Culture

Converting solar energy to hydrogen fuel, with help from photosynthesis

WASHINGTON, Aug. 17, 2020 -- Global economic growth comes with increasing demand for energy, but stepping up energy production can be challenging. Recently, scientists have achieved record efficiency for solar-to-fuel conversion, and now they want to incorporate the machinery of photosynthesis to push it further.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

"We want to fabricate a photocatalytic system that uses sunlight to drive chemical reactions of environmental importance," says Lilac Amirav, Ph.D., the project's principal investigator.

Specifically, her group at the Israel Institute of Technology is designing a photocatalyst that can break down water into hydrogen fuel. "When we place our rod-shaped nanoparticles in water and shine light on them, they generate positive and negative electric charges," Amirav says. "The water molecules break; the negative charges produce hydrogen (reduction), and the positive charges produce oxygen (oxidation). The two reactions, involving the positive and negative charges, must take place simultaneously. Without taking advantage of the positive charges, the negative charges cannot be routed to produce the desired hydrogen."

If the positive and negative charges, which are attracted to one another, manage to recombine, they cancel each other, and the energy is lost. So, to make sure the charges are far enough apart, the team has built unique heterostructures comprised of a combination of different semiconductors, together with metal and metal oxide catalysts. Using a model system, they studied the reduction and oxidation reactions separately and altered the heterostructure to optimize fuel production.

In 2016, the team designed a heterostructure with a spherical cadmium-selenide quantum dot embedded within a rod-shaped piece of cadmium sulfide. A platinum metallic particle was located at the tip. The cadmium-selenide particle attracted positive charges, while negative charges accumulated on the tip. "By adjusting the size of the quantum dot and the length of the rod, as well as other parameters, we achieved 100% conversion of sunlight to hydrogen from water reduction," Amirav says. A single photocatalyst nanoparticle can produce 360,000 molecules of hydrogen per hour, she notes.

The group published their results in the ACS journal Nano Letters. But in these experiments, they studied only half of the reaction (the reduction). For proper function, the photocatalytic system must support both reduction and oxidation reactions. "We were not converting solar energy into fuel yet," Amirav says. "We still needed an oxidation reaction that would continually provide electrons to the quantum dot." The water oxidation reaction occurs in a multi-step process, and as a result remains a significant challenge. In addition, its byproducts seem to compromise the stability of the semiconductor.

Together with collaborators, the group explored a new approach -- looking for different compounds that could be oxidized in lieu of water -- which led them to benzylamine. The researchers found that they could produce hydrogen from water, while simultaneously transforming benzylamine to benzaldehyde. "With this research, we have transformed the process from photocatalysis to photosynthesis, that is, genuine conversion of solar energy into fuel," Amirav says. The photocatalytic system performs true conversion of solar power into storable chemical bonds, with a maximum of 4.2% solar-to-chemical energy conversion efficiency. "This figure establishes a new world record in the field of photocatalysis, and doubles the previous record," she notes. "The U.S. Department of Energy defined 5-10% as the 'practical feasibility threshold' for generating hydrogen through photocatalysis. Hence, we are on the doorstep of economically viable solar-to-hydrogen conversion."

These impressive results have motivated the researchers to see if there are other compounds with high solar-to-chemical conversions. To do so, the team is using artificial intelligence. Through a collaboration, the researchers are developing an algorithm to search chemical structures for an ideal fuel-producing compound. In addition, they are investigating ways to improve their photosystem, and one way might be to draw inspiration from nature. A protein complex in plant cell membranes that comprises the electrical circuitry of photosynthesis was successfully combined with nanoparticles. Amirav says that this artificial system so far has proven fruitful, supporting water oxidation while providing photocurrent than is 100 times larger than that produced by other similar systems.

Credit: 
American Chemical Society

New practice guidelines on non-invasive ventilation in chronic stable Hypercapnic COPD

image: New ATS clinical practice guidelines on treating hypercapnia in COPD patients published.

Image: 
ATS

August 17, 2020 -- A subcommittee of the American Thoracic Society Assembly in Sleep and Respiratory Neurobiology has released new clinical practice guidelinesto help advise clinicians on the optimal management of patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. Hypercapnia is the buildup of carbon dioxide in the bloodstream. The guidelines, published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine, is titled "Long-Term Non-Invasive Ventilation in Chronic Stable Hypercapnic Chronic Obstructive Pulmonary Disease: An Official American Thoracic Society Guideline."

The committee, comprised of leading clinicians working in pulmonary and critical care medicine, as well as patient representatives, developed a consensus approach and summarized evidence for addressing five PICO (patients, intervention, comparator, outcome) questions related to non-invasive ventilation (NIV) for chronic hypercapnic COPD. Recommendations were formulated by the panel of pulmonary and sleep physicians, respiratory therapists and methodologists using the Evidence-to-Decision framework, a systematic and transparent approach to groups making well-informed health care recommendations.

While NIV is used for patients with COPD and chronic hypercapnia, up to this point, evidence for clinical efficacy and optimal management of therapy have been limited.

"This guideline is needed because patients with severe COPD are very sick and have few therapies that have been shown to improve outcomes," said guideline Chair Robert L. Owens, MD, associate professor, Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego. "Clinicians who care for these patients need information about whether to consider non-invasive ventilation and some practical advice on how to set up patients with NIV."

The group's main recommendations are to:

use nocturnal NIV in addition to usual care of patients with chronic stable hypercapnic COPD;

have patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea (OSA) before initiation of long-term NIV;

avoid initiating long-term NIV during admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution;

avoid the use of in-laboratory overnight polysomnography (PSG) to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV, and

use NIV with targeted normalization of PaCO2 in hypercapnic COPD patients on long-term NIV.

