Culture

In infectious disease outbreaks, digital contact tracing alone could reduce the number of cases, but not as much as manual contract tracing, new University of Otago-led research published in the Cochrane Library reveals.

Senior Research Fellow in the Department of Preventive and Social Medicine, Dr Andrew Anglemyer, led this systematic review of the effectiveness of digital technologies for identifying contacts of an identified positive case of an infectious disease, in order to isolate them and reduce further transmission of the disease.

The team of researchers summarised the findings of six observational studies from outbreaks of different infectious diseases in Sierra Leone, Botswana and the USA and six studies that simulated the spread of diseases in an epidemic with mathematical models.

The results of the review suggest the need for caution by health authorities relying heavily on digital contact tracing systems.

"Digital technologies, combined with other public health interventions, may help to prevent the spread of infectious diseases but the technology is largely unproven in real-world, outbreak settings," Dr Anglemyer says.

"Modelling studies provide low certainty of evidence of a reduction in cases, and this only occurred when digital contact tracing solutions were used together with other public health measures such as self-isolation," he says.

"However, limited evidence shows that the technology itself may produce more reliable counts of contacts."

Overall, the team of researchers from New Zealand, the USA, the UK and Australia conclude there is a place for digital technologies in contact tracing.

"The findings of our review suggest that to prevent the spread of infectious diseases, governments should consider digital technologies as a way to improve current contact tracing methods, not to replace them," the researchers state.

"In the real world, they won't be pitted against each other, the technology would hopefully just augment the current contact tracing methods in a given country."

They recommend governments consider issues of privacy and equity when choosing digital contact tracing systems.

"If governments implement digital contact tracing technologies, they should ensure that at-risk populations are not disadvantaged and they need to take privacy concerns into account.

"The COVID-19 pandemic is disproportionately affecting ethnic minorities, the elderly and people living in high deprivation. These health inequities could be magnified with the introduction of digital solutions that do not consider these at-risk populations, who are likely to have poor access to smartphones with full connectivity."

Contact tracing teams in the studies reviewed reported that digital data entry and management systems were faster to use than paper systems for recording of new contacts and monitoring of known contacts and possibly less prone to data loss.

But the researchers conclude there is "very low certainty evidence" that contact tracing apps could make a substantial impact on the spread of COVID-19, while issues of low adoption, technological variation and health equity persist.

Accessibility or privacy and safety concerns were identified in some of the studies. Problems with system access included patchy network coverage, lack of data, technical problems with hardware or software that were unable to be resolved by local technical teams and higher staff training needs including the need for refresher training. Staff also noted concerns around accessibility and logistical issues in administering the systems, particularly in marginalised or under-developed areas of the world.

The research, published today by the Cochrane Library a collection of high-quality, independent evidence to inform healthcare decision-making, has been carried out as the COVID-19 pandemic shows no signs of waning and the World Health Organization and more than 30 countries are exploring how digital technology solutions could help stop the spread of the virus.

Senior Research Fellow Tim Chambers from the University of Otago, Wellington, and Associate Professor Matthew Parry from the Department of Statistics, were also co-authors of the paper.

In their first follow-up to a high-profile 2017 study which showed microbes in Antarctica have a unique ability to essentially live on air, researchers from UNSW Sydney have now discovered this process occurs in soils across the world's three poles.

Specifically, researchers found the target genes responsible for the atmospheric chemosynthesis phenomenon they discovered are abundant and widely distributed in the polar soils of the Antarctic, Arctic and Tibetan Plateau in the Hindu Kush-Himalayas.

The new research was published in the journal Frontiers this month and was a collaboration between UNSW, the Australian Antarctic Division and China's Institute of Tibetan Plateau Research.

The study's senior author Associate Professor Belinda Ferrari, of UNSW Science, said living on air was such a minimalistic way to survive that their findings lent further potential for microbial life to exist on other planets.

"This is what NASA's Mars 2020 Perseverance Rover is aiming to do - to search for signs of ancient microbial life in core samples of Martian rock and soil," A/Prof Ferrari said.

"A future mission will take the samples back to Earth and NASA scientists will analyse the soil in a similar way we do, to try and see whether there are any indicators of life."

