Culture

Estimation of aerosol emissions from simulated individuals with asymptomatic to moderate COVID-19

What The Study Did: Viral aerosol emissions from simulated individuals with asymptomatic to moderate COVID-19 are estimated in this mathematical modeling study.

Authors: Michael Riediker, of the Swiss Centre for Occupational and Environmental Health, in Winterthur, Switzerland, is the corresponding author.

To access the embargoed study:  Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.13807)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Media advisory: The full study is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2020.13807?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=072720

About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

Credit: 
JAMA Network

Prevalence of SARS-CoV-2 infection among health care workers in Houston

What The Study Did: Rates of SARS-CoV-2 infection among asymptomatic health care workers and community residents in Texas are examined in this observational study.

Authors: Roberta L. Schwartz, Ph.D., of the Houston Methodist Academic Institute in Texas, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.16451)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Media advisory: The full study is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2020.16451?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=072720

About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

Credit: 
JAMA Network

Antibiotics alone successfully treat uncomplicated appendicitis in children

Appendicitis is the most common cause for emergency abdominal surgery in childhood, affecting 80,000 children in the United States each year, but nonoperative treatment options are viable. A study performed by the Midwest Pediatric Surgery Consortium, led by Peter Minneci, MD, and Katherine Deans, MD, co-founders and directors of the Center for Surgical Outcomes Research at Nationwide Children's Hospital, and published online today in JAMA, found antibiotics alone successfully treated children with uncomplicated appendicitis and was associated with fewer disability days at one year.

Of 1,068 patients from 10 health centers enrolled in the study, 67.1% of those who elected to initially manage their care through antibiotics alone experienced no harmful side effects and did not later require an appendectomy by their one-year follow-up appointment. Patients in the non-operative group experienced an average of 6.6 disability days, compared to the 10.9 days in the surgery group. Non-operative management was also associated with fewer disability days for caregivers.

This research, funded by a Patient Centered Outcomes Research Institute (PCORI) grant, expands on an initial pilot study Drs. Minneci and Deans published in 2015, which first demonstrated the efficacy and safety of non-operative management of appendicitis in children by showing that children who were hospitalized for uncomplicated appendicitis--who experienced abdominal pain for no more than 48 hours, had a white blood cell count below 18,000 and underwent an ultrasound or CT scan to rule out rupture and to verify that their appendix was 1.1 centimeter thick or smaller with no evidence of an abscess or fecalith--and who elected initially to be treated with antibiotics could be successfully sent home without the use of traditional surgery.

"For surgery, patients need to go under general anesthesia, and there is 1-2% chance of a major complication and 5-10% chance of a minor complication," said Dr. Minneci, principal investigator of the studies with Dr. Deans. "And patients will definitely experience post-operative pain and disability. Treatment-related disability is important to kids, because it means missing activities in their lives that may directly affect their development and quality of life such as school, athletics and vacations."

Additionally, the study, which was designed to mimic clinical practice and used a decision aid to educate patients about the risks and benefits of each treatment option, found that both the patients who elected to undergo surgery and those who chose nonoperative care management with antibiotics alone had similar rates of complicated appendicitis, and reported similar health care satisfaction at 30 days and quality of life at 1 year.

Drs. Minneci and Deans said future research could study how to disseminate these results so that more patients can be informed of the two options and the risks and benefits of each. The decision aid and treatment protocols developed for this study were developed to minimize risks and can be easily translated into pediatric clinical practice.

"Culture change and rethinking how we treat patients is always hard," said Dr. Deans. "Right now, some of the standards for success among surgeons are different than among patients and families. Surgeons' tend to be passionate about operations, and an appendectomy is a well-tested and trusted procedure. However, some patients want to avoid surgery at all costs, and the results of our studies reflect the effectiveness of offering a non-operative management to patients and their families in clinical practice. This allows us to move away from a one-size-fits-all model of appendicitis care and treat each child based on his or her values and preferences."

Credit: 
Nationwide Children's Hospital

Novel label-free imaging technique brings out the inner light within T cells

image: A novel label-free imaging technique differentiates T cells from blood when in a quiescent state (illustrated in blue) and when activated by antibody-stimulation (illustrated in red). Images are captured using a microscope paired with an infrared laser to capture autofluorescence of proteins involved in cellular metabolism.

Image: 
Image courtesy of Alexandra Walsh.

MADISON -- T cells are the immune soldiers at the frontlines of the battle with infiltrating pathogens that seek to cause disease. A new study published in Nature Biomedical Engineering describes a novel label-free imaging technique that can differentiate active T cells from those off duty.

The method could help assess T cell involvement in immunotherapies for cancer treatment or autoimmune diseases.

"T cells have a metabolic switch that regulates their activity," says Melissa Skala, principal investigator at the Morgridge Institute and associate professor of biomedical engineering at UW-Madison. In a healthy individual, most T cells are in a quiescent state--they're inactive, but ready and waiting for the signal to join in active combat against an invading virus or bacteria.

