Culture

Researchers from the Severinov Lab at Skoltech have looked at how a poorly studied type of CRISPR-Cas defense system from a bacterium living at extremely high temperature gets to know its enemy by selecting snippets of bacteriophage's genetic information for a genetic "database" it uses to ward off subsequent infections. Understanding of this mechanism opens new ways for further genomic manipulation of both the bacterial host and its virus. The paper was published in the journal Nucleic Acids Research.

CRISPR-Cas are powerful defense systems that most prokaryotes use to recognize and destroy invading genetic material such as bacteriophages. Each system is essentially a set of nucleic acid-cleaving Cas proteins armed with fragments of foreign sequences stored in CRISPR arrays, special databases located in the chromosome of the cell. Much like a police unit receiving a suspect profile, Cas proteins form complexes with short CRISPR RNAs containing information about the genetic invader, search for nucleic acids that are complementary to the CRISPR RNAs, and then recognize and destroy them.

Depending on the kind of Cas proteins, scientists distinguish six types of CRISPR-Cas systems. Type III is the least studied and the most complex. "Type III systems stand out from all others. First, they recognize foreign RNA, rather than DNA recognized by other systems. Second, in a bizarre twist, upon recognizing target RNA the Type III systems destroy the DNA from which this RNA is transcribed," explains the lead author Konstantin Severinov.

Severinov and his colleagues studied the Type III system in a hyperthermophilic bacterium Thermus thermophilus that inhabits hot springs around the world. They were interested in how the bacterium acquires spacers, or the "entries" for its CRISPR "database". Spacers are bits of foreign DNA in the CRISPR array that serve as printing plates for CRISPR RNAs that are used to recognize subsequent infections.

"Being a thermophilic bacterium, i.e. living at 65C and above, Thermus is a good model organism for biochemical and especially structural work, because its proteins are very robust. However, the downside of this is that most people never study Thermus as a microbe, but rather as a source of sturdy proteins," says Severinov. "Spacer acquisition is the least understood part of CRISPR immunity that in many respects operates through a Lamarckian rather than Darwinian mode. In the case of Type III CRISPR systems, the situation becomes especially complex, as only spacers acquired in a certain orientation will be able to target foreign RNA. This is not true for CRISPR-Cas systems of other types. So it was of high interest to determine how a Type III system ensures efficient acquisition of spacers capable of providing defense to the host."

The researchers cultivated T. thermophilus cells in the laboratory, infected them with bacteriophage they isolated earlier from a hot spring in Kamchatka, and observed how the attacked bacteria expanded their Type III CRISPR arrays. Among other things, the researchers were able to show that new spacers came from a tiny region of the phage genome that is first injected in the infected bacterial cell. The bias is likely due to the fact that recognizing the enemy early on allows infected cells to clear the infection and survive rather than due to any intrinsic properties of the Type III machinery, which presumably selects spacers randomly, meaning that 50% of acquired spacers are inserted in a wrong orientation and thus do not provide any defense. The researchers hypothesize that the region of the phage genome from which spacers are acquired may encode anti-CRISPR proteins, and thus it is crucial for the cell to deploy its defense before it is disabled.

The team also showed that some phages escaped the Type III CRISPR-Cas defense by losing small bits of their DNA from targeted regions.

"The observation that we can select "escaper" phages that deleted regions recognized by defensive CRISPR RNAs means that we can easily engineer mutant phages by targeting them with engineered CRISPR RNAs recognizing genomic regions of interest," says Severinov, "given how little we know about viruses infecting thermophilic bacteria, our finding opens a way to probe these viruses by designer CRISPR RNAs and determine the functions on individual viral genes."

Plant science research has tremendous potential to address pressing global issues including climate change, food insecurity and sustainability. However, without sustained investment in plant science, the necessary research to generate innovative discoveries that solve these urgent problems is at risk.

On September 1, the Plant Science Research Network (PSRN) released its Plant Science Decadal Vision 2020-2030: Reimagining the Potential of Plants for a Healthy and Sustainable Future, a report that outlines bold, innovative solutions to guide investments and research in plant science over the next 10 years.

The PSRN calls on its community to unite around the Decadal Vision's priorities and to inspire their government representatives and fellow community members.

"The Decadal Vision is a community-wide vision that is a powerful tool for communication and advocacy," said David Stern, President of the Boyce Thompson Institute and corresponding author. "After all, the public should be the ultimate beneficiary of the vision."

The Decadal Vision grew out of Plant Summit 2019, a conference held February 10-13, 2019, at Biosphere 2 in Arizona.

"Fifty diverse participants - including scientists, industry representatives, educators and advocates - discussed the future of research, training and infrastructure," says Stern, who is also an adjunct professor of plant biology in Cornell University's College of Agriculture and Life Sciences. "From that meeting, the writing team developed the Decadal Vision as a rallying cry for all plant scientists to unite around a common vision, inspire new collaborations to pursue interdisciplinary research goals, and implement new paradigms for professional development that will catalyze a more diverse, inclusive, and equitable future."