A/Prof Ferrari said the researchers' findings meant that microbes which use trace gases as their energy and carbon source to grow - unlike photosynthesis which uses light - was not a process isolated to Antarctica.

"There are whole ecosystems probably relying on this novel microbial carbon fixation process where microbes use the energy obtained from breathing in atmospheric hydrogen gas to turn carbon dioxide from the atmosphere into carbon - in order to grow," she said.

"We think this process occurs simultaneously alongside photosynthesis when conditions change, such as during the polar winter when there is no light, but we aim to confirm this hypothesis in the next stage of our research.

"So, while more work is needed to confirm this activity occurs globally, the fact that we detected the target genes in the soils of the three poles means this novel process likely occurs in cold deserts around the world, but has simply been overlooked until now."

Antarctic, Artic and Tibetan Plateau soil analysed

Researchers analysed 122 soil samples from 14 terrestrial cold desert sites across Antarctica (Windmill Islands and Vestfold Hills), the high Arctic and Tibetan Plateau, which they collected between 2005 and 2019.

The study's lead author, UNSW PhD candidate Angelique Ray, said one of the big questions the team had when they finished their previous study was whether this new process of atmospheric chemosynthesis - also known as carbon fixation or carbon sink - was similarly occurring in other places around the world.

"So, this time we did a global study. We collected the top 10-centimetre layer of soil from various sites at the three poles, which is the depth where most of the organisms we study are found," she said.

"The ground at those locations is completely frozen for most of the year - and there's not a lot of soil because it's mostly rock."

The researchers extracted DNA from the soil samples and then sequenced the DNA to detect the target genes responsible for the process of carbon fixation.

Ms Ray said the scientists also conducted environmental analyses of each location to gauge the conditions under which the microbes lived.

"By looking at the environmental parameters in the soil, that's how we knew there was low carbon, low moisture and other factors at play," she said.

"So, we correlated the target genes for the carbon fixation process against the different sites and found the locations which are drier and lower in nutrients - carbon and nitrogen - had a greater potential to support this process, which made sense."

Findings to change thinking on carbon fixation

A/Prof Ferrari said the researchers' findings would change the way scientists thought about the limitations required for life to exist, as well as how microbiology was taught.

"By investigating places outside Antarctica, we can determine how significant the contribution of this new form of chemotrophy is to the global carbon budget," she said.

"Before we discovered this new carbon sink process, the two main known chemotrophic forms were photosynthesis and geothermal chemotrophy - the latter is where bacteria harness inorganic compounds like hydrogen sulfide to fix carbon.

"But now we have found the genes involved in this process are abundant in cold deserts, although we are yet to study hot deserts, our finding probably indicates atmospheric chemosynthesis is contributing to the global carbon budget."

A/Prof Ferrari said it was likely the bacteria which survived on nothing but air had become key players in the environments in which they lived.

"A lot of these ecosystems are quite dry and nutrient poor - so, these locations are mostly dominated by bacteria," she said.

"Particularly at the original east Antarctic sites we studied, there is not much else there apart from some mosses and lichens (fungus).

"Because these bacteria have adapted to survive and have the ability to use trace gases to live, their environment has selected them to become significant contributors to their ecosystems."

A/Prof Ferrari said the researchers looked forward to making new discoveries in carbon fixation.

"As part of the next phase, we aim to isolate one of these novel bacteria in the laboratory - to obtain a pure culture," she said.

"This is difficult because the bacteria are used to growing on very little and an agar plate is different to their natural environment.

"Hopefully then, we can fully understand the conditions these bacteria need to carry out this unique process of living on air."

When talking to babies, humans slow down their speech, raise their pitch and change the "color" of their voice. This "baby talk," as people know it, increases the infant's attention and facilitates language learning. Among animals, mothers often engage in pup-directed vocalizations too, but does this also imply voice changes? A team of scientists that included Smithsonian Tropical Research Institute (STRI) researchers explored whether infant-directed communication in bats resulted in vocalization changes.

They focused on the greater sac-winged bat Saccopteryx bilineata, a common Central and South American species with a large vocal repertoire employed in the elaboration of complex songs for territorial defense and courtship. Female choice in mating is very pronounced in this species, which probably led to the complexity of courtship vocalizations in males.