"We wanted to test if our imaging technology could tell the difference between the quiescent T cells and activated T cells," says Alexandra Walsh, formerly an assistant scientist at the Morgridge Institute who is now an assistant professor of biomedical engineering at Texas A&M University.

Most methods for characterizing T cells are antibody-based, such as flow cytometry or immunohistochemistry. These require staining with antibodies or contrast agents, a process that is destructive to the cells.

Alternatively, Walsh and Skala's method detects autofluorescence from molecules within the cell that naturally emit light when imaged by a microscope paired with an infrared laser. This label-free process is non-damaging and doesn't alter the behavior of the cell. The technique could be adapted to image cells in a plate or dish, tissue samples, or even in vivo imaging of a complete organism.

"It's super novel," Skala says. "Most people aren't using these techniques--you don't see a lot of autofluorescence studies in immunology."

To validate their approach, the researchers acquired blood samples from healthy donors, isolated the T cells, and measured autofluorescence of NAD(P)H and FAD, two molecules that are involved in cellular metabolism.

"We kept some of the T cells in their quiescent state, and then we added antibodies to a group to activate them," says Walsh.

Images of the quiescent cells versus the activated cells revealed differences in metabolic function, most notably through a change in NAD(P)H autofluorescence in the activated T cell populations. They also observed that active T cells were slightly larger in size than quiescent cells.

The activation protocol and imaging capabilities will be useful for manufacturing the CAR-T cells used in immunotherapies, says Skala. These re-engineered T cells are often co-cultured with other cells, like cancer cells, to test their reactivity.

However, using additional harsh reagents or antibody-labels to further characterize the T cell is a bottleneck for CAR-T cell manufacturers. The autofluorescent approach provides an attractive way to perform those experiments by imaging the same cells across multiple timepoints in a way that's non-damaging.

"We showed that you can resolve temporal changes with our imaging technique," says Walsh. "We were able to see changes in the imaging endpoints within minutes after adding the activating antibodies."

Walsh adds that it would be difficult to see these dynamic changes using flow cytometry, since the time required for staining and incubation make it difficult to capture multiple timepoints.

The Skala lab plans to continue this line of investigation to better understand how a cancer patient's T cells might respond as the tumor grows or as they're treated with immunotherapies.

"These technologies could tell us something about tumors or about T cell manufacturing that we didn't know," adds Skala, "because previously we didn't have the methods to monitor T cell behavior over time.

While this new technique offers many advantages over traditional methods, there are still limitations. For one, autofluorescence imaging isn't very sensitive.

"We aren't relying on really specific labels, we're relying on the metabolism of the cells," Skala says. "That's only going to get you so far in differentiating the cell types."

Additionally, the technique requires experienced people to perform the microscopic imaging and analyze the data, says Walsh.

The Skala lab is working on developing a prototype to take the imaging capability of their large-scale microscope and translate it into a "box-sized" system.

"You won't have to be a specialized optical engineer to use it," Skala says. "That's the direction we're trying to go. We're trying to make it more accessible."

Mariel Mohns, mmohns@morgridge.org

Journal

Nature Biomedical Engineering

DOI

10.1038/s41551-020-0592-z

Credit: 
Morgridge Institute for Research

RNA biology provides the key to cell identity and health

Two papers in Genome Research by the FANTOM Consortium have provided new insights into the core regulatory networks governing cell types in different vertebrate species, and the role of RNA as regulators of cell function and identity.

The FANTOM Consortium was established at RIKEN two decades ago to go beyond genomics and examine RNA--known as the transcriptome. Understanding the transcriptome is crucial for further advances in biology because although the cells in our bodies share the same genomic DNA, their diversity is attributed to their RNA make up, with more than 400 types defined and many more thought to exist. Thus, understanding how RNA is expressed is a key for grasping how each cell type establishes its distinctive function, morphology, and behavior by activating specific transcriptional programs. Both studies published today were based on the CAGE technology that was developed at RIKEN to profile the transcriptome using next-generation sequencers.

The first study (Alam et al.) compares transcriptome data from matching primary cell types in human, mouse, rat, dog, and chicken. While the group found that the transcriptome measured by CAGE for the same cell type differed markedly between species, they identified a core regulatory network defining each cell type that is common between species. In general, the genes encoding products involved in RNA biology in the cell nucleus were found to be activated consistently in the same cell type regardless of the species. According to Michiel de Hoon, the corresponding author of the paper, "We identified genes acting within the nucleus whose usage was conserved for 100's of millions of years of evolution. On the other hand, genes that primarily act in communication between cells had diverged and were being used differently in different species, implying that the distinctive phenotype of each species is to a great extent due to the specific way that cells in an organism communicate with each other."