The Decadal Vision recognizes the intersection of human and scientific elements and demands integrated implementation of strategies to advance research, people and technology. The vision is presented through eight specific and interdisciplinary goals, each with an accompanying action plan.

Four research goals are presented: Harness plants for planetary resilience; Advance technology for diversity-driven sustainable plant production systems; Develop 21st-century applications of plant science to improve nutrition, health, and well-being; and Launch the "Transparent Plant", an interactive tool to discern mechanisms and solve urgent and vexing problems.

When it comes to agriculture, "Increasing food production may not be the solution," explains co-author Ole Wendroth, professor of soil science at the University of Kentucky. "Food needs to be produced more sustainably, and plant science plays an important role in this for the future. Farmers that I have worked with are very willing to take this bold step as long as they can produce a safe farm income."

The two goals emphasizing our people are: Reimagine the workplace to nurture adaptive and diverse scientists; and Build capacity and interest to engage with plant science.

"What I like about the Decadal Vision is that equity and justice were part of the vision right from the beginning, and not just tacked on at the end," says co-author Madelaine Bartlett, an associate professor of biology at the University of Massachusetts Amherst. "Everyone should have the same opportunities that I have had, but that is simply not the case right now. It is hard work, but it can be done and it must be done."

Bartlett adds that collaborations among people from many scientific disciplines is the new normal, and the PSRN has strengthened connections between scientific societies.

"My research is in the intersection of genetics, bioinformatics, developmental biology and evolutionary biology, so I belong to four different research societies," she says. "I hope this report will help knock down those barriers and stimulate more research that integrates multiple disciplines."

The two goals focused on technology infrastructure are: Develop new technologies to revolutionize research; and Manage and realize the potential of Big Data.

Co-author Eric Lyons, associate professor in the School of Plant Sciences at the University of Arizona, says such new technologies are necessary because plant research is a diverse set of sciences that span from molecules to the entire planet.

"Addressing the most pressing questions of plant research requires an unprecedented level of coordination, collaboration, and training across many disciplines of science," says Lyons. "This Decadal Vision is essential to bring a common voice to the needs of these diverse researchers and the central role that data science plays in facilitating integrating information to make new discoveries to improve the human condition through plants and agriculture."

While the Decadal Vision makes a case for new funding, obtaining that support will require plant scientists to engage the public and advocate for needed resources.

Indeed, federal funding agencies, private philanthropies, corporations and entrepreneurs, are all necessary for plant science to have a maximum impact on enhancing human health, improving environmental quality, boosting the economy, and benefitting global equity and justice.

"Plant science gets such a small piece of the funding pie. If there are going to be solutions to surviving climate change, then plants are going to be a critical part of those solutions," says Bartlett.

Wendroth believes that funding agencies can foster plant science discoveries to address pressing global issues by calling for proposals in forward-thinking, interdisciplinary research with speculative outcomes. "This would help harness scientific creativity in a similar way that venture capital is used to invest in long-term growth potential opportunities," he says.

Widespread use of contraceptives and, to a lesser extent, girls’ education through at least age 14 have the greatest impact in bringing down a country’s fertility rate.

Education and family planning have long been tied to lower fertility trends. But new research from the University of Washington analyzes those factors to determine, what accelerates a decline in otherwise high-fertility countries.

In a paper published July 23 in Population and Development Review, Daphne Liu, a doctoral student in statistics at the UW, and Adrian Raftery, a UW professor of statistics and sociology, explore two nuanced questions: Is increasing contraceptive use or reducing demand more effective in family planning? And, is it the number of years girls attend school or the overall enrollment of children in school that makes education a factor in fertility?

“Policymakers in countries with high fertility rates are often interested in accelerating their fertility decline, since rapid population growth can lead to a number of unwanted economic, environmental and public health consequences,” said Liu. “Policies that increase access to education and family planning are generally thought to accelerate fertility decline by empowering individuals, particularly girls and women, to achieve their own desires in life. Our work aims to explore what aspects of a country’s education and family planning have the greatest impact on fertility decline.”

As the world’s population builds toward a projected 10.9 billion by 2100, much of that growth is expected to occur in high-fertility countries of Latin America, Asia and sub-Saharan Africa. The United Nations’ Sustainable Development Goals note the role sustainable fertility can play in a country’s environmental, economic and population health, alongside the ways family planning can enable individuals to realize their own fertility goals.

Higher fertility rates can stretch a country’s available resources, while rates lower than the “replacement rate” of 2.1 births per woman can lead to a long-term lack of economic growth. Today’s global fertility rate of 2.5 births per woman is down from 3.2 in 1990, but is higher in parts of the world where some countries report fertility rates of at least 4 births per woman.

Liu and Raftery’s study uses UN data on fertility rates since 1970 and combines it with data on education and contraception to determine which factors have the greatest effect. All the countries in their study sample were categorized as transitioning downward, however slowly, from a period of high fertility.

