have a known industrial input of these compounds. The study examined the entire aquatic ecosystem for PFAS compounds and identified strong links between ecosystem groups that lead to biomagnification, the process that leads to greater concentrations of these substances in animals that sit higher on the food chain - including humans.

PFAS compounds were engineered to resist friction and heat, and are in many products that we use daily, from furniture to meat packaging. However, it is this "slippery" characteristic that makes them persist in ecosystems and poses a risk to our health.

"These compounds are engineered to be persistent on purpose; this is how they keep stains off your couch and eggs from sticking to your frying pan," says Tom Kwak, unit leader of NC Cooperative Fish and Wildlife Research Unit, professor of applied ecology at NC State, and a co-author of the study. "We pay the price for these compounds when they enter the aquatic ecosystem."

In a study measuring real-time PFAS contamination levels along the entire food chain of this major Atlantic river - from water and sediment to insects and fish - the researchers identified two PFAS hot spots along the Pee Dee and were able to establish strong links of PFAS transmission up the aquatic food chain.

The research team collected water, sediment, algae, plant, insect, fish, crayfish, and mollusk samples at five study sites along the length of the Yadkin-Pee Dee River, which begins in Blowing Rock, N.C., and runs 230 miles to empty into the Atlantic Ocean at Winyah Bay, South Carolina. They analyzed the samples for 14 different PFAS compounds.

While nearly every sample contained PFAS compounds, the site with the greatest PFAS concentrations was just downstream of the Rocky River input, which drains part of the watershed from Charlotte, N.C. and the surrounding area. The site with the second greatest PFAS concentrations was downstream in South Carolina, but there is no known or plausible input of PFAS for that region.

In aquatic food chains, biofilm - the soupy mixture of algae and bacteria that sticks to your boat - is the base resource for all life further up the chain. In this study, the largest concentrations of 10 of the 14 PFAS compounds measured were in biofilm samples. Unsurprisingly, aquatic insects, which primarily eat biofilm, had the greatest accumulation of PFAS compounds of all the living taxa the researchers sampled. This confirms a strong trophic link, or step in the food chain, showing how PFAS transfers from biofilm to insects, which are then eaten by freshwater fish.

When PFAS is in every step of the food chain, the compounds accumulate at each step. For example, a fish caught in an area with PFAS may have eaten hundreds of insects, each of which has consumed contaminated biofilm and other plants.

"We are part of the food chain and when we ingest these foods, we accumulate their PFAS loads, too," says Greg Cope, William Neal Reynolds Distinguished Professor of Applied Ecology, coordinator of the NC State Agromedicine Institute, and corresponding author of the study. "This gives new meaning to the phrase, 'You are what you eat.'"

"Even if you are not concerned about chemical exposure and effects to the native aquatic taxa, would you want to drink water or eat a fish with known PFAS contamination?" asks Tiffany Penland, former NC State graduate student and first author of the study. "We need to educate ourselves and each other so that we are cognizant of the contamination to the natural resources that we depend on every day."

"Studying only one species or link in the food chain could not tell the whole story, and might even yield erroneous conclusions on the amounts of PFAS in river ecosystems," says Cope. "Studies like this that show how widely prevalent PFAS are within entire ecosystems, even when they do not have a direct industrial input, highlight our need to understand how these compounds impact the health of ecosystems, and ultimately, our health."

Credit: 
North Carolina State University

Ancient genomic insights into the early peopling of the Caribbean

image: Canimar Abajo

Image: 
Kathrin Nägele

The Caribbean was one of the last regions of the Americas to be settled by humans. Now, a new study published in the journal Science sheds new light on how the islands were settled thousands of years ago.

Using ancient DNA, an international team of researchers found evidence of at least three population dispersals that brought people to the region.

"Our results give a glimpse of the early migration history of the Caribbean and connect the region to the rest of the Americas," says Hannes Schroeder, Associate Professor at the Globe Institute, University of Copenhagen, and one of the senior authors of the study. "The DNA evidence adds to the archaeological data and enables us to test specific hypotheses as to how the Caribbean was first settled."