The second study (Ramilowski J., Yip CW., et al.), part of FANTOM 6--the latest edition of the project--looked at human long non-coding RNAs, which outnumber protein-coding genes in mammals but whose function is still poorly understood. The researchers selectively targeted nearly 300 long non-coding RNAs for suppression in human fibroblast cells using an automated robotics system (Figure 1), and combined live cell imaging with CAGE to observe how cells respond at both the cellular and the molecular level. Jay Shin, one of the corresponding authors of this study, emphasized that "it was critical to automate our efforts as much as possible to reduce biases in our experimental design, and to quickly identify and correct any that remained." Based on the analysis, over 25 percent of long non-coding RNAs were found to affect cell growth and morphology, as well as cell migration, which is important in cancer. Surprisingly, targeting different isoforms (variants) of the same long non-coding RNA led to profoundly different cellular and molecular phenotypes, giving rise to the enticing conjecture that each long non-coding RNA isoform produced by a cell might have its own specific regulatory function.

According to Jordan Ramilowski, one of the first authors of the study, "Deep CAGE profiling of the molecular state of the cells after suppression of each long non-coding RNA allowed us to perform a functional analysis of long non-coding RNAs at an unprecedented level, and provides a valuable resource for a detailed investigating and understanding of the RNA biology and its potential application to enhancing human health."

Piero Carninci commented that "although this is still a pilot project, the results show involvement of lncRNAs in a broad variety of cellular processes and functions, which makes the case for extension of these studies to a broader number of cells and lncRNAs. We are excited to see that these RNAs, often considered 'junk' when discovered some 15 years ago, are often proven to be functional. We also believe that that the nomenclature should shift from 'non-coding' to terminology that better reflects their role, such as 'regulatory RNAs' or 'structural RNAs'."

Credit: 
RIKEN

European maize highlights the hidden differences within a species

image: Metaphase chromosomes of maize after fluorescence in situ hybridization (FISH) with probes recognizing different types of repeats (in purple, green and yellow).

Image: 
Picture : A. Ruban and A. Houben, IPK, Gatersleben

Maize (Zea mays ssp. mays) was initially domesticated by Native Americans over 10.000 years ago. Nowadays, America's "favourite corn" is cultivated throughout the world and is used in varying ways, ranging from animal feed to biofuel. Maize has been able to adapt to different climates and conditions around the world, indicating that the genetic variability between lines must be large. And when considering that maize also is one of the plants which can reproduce via self- as well as cross-pollination, it becomes evident that sequencing the genome of only one maize line is insufficient, when attempting to fully understand the genetics of maize. Instead, for genetically diverse crops, researchers aim towards establishing the species' pangenome - the entire sequence of all lines of a species.

Scientists from plant breeding and research institutions throughout Germany recently picked up this challenge in maize and published their contribution to the maize pangenome in the journal Nature Genetics.

Dent and flint corn are the two classes of maize with the greatest commercial importance. As such, it is unsurprising that the complete genome sequence of a dent maize line B73 was established as the go to reference for maize breeding and research. However, within their recent project, the researchers led by Dr. Klaus Haberer from the Helmholtz Center in Munich, concentrated on the investigation of four European flint lines. As Dr. Haberer let us know: "Whilst the dent line B73 is a high-quality reference sequence, very high diversity at the sequence level has been found between different maize lines. This indicates that the sequence of the line B73 captures only a portion of the maize pangenome."

Within their research, the scientists utilised a complementary approach which combined modern sequencing techniques and bioinformatics with cytogenetic technologies. Whilst the sequencing techniques delivered the main share of information on the maize genomes, cytogenetic methods such as FISH (Fluorescence in situ hybridization) facilitated the researchers to test for misinterpretations of the sequenced genomes at the chromosomal level. But more importantly, it enabled the scientists to spot differences between the maize lines by looking through the microscope.

Prof. Dr. Andreas Houben, who led the cytogenetic tests at the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) in Gatersleben, told us: "Flint and dent maize have a high similarity on the gene level. However, both maize types have a large number of non-coding sequences, for example, so-called knob repeats, which vary between different lines. We were able to show these differences on the chromosomal level."

The study of the flint lines is an important addition to the current maize pangenome. And maybe even more importantly, the findings show that while the overall conservation of the gene content within a species might be high, differences in the non-coding genome fraction exist. And these small differences help us to truly understand and utilize maize biology.

Credit: 
Leibniz Institute of Plant Genetics and Crop Plant Research

New study provides valuable historical dataset for Yellow River water management

image: Thirty-one tree-ring sites (red dots) in the middle-upper reaches of the Yellow River (YR). Thick blue line denotes the YR, while the thin blue lines denote the large tributaries the YR; blue triangles represent the stream flow gauge stations in the main channel; green shaded areas are irrigation districts

Image: 
LIU Yu, et al

The Yellow River (YR) is the fifth-longest and the most sediment-laden river in the world. Although the YR accounts for only 3% of China's water resources, it irrigates 13% of its cropland.