Within the category of family planning, Liu and Raftery looked at two factors over time: contraceptive prevalence, which is the percentage of women using modern contraception; and unmet need, the percentage of women who say they want to delay or stop childbearing but are not using contraception. While the difference between the two metrics may appear small, Liu pointed out that unmet need can reflect hypothetical interest in family planning, whereas contraceptive prevalence reflects actual use. The study found that contraceptive prevalence had a significantly greater effect.

For example, data from El Salvador shows that the link between an increase in contraceptive use and a corresponding decline in fertility rate is especially pronounced. The country’s total fertility rate went from 5.44 births per woman in the mid-1970s — when 28% of women used birth control — to 2.72 births in the mid-2000s, when contraceptive prevalence had more than doubled.

Liu and Raftery also wanted to look at the effect of education on fertility changes. For this, they examined two different aspects of education, both tied to cultural values and economic outcomes: school enrollment and the highest level of education girls typically attain. The latter stems from the academic and professional opportunities available to women and girls, which may affect their childbearing decisions. The former has been hypothesized to affect fertility because if more children go to school, it is more expensive to bring them up, which may discourage families from having more children.

Liu and Raftery found that education affected fertility mostly through the educational attainment of girls, particularly through their early teens (the “lower secondary” level of schooling). Generally considered the last stage of basic education, completing at least the lower secondary level had a greater effect on fertility decline than completing only primary schooling.

Kenya showed a substantial increase in girls’ educational attainment, from 12% reaching the lower secondary level in the mid-1970s to 59% in the mid-2010s. Contraceptive prevalence in Kenya also grew steadily, from 5% to 51%, while the total fertility rate dropped from 7.64 births per woman to 4.06.

Still, of the two factors — family planning and education — family planning played a bigger role in accelerating the transition. “It is important to know that family planning is so critical,” said Raftery. “However, both factors are important and they work together. Education gives women more opportunities as alternatives to having large families, while family planning gives them the means to achieve their goals.”

Overall, sub-Saharan Africa, where the highest-fertility countries are located, showed reductions in fertility but at a slower pace than other high-fertility regions of the world. This may be associated with economic development and cultural values around family size, as well as the quality of education. In line with the UN Sustainable Development Goals, policymakers and NGOs should continue to focus on education and on availability and acceptance of contraceptives for women, the researchers said.

The study was funded by the National Institute for Child Health and Human Development. For more information, contact Liu at dhliu@uw.edu.

Journal

Population and Development Review

DOI

10.1111/padr.12347

When vegetable farmers harvest crops, they often rely on postharvest washing to reduce any foodborne pathogens, but a new University of Georgia study shows promise in reducing these pathogens - as well as lowering labor costs-- by applying sanitizers to produce while it is still in the fields.

Salmonella, Shiga toxin-producing E. coli and Listeria monocytogenes are major causes of foodborne diseases and of public health concern in the U.S. Tomato-associated Salmonella outbreaks reported to the Centers for Disease Control and Prevention have increased in frequency and magnitude in recent years, and fresh produce accounted for 21% of E. coli outbreaks reported to the CDC over a 20-year span.

Initially researchers were going to study the use of a nonchlorine-based sanitizer made of two food additives approved by the U.S. Food and Drug Administration -- levulinic acid and sodium dodecyl sulfate -- as a postharvest wash solution. However, at the suggestion of a producer involved in the study -- Bill Brim of Lewis Taylor Farms in Tifton, Georgia -- they designed the study using the solution in a preharvest spray, said Tong Zhao, associate research scientist with the Center for Food Safety on the UGA Griffin campus.

While producers commonly use chlorine-based disinfectants -- including chlorine gas, sodium hypochlorite, calcium hypochlorite and chlorine dioxide -- to treat produce postharvest, the preharvest application of bactericides is not a common practice, Zhao said.

Building on previous studies of levulinic acid and sodium dodecyl sulfate that showed the combination substantially reduces both Salmonella and E. coli on romaine lettuce without adversely affecting lettuce quality, Zhao hoped to prove the combination's effectiveness on reducing foodborne pathogens on tomato plants contaminated with Salmonella, Shiga toxin-producing E. coli and Listeria monocytogenes.

In the field studies, the spray treatment significantly reduced the total bacterial population on the surface of tomatoes, determining that this preharvest treatment is a practical, labor-cost effective and environmentally friendly approach for the control and reduction of foodborne pathogens. The study was recently published in the journal Food Control.

"This combination of chemicals had never been used for preharvest treatment," said Zhao, who studied the combination 10 years ago as an alternative to chlorine treatment as a postharvest wash. "Free chlorine is easily neutralized by organic material, which is a big problem when you are using it to reduce pathogens."

In both laboratory and field tests, tomato plants were sprayed all over with a solution containing five strains of E. coli, five strains of Salmonella and five strains of Listeria specially grown for the study in the lab.