During their first three months of life, as S. bilineata pups start experimenting with their "speech," female and male adult bats respond to them differently. Through sound recordings of their vocal interactions, the research team found that mother bats interact with pups as they "babble," which could be interpreted as positive feedback to pups during vocal practice.

Much like human "baby talk," the pup-directed vocalizations of adult females presented a different "color" and pitch than the calls directed towards other adult bats. Male bats also communicated with the pups, but in a way that seemed to transmit the "vocal signature" of their social group.

"Pup isolation calls are acoustically more similar to those of males from the same social group than to those of other males," said Mirjam Knörnschild, STRI research associate and co-author of the paper. "These results suggest that adult male vocalizations may serve as guidance for the development of group signatures in pup calls."

This is the first time that scientists describe a phenomenon that could resemble "baby talk" among bats, indicating that parent-offspring communication in bats is more complex than previously thought and opening new avenues for further research.

"These results show that social feedback is important during vocal development, not only in humans but also in other vocal-learning species like Saccopteryx bilineata," said Ahana Fernandez, former STRI visiting scientist who conducted this research as part of her doctoral thesis at the Free University Berlin and is now a post-doctoral researcher at the Natural History Museum in Berlin. "I believe that bats are a very promising taxon to investigate key shared features of language, such as the vocal learning ability, and that this study will inspire further studies in the biolinguistics field."

New research from a European group of smell disorder experts, including Prof Philpott at the University of East Anglia, shows how smell loss associated with Covid-19 infection differs from what you typically might experience with a bad cold or flu.

The new study published today is the first to compare how people with Covid-19 smell and taste disorders differ from those with other causes of upper respiratory tract infections.

The main differences found are that, although Covid-19 patients also lose their sense of smell, they can breathe freely, do not tend to have a runny or blocked nose, and they cannot detect bitter or sweet tastes.

These findings lend weight to the theory that Covid-19 infects the brain and central nervous system.

The research team hope that their work could help develop smell and taste tests for fast Covid-19 screening - in primary care and emergency departments.

Lead researcher Prof Carl Philpott, from UEA's Norwich Medical School, said: "The loss of smell and taste is a prominent symptom of Covid-19, however it is also a common symptom of having a bad cold. We wanted to find out exactly what differentiates Covid-19 smell loss with the kind of smell loss you might have with a cold and blocked-up nose."

The research team carried out smell and taste tests on 10 Covid-19 patients, 10 people with bad colds and a control group of 10 healthy people - all matched for age and sex.

Prof Philpott said: "We wanted to see if their smell and taste test scores could help discriminate between Covid-19 patients and those with a heavy cold.

"We know that Covid-19 behaves differently to other respiratory viruses, for example by causing the body's immune system to over-react, known as a cytokine storm, and by affecting the nervous system.

"So we suspected that patterns of smell loss would differ between the two groups.

"We found that smell loss was much more profound in the Covid-19 patents. They were less able to identify smells, and they were not able to identify bitter or sweet tastes. In fact it was this loss of true taste which seemed to be present in the Covid-19 patients compared to those with a cold.

"This is very exciting because it means that smell and taste tests could be used to discriminate between Covid-19 patients and people with a regular cold or flu.

"Although such tests could not replace formal diagnostic tools such as throat swabs, they could provide an alternative when conventional tests are not available or when rapid screening is needed - particularly at the level of primary care, in emergency departments or at airports.

"This research also shows that there are altogether different things going on when it comes to smell and taste loss for Covid-10 patients, compared to those with a bad cold.

"It has previously been suggested that the Covid-19 virus affects the central nervous system, based on the neurological signs developed by some patients. There are also similarities with SARS, which has also been reported to enter the brain, possibly via smell receptors in the nose.

"Our results reflect, at least to some extent, a specific involvement at the level of central nervous system in some COVID-19 patients.

"It is particularly interesting that Covid-19 seems to particularly affect sweet and bitter taste receptors, because these are known to play an important role in innate immunity.

"More research is needed to see whether genetic variation in people's bitter and sweet taste receptors might predispose them to Covid-19, or conversely, whether Covid-19 infection changes how these receptors function, either directly or through a cytokine storm - the over-reaction of the body's immune system."