To develop each of the recommendations, the panel reviewed results from numerous randomized clinical trials, and looked at such factors as health equity and availability of pulmonary and critical care specialists in medically underserved areas, as well as the likelihood of patient compliance. Because some or all of these issues may impact each of the recommendations, all recommendations were considered conditional. The group outlined unanswered questions for each recommendation, as well as future research directions. They also examined what other specialty organizations were saying on these issues.

"It is exciting to consider NIV as additional therapy for those with hypercapnic COPD," the authors stated. "However, there are many issues to consider."

Among these issues are: appropriate patient selection; implementation barriers; the need for more data to guide the goals of therapy, especially on how clinicians should target PaCO2; addressing regulatory/payor considerations on the ability to obtain home NIV for COPD, and the potential for worsening health care disparities due to the cost and expertise needed to provide NIV for patients with stable hypercapnic COPD.

Dr. Owens concluded, "This guideline is needed now because studies in the last few years have shown improved outcomes with non-invasive ventilation for patients with severe COPD. The guideline incorporates recent studies, while also highlighting priority areas for research."

Credit: 
American Thoracic Society

New Guidelines for Phage Preparation Can Accelerate Lifesaving Treatment

image: San Diego State University microbiologist Dwayne Roach's phage lab has developed new guidelines to prepare phage that will accelerate the time to therapy while streamlining the process.

Image: 
SDSU Roach Lab

When clinicians resort to phage therapy for patients who don't respond to antibiotics, the patients are usually very ill and time is of the essence. But the average time for labs to produce therapeutic phages is more than a month.

The main reason for this is the lack of a standardized phage purification process for research labs, despite the fact that phage therapy -- which uses viruses to destroy disease causing bacteria -- has been around for over a century.

Now, a San Diego State University lab that produces phage therapeutics for clinicians across the country for compassionate use has developed standardized guidelines intended to not only streamline the process using existing lab equipment, but also shorten it to two to three weeks, cutting the typical processing time by half.

"Many of our patients have so little time, so speed is of the essence and this protocol would really make a difference, since one run can produce enough doses to treat a patient for months," said Dwayne Roach, the Conrad Prebys chair of virology and assistant professor at SDSU.

The protocol, he said, combines traditional techniques with modern filtration technology to produce higher phage yields and reduce endotoxin levels compared to previously developed methods.

The open source guidelines were published in a paper in Nature Protocols in July.

Bacteriophages and phage therapy

Typical candidates for phage therapy are patients who have multi-drug resistant bacteria, a more and more common fallout of overusing antibiotics. Phage is short for bacteriophage, which literally means "bacteria eater." They are viruses that only attack bacteria, not people, and are found in soil, water and sewage, requiring them to be purified before use.

Phage therapy is not approved yet in the United States and Europe, except on a case-by-case basis under compassionate use. The military is also interested in phage therapy for the battlefield, where it could be used as a sterilizing wash to remove bacteria from wounds.

Since this is still an emerging field, labs take varying approaches to phage purification. The protocols developed by the SDSU researchers are straightforward, and use simple, standard microbiology lab equipment to remain affordable. They are suitable even for labs in countries with limited resources that wish to ramp up phage production.

Lack of protocols a key bottleneck

Since Roach's lab has a library of phages on hand, much of the back-end work of collecting and cultivating them has already been completed. The protocols allow his team to supply clinicians with the best-fit phages in as little as a week.

"Our protocol provides a standard of production for medicinal phages that consistently provides potentially thousands of phage treatment doses," said Tiffany Luong, first author and a doctoral student in Roach's lab. "We provide instruction and rationale for each step in our process which allows the user to tailor the procedure to their specific equipment and bacterial species."

Identifying groups of phages that are effective against multi-drug resistant bacteria has become easier over the years.

But Dr. Robert 'Chip' Schooley, director of the Center for Innovative Phage Applications and Therapeutics at the University of California San Diego, said however that the absence of rigorous, scalable approaches for producing therapeutic phages in academic laboratories and delivering them to the patient's bedside is a major bottleneck.

"Dr. Roach's protocol guidelines are an outstanding example of the rigor required to safely take phages into the clinic," Schooley said. "These guidelines will be of great interest to other academic laboratories and to regulatory agencies as we move into the next phases of phage therapeutics."

Reducing endotoxins

When Roach's team began working with physicians in spring 2019, they had to figure out how to streamline the process. By scrutinizing each step and comparing different methods, the team identified cross-flow filtration -- when the flow travels across the surface of the filter instead of into it -- as the most efficient and effective purification method, and Roach presented the results and accelerated timeline at a conference later in the year.

While Roach and Luong looked at process optimization, Ann-Charlott Salabarria, a postdoctoral researcher, worked on setting parameters for ensuring safety of the end product with multiple tests, including confirming that endotoxin levels met U.S. Food and Drug Administration (FDA) guidelines.

One of the FDA's major concerns with phage products is its endotoxin levels, which can harm patients and need to be removed as part of the purification process. The published protocol will help ensure the phage products are safe above and beyond the FDA minimum requirements, Roach explained.

"Our tests do validate that this process removes almost all endotoxins and exotoxins," Roach said. "We wanted to publish our protocol as a resource for other labs because purification has been very time consuming, taking away time from research."

Phage strain selection is another important aspect to developing phage therapeutics. To screen out unwanted genes in phage genomes, Roach enlisted the help of SDSU microbial geneticist and bioinformatics expert Robert Edwards.

"Phage genomes contain so many different components and may mobilize other toxins or antibiotic resistance genes," Edwards said. "It is absolutely imperative that we understand these viruses at the molecular level to ensure that we are not introducing anything potentially harmful into already ill patients."

The researchers will continue to focus on improving safety in phage therapy, by testing it on tissue and mice cell cultures.

"We hope this protocol will allow more research labs to participate in re-introducing phages to Western medicine," Luong said.