To test the effectiveness of the chemicals in the lab as a preventative and as a treatment, tomato plants were separated into three equal groups then sprayed with the bacteria solution. The first group was treated with acidified chlorine as the positive control, the second with a treatment solution containing levulinic acid and sodium dodecyl sulfate as the test group, and the third treated with tap water only as the negative control.

For the three plots used for farm application testing, the positive and negative control groups were treated the same way, and a commercial product -- Fit-L -- was diluted according to the manufacturer's description and used as the treatment solution. Before treatment studies on the farm, two concentrations of the treatment solution were tested for safety on tomato seedlings in the greenhouse.

Results from the studies showed that the application, used either as a preventative or as a treatment, significantly reduced the populations of inoculated Shiga toxin-producing E. coli, Salmonella and L. monocytogenes on tomato plants.

"I have to express appreciation to the Georgia Fruit and Vegetable Association for funding this and other research that is of benefit to agricultural producers in the state," Zhao said.

In addition to being effective and affordable, preharvest treatment with levulinic acid and sodium dodecyl sulfate to reduce pathogens also saves labor costs for producers who need workers to perform postharvest washing and drying of produce before packaging.

"This method can easily be adopted using equipment that most farms are already using," Zhao said. "Preharvest treatment is very effective, efficient and easy considering the amount of labor needed for postharvest washing."

New research from Oregon Health & Science University for the first time documents the presence of astrocytes in zebrafish, a milestone that will open new avenues of research into a star-shaped type of glial cell in the brain that is critical for nearly every aspect of brain assembly and function.

The research was published this week in the journal Nature Neuroscience.

With their transparent bodies, zebrafish larvae provide a unique opportunity to gaze into the inner workings of the central nervous system, including the brain, even in living animals. The identification of astrocytes and the generation of tools to work with them in zebrafish will enable researchers around the world to open new lines of research to advance scientific understanding of how astrocytes function.

Astrocytes, it turns out, are the most abundant and mysterious cell type in the human brain, and OHSU is becoming a hub for research into their roles in development, brain function and disease.

"There is no neurodegenerative disease that I know of where astrocytes are not profoundly affected in some way," said senior author Kelly Monk, Ph.D., professor and co-director of the Vollum Institute at OHSU. "This gives us a powerful tool to get a handle on what these cells do and how they do it."

Monk and co-author Marc Freeman, Ph.D., credit lead author Jiakun Chen, Ph.D., a post-doctoral researcher in the Monk and Freeman labs, with developing a panoply of tools, including a cell-specific approach using the gene editing tool CRISPR to label and manipulate astrocyte precursors and incisively study their development and functions.

"He was able to capture the birth of an astrocyte from a stem cell and its entire development, which has never been visualized before in a vertebrate animal," Monk said.

Freeman said the discovery will dramatically enhance the study of how glia regulate brain development and physiology.

"This opens the door to experiments that you can't do in any other organism," Freeman said. "Zebrafish is the only animal in which you can now live-image all types of vertebrate glial cells - astrocytes, microglia, oligodendrocytes and OPCs - along with any neuron in intact neural circuits, from the earliest stages of development. Zebrafish is also the only vertebrate in which you can image the entire brain in live, behaving animals to figure out how it works. Understanding the role of these cells (astrocytes) in brain development will be key to understanding devastating neurodevelopmental disorders like autism spectrum disorder and schizophrenia.

"It's a major step forward and should power a lot of exciting work in the coming years."

On Sep. 07, 2020, NOAA/NASA's Suomi NPP satellite provided two different views of how fires are affecting the U.S. A true-color image of the United States shows a blanket of smoke obscuring the surface from California to Arkansas with a haze present over the East Coast as well. The Suomi NPP satellite also provided information about aerosols that were released from these fires and have traveled across the United States' landscape.

Although the OMPS suite was designed to measure ozone it also has the capability of measuring other atmospheric particles like sulfur dioxide and ash. The aerosol index (AI) value is related to both the thickness and height of the atmospheric aerosol layer. For most atmospheric events involving aerosols, the AI ranges from 0.0 to 5.0, with 5.0 indicating heavy concentrations of aerosols that could reduce visibilities or impact health. Color codes range from colorless (0.0) through yellow (.5 - 2.6), orange (2.7-3) deep red (>3 - 5.0). This image shows a significant area of deep red range which means aerosols in the area could potentially be dangerous to the health of those in that area.

The smoke released by any type of fire (forest, brush, crop, structure, tires, waste or wood burning) is a mixture of particles and chemicals produced by incomplete burning of carbon-containing materials. All smoke contains carbon monoxide, carbon dioxide and particulate matter (PM or soot). Smoke can contain many different chemicals, including aldehydes, acid gases, sulfur dioxide, nitrogen oxides, polycyclic aromatic hydrocarbons (PAHs), benzene, toluene, styrene, metals and dioxins. The type and amount of particles and chemicals in smoke varies depending on what is burning, how much oxygen is available, and the burn temperature.