Since the 1960s, an increasing number of large-scale dams and reservoirs have been built in the main YR channel, and water consumption by agricultural irrigation along the YR middle course has risen sharply. In recent decades, YR runoff and sediment load have fallen sharply.

The earliest observational record of YR runoff began in 1919 at the Shanxian gauge station, which is too short to study centennial-scale variability. Researchers led by Prof. LIU Yu from the Institute of Earth Environment of the Chinese Academy of Sciences and their collaborators reconstructed natural runoff history for the middle reach of the YR from 1492 to 2013 CE to assess the effects of human activities.

The study was published in Proceedings of the National Academy of Sciences of the United States of America (PNAS) on July 20.

Tree rings, with the merits of accurate dating and annual resolution, have been widely used in runoff reconstruction worldwide. In this study, the researchers collected 31 moisture-sensitive tree-ring width chronologies, including 860 trees and 1707 cores, within the upper-middle YR basins.

They found that the YR runoff in 1781 is the highest, and prior to anthropogenic interference that started in the 1960s, the lowest natural runoff over the past 500 y occurred during 1926 to 1932 CE. These two extreme values could be regarded as a benchmark for future judicious planning of YR water allocation.

Since the late 1980s, the low observed YR runoff has exceeded the natural range of runoff variability, which is caused by the combination of decreasing precipitation and increasing water consumption by direct and indirect human activities, particularly agricultural irrigation.

"This reduced runoff has resulted in an estimated 58% reduction of the sediment load in the upper reach of the YR and 29% reduction in the middle reach," said Prof. LIU.

Human activities, mainly expansive agricultural irrigation in the upper course, have contributed to reduced runoff and sediment load in the upper-middle course of the YR. If these human activities continue to intensify, future YR runoff will be further reduced, and this will negatively impact agriculture, human lives, and socioeconomic development in the middle and lower basins of the YR.

To reduce the risk of recurring cutoff of stream flow in the YR lower basin, water should be allocated judiciously. Policies should balance water allocation among the needs of agriculture, industry and ecosystems.

In addition, the study also provides an important model of how to distinguish and quantify anthropogenic influence from natural variability in global change studies.

Credit: 
Chinese Academy of Sciences Headquarters

New review on management of osteoporosis in premenopausal women

Osteoporosis, a disease which leads to bone fragility and an increased risk of fractures, is very common among postmenopausal women, affecting around one in three over the age of 50 worldwide. However, as osteoporosis and related fragility fractures are rare in younger women, there is far less research, and consequently a lack of consensus and guidance on its diagnosis and management in this population group.

A newly published narrative review by a working group of the ECTS and IOF provides an updated review of literature published after 2017 on premenopausal osteoporosis (1). Based on the latest evidence, the authors outline key information on factors affecting peak bone mass and distinguishing low bone mass from proper osteoporosis with increased fracture risk at a young age, including causes of secondary osteoporosis versus idiopathic osteoporosis, as well as pregnancy-and lactation-associated osteoporosis. They also provide an update on the management and treatment of this condition (including a helpful flow-chart as general guidance).

Professor Serge Ferrari, Vice-Chair of the IOF Committee of Scientific Advisors and Head of the Service and Laboratory of Bone Diseases, Geneva University Hospital, Switzerland, stated:

"Premenopausal women with known causes of secondary osteoporosis have been found to have a high prevalence of bone fragility. As well, those with prior fracture have a 35% to 75% higher risk of having a fracture in their postmenopausal years, compared to premenopausal women without fracture. It is therefore important that physicians are aware of the latest evidence and best practice in diagnosis and clinical management of osteoporosis in younger women, especially in that specific therapy of the underlying disease in many cases can significantly improve bone mineral density and bone microarchitecture."

For example, in celiac disease, an increase of 9% in radius trabecular volumetric density was achieved after one year of gluten-free diet. Similarly, in amenorrhea, including anorexia nervosa, appropriate estrogen replacement therapy can also improve bone mineral density (BMD).

The Working Group experts conclude:

Fragility fractures are rare in premenopausal women and mostly due to secondary osteoporosis (typically underlying hormonal, inflammatory or digestive disorders);

Treating the disorders which cause secondary osteoporosis benefits both BMD and bone microstructure. In case treatment of the underlying cause is not successful, and/or in the presence of severe osteoporosis , antiresorptive and bone-forming drugs can be used;

In absence of an underlying disorder, BMD together with fragility fractures, qualifies as idiopathic osteoporosis;

Low BMD alone does not necessarily represent osteoporosis in the absence of bone microarchitectural abnormalities;

Further clinical trials are needed - especially those focused on fracture risk reduction as primary outcome, as well as on safety of bisphosphonates and other osteoporosis drugs in women of childbearing age.