More data, more details

The researchers analysed the genomes of 93 ancient Caribbean islanders who lived between 400 and 3200 years ago using bone fragments excavated from 16 different archaeological sites across the Caribbean.

Due to the region's warm climate, the DNA from the samples is not very well preserved. Using targeted enrichment techniques, the researchers managed to extract genome-wide information from the remains.

"New methods and technology allowed us to increase the number of ancient genomes from the Caribbean by almost two orders of magnitude," says Johannes Krause, Director of the Max Planck Institute for the Science of Human History in Jena, Germany, another senior author of the study. "With all that data we are able to paint a very detailed picture of the early migration history of the Caribbean."

The researchers' findings indicate that there have been at least three different population dispersals into the region: two earlier dispersals into the western Caribbean, one of which seems to be linked to earlier population dispersals in North America, and a third, more recent wave, which originated in South America.

Connections across the Caribbean Sea

Although it is still not entirely clear how the early settlers reached the islands, there is growing archaeological evidence that, far from being a barrier, the Caribbean Sea served as a kind of 'aquatic highway' that connected the islands with the mainland and each other.

"Big bodies of water are traditionally considered barriers for humans and ancient fisher hunter gatherer communities are usually not perceived as great seafarers. Our results continue to challenge that view, as they suggest there was repeated interaction between the islands and the mainland," says Kathrin Nägele, PhD student at the Max Planck Institute for the Science of Human History in Jena, Germany and one of the lead authors of the study.

Biological and cultural diversity in the ancient Caribbean

"The new data support our previous observations that the early settlers of the Caribbean were biologically and culturally diverse, adding resolution to this ancient period of our history," says Yadira Chinique de Armas, Assistant Professor in Bioanthropology at the University of Winnipeg and co-director of three large-scale excavations in Cuba.

The researchers also found genetic differences between the early settlers and the newcomers from South America who, according to archaeological evidence, entered the region around 2800 years ago.

"Although the different groups were present in the Caribbean at the same time, we found surprisingly little evidence of admixture between them," adds Cosimo Posth, group leader at the Max Planck Institute for the Science of Human History and joint-first author of the study.

"The results of this study provide yet another layer of data that highlights the complex and multi-nature of pre-Columbian Caribbean societies and their connections to the American mainland prior to the colonial invasion. It's reflected in the archaeology of the region, but it is fascinating to see it supported by the biological data," says Corinne Hofman, Professor of Archaeology at Leiden University and PI of the ERC Synergy project NEXUS1492. "Genetic data provide a new depth to our findings," agrees Mirjana Roksandic, Professor at the University of Winnipeg and the PI on the SSHRC project.

Credit: 
Max Planck Institute of Geoanthropology

Identifying survivors at high risk of secondary cancers

image: Left to right: Nan Qi, PhD, Zhaoming Wang, Ph.D., of St. Jude, and Nan Song, Ph.D., of the St. Jude Department of Epidemiology and Cancer Control.

Image: 
St. Jude

Scientists at St. Jude Children's Research Hospital are studying the combined effect of cancer treatments and inherited mutations in DNA-repair genes. Their results may help predict which survivors are at increased risk of another cancer. The work appears as an advance online publication today in the Journal of Clinical Oncology.

Childhood cancer survivors experience a substantial burden of long-term chronic health conditions, including a high rate of secondary cancers. The development of secondary cancers among survivors can be therapy-related, but inherited mutations can also play a role.

"Our study is one of the largest and most in-depth looking at the combined effects of therapy and inherited genetics," said corresponding author Zhaoming Wang, Ph.D., of the St. Jude departments of Epidemiology and Cancer Control and Computational Biology. "We were particularly interested in mutations involved in DNA repair, which play a role in how the body responds to and remediates DNA damage caused by cancer treatments."