High aerosol concentrations not only can affect climate and reduce visibility, they also can impact breathing, reproduction, the cardiovascular system, and the central nervous system, according to the U.S. Environmental Protection Agency. Since aerosols are able to remain suspended in the atmosphere and be carried in prevailing high-altitude wind streams, they can travel great distances away from their source as evidenced in these images and their effects can linger.

WASHINGTON, September 8, 2020 -- When looking at humanity from a macroscopic perspective, there are numerous examples of people cooperating to form societies, countries, religions, and other groupings.

Yet at the basic two-person level, people tend to betray each other, as found in social dilemma games like the prisoner's dilemma, even though people would receive a better payoff if they cooperated among themselves.

The topic of cooperation and how and when people start trusting one another has been studied by various researchers who have addressed this problem numerically. In a paper in Chaos, by AIP Publishing, researchers investigate what drives cooperation analytically.

In order to investigate what happens when an infinite number of people, instead of two people, play a game like the prisoner's dilemma, the researchers mapped the two-player game to a two-spin ID Ising model, which is a 1D line of interacting spins in the presence of an external magnetic field.

Spins can either point clockwise, which is up, or counterclockwise, which is down. The net difference between the fraction of spins pointing up to those pointing down provides the analytic result for the magnetization.

"Game magnetization is an excellent measure of how in the overall scheme of things the total number of players respond to different payoffs," said Colin Benjamin, one of the authors. "In our work, we go beyond game magnetization and look at game susceptibility, too."

An analytical result for susceptibility probes the net change in the fraction of players adopting a certain strategy for both classic and quantum social dilemmas and pinpoints the real drivers of cooperative behavior, which can vary given the situation.

The findings in this research can be applied to analytical solutions to numerous other social dilemma games, such as rock-paper-scissors, Battle of the Sexes, or Stag Hunt. The mapping to ID Ising model can help understand cooperative behavior in many other social dilemmas as well.

"One future area to explore is that of recent COVID-19 infection dynamics," said Benjamin. "A lot of numerical work has been done to explore COVID-19 infection dynamics using tools of evolutionary game theory. An analytical model, however, is lacking."

WASHINGTON, September 8, 2020 -- Inspired by the need for new and better therapies for neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease, Rutgers University researchers are exploring the link between uncontrolled inflammation within the brain and the brain's immune cells, known as microglia.

Most therapies for brain health disorders focus on the major cells of the nervous system: neurons. But microglia cells are emerging as a promising cellular target because of the prominent role they play in brain inflammation. In addition, microglial behavior can be engineered to rein in inflammation, which is caused by different factors, and the damage it causes.

In APL Bioengineering, from AIP Publishing, the group highlights the design considerations and benefits of creating therapeutic nanoparticles for carrying pharmacological factors directly to the sites of the microglia.

Microglia are essentially first responders to pathological changes within the brain and can readily clear out undesired and foreign substances.

"Emerging drugs and biological factors can be targeted and released in controlled ways within the brain if their nanoscale carriers can be engineered," said Prabhas V. Moghe, co-author on the paper. "We believe this field is ripe for technological, biological, and clinical breakthroughs."

The group's ultimate goal is to tamp down the uncontrolled activation of microglial inflammation.

"Within our lab at Rutgers, we are developing a new therapeutic strategy targeted to the microglia activated by the excessive deposition of the protein alpha-synuclein," Moghe said. "This will potentially address a major therapeutic barrier of microglial activation in neurodegenerative diseases."

Targeting microglia in this manner may open up avenues for the development of novel therapeutics.

"Studying nanoparticle interactions with microglia can guide the design of successful nanomedicine platforms that enable targeted delivery of drugs while minimizing off-target effects and system-level toxicity," Moghe said. "Considering the complex nature of neurodegenerative disorders, rather than solely focusing on therapies for neurons, it may be worth directing therapeutics to the mediator, microglia, whose functional restoration will protect neurons."

Scientists from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago were the first to examine endothelial cells - one of the main sources of blood production - for clues as to why people with Down syndrome have higher prevalence of leukemia. They identified a new set of genes that are overexpressed in endothelial cells of patients with Down syndrome. This creates an environment conducive to leukemia, which is characterized by uncontrolled development and growth of blood cells. Their findings, published in the journal Oncotarget, point to new potential targets for treatment and possibly prevention of leukemia, in people with Down syndrome and in the general population.

"We found that Down syndrome, or Trisomy 21, has genome-wide implications that place these individuals at higher risk for leukemia," says co-lead author Mariana Perepitchka, BA, Research Associate at the Manne Research Institute at Lurie Children's. "We discovered an increased expression of leukemia-promoting genes and decreased expression of genes involved in reducing inflammation. These genes were not located on chromosome 21, which makes them potential therapeutic targets for leukemia even for people without Down syndrome."