Credit: 
San Diego State University

Gender parity & heart failure research: Female authors could mean more female participants

PHILADELPHIA-- While about a quarter of physicians and researchers working in advanced heart failure (HF) and transplant cardiology are women, representation of women leading HF research remains limited, according to new research led by Penn Medicine. The authors say the findings point to a need to support great gender diversity among researchers to drive diversity among clinical trial participants and even improve patient outcomes. The analysis, published this month in Circulation: Heart Failure, showed that that less than 20 percent of first authors on manuscripts cited to support the highest recommendations in HF treatment guidelines were women, and less than 15 percent of the senior authors were women. Furthermore, only 16 percent of contemporary clinical trials in HF had a woman as a first or senior author. The research is the first of its kind to explore gender disparities in authorship of HF guideline citations and clinical trials.

Despite this lack of representation in authorship, researchers found that clinical trials with higher proportions of women authors had a higher number of female participants--aligning with a longstanding priority from federal organizations to increase the enrollment of women in clinical trials.

"Diversity in authorship can have a snowball effect across the field--not only in improving gender equity in cardiovascular medicine, but also perhaps in reducing the underrepresentation of women in clinical trials," said Nosheen Reza, MD, the study's lead author, an instructor of Cardiovascular Medicine, and advanced HF and transplant cardiologist in the Perelman School of Medicine at the University of Pennsylvania. "For many reasons, institutions are now taking a hard look at improving diversity, inclusion, and equity, and our findings represent benchmarking data that organizations can utilize and build from."

The researchers identified authors of publications referenced in so-called class I recommendations--representing the strongest clinical guidelines and recommendations--in the United States (173) and European HF guidelines (100), and of publications of HF trials with more than 400 participants published between 2001 and 2016 (118). After authors' genders were determined by using a multinational database and name matching algorithm, the researchers evaluated the authorship patterns--with a focus on those who led the research for each paper--over time.

On average, the overall proportions of women as first authors of referenced publications in the United States HF guidelines was 18 percent and 16 percent for European HF guidelines, and as last authors 13 percent and 12 percent, respectively. From 1986 to 2016, the percentage of women authorship modestly increased overall in guideline citations.

The proportions of women as first or last authors in HF clinical trials did not change significantly over time, and only 16 percent of the HF clinical trials examined had a woman as a first or senior author. However, HF trials with a woman first or senior author were associated with a higher proportion of enrolled female clinical trial participants (39 percent versus 26 percent).

"While the reasoning behind this interesting phenomenon is still unknown, it's clear representation is an important element for improving care for women," Reza said. "One hypothesis we have for this finding is that women may be more likely to enroll as participants in clinical trials that they know are being conducted by women investigators. Another possibility could be that women investigators are more likely to refer women patients for enrollment in clinical trials. This is certainly an area in which future research is needed."

The authors call for efforts to rectify these disparities, especially since women authorship of HF clinical trials is an important predictor of the enrollment of female participants, which may help to reduce the underrepresentation of women in HF clinical trials.

"Institutions must come together to make a committed effort to improve diversity, inclusion, and equity on promotions committees, editorial boards, steering committees, and other leadership bodies in the HF research enterprise. Women will not overcome these hurdles if these metrics and efforts don't change. By advocating for broad scale efforts in these domains, such as including more women in leadership positions and increasing the mentorship of women across career stages in medicine, we'll be able to develop future generations of experienced and accomplished women investigators and mentors in HF, and advance science together without leaving anyone behind," Reza said.

Co-authors include Ayman Samman Tahhan, Penn's Nadim Mahmud, Ersilia M. DeFilippis, Alaaeddin Alrohaibani, Muthiah Vaduganathan, Stephen J. Greene, Annie Hang Ho, Gregg C. Fonarow, Javed Butler, Christopher O'Connor, Mona Fiuzat, Orly Vardeny, Ileana L. Piña, JoAnn Lindenfeld, Mariell Jessup.

Credit: 
University of Pennsylvania School of Medicine

Nitrate supplementation could help breathing and lung clearance in the elderly

New research published today in
The Journal of Physiology shows that nitrate improves function in the diaphragm, the muscle involved in coughing and breathing, by improving power. The study done in old mice, if replicated in humans, could provide a strategy for helping elderly people clear the lungs more effectively and avoid infection.

Previous studies showed nitrate was helping muscles by improving use of calcium in the muscle. This finding that it's additionally affecting power is significant, especially in the context of COVID-19, because the diaphragm is the primary inspiratory muscle used for breathing and coughing, the latter being relevant for clearing the lungs.

The research team at the University of Florida found that dietary nitrate supplementation elicited a pronounced increase in contractile function (power) of the diaphragm, a respiratory muscle, of old mice.

They made their measurements during maximal activation, so the effects observed seem to be caused by an improvement in the function of contractile proteins rather than calcium handling.

Few short-term interventions have such a profound impact on muscle contractile function, as was observed in this study.

Dietary nitrate is readily available for humans and could be used, under proper supervision, to improve respiratory muscle dysfunction that contributes to shortness of breath and morbidity in the elderly.

The researchers gave sodium nitrate to old mice in their drinking water daily for 14 days. The control group received regular water. Diaphragm muscle contractile function cannot be assessed directly in live animals or humans. Thus, they tested diaphragm function in muscle tissues under controlled conditions for muscle stimulation and oxygenation.

The main limitations are that mouse and human diaphragm have different percentages of fast and slow muscle cells. Mouse diaphragm consists of 90% fast muscle cells; the human diaphragm consists of 25-50% fast muscle cells depending on several factors that include and age and sex.

Dietary nitrate seems to exert a greater impact on the contractile function of fast muscle cells. Thus, the benefits to the human diaphragm may not as pronounced as was observed in mice. They also only tested male mice, and the benefits for females is unknown.

Leonardo Ferreira, senior author on the study said:

"Our findings are especially important in light of the current COVID-19 pandemic as they suggest that, if replicated in humans, dietary nitrate is useful to improve respiratory muscle dysfunction that contributes to difficulty in weaning patients from mechanical ventilation."