Clues in the data

The team performed whole genome sequencing on DNA from blood samples to evaluate 127 genes from six DNA-repair pathways. The data were compared to clinical records detailing the cumulative doses of chemotherapy and maximum dose of region-specific radiotherapy given to the patients.

"We identified mutations affecting specific types of DNA-repair mechanisms, which combined with certain intensities of therapies, could dramatically increase the risk of developing subsequent cancers like breast cancer, sarcoma and thyroid cancer," said co-first author Na Qin, Ph.D., of St. Jude Epidemiology and Cancer Control.

The team looked at the records of 4,402 pediatric cancer survivors. Of those survivors, 495 individuals developed 1,269 secondary cancers. The team identified 538 germline mutations in 98 DNA-repair genes including POLG, MUTYH, ERCC2 and BRCA2.

"These data truly reflect how inherited mutations in DNA-repair genes and cancer therapy can have a combined effect, increasing significantly the risk of developing another cancer later in life," said co-senior author Yutaka Yasui, Ph.D., of St. Jude Epidemiology and Cancer Control.

Protecting the health of childhood cancer survivors

The work relied on whole genome sequencing of DNA from blood samples gathered through the St. Jude Lifetime Cohort study (St. Jude LIFE). The team in St. Jude LIFE brings long-term childhood cancer survivors back to the hospital for regular health screenings throughout their adult lives. Findings from St. Jude LIFE help childhood cancer survivors learn more about their health needs, while providing novel insights into the late effects of childhood cancer treatment.

"A more precise ability to identify survivors at high risk of subsequent cancers may help facilitate access to genetic counseling and testing, which can inform personalized cancer surveillance and prevention strategies," said co-senior author Leslie Robison, Ph.D., St. Jude Department of Epidemiology and Cancer Control chair.

The genomic data generated through St. Jude LIFE is freely available to researchers on the St. Jude Cloud platform, a data-sharing resource available to the research community worldwide.

"St. Jude Cloud is one of the world's largest repositories of pediatric genomics data and offers a suite of unique analysis tools and visualizations," said co-senior author Jinghui Zhang, Ph.D., St. Jude Department of Computational Biology chair. "By making these tools available to researchers around the world, we hope to accelerate the pace of research into pediatric cancer."

Credit: 
St. Jude Children's Research Hospital

Study shows some infants can identify differences in musical tones at six months

video: New research from neuroscientists at York University suggests the capacity to hear the highs and lows, also known as the major and minor notes in music, may come before you take a single lesson; you may actually be born with it.

Image: 
York University News

TORONTO, June 4, 2020 - There's a common belief that musicians are born with a natural ability to play music, while most of us have to work twice as hard to hear the difference between musical notes. Now, new research from neuroscientists at York University suggests the capacity to hear the highs and lows, also known as the major and minor notes in music, may come before you take a single lesson; you may actually be born with it.

The study, published in the Journal of the Acoustical Society of America, examined the capacity of six-month-old infants to discriminate between a major and a minor musical tone sequence with a unique method that uses eye movements and a visual stimulus.

Previous research with adults has shown that approximately 30 per cent of adults can discriminate this difference but 70 per cent cannot, irrespective of musical training. Researchers found that six-month-old infants show exactly the same breakdown as adults: approximately 30 per cent of them could discriminate the difference and 70 per cent could not.

"At six months, it's highly unlikely that any of these infants have had any formal training in music," says Scott Adler, associate professor, Department of Psychology in the Faculty of Health and member of Vision: Science to Applications (VISTA) Program at the Centre for Vision Research. "Yes, parents play music for children. All children in western civilization hear music, but they don't get that specific training in music. This breakdown, therefore, is due to some inborn mechanism."

Adler's team at York collaborated on the study with Professor Charles Chubb, of the University of California at Irvine, whose earlier research with adults and adolescents found there are two populations of individuals: some who can discriminate between the major and minor tones and most who cannot discriminate. In adults, the capacity to discriminate between major and minor was shown not to be due to their level of musical training or their level of music exposure.