Down syndrome is a congenital genetic disorder caused by additional genetic material from an extra copy of chromosome 21. The condition occurs in about one in 700 babies. In addition to developmental and physical impairments, people with Down syndrome have a 500-fold risk of developing acute megakaryoblastic leukemia (AMKL) and a 20-fold risk of being diagnosed with acute lymphoblastic leukemia (ALL).

"Our discovery of leukemia-conducive gene expression in endothelial cells could open new avenues for cancer research," says co-lead author Yekaterina Galat, BS, Research Associate at the Manne Research Institute at Lurie Children's.

The study used skin samples from patients with Down syndrome to create induced pluripotent stem cells (iPSC) that were then differentiated into endothelial cells. Impairment in endothelial cell genetic expression was found to produce altered endothelial function throughout the cell maturation.

"Fortunately, advances in iPSC technology have provided us with an opportunity to study cell types, such as endothelial cells, that are not easily attainable from patients," says senior author Vasil Galat, PhD, Director of Human iPS and Stem Cell Core at Manne Research Institute at Lurie Children's and Research Assistant Professor of Pathology at Northwestern University Feinberg School of Medicine. "If our results are confirmed, we may have new gene targets for developing novel leukemia treatments and prevention."

What The Study Did: Clinical features of COVID-19 are compared in this observational study with those of influenza A and B in U.S. children.

Authors: Xiaoyan Song, Ph.D, M.B.B.S., of the Children's National Hospital  in Washington, D.C., 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.2020.20495)

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.

As the fall approaches, pediatric hospitals will start seeing children with seasonal influenza A and B. At the same time, COVID-19 will be co-circulating in communities with the flu and other respiratory viruses, making it more difficult to identify and prevent the novel coronavirus.

With little published data directly comparing the clinical features of children with COVID-19 to those with seasonal flu, researchers at Children's National Hospital decided to conduct a retrospective cohort study of patients in the two groups. Their findings -- published September 8 in JAMA Network Open -- surprised them.

The study -- detailed in the article "Comparison of Clinical Features of US Children With COVID-19 vs Seasonal Influenza A and B" -- showed no statistically significant differences in the rates of hospitalization, admission to the intensive care unit and mechanical ventilator use between the two groups.

The other unexpected finding was that more patients with COVID-19 than those with seasonal influenza reported fever, cough, diarrhea or vomiting, headache, body ache or chest pain at the time of diagnosis, says Xiaoyan Song, Ph.D., M.Sc., M.B., the study's principal investigator.

"I didn't see this coming when I was thinking about doing the study," says Dr. Song, director of Infection Control and Epidemiology at Children's National since 2007 and a professor of pediatrics at the George Washington University School of Medicine and Health Sciences. "It took several rounds of thinking and combing through the data to convince myself that this was the conclusion."

Given that much remains unknown about COVID-19, the researchers' discovery that children with the disease present with more symptoms at the time of diagnosis is a valuable one.

"It's a good cue from a prevention and planning perspective," says Dr. Song. "We always emphasize early recognition and early isolation with COVID. Having a clinical picture in mind will assist clinicians as they diagnose patients with symptoms of the coronavirus."

The study included 315 children who were diagnosed with a laboratory-confirmed COVID-19 between March 25, 2020, and May 15, 2020, and 1,402 children who were diagnosed with a laboratory-confirmed seasonal influenza between Oct. 1, 2019, and June 6, 2020, at Children's National. Asymptomatic patients who tested positive for COVID-19 during pre-admission or pre-procedural screening were excluded from the study.

Of the 315 patients who tested positive for COVID-19, 52% were male, with a median age of 8.4 years. Of these patients, 54 (17.1 %) were hospitalized, including 18 (5.7%) who were admitted to the intensive care unit (ICU) and 10 (3.2%) who received mechanical ventilator treatment.

Among the 1,402 patients who tested positive for influenza A or B, 52% were male, with a median age of 3.9 years, and 291 (21.2%) were hospitalized, including 143 for influenza A and 148 for influenza B. Ninety-eight patients (7.0%) were admitted to the ICU, and 27 (1.9%) received mechanical ventilator support.

The study showed a slight difference in the age of children hospitalized with COVID-19 compared to those hospitalized with seasonal influenza. Patients hospitalized with COVID-19 had a median age of 9.7 years vs. those hospitalized with seasonal influenza who had a median age of 4.2 years.

In both groups, fever was the most often reported symptom at the time of diagnosis followed by cough. A greater proportion of patients hospitalized with COVID-19 than those hospitalized with seasonal influenza reported fever (76% vs. 55%), cough (48% vs. 31%), diarrhea or vomiting (26% vs. 12%), headache (11% vs. 3%), body ache/myalgia (22% vs. 7%), and chest pain (11% vs. 3%).

More patients hospitalized with COVID-19 than those with seasonal influenza reported sore throat or congestion (22% vs. 20%) and shortness of breath (30% vs. 20%), but the differences were not statistically significant.