Credit: 
The Physiological Society

How power distance belief affects consumers' price sensitivity

Researchers from Indiana University and Miami University-Ohio published a new paper in the Journal of Marketing that examines how power distance belief affects consumers' price sensitivity.

The study forthcoming in the Journal of Marketing is titled "Price No Object!: The Impact of Power Distance Belief on Consumers' Price Sensitivity" and is authored by Hyejin Lee, Ashok Lalwani, and Jessie Wang.

Most marketers dream of being able to charge high prices for their products. However, few can do so without spending vast sums to enhance perceptions of value (e.g., by improving product benefits). Consequently, marketers continuously strive to identify and target consumer segments that are less price-sensitive because these consumers are more likely to find price increases palatable.

A new study in the Journal of Marketing identifies a cultural variable, namely power distance belief (PDB)--the extent to which people accept and endorse hierarchy--as an important determinant of consumers' price sensitivity. Across multiple studies, the researchers find that consumers high (vs. low) in PDB are less price-sensitive. Lee explains that "These consumers have a higher need for closure (NFC), which increases their tendency to 'seize and freeze' on a current offer and reduces their likelihood of searching for better priced options, thereby reducing price sensitivity."

Study 1a provides evidence of the negative relationship between PDB and price sensitivity using A.C. Nielsen scanner panel data.

Study 1b provides convergent evidence for external validity using a consequential measure to assess consumers' actual purchasing behavior driven by their price sensitivity.

Study 1c provides evidence of the relationship via a field study at a small local grocery store.

Study 2a directly assesses the mediating role of the need for closure and rules out other cultural variables and all alternative explanations.

Study 2b provides evidence for serial mediation through need for closure (mediator 1) and price search tendency (mediator 2) using four different established measures of price sensitivity.

The last study reveals that a high social density reduces the price sensitivity of low (but not high) PDB consumers. The effect is independent of numerous psychological (e.g., risk aversion, perceptions of self-efficacy, sacrifice mindset, need for status, self-regulation), cultural (e.g., uncertainty avoidance, long-term orientation, masculinity, interdependence), and demographic (income, occupation, education, household size, type of residence) variables.

Thus, low PDB consumers are identified as the roadblocks for marketers who seek to raise prices. To meet this challenge, the study offers several strategies, including: (1) targeting consumer segments high (vs. low) in PDB, (2) activating a high PDB via ads, slogans, or POP material, (3) heightening the need for closure using contextual cues, and (4) increasing social density in stores.

Credit: 
American Marketing Association

Targeting the LANDO pathway holds a potential clue to treating Alzheimer's disease

image: Bradlee Heckmann, Ph.D., of St. Jude Immunology

Image: 
St. Jude Children's Research Hospital

Scientists at St. Jude Children's Research Hospital are advancing understanding of a potential Alzheimer's disease treatment. The work focuses on LC3-associated endocytosis (LANDO) and its role in neuroinflammation. The results appeared as an advance online publication today in Science Advances.

The researchers previously discovered the LANDO pathway in microglial cells, the primary immune cells of the brain and central nervous system. Scientists found that when genes required for this pathway are deleted, Alzheimer's disease progression accelerates in a mouse model. The investigators also showed that LANDO protects against neuroinflammation, one of the hallmarks of Alzheimer's disease.

While continuing to investigate LANDO, the researchers identified a novel function of the protein ATG16L. This protein is critical for autophagy, the normal process by which a cell recycles its components during periods of stress or energy deprivation. While ATG16L is important for autophagy, it can also play a role in LANDO. The investigators found that if a region of ATG16L called the WD domain is deleted, LANDO is inhibited while autophagy continues.

"We learned about this pathway in the context of brain tumor research, but it has major implications for neuroinflammatory and neurodegenerative disease," said senior author Douglas Green, Ph.D., chair of the St. Jude Immunology Department. "We've shown that deficiency in LANDO, combined with aging, can lead to Alzheimer's disease in a unique mouse model, and there is evidence suggesting that this could also be the case in humans."

A model for Alzheimer's disease research

Most mouse models used in Alzheimer's disease research rely on making genetic changes to recreate the disease. For this work, researchers used a new model with a specific deficiency of just the WD domain of ATG16L. This means the model carries out autophagy normally but lacks the LANDO pathway. By the time the mice are 2 years old, they exhibit symptoms and pathology that mimic human Alzheimer's disease. This spontaneous age-associated model of Alzheimer's disease is the first created by deleting a single protein domain (WD on ATG16L), not previously associated with Alzheimer's disease.

The researchers also analyzed human Alzheimer's disease tissue samples, looking at the expression of proteins that regulate LANDO, including ATG16L. Expression of these proteins is decreased by more than 50% in people with Alzheimer's disease. This finding shows a correlation between how deficiency in LANDO combined with aging may lead to Alzheimer's disease in the mouse model and in humans.

A strategy for treatment emerges

Reducing neuroinflammation has been proposed as a potential way to treat Alzheimer's disease. To treat their new mouse model, researchers used a compound that inhibits the inflammasome - a complex of proteins that activates pro-inflammatory immune reactions. The scientists targeted the inflammasome responsible for neuroinflammation in people with Alzheimer's disease. Researchers profiled the model's behavior and found evidence of improved cognition and memory in addition to a decrease in neuroinflammation.

"This work solidifies LC3-associated endocytosis as a pathway that prevents inflammation and inflammatory cytokine production in the central nervous system," said first author Bradlee Heckmann, Ph.D., of St. Jude Immunology. "While much of the data on LANDO suggests a significant role in neuroinflammatory and neurodegenerative diseases, there is also a strong possibility that it could be targeted as a therapy against cancer or even infectious diseases that rely on similar processes for survival."

Credit: 
St. Jude Children's Research Hospital

Cardiovascular risk factors tied to COVID-19 complications and death

image: Cardiovascular risk profile of hospitalized COVID-19 patients.
Each line represents the result of the meta-analysis for a single endpoint. The square represents the summary effect size (proportion) and the horizontal line the relative 95% Confidence Interval.