DENVER--Public health screening guidelines for lung cancer followed by the United States Preventive Services Task Force (USPSTF) and the Center for Medicare and Medicaid Services (CMS) undercount African Americans, contributing to disparities in lung cancer screening and treatment, according to a study published today in the Journal of Thoracic Oncology. The JTO is the official journal of the International Association for the Study of Lung Cancer.

Current USPSTF and CMS guidelines, established by results from the National Lung Cancer Screening Trial, recommend low dose computed tomography screening for individuals that meet the following criteria: age 55-80 or 55-77 years, respectively, 30 or more pack-years cigarette smoking history, and in former smokers having quit smoking within the past 15 years.

However, African American individuals are more likely to start smoking at a later age, smoke fewer cigarettes per day, have a longer duration of smoking, are less likely to quit, and tend to be diagnosed with lung cancer at an earlier age. Previous research conducted of 48,364 ever-smokers in the Southern Community Cohort Study showed that a smaller proportion of African American individuals would have met the current USPSTF criteria compared to Whites - 17 % versus 31 %, respectively. African American ever-smokers are at increased risk for lung cancer compared to their White counterparts after adjusting for age and smoking history.

Even among those African Americans or Hispanics who are appropriately screened, access to treatment and participation in leading edge clinical trials is limited.

"Black and Hisptanic patients are under represented in cancer clinical trials and COVID-19 trials, even though they are more likely to be more affected by both diseases," said Janet Freeman-Daily at the IASLC World Conference on Lung Cancer Virtual Presidential Symposium last week. Freeman-Daily is a lung cancer patient advocate and runs the weekly lung cancer Twitter discussion #LCSM.

"In a rapid moving area like cancer care, clinical trials are treatment and represent hope," she said.

To follow up on the Southern Community Cohort Study, researchers from the University of Illinois at Chicago performed a retrospective analysis of 1,050 patients with thoracic cancer from their cancer registry. The cohort was assessed for whether each case would have been eligible by USPSTF criteria for screening based on age, pack-years (average packages of 20 cigarettes smoked per day times years smoked) and quit time. After some exclusions, the cohort of 883 ever-smokers was comprised of the following racial/ethnic makeup: 258 (29.2%) White, 497 (56.3%) African American, 69 (7.8%) Hispanic, 24 (2.7%) Asian, and 35 (4.0%) other.

The researchers analyzed this cohort using the PLCOm2012 lung cancer risk prediction screening model, based on data collected from the control arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), a randomized controlled trial studying screening to reduce cancer mortality. The PLCOm2012 model incorporates 11 predictors, which include sociodemographic, medical history, and four smoking exposure variables.

Compared to the USPSTF criteria, the PLCOm2012 model increased the sensitivity for the African American cohort at lung cancer risk thresholds of 1.51%, 1.70%, and 2.00% per 6-years. The USPSTF criteria and the PLCOm2012 model with 1.70% risk threshold identified 62.4% and 66.0% of White cases, respectively, and 50.3% and 71.3% of African American cases, respectively. Thus, the PLCOm2012 model improved sensitivity in both Whites and African American ever-smokers and eliminated the eligibility disparity. Of the 64 African Americans ever smokers who were USPSTF-ineligible because their ages were less than 55 years, 23.4% would have qualified by the PLCOm2012 with risk threshold of 1.7%. Of 53 African American ever smokers who were USPSTF-ineligible because they had quit smoking more than 15 years ago, 49.1% would have qualified by the PLCOm2012. And of the 193 of African American ever smokers who were USPSTF-ineligible because they had pack-years less than 30, 40.4% would have qualified by the PLCOm2012.

"We found that the PLCOm2012 model was significantly more sensitive in selecting lung cancer patients as being eligible for screening for the entire cohort," said lead author Mary Pasquinelli, DNP, from the University of Illinois at Chicago. "Broader use of this model in racially diverse populations may help overcome disparities in lung cancer screening and outcomes."

When stony corals have their renowned mass spawning events, in sync with the moon’s cycle, colonies simultaneously release an underwater “cloud” of sperm and eggs for fertilization. But how do the sperm and eggs survive several hours as plankton, given threats from predators, microbes and stresses such as warming waters?