The new study extends the existence of those different populations down to infants, suggesting that the source of this difference might be genetic - a capacity that we are born with.

This capacity would have implications for developing appreciation of the emotional content of music, because it's the major and minor notes that give music their emotion.

In the study, researchers conducted trials with 30 six-month-old infants in which they heard a tone-scramble, a series of notes whose quality (major vs. minor) signalled the location (right vs. left) where a subsequent picture (target) would appear. The babies were tasked with determining which side to look when they heard a major or a minor sound. Once they heard a series of notes, a picture would either appear on the right or the left depending on whether it was a major or minor tone scramble. In a second experiment, tone-scrambles did not reliably predict the location of subsequent pictures.

"What we measured over time was how the infants learned the association between which tone they heard and where the picture is going to show up. If they can tell the difference in the tone, over time, when they hear the major notes for example, they'll make an eye movement to the location for the picture even before the picture appears because they can predict this. This is what we are measuring," says Adler.

The researchers found that for 33 per cent or one-third of infants, these anticipatory eye movements predicted the picture location with near perfect accuracy; for the other 67 per cent, they were unrelated to the picture location.

These results may also have implications for language development, which relies on some of the same mechanisms and auditory content as music, says Adler.

"There is a connection between music, music processing and mathematical abilities, as well as language, so whether these things connect up to those abilities is an unknown. However, when people talk to babies they change the intonation of their voice and the pitch of their voice so they're changing from major to minor. That is actually an important component for babies to learn language. If you don't have the capacity it might affect that ability in learning language."

Credit: 
York University

Molecular landscape of the hematopoietic stem cell cradle

image: A large cluster of hematopoietic stem cells and progenitor cells (green) attached to the wall of the aorta (red) of an embryo in which the Svep1 gene was disabled.

Image: 
Laurent Yvernogeau, copyright Hubrecht Institute

Researchers from the group of Catherine Robin at the Hubrecht Institute characterized the molecular landscape of the aorta that supports the generation of the first Hematopoietic Stem Cells (HSCs) in the embryo. Such HSCs are responsible for the constant replenishment of all blood cells throughout life. The researchers investigated which genes and regulatory pathways were active in the aorta of zebrafish, chicken, mouse and human embryos at the time of HSC formation. By comparing the different species, they uncovered the complexity of the aortic microenvironment landscape and the finetuning of various factors interplaying to control HSC generation both in time and space in vivo. Understanding the regulatory function of the local environment where HSCs are formed will pave the way for improved HSC production in vitro and clinical cell therapy for blood related diseases. The results are presented in the scientific journal Blood.

Hematopoietic stem cell need for the clinic

The constant production of short-lived hematopoietic cells, or blood cells, throughout life relies on a small number of hematopoietic stem cells (HSCs) present in the bone marrow in adults. Defective HSCs lead to various blood-related disorders and cancers that are partly treated by HSC transplantations. Since decades, efforts have been made to generate bona fide HSCs in vitro to circumvent the limited supply of donor compatible HSCs for clinical use. Despite recent progress, the culture protocols for HSCs in the lab remain sub-optimal in mimicking the physiological HSC surrounding microenvironment or niche. Such a niche is needed to induce the formation of HSCs and to preserve their stem cell properties at long-term (i.e. generation of all blood cell type with no exhaustion). A better knowledge of the regulatory factors and pathways involved in HSC formation in vivo is therefore required to improve in vitro culture protocols and HSC engineering (i.e. HSC generation, gene correction).