Image: 
Sabatino et al, 2020 (PLOS ONE, CC BY 4.0)

COVID-19 patients with cardiovascular comorbidities or risk factors are more likely to develop cardiovascular complications while hospitalized, and more likely to die from COVID-19 infection, according to a new study published August 14, 2020 in the open-access journal PLOS ONE by Jolanda Sabatino of Universita degli Studi Magna Graecia di Catanzaro, Italy, and colleagues.

For most people, the Novel Coronavirus Disease 2019 (COVID-19) causes mild illness, however it can generate severe pneumonia and lead to death in others. It is crucial for clinicians working with cardiovascular patients to understand the clinical presentation and risk factors for COVID-19 infection in this group.

In the new study, researchers analyzed data from 21 published observational studies on a total of 77,317 hospitalized COVID-19 patients in Asia, Europe and the United States. At the time they were admitted to the hospital, 12.89% (95% CI 8.24-18.32) of the patients had cardiovascular comorbidities, 36.08% (95% CI 20.25-53.64) had hypertension and 19.45% (95% CI 12.55-27.45) had diabetes.

Cardiovascular complications were documented during the hospital stay of 14.09% (95% CI 10.26-20.23) of the COVID-19 patients. The most common of these complications were arrhythmias or palpitations; significant numbers of patients also had myocardial injury. When the researchers analyzed the data, they found that pre-existing cardiovascular comorbidities or risk factors were significant predictors of cardiovascular complications (p=0.019), but age (p=0.197) and gender (p=0.173) were not. Both age and pre-existing cardiovascular comorbidities or risk factors were significant predictors of death.

The authors add: "Cardiovascular complications are frequent among COVID-19 patients and might contribute to adverse clinical events and mortality."

Credit: 
PLOS

Newly identified gut cells nurture lymph capillaries

image: Lacteals (in green) are shown in normal conditions (left) and with YAP/TAZ hyperactivation (right).

Image: 
IBS

You have just enjoyed a delicious summer BBQ. After approximately eight hours, food molecules reach your small intestine, where specialized lymph capillaries, called lacteals, absorb fat nutrients. Lacteals are different from other lymphatics, as they continue to regenerate during adulthood, with a slow, but steady pace. Their unique renewal capacity is still poorly understood.

A team of scientists led by KOH Gou Young at the Center for Vascular Research, within the Institute for Basic Science (IBS, South Korea) have identified new subsets of gut connective cells, which are crucial for lymphatic growth. Their new findings have been reported in the journal Nature Communications.

The walls of the small intestine are covered with fingerlike projections, called villi. Lining these villi, heterogeneous populations of epithelial, immune, vascular, connective and even neural cells co-exist and help the digestive process. Lacteals and blood capillaries run inside the villi and take in different food molecules. The gut environment needs to cope with water secretion and reabsorption (osmotic stress), as well as the repetitive muscular activity that moves food through the intestine. How all these complex mechanisms are harmonized is still a mystery.

The research team was able to place a new piece towards completing this mysterious puzzle. The researchers found that the regulatory proteins YAP/TAZ in villi's connective cells, the intestinal stromal cells, play a role in the growth of nearby lacteals. In mice with an abnormal hyperactivation of YAP/TAZ, the team observed atypical sprouting of lacteals and impaired dietary fat uptake.

"The lacteals in these mice looked like tridents, which is very intriguing, since we did not manipulate the lacteals themselves, but the surrounding cells," says HONG Seon Pyo, first co-author of this study.

The researchers took a step further and discovered that intestinal stromal cells belong to several subtypes, with distinct gene expression and localizations within the villi. Among these subsets, three newly identified populations secrete VEGF-C - an essential molecule for lymphatic growth - upon YAP/TAZ activation. YANG Myung Jin, first co-author of this study, explains, "We were very surprised to see such heterogeneity in a cell population that was considered homogeneous."

Lastly, researchers showed that mechanical force and osmotic stress regulate YAP/TAZ activity in stromal cells. In summary, mechanical stimulation activates YAP/TAZ in the intestinal stromal cells, which in turn release VEGF-C and can account for lacteal growth. CHO Hyunsoo, first co-author of this study notes, "This result implies a crucial link between the physiology of intestinal environment and biological interactions between cell types."

"We are interested in investigating how each newly identified cell type works in healthy and diseased conditions," adds Koh.

Credit: 
Institute for Basic Science

UMD discovers a new role for a well-known molecule as a plant hormone

image: ACC facilitates fertilization. The pollen tubes (stained in blue) fertilize only some of the ovules when there is less ACC. Successful fertilization is seen as blue dots inside the white ovules.

Image: 
Dr. Wangshu Mou

Researchers at the University of Maryland (UMD) have discovered an entirely new role for a well-known plant molecule called ACC, providing the first clear example of ACC acting on its own as a likely plant hormone. Just like in humans and animals, hormones in plants carry messages to signal and trigger essential processes for plant health and functionality, from reproduction to defense. Without these processes, crops can't reproduce and thrive to provide the food we need to feed a growing global population. In a new publication in Nature Communications, researchers show that ACC has a critical role in pollination and seed production by activating proteins similar to those involved in nervous system responses in humans and animals. These findings could not only change textbooks that have previously attributed plant responses to the hormone ethylene instead of ACC, but could also open the door for new research to improve plant health and crop yield.

"There are several novel things about this paper," explains Caren Chang, UMD. "But the main impact is that it introduces a new plant growth regulator or plant hormone, alongside a small handful of other publications. It isn't a newly identified molecule, but it has never been thought of before as a plant hormone, only as the precursor to ethylene."