During the study period, the researchers noticed an abrupt decline of influenza cases at Children's National after local schools closed in mid-March and stay-at-home orders were implemented about two weeks later to combat the community spread of COVID-19. Dr. Song says the impact of school closures on the spread of COVID-19 among children is the next area of study for her research team.

"We want to assess the quantitative impact of school closures so we can determine at what point the cost of closing schools and staying at home outweighs the benefit of reducing transmission of COVID-19 and burdens on the health care system," she says.

Dr. Song urges members of the community "first and foremost to stay calm and be strong. We're learning new and valuable things about this virus each day, which in turn improves care. The collision of the flu and COVID-19 this fall could mean an increase in pediatric hospitalizations. That's why it's important to get your flu shot, because it can help take at least one respiratory virus out of circulation."

What The Study Did: Anonymous mobile phone location data were used to examine travel and home dwelling time patterns before and after enactment of stay-at-home orders in U.S. states to examine associations between changes in mobility and the COVID-19 curve.

Authors: Song Gao, Ph.D., and Jonathan A. Patz, M.D., of the University of Wisconsin in Madison, are the corresponding authors.

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

(doi:10.1001/jamanetworkopen.2020.20485)

Editor's Note: The article includes conflict of interest and 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.

Parents might be familiar with their toddlers gotten messy with flour. Feeling the soft texture of flour, kids can spend the whole time and create, explore and learn through the messy play. Such tactile sensory play is an effective stimulus for children's senses as the tactile system includes the entire network of skin. Thalamus in the brain is where general sensory inputs are filtered in and out, yet it has remained elusive as to what specific mechanism fine-tunes the sense of touch.

Led by Dr. C. Justin Lee at the Center for Cognition and Sociality within the Institute for Basic Science (IBS) in Daejeon, South Korea, and Dr. CHEONG Eunji at Yonsei University, the joint research team has revealed the production pathway of the sense of touch. They found that the persistent regulation (tonic) of γ-aminobutyric acid (GABA), which is the main inhibitory transmitter in the astrocytes (star-shaped cells), generates the sense of touch. "Contrary to the conventional assumption, thalamic astrocytes were found to synthesize GABA using an enzyme called diamine oxidase (DAO), rather than MAOB, previously known as a GABA-producing enzyme in cerebellar astrocytes," says KOH Wuhyun, first author of the study. The research team also found that the production of GABA is completed by an enzyme called Aldh1a1. The team confirmed that the GABA produced is released through Best1 channel in astrocytes. They also experimentally proved that astrocytic tonic GABA in the thalamus controls our brain's acuity to make sense of touch.

The study reports a rather surprise finding as to how GABA works to control the tactile sense. GABA, known for its inhibitory function, actually enhances the sensory input processing by accelerating the signal processing and sharpening the sensitivity of signal magnitude. "The brain cannot accurately distinguish saturated neuronal signals. It is like that too much exposure to light results in an overly bright photo. GABA's inhibitory action removes extreme values of signals and accentuates the information of each signal. This fine-tuning helps neurons to be more sensible to various range of signals," explains Koh.

In behavioral experiments, the research team verified that tonic GABA dynamically controls tactile discrimination. They used sandpaper with various grits; the smaller the grit number the more coarse the particles, the larger the number the more fine. Its tactile-based novel object recognition test showed that astrocytic knockdown models of Best1, DAO, and Aldh1a1 reported a significantly lower discrimination ability compared to the control group. The team also confirmed the effect of enhancement of tonic GABA: Overly-charged models demonstrated a greatly enhanced ability of discrimination. They were able to notify relatively small change of textile, (?80). Normal models usually recognize a difference of ?180 or more.

Co-corresponding author, Dr. CHEONG Eunji states, "Detecting a small change of the surroundings marks the beginning of our cognitive function. This study uncovered a novel mechanism of manipulating sensory acuity, offering a breakthrough for the study of sensory and cognitive functions."

"This is the first example of how the astrocytes in the thalamus actively participate in important cognitive processes, such as sensory discrimination. Astrocytes "shine" in the brain to actively engage in cognitive functions, just as the stars in the night sky." notes Dr. C. Justin Lee, co-corresponding author.

One of the biggest scientific advances of the last decade is getting better thanks to researchers at The University of Texas at Austin; the University of California, Berkeley; and Korea University. The team has developed a new tool to help scientists choose the best available gene-editing option for a given job, making the technology called CRISPR safer, cheaper and more efficient. The tool is outlined in a paper out today in Nature Biotechnology.

The CRISPR gene-editing technique holds tremendous potential to improve human health, agriculture and the future of people on the planet, but the challenge lies in the delicate nature of gene editing -- there is almost no room for error.

To edit genes, scientists use dozens of different enzymes from a naturally occurring system called CRISPR. Researchers locate a problematic DNA sequence and use these specialized enzymes to snip it as if using a pair of scissors, allowing genetic material to be added, removed or altered. But these scissors are not perfect. Accuracy and effectiveness vary by the CRISPR enzyme and the project. The new tool guides users, so they can pick the best CRISPR enzyme for their high-stakes gene edit.