Exploring the aorta, the cradle of hematopoietic stem cells

The defined location of a stem cell within a specific microenvironment regulates the fate, behavior and molecular identity of the stem cell via a complex extrinsic regulation that is far from being fully elucidated yet. All HSCs derive from a specialized subset of endothelial cells, which form the blood vessels, named hemogenic endothelial cells, through a process called endothelial-to-hematopoietic transition (EHT). EHT occurs in the main arteries of the embryo, such as the aorta, during early embryogenesis. After EHT, hematopoietic cells are organized in clusters transiently attached to the wall of the aorta where cells progressively acquire their HSC properties. EHT is a well conserved process occurring in all vertebrates at precise locations in the aorta and at defined time points of development. This spatio-temporal restriction clearly indicates the presence of specific molecular cues in the surroundings of the aorta that instruct the aortic hemogenic endothelial cells, drive EHT and therefore HSC formation. How the aortic niche regulates these essential processes in vivo is still poorly understood.

The molecular landscape of the aortic niche and beyond

To explore the molecular characteristics and key components of the aortic microenvironment where HSC emergence is spatially restricted, the researchers performed genome-wide RNA tomography sequencing (tomo-seq) on zebrafish, chicken, mouse and human embryos. Using this technique, they could determine which genes were active in each embryo section along the anterior to posterior and dorsal to ventral axes of the embryo. They used the resulting transcriptional maps to specifically explore the genes and regulatory pathways active in the aortic microenvironment. By comparing the data between species and doing functional analyses, they uncovered the complexity of the aortic microenvironment landscape. They found that a finetuning of various factors controls the generation of HSCs. While some of these factors were specific for certain species, others were common to all species. The anterior-posterior (head to tail) and dorsal-ventral (back to front) transcriptional maps generated in this study also provide a powerful and unprecedented resource for the scientific community. The researchers indeed offer the possibility to perform broader analysis via an interactive website (http://multi-species.embryos.tomoseq.genomes.nl), such as (i) to compare with precision the expression pattern of any given gene of interest in any structure or microenvironment along the body axes of four embryo species, (ii) to identify molecular signals that are potentially involved in tissue patterning (e.g. induction signal from neural tube/somite, notochord/somite) or (iii) to identify new genes that follow an expression pattern similar to that of a known gene.

New conserved regulators of HSC generation in vivo

HSC regulation by extrinsic signals is a complex process that occurs via direct cell-cell contact or long-range distribution of secreted molecules, acting directly or by inducing secondary signals. By combining the tomo-seq data on the aortic microenvironment and previously published RNA-seq data on HSC cluster cells, the researchers identified ADM and RAMP2 as an important conserved ligand-receptor couple involved in the production of HSCs in vivo. They also uncovered the secreted protein SVEP1 as the first extrinsic regulator of both cluster cellularity and cluster cell fate towards an HSC fate.

Overall, the current study emphasizes the complexity of the aortic microenvironment landscape at the time of HSC formation and provides insights on the finetuning of various factors that interact with each other to control HSC production both in time and space as it occurs in vivo.

Credit: 
Hubrecht Institute

Mortality of mechanically ventilated COVID-19 patients is lower than previously reported reveals study in Critical Care Medicine

June 4, 2020 - An online first study published in Critical Care Medicine indicates the actual mortality rate of adults with critical illness from COVID-19 is less than what was previously reported. Compared to earlier reports of a 50 percent mortality rate, the study finds that the mortality rate of critically ill patients who required mechanical ventilation was only 35.7 percent. About 60 percent of patients observed in the study survived to hospital discharge.

The study observed patients 18 years and older from six COVID-19 designated intensive care units in three hospitals in Atlanta, Ga. from March to April 2020. The authors note that several considerations may have influenced the outcomes of the study including that all critically ill patients with COVID-19 in the hospital network were admitted to pre-existing ICUs that had adequate staffing ratios and equipment.

An accompanying online first editorial examines the role of mainstream and social media in creating the narrative that intubation and mechanical ventilation were "the cause of suboptimal outcomes" for critically ill COVID-19 patients, without accounting for hospital staffing and equipment shortages.

Credit: 
Wolters Kluwer Health

Childhood trauma affects the timing of motherhood

image: Lotta Svärd women in 1940.