Chang, a professor in Cell Biology & Molecular Genetics and affiliate professor of Plant Science & Landscape Architecture supported by the Maryland Agricultural Experiment Station (MAES), explains that ethylene is one of the five major plant hormones and has been studied for over a century. It is important for many processes that are vital to plant health and crop production, including fruit ripening, stress responses to flooding and drought, plant disease defenses, germination, and flowering.

"In much of the research, ACC has been used in place of ethylene, knowing that it's a precursor that plants convert into ethylene. This is because ACC is easy to work with in powder form and can even be sprayed on the plant, but working with ethylene is very difficult because it is a gas. So researchers have used ACC for decades in place of ethylene, and the literature would interpret the observed responses as ethylene responses. What our paper shows is that an ACC response is not necessarily an ethylene response. While ethylene is an important plant hormone with its own set of functions, some of these responses that have been attributed to ethylene through ACC may actually be separate ACC responses, acting as a growth regulator or hormone itself."

This finding opens the door for many papers across decades of research, as well as textbooks and future education on plant hormone responses, to be revised in the event that ACC is actually triggering important plant processes previously attributed to ethylene.

According to Chang, the paper also presents advances in plant reproduction. "In the plant reproduction field, there are many steps that are critical in pollination, and one of these steps requires the pollen to reach the ovules to actually produce a seed," says Chang. "Our paper shows that ACC signaling in the ovule is involved in getting the pollen tube to turn and effectively deliver the pollen, which makes it essential for seed production. It's probably the first example showing how the maternal ovule tissue actually helps attract the pollen tube." And this isn't a small effect, Chang stresses. "The seed number pretty much doubles in the presence of ACC. There is potential here to improve the seed number, which can increase food production in certain crops and have an impact on food security long-term."

Led by José Feijó, another professor in Cell Biology & Molecular Genetics and affiliate professor of Plant Science & Landscape Architecture, another major finding of this paper shows clear connections between human, animal, and plant hormone signaling pathways by identifying a potential receptor for ACC activity.

"The most interesting parallel is cell-cell communication," explains Feijó. "Animal glutamate receptors are proteins which are needed for information to jump from one neuron to the next, either through an electric impulse or through calcium signaling, which is essential for things like memory. Problems in the processes mediated by glutamate receptors are known to be related to neurodegeneration and depression."

Chang adds, "These receptors have been found in the human nervous system, and neuroscientists have been studying them for drug development to treat nervous system issues like depression. They found that ACC can actually affect the nervous system in humans. So we decided to look for the same receptors, named glutamate-like receptors (GLRs) in plants, to see if they respond to ACC in plants. We found that ACC can actually affect GLRs in plants as well."

This finding opens an entirely new avenue of research in plant biology and points to similarities in plants and humans that are currently not well understood. "In plants, GLRs all seem to convey functions related to communication, either to bring male and female genes into an egg, or in pathogen or stress alert systems and defenses," says Feijó.

"Emerging trends suggest that GLRs underlie long distance electric signaling through the plant vascular system, where injury to tissues in one leaf inform the whole plant to create nasty substances to deter insects. All these lines seem to point into the existence of electric communication within plant tissues and organs, and that these functions involve GLRs. This is an interesting parallel evolution of a function for glutamate receptors as they evolved to be associated with the animal nervous systems to perform similar functions."

With ACC as a new candidate activating GLRs and all the newly discovered roles it is playing as a plant hormone, Chang and the team are excited about the directions this work can go. "There is still a lot of research to be done to see how this is all happening and can be used in different crops, but all that new research can happen now."

Credit: 
University of Maryland

The flax wilt agent has been sequenced

image: The flax wilt agent has been sequenced

Image: 
Peter the Great St.Petersburg Polytechnic University

Molecular and computational biologists from Peter the Great St. Petersburg Polytechnic University (SPbPU), St. Petersburg State University and Federal Centre for Bast Fiber Crops teamed up to sequence and assemble genome of Fusarium oxysporum f.sp. lini, a highly destructive fungal parasite infecting flax. The results of the study were published in the Molecular Plant-Microbe Interactions.

Fusarium wilt is a nasty but common disease affecting economically important crops such as banana, cotton, flax, canola, melons, onions, potato and tomato. The release of the complete genome sequence is a milestone in comparative genomics studies of fungal parasites; it contributes to the global efforts aimed at elimination of plant disease outbreaks by aiding in engineering of new resistant crops varieties.

Fusarium wilt is a plant disease caused by various species of Fusarium fungi. Botanists and plant scientists are aware of approximately 120 species of the parasite, capable of infecting a wide spectrum of crops, such as tomatoes, cucumbers, melons, cabbages, peas, corn, barley, wheat, and many other plants. This study focuses on detailed characterization of F. oxysporum f.sp. lini which infects flax, a major source of textile fibre, seed and flaxseed (linseed) oil in Russia.

"The pathogen has a remarkable resistance to chemical agents and its spores may persist quite comfortably in soil for years. It is a widely accepted opinion in modern crop science that the most promising approach to fight the infection is to breed new resistant varieties,' says Anastasia Samsonova, Professor at the Centre for Genome Bioinformatics at St Petersburg University. "The host and parasite are engaged in an endless "arms race" to survive. Sooner or later, the flax varieties that are currently commercially cultivated may lose their resistance, succumb to the disease completely and become unprofitable to grow. Naturally, this creates a demand for breeding new resistant crops."

The whole genome chromosome-level assembly of the Fusarium oxysporum f.sp. lini was completed in a joint research effort by scientists from St. Petersburg University, Peter the Great St. Petersburg Polytechnic University, and the Centre for Bast Fiber Crops in Torzhok. "The parasite's genome consists of two components; the stable one, which is almost identical in different Fusariums, and the variable part which is mainly responsible for amazing adaptation of the fungus to various plants." says Alexander Kanapin, Professor at the Centre for Genome Bioinformatics at St Petersburg University. "The chromosome-level assembly of the genome is a significant step towards understanding the parasite evolution and adaptation to a particular host."