A Rutgers-led team has discovered some surprising features in coral sperm and eggs (collectively called gametes), according to a study in the journal PeerJ.

While coral eggs are large and sperm cells are tiny and far more numerous, the scientists showed for the first time that eggs and sperm appear to be surprisingly similar when it comes to the gene functions they express during the planktonic stage. Proteins encoded by genes, in a process called gene expression, play many critical roles and perform most of the work in cells.

The scientists also identified two genes that may be involved in how coral sperm and eggs recognize each other in dynamic ocean waters, allowing fertilization.

“Much more attention needs to be paid to coral gametes because both egg and sperm are vulnerable to climate change and other insults,” said senior author Debashish Bhattacharya, a distinguished professor in the Department of Biochemistry and Microbiology in the School of Environmental and Biological Sciences at Rutgers University–New Brunswick. “It goes without saying that without robust sperm and egg, the coral reproductive cycle will be significantly weakened. Therefore, we need to understand in more detail how natural selection has acted on coral gametes to ensure their survival, leading to successful fertilization.”

Coral reefs protect coastlines from erosion and storms; serve as habitat, nursery and spawning grounds for fish; and provide food for about 500 million people as well as their livelihoods, according to the National Oceanic and Atmospheric Administration. But corals are threatened by global climate change that warms the ocean and leads to coral bleaching, disease, sea-level rise and ocean acidification. Other threats include unsustainable fishing, land-based pollution, tropical storms, damage from vessels, marine debris and invasive species.

By analyzing the genes of the Hawaiian stony coral Montipora capitata, the scientists revealed a blueprint for how coral eggs and sperm function. The next steps include further analyses of coral genomes to identify the substances they produce to ensure their survival and fertilization. The scientists are also interested in investigating coral species that don’t release sperm and eggs into the water before fertilization and comparing the results to the stony coral study.

“Our results pave the way for future genetic investigations, particularly in the context of climate change influences on the marine environment,” Bhattacharya said.

Philadelphia, August 18, 2020 - Fluid milk consumption among children is vital, as adequate consumption of dairy products, especially during childhood, has beneficial health outcomes later in life. These benefits include reduced risk of osteoporosis, hypertension, obesity, and cancer in adulthood. Milk consumption among children has been declining for decades, so understanding and fulfilling the needs of children is crucial to reverse the decline. In an article appearing in the Journal of Dairy Science, scientists from North Carolina State University and Cornell University studied key contributors to increasing milk consumption among children.

Factors evaluated in the study included food trends, nutritional and school meal program requirements, children's perceptions and preferences, and environmental influences. Among these influences, flavor and habit were the primary drivers for long-term milk consumption. Intrinsic factors ranged in influence over milk preference in the examination, showing that flavoring, heat treatment, and sweeteners positively correlated with higher milk consumption. Extrinsic factors, such as social influence (i.e., peers, parents or caregivers, and school staff), packaging, and health benefits, all affected children's attitudes toward milk as well.

"Making milk more appealing to children, having schools include milk in their meal plans, and increasing the types of milk available in schools are all positive options to encourage children consume fluid milk and receive those health benefits," said senior author MaryAnne Drake, PhD, Department of Food, Bioprocessing, and Nutrition Sciences, North Carolina State University, Raleigh, NC, USA. "The findings in this study, however, reveal critical insights that will aid in efforts to increase milk consumption among children."

Understanding how to create milk products that are appealing to children without compromising the health benefits and taking note of the various factors that influence a child's choice are necessary to encourage and increase lifelong milk consumption.

Low levels of HDL cholesterol, the so-called 'good' cholesterol, are the most common lipid disorder in countries in Latin America and the Caribbean, a new meta-analysis published in eLife shows.

Cholesterol levels in the blood can be important indicators of heart health or cardiovascular disease. By providing regional insights on cholesterol patterns, the study may help local public health leaders develop new strategies to reduce rates of cardiovascular disease by improving cholesterol levels in their communities.