Image: 
Finnish Wartime Photograph Archive

Women who have experienced childhood trauma become mothers earlier than those with a more stable childhood environment shows a new study conducted in collaboration between the University of Turku and the University of Helsinki in Finland. The trauma children experience form living in war zones, natural disasters or perhaps even epidemics can have unexpected effects that resurface later in their lives.

During the Second World War, thousands of Finnish women and girls volunteered to aid in the war effort as part of the paramilitary organisation 'Lotta Svärd' exposing some to the trauma of war. Researcher and lead author of the study Robert Lynch from the University of Turku used extensive data collected on these volunteers to study the effects of childhood trauma on adults.

The study showed that young girls and women who served in the war became mothers earlier and had more children compared to women of the same age who did not participate in the war effort.

- If we can measure the effects of trauma on basic things such as the timing of motherhood, then it almost certainly has major effects on many of our other important behaviours, such as overall aversion to risk, sociality or the pace of sexual development, explains Lynch.

- This study is groundbreaking because it overcomes many of the pitfalls of research on humans that has made it difficult to know whether trauma is actually the root cause of starting a family at a younger age. The extensive dataset made it possible for us to compare women before and after the war and also take family background into account by comparing sisters. This is strong evidence in support of the idea that trauma affects reproductive schedules, adds senior author, Researcher John Loehr from the University of Helsinki.

The study has clear relevance for the millions of children and adults worldwide who experience trauma through wars. However, relevance likely also extends to other sources of trauma, such as natural disasters or even the current COVID-19 epidemic.

Evolutionary theory predicts that individuals experiencing an unstable environment with high mortality are better off reproducing sooner rather than taking the risk of not having the chance later.

- There appears to be a sensitivity window that extends from childhood into early adulthood where behaviour adjusts to match the circumstances experienced. The consequences can be far-reaching even after the situation stabilises. A childhood trauma can influence people's adult lives in ways that they are unaware of, such as the timing of their motherhood, explains Academy Professor Virpi Lummaa from the University of Turku.

Background:

Prior to and during the Second World War, many Finnish girls and women volunteered for the 'Lotta Svärd' organisation that was a major part of the war effort. Tasks within the organisation varied greatly, and many of the women performed duties that exposed them to the trauma of war. Towards the end of the war, girls as young as fourteen years of age were entrusted with some of the more demanding jobs usually reserved for adults. The project was funded by the Kone Foundation with data from Karjala Liitto registers and digitised church register data provided by Karjalan tietokantasäätiö.

Credit: 
University of Turku

NASA finds Nisarga's remnants over Central India

image: On June 4, 2020, the MODIS instrument that flies aboard NASA's Terra satellite provided a visible image of the remnants of Tropical Cyclone Nisarga in central India.

Image: 
NASA Worldview

Tropical Cyclone Nisarga made landfall in west central India on June 4, and the next day NASA's Terra satellite provided a look at the remnants of the storm.

On June 4 at 11 a.m. EDT (1500 UTC), the Joint Typhoon Warning Center issued their final warning on Tropical cyclone Nisarga. At that time, Nisarga was located near latitude 19.1 degrees north and longitude 73.7 degrees east, about 48 nautical miles east of Mumbai, India. Nisarga was moving to the north-northeast and still maintained maximum sustained winds 65 knots (75 mph/120 kph). As Nisarga tracked inland to the east of Mumbai the storm weakened from hurricane force to a depression, and finally into a remnant low-pressure area.

On June 4, the Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Terra satellite provided a visible image of Nisarga's remnant clouds, now located over central India.

At 1130 IST (2 a.m. EDT), India's Regional Specialized Meteorological Centre (RSMC) noted that the remnants of Nisarga was located over south Madhya Pradesh state and adjoining Vidarbha state near latitude 21.8 degrees north and longitude 77.6 degrees east, about 87 miles (140 km) north-northeast of Akola (Maharashtra) and 99 miles (160 km) south-southeast of Bhopal (Madhya Pradesh).