"We designed a new method that tests the specificity of these different CRISPR enzymes -- how precise they are -- robustly against any changes to the DNA sequence that could misdirect them, and in a cleaner way than has ever been done before," said Steve Jones, a UT research scientist who co-wrote the paper with Ilya Finkelstein, an associate professor of molecular biosciences.

Problems can occur when a CRISPR enzyme targets the wrong sections of DNA. Each CRISPR enzyme has strengths and weaknesses in editing different sequences, so the researchers set out to create a tool to help scientists compare the different enzymes and find the best one for a given job.

"CRISPR wasn't designed in a lab. It wasn't made by humans for humans. It was made by bacteria to defend against viruses," said John Hawkins, a Ph.D. alumnus who was recently with UT's Oden Institute for Computational Engineering and Sciences. "There is incredible potential for its use in medicine, but the first rule of medicine is 'do no harm.' Our work is trying to make CRISPR safer."

The team of researchers developed a library of DNA sequences and measured how accurate each CRISPR enzyme was, how long it took the enzyme to edit the sequences and how precisely they edited the sequence. For some tasks the commonly used enzyme CRISPR-Cas9 worked best; in others, different enzymes performed much better.

"It's like a standardized test," Hawkins said. "Every student gets the same test, and now you have a benchmark to compare them."

The tool allows scientists to choose the best enzyme for editing on the first try, so the process becomes more efficient and cheaper. Additionally, it gives scientists information about where mistakes are most likely to occur for each enzyme, saving time.

"This technique gives us a new way to reduce risk," Jones said. "It allows gene edits to be more predictable."

A global analysis reveals for the first time that across almost all tree species, fast growing trees have shorter lifespans. This international study further calls into question predictions that greater tree growth means greater carbon storage in forests in the long term.

Currently, forests absorb large amounts of carbon dioxide (CO2) from the atmosphere. This is thought to be due to higher temperatures and abundant CO2 stimulating growth in trees, allowing them to absorb more CO2 as they grow.

Most earth system models predict that this growth stimulation will continue to cause a net carbon uptake of forests this century. But, the study, led by the University of Leeds and published today in Nature Communications, casts doubts on these predictions.

The international study is the largest to date looking at the relationship between tree growth and tree lifespan. The researchers examined more than 200 thousand tree-ring records from 82 tree species from sites across the globe.

It confirms that accelerated growth results in shorter tree lifespans, and that growth-lifespan trade-offs are indeed near universal, occurring across almost all tree species and climates.
This suggests that increases in forest carbon stocks may be short lived.

Lead author of the study, Dr Roel Brienen from the School of Geography at Leeds, said: "While it has been known for a long time that fast-growing trees live shorter, so far this was only shown for a few species and at a few sites.

"We started a global analysis and were surprised to find that these trade-offs are incredibly common. It occurred in almost all species we looked at, including tropical trees.

"Our modelling results suggest there is likely to be a time lag before we see the worst of the potential loss of carbon stocks from increases in tree mortality. They estimate that global increases in tree death don't kick in until after sites show accelerated growth.

"This is consistent with observations of increased tree death trends across the globe. For example, previous Leeds research has shown long-term increases in tree mortality rates lagging behind tree growth increases in the Amazon forest."

Co-author Prof Manuel Gloor, also from the School of Geography, said: "Earth system models often do not, or cannot by design, take into account this negative feedback, and model projections of the global forest carbon sink persistence are thus likely inaccurate and too optimistic. Our findings imply that a much reduced future forest carbon sink further increases the urgency to curb greenhouse emissions."

The trade-off may be due to environmental variables affecting tree growth and lifespan. For example, co-author, Dr Alfredo Di Filippo from Tuscia University, Italy previously reported that lifespan of beech trees in the Northern Hemisphere decreases by roughly 30 years for each degree of warming.

The current analysis confirms that, across biomes, reductions in lifespan are not due directly to temperature per se, but are a result of faster growth at warmer temperatures.

Their findings suggests that a prominent cause of the widespread occurrence of a growth lifespan trade-off is that chances of dying increase dramatically as trees reach their maximum potential tree size.

Nonetheless, other factors may still play a role as well. For example, trees that grow fast may invest less in defences against diseases or insect attacks, and may make wood of lower density or with water transport systems more vulnerable to drought.

Study co-author Dr Steve Voelker, from the Department of Environmental and Forest Biology, Syracuse, New York, said: "Our findings, very much like the story of the tortoise and the hare, indicate that there are traits within the fastest growing trees that make them vulnerable, whereas slower growing trees have traits that allow them to persist.

"Our society has benefitted in recent decades from the ability of forests to increasingly store carbon and reduce the rate at which CO2 has accumulated in our atmosphere. However, carbon uptake rates of forests are likely to be on the wane as slow-growing and persistent trees are supplanted by fast-growing but vulnerable trees."