Tracking cholesterol data in Europe, North America, Australia and New Zealand has helped guide initiatives that have delayed the onset of heart disease. Monitoring rising cholesterol levels in Asia and the Pacific is helping clinicians in those regions test strategies to curb this trend. But limited population-level data have been available to guide heart health initiatives in Latin America and the Caribbean. "We wanted to find out which kind of lipid disorder is most common in these two regions," says lead author Rodrigo M. Carrillo-Larco, a Wellcome Trust International Training Fellow at the School of Public Health, Imperial College London, UK, and Research Associate at CRONICAS Centre of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Peru.

Carrillo-Larco and colleagues based in Peru analysed data from 197 studies between 1964 and 2016 that collected information on blood cholesterol and lipid levels from individuals in Latin America and the Caribbean. Their results showed no substantial changes in blood cholesterol or lipid levels in these areas over time. "Since 2005, the most common lipid disorder in this region has been low HDL cholesterol, followed by high triglycerides and high LDL cholesterol," Carrillo-Larco explains.

Their analysis provides a starting point for researchers to track cholesterol and lipid levels in these populations by collecting the data during routine visits, or by conducting large studies that follow thousands of individuals over time.

"Our results also suggest that efforts to boost levels of HDL cholesterol may provide the greatest heart health benefits to people living in these regions," concludes senior author Antonio Bernabe-Ortiz, Research Associate at the CRONICAS Center of Excellence in Chronic Disease, Universidad Peruana Cayetano Heredia, Peru. "Such efforts could include public health campaigns to increase physical activity by improving walking infrastructure, or to reduce rates of diabetes or obesity by promoting access to healthy foods."

By Maria Fernanda Ziegler | Agência FAPESP – Researchers at the Brazilian Center for Research in Energy and Materials (CNPEM) have genetically engineered a fungus to produce a cocktail of enzymes that break down the carbohydrates in biomass, such as sugarcane trash (tops and leaves) and bagasse, into fermentable sugar for industrially efficient conversion into biofuel.

The development of low-cost enzyme cocktails is one of the main challenges in producing second-generation ethanol.

Second-generation biofuels are manufactured from various kinds of nonfood biomass, including agricultural residues, wood chips and waste cooking oil. The CNPEM research group’s process paves the way for optimized use of sugarcane residues to produce biofuels.

The fungus Trichoderma reesei is one of the most prolific producers of plant cell wall-degrading enzymes and is widely used in the biotechnology industry. To enhance its productivity as a biofactory for the enzyme cocktail in question, the researchers introduced six genetic modifications into RUT-C30, a publicly available strain of the fungus. They patented the process and reported it in an article published in the journal Biotechnology for Biofuels.

“The fungus was rationally modified to maximize production of these enzymes of biotechnological interest. Using the CRISPR/Cas9 gene-editing technique, we modified transcription factors to regulate the expression of genes associated with the enzymes, deleted proteases that caused problems with the stability of the enzyme cocktail, and added important enzymes the fungus lacks in nature. As a result, we were able to allow the fungus produce a large amount of enzymes from agroindustrial waste, a cheap and abundant feedstock in Brazil,” Mario T. Murakami, Scientific Director of CNPEM’s Biorenewables Laboratory (LNBR), told Agência FAPESP.

Some 633 million tons of cane are processed per harvest in Brazil, annually generating 70 million metric tons of cane trash (dry mass), according to the National Food Supply Company (CONAB). This waste is underutilized for fuel ethanol production.

Murakami stressed that practically all the enzymes used in Brazil to decompose biomass are imported from a few foreign producers that keep the technology under trade secret protection. In this context, the imported enzyme cocktail can represent as much as 50% of a biofuel’s production cost.

“Under the traditional paradigm, decades of studies were needed to develop a competitive enzyme cocktail production platform,” he said. “Moreover, the cocktails couldn’t be obtained solely by synthetic biology techniques from publicly available strains because the producers used different methods to develop them, such as adaptive evolution, exposing the fungus to chemical reagents, and inducing genomic mutations in order to select the most interesting phenotype. Now, however, thanks to advanced gene editing tools such as CRISPR/Cas9, we’ve succeeded in establishing a competitive platform with just a few rational modifications in two and a half years.”

The bioprocess developed by the CNPEM researchers produced 80 grams of enzymes per liter, the highest experimentally supported titer so far reported for T. reesei from a low-cost sugar-based feedstock. This is more than double the concentration previously reported in the scientific literature for the fungus (37 grams per liter).