RSMC noted, "Light to moderate rainfall at most places with heavy to very heavy falls at isolated places very likely over east Madhya Pradesh and Chhattisgarh. Light to moderate rainfall at most places with heavy falls at isolated places very likely over Vidarbha and west Madhya Pradesh during next 24 hours."

RSMC forecasters said the remnants are likely to move northeastward and weaken into a low-pressure area by the evening hours.

NASA's Terra satellite is one in a fleet of NASA satellites that provide data for hurricane research.

Tropical cyclones/hurricanes are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

Credit: 
NASA/Goddard Space Flight Center

Environmental damage from fog reduction is observable from outer space, find hydrologists

image: Two satellite images show vegetation change from fog in two areas of the Namib desert. The left image shows the areas during periods of lower fog; the right image shows the areas during periods of higher fog. Greener areas inside the squares indicate vegetation greening.

Image: 
Image courtesy of Lixin Wang, Indiana University.

INDIANAPOLIS -- A new study led by ecohydrologists at IUPUI has shown for the first time that it's possible to use satellite data to measure the threat of climate change to ecological systems that depend on water from fog.

The paper, published in the journal Geophysical Research Letters, presents the first clear evidence that the relationship between fog levels and vegetation status is measurable using remote sensing. The discovery opens up the potential to easily and rapidly assess fog's impact on ecological health across large land masses -- as compared to painstaking ground-level observation.

"It's never been shown before that you can observe the effect of fog on vegetation from outer space," said Lixin Wang, an associate professor in the School of Science at IUPUI, who is the senior author on the study. "The ability to use the satellite data for this purpose is a major technological advance."

The need to understand the relationship between fog and vegetation is urgent since environmental change is reducing fog levels across the globe. The shift most strongly affects regions that depend upon fog as a major source of water, including the redwood forests in California; the Atacama desert in Chile; and the Namib desert in Namibia, with the latter two currently recognized as World Heritage sites under the United Nations due to their ecological rarity.

"The loss of fog endangers plant and insect species in these regions, many of which don't exist elsewhere in the world," said Na Qiao, a visiting student at IUPUI, who is the study's first author. "The impact of fog loss on vegetation is already very clear. If we can couple this data with large-scale impact assessments based on satellite data, it could potentially influence environmental protection policies related to these regions."

The IUPUI-led study is based upon optical and microwave satellite data, along with information on fog levels from weather stations at two locations operated by the Gobabeb Namib Research Institute in the Namib desert. The satellite data was obtained from NASA and the U.S. Geological Survey. The fog readings were taken between 2015 and 2017.

Wang's work with the Gobabeb facility is supported under a National Science Foundation CAREER grant. At least once a year, he and student researchers, including both graduate and undergraduate students from IUPUI, travel to the remote facility -- a two-hour drive on a dirt road from the nearest city -- to conduct field research.

The study found a significant correlation between fog levels and vegetation status near both weather stations during the entire time of the study. Among other findings, the optical data from the site near the research facility revealed obvious signs of plant greening following fog, and up to 15 percent higher measures during periods of fog versus periods without fog.

Similar patterns were seen at the second site, located near a local rock formation. The microwave data also found significant correlation between fog and plant growth near the research facility, and up to 60 percent higher measures during periods of fog versus periods without fog.

The study's conclusions are based upon three methods of remotely measuring vegetation: two based upon optical data, which is sensitive to the vibrance of greens in plants, and a third based upon microwave data, which is sensitive to overall plant mass, including the amount of water in stems and leaves. Although observable by machines, the changes in vegetation color are faint enough to go undetected by the human eye.

Next, the team will build upon their current work to measure the effect of fog on vegetation over longer periods of time, which will assist with future predictions. Wang also aims to study the relationship in other regions, including the redwood forests in California.