"Thanks to recent advances in omics technologies and computational biology, and to our fantastic collaborators at the Centre for Bast Fiber Crops, we generated a high quality data resource for comparative studies of Fusarium pathogenic diversity and molecular mechanisms of interaction between the fungus and the host. This will undoubtedly increase the power of integrative systems genetics analyses and thus contribute to the global efforts aimed at elimination of plant disease outbreaks by aiding in engineering of new resistant crops varieties.", explains Maria Samsonova, Head of the Laboratory for Mathematical Biology and Bioinformatics at Peter the Great St Petersburg Polytechnic University.

Further research will address many important questions left unanswered; the team will try to find a genetic determinants of the fungus "taste". In other words, why certain species "enjoys" melons, while the other one "fancies" tomatoes. Knowing parasite's preferences will help to elucidate specific mechanisms of Fusarium adaptation to different hosts and find genes responsible.

Credit: 
Peter the Great Saint-Petersburg Polytechnic University

Remains of 17th century bishop support neolithic emergence of tuberculosis

image: Portrait of Bishop Peder Jensen Winstrup

Image: 
Orf3us / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)

When Anthropologist Caroline Arcini and her colleagues at the Swedish Natural Historical Museum discovered small calcifications in the extremely well preserved lungs of Bishop Peder Winstrup, they knew more investigation was needed. "We suspected these were remnants of a past lung infection," says Arcini, "and tuberculosis was at the top of our list of candidates. DNA analysis was the best way to prove it."

Up to one quarter of the world's population is suspected to have been exposed to bacteria of the Mycobacterium tuberculosis complex, which cause tuberculosis (TB). Bishop Winstrup would have been one of many to fall ill during the onset of the so-called "White Plague" TB pandemic that ravaged post-medieval Europe. Today, TB is among the most prevalent diseases, accounting for the highest worldwide mortality from a bacterial infection.

The global distribution of TB has led to the prevailing assumption that the pathogen evolved early in human history and reached its global distribution via the hallmark Out of Africa human migrations tens of thousands of years ago, but recent work on ancient TB genomes has stirred up controversy over when this host-pathogen relationship began. In 2014, a team led by scientists from the University of Tübingen and Arizona State University reconstructed three ancient TB genomes from pre-contact South America - not only were the ancient strains unexpectedly related to those circulating in present-day seals, but comparison against a large number of human strains suggested that TB emerged within the last 6000 years. Understandably, skepticism surrounded this new estimate since it was based entirely on ancient genomes that are not representative of the TB strains associated with humans today.

"Discovery of the Bishop's lung calcification gave us the opportunity to revisit the question of tuberculosis emergence with data from an ancient European," comments Kirsten Bos, group leader for Molecular Paleopathology at the Max Planck Institute for the Science of Human History (MPI-SHH), who co-led the study. "If we could reconstruct a TB genome from Bishop Winstrup, where we know his date of death to the day, it would give a secure and independent calibration for our estimates of how old TB, as we know it, actually is."

The highest quality ancient TB genome to date

In a new study published this week in Genome Biology, Susanna Sabin of MPI-SHH and colleagues reconstruct a tuberculosis genome from the calcified nodule discovered in Bishop Winstrup's remains.

"The genome is of incredible quality - preservation on this scale is extremely rare in ancient DNA," comments Bos.

Together with a handful of tuberculosis genomes from other work, the researchers revisit the question of the age of the Mycobacterium tuberculosis complex, with the year of the Bishop's death as a fine-tuned calibration point. Using multiple molecular dating models, all angles indeed point to a relatively young age of the Mycobacterium tuberculosis complex.

"A more recent emergence of the tuberculosis pathogen complex is now supported by genetic evidence from multiple geographic regions and time periods," comments Sabin, first author of the study. "It's the strongest evidence available to date for this emergence having been a Neolithic phenomenon."

This most recent shift in the narrative for when bacteria in the Mycobacterium tuberculosis complex became highly infectious to humans raises further questions about the context of its emergence, as it appears to have coincided with the rise of pastoralism and sedentary lifestyles.

"The Neolithic transition seems to have played an important role for the emergence of a number of human pathogens," comments Denise Kühnert, group leader for disease transmission research at MPI-SHH who co-led the investigation.

"For TB in particular, stronger evidence could only come from an older genome, though these deeper time periods are unlikely to yield preservation on the scale of what we've seen for Bishop Winstrup," adds Bos.

"Moving forward," Sabin further comments, "the hope is we will find adequately preserved DNA from time periods close to the emergence of the complex, or perhaps from its ancestor."

Credit: 
Max Planck Institute of Geoanthropology

Organic chemistry -- a brilliant tool

An international team led by the chemist Heinz Langhals of LMU Munich succeeded in molecular deflection of light radiation by means of Diamantane. Novel applications such as efficient light collectors or broadband light absorbers are promising.

Diamantane, the second smallest and thus molecular diamond, is a highly fascinating material for chemists. It can be applied as rigid spacer and stiff pillar in molecular architectures so that optically functional units can be three-dimensionally arranged in well-defined larger assemblies. Noteworthy is: The diamond allows the vibration-mediated transmission of optical energy in light-collecting systems in spite of his firmness; this proceeds according to a mechanism that was recently discovered by an international group of researchers led by the chemist Heinz Langhals of LMU Munich, in which slow molecular bending vibrations play the key role.

The work refers to an international co-operation. Researchers at the University of Stanford isolated the preparatively only laboriously accessible Diamantane efficiently from crude oil. Chemists in Taipei were responsible for the targeted functionalization. The researchers at the LMU Munich constructed the optical functional unit from adapted components. The newly found mechanism of energy transfer in such units causes consequences in physics because it requires a correction and extension of the theory of FRET where the familiar dipole interaction for the energy transfer is disproved as the exclusive mechanism and slow molecular vibronic processes have to be considered. On the other hand, this allows a 90° deflection of light simulating a 45° oriented molecular mirror useful for optical devices such as solar light-collecting systems where the high stability and rigidity of diamondoid spacers mean a special advantage for the construction of well-defined complex molecular structures.