“An interesting aspect of this research is that it wasn’t confined to the lab,” Murakami said. “We tested the bioprocess in a semi-industrial production environment, scaling it up for a pilot plant to assess its economic feasibility.”

Although the platform was customized for the production of cellulosic ethanol from sugarcane residues, he added, it can break down other kinds of biomass, and advanced sugars can be used to produce other biorenewables such as plastics and intermediate chemicals.

Novel enzyme class

The process was the practical result (in terms of an industrial application) of wide-ranging research conducted by LNBR to develop enzymes capable of breaking down carbohydrates. In another study supported by FAPESP and published in Nature Chemical Biology, the researchers revealed seven novel enzyme classes present above all in fungi and bacteria.

The novel enzymes belong to the glycoside hydrolase (GH) family. According to Murakami, these enzymes have significant potential for applications not just in the field of biofuels but also in medicine, food processing and textiles, for example. The enzymes will inspire novel industrial processes by leveraging the different ways in which nature decomposes polysaccharides (carbohydrates made up of many simple sugars).

These enzymes break down beta-glucans, some of the most abundant polysaccharides found in the cell walls of cereals, bacteria and fungi, and a large fraction of the world’s available biomass, indicating the enzymes’ potential use in food preservatives and textiles. In the case of biofuels, the key property is their capacity to digest material rich in vegetable fibers.

“We set out to study nature’s diversity in degrading polysaccharides and how this knowledge can be applied to processes in different industries,” Murakami said. “In addition to the discovery of novel enzymes, another important aspect of this research is the similarity network approach we use to produce systematic and profound knowledge of this enzyme family. The approach enabled us to start from scratch and in a relatively short time, arrive at the most studied family of enzymes active on beta-1,3-glucans to date, with information available on specificity and action mechanisms.”

The main criterion for classifying enzymes is usually phylogeny, i.e., the evolutionary history of the molecule, whereas CNPEM researchers focus on functionality.

“Thanks to advances in DNA sequencing technology, we now have many known genetic sequences and a well-established capacity to study and characterize molecules and enzymes in terms of their functionality. As a result, we’ve been able to refine the similarity network methodology and use it for the first time to study enzymes active on polysaccharides,” Murakami said.

Using the similarity network approach, the group classified seven subfamilies of the enzymes based on functionality. Characterizing at least one member of each subfamily, the researchers accessed in systematic terms the diversity of molecular strategies for degrading beta-glucans contained in thousands of members of the enzyme family.

Biochemical tour de force

Phylogenetic analysis focuses on DNA regions that have been conserved over time, whereas classification by functionality is based on nonconserved regions associated with functional differentiation. “This gave us efficiency and enabled us to group more than 1,000 sequences into only seven subgroups or classes with the same function,” Murakami said.

Because the approach was novel, the researchers performed several other studies to double-check and validate the classification method. From the seven groups of enzymes capable of degrading polysaccharides, they obtained 24 entirely novel structures, including various substrate-enzyme complexes, considered crucial in providing information to help understand the action mechanisms involved.

The study comprised functional and structural analyses to understand how these enzymes act on the carbohydrates concerned. “Polysaccharides come in dozens of configurations and are capable of many kinds of chemical bonds,” Murakami said. “We wanted to observe exactly which chemical bonds and architectures are recognized by each enzyme. For this reason, it had to be a multidisciplinary study, combining structural and functional data supported by analysis using mass spectrometry, spectroscopy, mutagenesis and diffraction experiments to elucidate the atomic structure.”

In the “News & Views” section of the same issue of Nature Chemical Biology, Professor Paul Walton, Chair of Bioinorganic Chemistry at the University of York in the United Kingdom, rated the glycoside hydrolase study a “biochemical ‘tour de force’” for its innovative approach and praised its “tremendous insights”, adding that the researchers were “able to express and isolate exemplars from each class [of enzymes] to examine whether the differences in sequences between the classes were reflected in their structures and activities”.