Professor Bente L. Langdahl, ECTS Past-President and Chief Physician, Department of Endocrinology and Internal Medicine at Aarhus University Hospital, Denmark, added:

"With this review of the latest literature, the ECTS and IOF Working Group aims to provide a succinct overview of current best practice and general guidance on clinical management which can be of help to a wide range of practitioners. The review also points to the areas where future clinical studies are needed, including, first and foremost, the prevention of osteoporosis in women suffering from conditions known to negatively affect bone and the potential impact of osteoporosis-specific treatments on fracture reduction."

Credit: 
International Osteoporosis Foundation

European and American maize: Same same, but different

The maize genome tells an intriguing story about domestication and the shaping of the genome by human selection. Around 10,000 years ago, Native Americans started to domesticate maize in what is Mexico today. They created the basis for one of today's most important sources of food for both humans and livestock. After the discovery of the "new world" by Columbus, maize was brought from the Americas to Europe. Maize adapted to new growing and climate regimes through directed breeding and selection and finally spread around the globe.

Due to its history, today's maize lines do not only differ in appearance, their genome contains many differences (presence and absence of genes as well as structural variations). In 2009, researchers decoded the genome of the North American maize accession "B73". This reference sequence, however, only covers a small part of the global maize genome (pan-genome) and is of limited use as a benchmark for European lines. In order to improve maize breeding and adapt to climate change, basic research on the genome of other maize lines is needed.

European maize genome decoded for the first time

German researchers now succeeded in decoding the European maize genome. They analyzed four different European maize lines using modern sequencing technologies and bioinformatics approaches. In comparison with two lines from North America, they found significant differences in the genetic content and genome structure of these lines - after a few hundred to a thousand years of genetic separation only.

Moreover, so-called "knob" regions (condensed chromatin regions in the maize DNA) vary substantially in those maize lines. Knob regions are known to affect adjacent genes. In areas where knobs tend to be more pronounced, surrounding genes cannot be read. This results in a loss of genetic function.

Potential cause for heterosis

„We hypothesize that differences in gene content, gene regulation and the influence of knob regions might cause the heterosis effect," says Prof. Klaus Mayer, genomicist at Helmholtz Zentrum München and honorary professor of TUM School of Life Sciences at the Technical University of Munich.

Heterosis occurs when the descendants of crossbreeds are significantly larger and produce higher yields than their parents. If specific genes of a parental generation, e.g. those which determine the height of the maize plant, are not present in a certain region or cannot be read, this will affect the height of the offspring as well. Through crossbreeding with a plant that contains the necessary genetic factor, the defect can be compensated in the next generation. "This results in larger plants with higher yields - without the parents showing these characteristics. In some crossings, this effect can even result in doubling the yield. Although it has been exploited in breeding for a long time, the genetic and molecular basis of heterosis is not yet fully understood," says Prof. Chris-Carolin Schön, professor of Plant Breeding at TUM.

"In a next step, we will test our hypothesis. To this end, we will not only analyze the genomes of the different maize lines, but focus on potential epigenetic processes that may affect the functionality of particular genes," adds Klaus Mayer.

If the researchers' hypothesis proves right, heterosis could be applied even more effectively in future maize breeding. Areas with low yields could benefit from heterosis. Furthermore, these findings could become highly relevant in view of a growing world population and climate change, which poses increasing challenges onto agricultural production.

Credit: 
Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH))

Artificial Intelligence to identify individual birds of a same species

image: Photo of a great tit illustrating the individual identification of birds by computer.

Image: 
André Ferreira

Humans have a hard time identifying individual birds just by looking at the patterns on their plumage. An international study involving scientists form the CNRS, Université de Montpellier* and the University of Porto in Portugal, among others, has shown how computers can learn to differentiate individual birds of a same species. The results are published on 27 July 2020 in Methods in Ecology and Evolution.

Differentiating between individuals of a same species is essential in the study of wild animals, their processes of adaptation and behaviour. Scientists from the CEFE research centre in Ecology and Evolutionary Ecology (CNRS/ Université de Montpellier/ Université Paul-Valéry-Montpellier/ IRD/ EPHE) and the Research Centre in Biodiversity and Genetic Resources (CIBIO) at Porto University** have for the very first time identified individual birds with the help of artificial intelligence technology.

They have developed a technique that enables them to gather a large number of photographs, taken from various angles, of individual birds wearing electronic tags. These images were fed into computers which used deep learning technology to recognise the birds by analysing the photographs. The computers were able to distinguish individual birds according to the patterns on their plumage, something humans can't do. The technology was able to identify specimens from populations of three different species: sociable weavers, great tits and zebra finches.

This new technique could not only result in a less invasive method of identification but also lead to new insights in ecology, for example, by opening ways of using AI to study animal behaviour in the wild.