"We didn't even know you could use satellite data to measure the impact of fog on vegetation until this study," he said. "If we can extend the period under investigation, that will show an even more robust relationship. If we have 10 years of data, for example, we can make future predictions about the strength of this relationship, and how this relationship has been changing over time due to climate change."

Credit: 
Indiana University

IU researchers grow hairy skin from human stem cells

image: Pictured from left, Jiyoon Lee, PhD, and Karl Koehler, PhD

Image: 
IU School of Medicine

Building on years of groundbreaking discoveries in stem cell research, scientists from Indiana University School of Medicine and Harvard Medical School have determined how to grow hairy skin using human stem cells--developing one of the most complex skin models in the world.

The study, published June 3 in Nature, shows that skin generated from pluripotent stem cells can be successfully grafted on a nude mouse to grow human skin and hair follicles. That discovery could lead to future studies in skin reconstruction, disease modeling and treatment.

"This is the first study to show that human hair can be grown completely from stem cells in a dish, which has been a goal of the skin biology community for decades," said Karl Koehler, PhD, assistant professor of otolaryngology--head and neck surgery at Harvard Medical School and Boston Children's Hospital.

The team of researchers was led by Koehler, who's also an adjunct assistant professor of otolaryngology--head and neck surgery at IU School of Medicine, and Jiyoon Lee, PhD, a research associate in Koehler's lab.

The group's findings originate from several years of stem cell research within the Department of Otolaryngology--Head and Neck Surgery at IU School of Medicine. In 2013, scientists created inner ear tissue from mouse embryonic stem cells using a three-dimensional cell culture method. In 2017, they developed a method to grow inner ear tissue from human stem cells, and in 2018, the researchers grew hairy skin in a dish using mouse stem cells, a scientific first.

Through the three-dimensional culture technique developed in past experiments, the team incubated human stem cells for about 150 days in a ball-shaped cluster of cells, called a skin organoid. The interior of the aggregate of cells represent the top layer of skin (the epidermis) and the outside of the cluster develops the bottom layer of skin (the dermis).

"We've developed a new cooking recipe for generating human skin that produces hair follicles after about 70 days in culture," Koehler said. "When the hair follicles grow, the roots extend outward radially. It's a bizarre-looking structure, appearing almost like a deep-sea creature with tentacles coming out from it."

After the incubation period, researchers tested whether skin organoids could integrate on the skin of nude mice. More than half of the organoids they grafted on the mice grew human hair follicles. The skin organoid developed from culture is akin to fetal facial skin and hair, Koehler said.

The experiments show that organoid generated hairy skin can integrate into mouse skin, Koehler said, which suggests potential applications in skin and facial reconstruction. Physicians typically perform skin grafts in surgery, meaning the removal of skin from one area of the body to transplant on skin that's been wounded.

"This could be a huge innovation, providing a potentially unlimited source of soft tissue and hair follicles for reconstructive surgeries," said Lee, the first author of the study.

Taha Shipchandler, MD, associate professor of clinical otolaryngology--head and neck surgery at IU School of Medicine and one of the paper's authors, specializes in facial plastic and reconstructive surgery. Skin regeneration is of great interest for treating patients, he said.

"If we can harness this growth into a medium, and easily apply it to patients, it would change the way we treat many injuries or reconstructions," Shipchandler said. "This would have a profound effect on the medical field."

The other potential uses of hairy skin organoids vary widely, from developing drug or gene therapies for congenital skin disorders to recreating the earliest stages of skin cancer formation. In addition, more research is needed to analyze the development of sensory neurons and Merkel cells--specialized touch sensing cells of the skin--bundled within the organoid hair follicles, Koehler said, adding that the neurons potentially mimic the nerves mediating touch sensations.

"We're setting up experiments where we wiggle the hairs and see if the neurons activate," Koehler said, "as proof of concept that our skin can respond to touch in some way."

Credit: 
Indiana University School of Medicine