Credit: 
Ludwig-Maximilians-Universität München

200 000 years ago, humans preferred to kip cozy

image: Border Cave in the Lebombo Mountains. Panorama from drone images. A. Kruger

Image: 
A. Kruger

Researchers in South Africa's Border Cave, a well-known archaeological site perched on a cliff between eSwatini (Swaziland) and KwaZulu-Natal in South Africa, have found evidence that people have been using grass bedding to create comfortable areas for sleeping and working on at least 200 000 years ago.

These beds, consisting of sheaves of grass of the broad-leafed Panicoideae subfamily were placed near the back of the cave on ash layers. The layers of ash was used to protect the people against crawling insects while sleeping. Today, the bedding layers are visually ephemeral traces of silicified grass, but they can be identified using high magnification and chemical characterisation.

The Border Cave study was conducted by a multidisciplinary team from the University of the Witwatersrand, South Africa, the CNRS (University of Bordeaux), and Université Côte d'Azur, France, the Instituto Superior de Estudios Sociales, Tucumán, Argentina, and the Royal Institute for Cultural Heritage, Belgium. The research was published in the high impact journal Science.

"We speculate that laying grass bedding on ash was a deliberate strategy, not only to create a dirt-free, insulated base for the bedding, but also to repel crawling insects," says Professor Lyn Wadley, principal researcher and lead author.

"Sometimes the ashy foundation of the bedding was a remnant of older grass bedding that had been burned to clean the cave and destroy pests. On other occasions, wood ash from fireplaces was also used as the clean surface for a new bedding layer."

Several cultures have used ash as an insect repellent because insects cannot easily move through fine powder. Ash blocks insects' breathing and biting apparatus, and eventually dehydrates them. Tarchonanthus (camphor bush) remains were identified on the top of the grass from the oldest bedding in the cave. This plant is still used to deter insects in rural parts of East Africa.

"We know that people worked as well as slept on the grass surface because the debris from stone tool manufacture is mixed with the grass remains. Also, many tiny, rounded grains of red and orange ochre were found in the bedding where they may have rubbed off human skin or coloured objects," says Wadley.

Modern hunter-gatherer camps have fires as focal points; people regularly sleep alongside them and perform domestic tasks in social contexts. People at Border Cave also lit fires regularly, as seen by stacked fireplaces throughout the sequence dated between about 200 000 and 38 000 years ago.

"Our research shows that before 200 000 years ago, close to the origin of our species, people could produce fire at will, and they used fire, ash, and medicinal plants to maintain clean, pest-free camps. Such strategies would have had health benefits that advantaged these early communities."

Although hunter-gatherers tend to be mobile and seldom stay in one place for more than a few weeks, cleansing camps had the potential to extend potential occupancy.

Credit: 
University of the Witwatersrand

The flax wilt agent has been sequenced

image: Cultures of different strains of the fungus Fusarium oxisporum f. sp. lini

Image: 
SPbU

Crop scientists, molecular and computational biologists from two leading St. Petersburg Universities and Federal Centre for Bast Fiber Crops teamed up to sequence and assemble genome of Fusarium oxysporum f.sp. lini, a highly destructive fungal parasite infecting flax.

Fusarium wilt is a plant disease caused by various species of Fusarium fungi. Botanists and plant scientists are aware of approximately 120 species of the parasite, capable of infecting a wide spectrum of crops, such as tomatoes, cucumbers, melons, cabbages, peas, corn, barley, wheat, and many other plants. This study focuses on detailed characterization of F. oxysporum f.sp. lini which infects flax, a major source of textile fibre, seed and flaxseed (linseed) oil in Russia.

"The pathogen has a remarkable resistance to chemical agents and its spores may persist quite comfortably in soil for years. It is a widely accepted opinion in modern crop science that the most promising approach to fight the infection is to breed new resistant varieties,' says Anastasia Samsonova, Professor at the Centre for Genome Bioinformatics at St Petersburg University. "The host and parasite are engaged in an endless "arms race" to survive. Sooner or later, the flax varieties that are currently commercially cultivated may lose their resistance, succumb to the disease completely and become unprofitable to grow. Naturally, this creates a demand for breeding new resistant crops."

The whole genome chromosome-level assembly of the Fusarium oxysporum f.sp. lini was completed in a joint research effort by scientists from St. Petersburg University, Peter the Great St. Petersburg Polytechnic University, and the Centre for Bast Fiber Crops in Torzhok. "The parasite's genome consists of two components; the stable one, which is almost identical in different Fusariums, and the variable part which is mainly responsible for amazing adaptation of the fungus to various plants." says Alexander Kanapin, Professor at the Centre for Genome Bioinformatics at St Petersburg University. "The chromosome-level assembly of the genome is a significant step towards understanding the parasite evolution and adaptation to a particular host."

"Thanks to recent advances in omics technologies and computational biology, and to our fantastic collaborators at the Centre for Bast Fiber Crops, we generated a high quality data resource for comparative studies of Fusarium pathogenic diversity and molecular mechanisms of interaction between the fungus and the host. This will undoubtedly increase the power of integrative systems genetics analyses and thus contribute to the global efforts aimed at elimination of plant disease outbreaks by aiding in engineering of new resistant crops varieties.", explains Maria Samsonova, Head of the Laboratory for Mathematical Biology and Bioinformatics at Peter the Great St Petersburg Polytechnic University.

Further research will address many important questions left unanswered; the team will try to find a genetic determinants of the fungus "taste". In other words, why certain species "enjoys" melons, while the other one "fancies" tomatoes. Knowing parasite's preferences will help to elucidate specific mechanisms of Fusarium adaptation to different hosts and find genes responsible.

Credit: 
St. Petersburg State University