Credit: 
CNRS

Unparalleled inventory of the human gut ecosystem

image: Artist's interpretation of the human gut ecosystem.

Image: 
Spencer Phillips/EMBL

An international team of scientists has collated all known bacterial genomes from the human gut microbiome into a single large database. Their work, published in Nature Biotechnology, will allow researchers to explore the links between bacterial genes and proteins, and their effects on human health.

This project was led by EMBL's European Bioinformatics Institute (EMBL-EBI) and included collaborators from the Wellcome Sanger Institute, the University of Trento, the Gladstone Institutes, and the US Department of Energy Joint Genome Institute.

More microbes than human cells

Bacteria coat the human body, inside and out. They produce proteins that affect our digestion, our health, and our susceptibility to diseases. They are so prevalent that the body is estimated to contain more cells in its microbiome - the bacteria, fungi, and other microbes - than it has human cells.

To understand the role that bacterial species play in human biology, scientists usually isolate and culture them in the lab before they sequence their DNA. However, many bacteria thrive in conditions that are not yet reproducible in a laboratory setting.

To obtain information on such species, researchers take another approach: they collect a single sample from the environment - in this case, the human gut - and sequence the DNA from the whole sample. They then use computational methods to reconstruct the individual genomes of thousands of species from that single sample. This method, called metagenomics, offers a powerful alternative to isolating and sequencing the DNA of individual species.

Biodiversity in the human gut

"Last year, three independent teams, including ours, reconstructed thousands of gut microbiome genomes. The big questions were whether these teams had comparable results, and whether we could pool them into a comprehensive inventory," says Rob Finn, Team Leader at EMBL-EBI.

The scientists have now compiled 200 000 genomes and 170 million protein sequences from more than 4 600 bacterial species in the human gut. Their new databases, the Unified Human Gastrointestinal Genome collection and the Unified Gastrointestinal Protein catalogue, reveal the tremendous diversity in our guts and pave the way for further microbiome research.

"This immense catalogue is a landmark in microbiome research, and will be an invaluable resource for scientists to start studying and hopefully understanding the role of each bacterial species in the human gut ecosystem," explains Nicola Segata, Principal Investigator at the University of Trento.

The project revealed that more than 70% of the detected bacterial species had never been cultured in the lab - their activity in the body remains unknown. The largest group of bacteria that falls into that category is the Comantemales, an order of gut bacteria first described in 2019 in a study led by the Bork Group at EMBL Heidelberg.

"It was a real surprise to see how widespread the Comantemales are. This highlights how little we know about the bacteria in our gut," explains Alexandre Almeida, EMBL-EBI/Sanger Postdoctoral Fellow in the Finn Team. "We hope our catalogue will help bioinformaticians and microbiologists bridge that knowledge gap in the coming years."

A freely accessible data resource

All the data collected in the Unified Human Gastrointestinal Genome collection and the Unified Human Gastrointestinal Protein catalogue are freely available in MGnify, an EMBL-EBI online resource that allows scientists to analyse their microbial genomic data and make comparisons with existing datasets.

The project already has a number of users in the scientific community. As new datasets emerge from research teams around the world, the catalogue might expand to include the microbiomes of other body parts, like the skin or inside the mouth.

"This catalogue provides a very rich source of information for microbiologists and clinicians. However, we will likely discover many more novel bacterial species in under-represented geographical areas like South America, Asia, and Africa. We still don't know much about the variation in bacterial diversity across different human populations," explains Almeida.

Credit: 
European Molecular Biology Laboratory - European Bioinformatics Institute

Hedonism leads to happiness

Relaxing on the sofa or savoring a delicious meal: Enjoying short-term pleasurable activities that don't lead to long-term goals contributes at least as much to a happy life as self-control, according to new research from the University of Zurich and Radboud University in the Netherlands. The researchers therefore argue for a greater appreciation of hedonism in psychology.

We all set ourselves long-term goals from time to time, such as finally getting into shape, eating less sugar or learning a foreign language. Research has devoted much time to finding out how we can reach these goals more effectively. The prevailing view is that self-control helps us prioritize long-term goals over momentary pleasure and that if you are good at self-control, this will usually result in a happier and more successful life.

"It's time for a rethink," says Katharina Bernecker, researcher in motivational psychology at the University of Zurich. "Of course self-control is important, but research on self-regulation should pay just as much attention to hedonism, or short-term pleasure." That's because Bernecker's new research shows that people's capacity to experience pleasure or enjoyment contributes at least as much to a happy and satisfied life as successful self-control.

Distraction disrupts pleasure

Bernecker and her colleague Daniela Becker of Radboud University developed a questionnaire to measure respondents' capacity for hedonism, i.e. their ability to focus on their immediate needs and indulge in and enjoy short-term pleasures. They used the questionnaire to find out whether people differ in their capacity to pursue hedonic goals in a variety of contexts, and whether this ability is related to well-being.

They found that certain people get distracted by intrusive thoughts in moments of relaxation or enjoyment by thinking about activities or tasks that they should be doing instead. "For example, when lying on the couch you might keep thinking of the sport you are not doing," says Becker. "Those thoughts about conflicting long-term goals undermine the immediate need to relax." On the other hand, people who can fully enjoy themselves in those situations tend to have a higher sense of well-being in general, not only in the short term, and are less likely to suffer from depression and anxiety, among other things.

More isn't always better

"The pursuit of hedonic and long-term goals needn't be in conflict with one another," says Bernecker. "Our research shows that both are important and can complement each other in achieving well-being and good health. It is important to find the right balance in everyday life."

Unfortunately, simply sitting about more on the sofa, eating more good food and going to the pub with friends more often won't automatically make for more happiness. "It was always thought that hedonism, as opposed to self-control, was the easier option," says Bernecker. "But really enjoying one's hedonic choice isn't actually that simple for everybody because of those distracting thoughts."

Conscious planning of downtime

This is currently a topical issue with more people working from home, as the environment where they normally rest is suddenly associated with work. "Thinking of the work you still need to do can lead to more distracting thoughts at home, making you less able to rest," says Bernecker.

So what can you do to enjoy your downtime more? More research is needed, but the researchers suspect that consciously planning and setting limits to periods of enjoyment could help to separate them more clearly from other activities, allowing pleasure to take place more undisturbed.

Credit: 
University of Zurich

Not just light: The sensitivity of photoreceptors to mechanical stimuli is unveiled

image: At the top, a trapped bead on the outer segment of a rod. At the bottom, the corresponding fluorescence change.

Image: 
Bocchero et al

Thanks to optical tweezers, a new study reveals unexpected properties of the neurons responsible for the transduction of light signals. The research has been published in PLOS Biology.

"We thought we knew almost everything about photoreceptors, but we have proved that is not the case." With these words, Vincent Torre, Professor of neurobiology of SISSA - Scuola Internazionale Superiore di Studi Avanzati, comments the results of a new study that, thanks to a multidisciplinary approach and to the use of optical tweezers, reveals for the first time the sensitivity of nerve cells present on the retina to mechanical stimuli and opens up new questions on how they function. The work has been published in PLOS Biology.

Cones and rods, also known as photoreceptors. It is thanks to them that the light that reaches our eyes transforms into information. They are cells with a characteristic shape, as the names suggest, mutually complementary. If the cones are principally involved in daytime vision and colour recognition, the rods on the other hand are very sensitive to light and allow to see even in low-light conditions.

The mechanisms for transduction of light signals have been known for some time, but the development of new experimental methodologies inspired by nanotechnology has allowed a group of researchers of SISSA, the National Research Council (CNR) and the Australian National University to better understand the complexity of their functioning.

In particular, scholars have investigated the mechanical sensitivity of frog rods using optical tweezers. "This highly innovative technique uses an infrared laser beam to trap particles of very small dimensions and handle biological systems with extreme precision without damaging them" explains Dan Cojoc, head of the Optical Manipulation Laboratory of the 'Istituto Officina dei Materiali' of CNR. In this way the scientists could apply a slight pressure to the surface of isolated rods, while monitoring the response with calcium imaging techniques, which allows to detect the concentration of intracellular calcium through the presence of fluorescent molecules. They observed consistent variations in fluorescence thus showing an unexpected sensitivity of the photoreceptors to the mechanical stimuli.

In line with this interpretation, the research team, which included SISSA PhD students Ulisse Bocchero, Fabio Falleroni, Simone Mortal and Yunzhen Li, ascertained the presence in photoreceptors of specific molecules sensitive to mechanical stress. They detected a variation in electrical signals in the presence of drugs able to block the functionality of some of these molecules and, then, analysed their distribution in the retina through specific fluorescent markers. Finally, they demonstrated the existence in vertebrates of an association between the genes connected to phototransduction and some genes connected instead to mechanical transduction.

What are the physiological mechanical stimuli able to activate the photoreceptors? "It is still an open question," answers Torre. "Thanks to the optical tweezers we have shown the sensitivity of the rods to mechanical stimuli. However, we have also been able to observe a reduction in the length of their external segment when subjected to particularly intense light flashes, a phenomenon known as phototropism. In situations like these, it is more than plausible to think that mechanical stimulations are involved."

Undoubtedly, there are still many steps to understand: "We believe that sensitivity to mechanical stimuli is necessary to guarantee both cell integrity and optimal functioning of phototransduction," concludes Torre. "Once again, biology shows that there is always a greater complexity and it is incredible how the development of new technologies allows us to discover new things all the time."

Credit: 
Scuola Internazionale Superiore di Studi Avanzati

Hydrogel mimics human brain with memorizing and forgetting ability

video: The pattern of an airplane on the gel, or the memory, slowly faded. The stronger the memory, the longer it took to forget. (Chengtao Yu et al., PNAS, July 27, 2020)

Image: 
Chengtao Yu et al., PNAS, July 27, 2020

Hokkaido University researchers have found a soft and wet material that can memorize, retrieve, and forget information, much like the human brain. They report their findings in the journal Proceedings of the National Academy of Sciences (PNAS).

The human brain learns things, but tends to forget them when the information is no longer important. Recreating this dynamic memory process in manmade materials has been a challenge. Hokkaido University researchers now report a hydrogel that mimics the dynamic memory function of the brain: encoding information that fades with time depending on the memory intensity.

Hydrogels are flexible materials comprised of a large percentage of water -- in this case about 45% -- along with other chemicals that provide a scaffold-like structure to contain the water. Professor Jian Ping Gong, Assistant Professor Kunpeng Cui, and their students and colleagues in Hokkaido University's Institute for Chemical Reaction Design and Discovery (WPI-ICReDD) are seeking to develop hydrogels that can serve biological functions.

"Hydrogels are excellent candidates to mimic biological functions because they are soft and wet like human tissues," says Gong. "We are excited to demonstrate how hydrogels can mimic some of the memory functions of brain tissue."

In this study, the researchers placed a thin hydrogel between two plastic plates; the top plate had a shape or letters cut out, leaving only that area of the hydrogel exposed. For example, patterns included an airplane and the word "GEL." They initially placed the gel in a cold water bath to establish equilibrium. Then they moved the gel to a hot bath. The gel absorbed water into its structure causing a swell, but only in the exposed area. This imprinted the pattern, which is like a piece of information, onto the gel. When the gel was moved back to the cold water bath, the exposed area turned opaque, making the stored information visible, due to what they call "structure frustration." At the cold temperature, the hydrogel gradually shrank, releasing the water it had absorbed. The pattern slowly faded. The longer the gel was left in the hot water, the darker or more intense the imprint would be, and therefore the longer it took to fade or "forget" the information. The team also showed hotter temperatures intensified the memories.

"This is similar to humans," says Cui. "The longer you spend learning something or the stronger the emotional stimuli, the longer it takes to forget it."

The team showed that the memory established in the hydrogel is stable against temperature fluctuation and large physical stretching. More interestingly, the forgetting processes can be programmed by tuning the thermal learning time or temperature. For example, when they applied different learning times to each letter of "GEL," the letters disappeared sequentially.

The team used a hydrogel containing materials called polyampholytes or PA gels. The memorizing-forgetting behavior is achieved based on fast water uptake and slow water release, which is enabled by dynamic bonds in the hydrogels. "This approach should work for a variety of hydrogels with physical bonds," says Gong.

"The hydrogel's brain-like memory system could be explored for some applications, such as disappearing messages for security," Cui added.

Credit: 
Hokkaido University

Identified a new regulatory mechanism of response to metabolic stress

Chromatin Biology group aims to define the mechanisms involved in the cellular response to different types of stress such as metabolic, oxidative and genotoxic stress. In particular, they focus their studies on the impact of a family of enzymes, Sirtuins (responsible of the cellular stress response) in the maintenance of genome stability under these conditions and their impact in aging and different types of cancers, with a special focus on hematologic malignancies.

Dr. Vaquero's group has just published an article at Science Advances journal in which they have identified and characterized a new enzymatic activity of the Sirtuin SIRT7 that provides new evidence to understand its regulatory capacity in the cellular response to different types of stress damaging cellular integrity.

The regulation of this response acquires special relevance since these types of stress can produce alterations in the DNA and instability at cell's energy flow, and are directly involved in the appearance of pathologies such as cancer, neurodegenerative diseases or a number of endocrine pathologies.

The regulatory mechanism identified may represent an important advance towards new therapeutic targets in the treatment of cancer, particularly in hematological cancers, since previous studies have shown that both genome instability and metabolic stress contribute significantly to the development of leukemias and lymphomas.

Other groups have also collaborated in this multidisciplinary study, whose first author is Dr. Nicolas Simonet, including the research groups led by Dr. Manel Esteller and Dr. Marcus Buschbeck (both from the Josep Carreras Leukaemia Research Institute),the Proteomics Unit of this Inste, led by Dr. Carolina de la Torre, as well as groups from Pompeu Fabra University, the Centre for Genomic Regulation, Rutgers University (USA) and the Max Plank Institute (Germany).

This research has been funded by the Ministry of Economy and Competitiveness, the Agency for the Management of University and Research Grants (AGAUR) of the Government of Catalonia and co-financed by FEDER funds.

Credit: 
Josep Carreras Leukaemia Research Institute