The article “Rational engineering of the Trichoderma reesei RUT-C30 strain into an industrially relevant platform for cellulase production” (doi: 10.1186/s13068-020-01732-w) by Lucas Miranda Fonseca, Lucas Salera Parreiras and Mario Tyago Murakami can be read at: biotechnologyforbiofuels.biomedcentral.com/articles/10.1186/s13068-020-01732-w.

The article “Structural insights into β-1,3-glucan cleavage by a glycoside hydrolase family” (doi: 1 0.1038/s41589-020-0554-5) by Camila R. Santos, Pedro A. C. R. Costa, Plínio S. Vieira, Sinkler E. T. Gonzalez, Thamy L. R. Correa, Evandro A. Lima, Fernanda Mandelli, Renan A. S. Pirolla, Mariane N. Domingues, Lucelia Cabral, Marcele P. Martins, Rosa L. Cordeiro, Atílio T. Junior, Beatriz P. Souza, Érica T. Prates, Fabio C. Gozzo, Gabriela F. Persinoti, Munir S. Skaf and Mario T. Murakami can be retrieved from www.nature.com/articles/s41589-020-0554-5.

Journal

Nature Chemical Biology

DOI

10.1038/s41589-020-0554-5

Earlier this year, a study led by researchers at Johns Hopkins Medicine provided strong evidence that hundreds of deceased donor kidneys with acute kidney injury (AKI) -- traditionally discarded as unsuitable for transplantation -- could be safely and successfully used. Now, a follow-up investigation by the same team, in collaboration with researchers at 13 other medical institutions in the United States, has shown that two proteins found in deceased donor urine can be measured to define which donor organs -- including those with AKI -- are the best candidates for saving the lives of patients with kidney failure.

The team's findings were reported online July 27, 2020, by the journal Transplantation.

Currently, the national discard or rejection rate for all potential donor kidneys is approximately 18%, but for AKI kidneys, it jumps to 30%. According to statistics from the U.S. Department of Health and Human Services, nearly 100,000 Americans with kidney failure, also known as end-stage renal disease, are awaiting donor organs. Unfortunately, as reported by the U.S. Centers for Disease Control and Prevention, nearly 9,000 of these patients drop off the waiting list each year, succumbing to death or deteriorating in health so that transplantation is no longer possible.

Making matters worse, says the National Institute of Diabetes and Digestive and Kidney Diseases, the need for donor kidneys is rising at 8% per year. However, their availability has not grown to match.

To better identify which deceased donor kidneys have a higher probability for successful transplantation and long-term survival as grafted organs, the new study looked to two proteins -- both easily obtained from the urine of donors at the time of organ harvesting -- that the researchers felt could be used as clinical biomarkers.

The two proteins, uromodulin and osteopontin, had been shown in previous studies to play a protective role in kidney health and proper functioning, helping to repair cells damaged by AKI and stimulating immune responses against foreign invaders. Therefore, the research team believed that their presence in deceased donors might indicate which kidneys were most likely to recover from injuries or infections.

"We determined that if the ratio of the amounts of the two proteins, as precisely measured in samples of a deceased donor's urine, was less than or equal to three, then that person's kidneys were the most suitable for transplantation and had a higher chance for staying healthy and functioning longer after the surgery," says Chirag Parikh, M.D., Ph.D., director of the Division of Nephrology at the Johns Hopkins University School of Medicine and senior author of the study.

There were 1,298 donors and 2,430 recipients participating in the study. A total of 322 deceased donors (25%) had signs of AKI. The recipients were followed for a median time of four years after surgery to document any graft failures or deaths.

The researchers say that additional studies are needed to validate the use of the uromodulin-to-osteopontin ratio as a clinical tool for timely and accurate evaluation of kidneys for transplantation.

"We estimate that using this strategy, once confirmed as reliable, we can annually reduce the number of kidneys discarded and add a few thousand suitable-for-transplant organs to the pool," Parikh says.

Increasing the donor pool, Parikh adds, would help achieve the goal of the Advancing American Kidney Health initiative, a 2019 presidential directive that aims to double the number of kidneys available for transplant by 2030.

WASHINGTON, August 18, 2020 -- Think you don't need to worry about COVID-19 while using a public restroom? A group of researchers from Yangzhou University in China recently reported that flushing public restroom toilets can release clouds of virus-laden aerosols for you to potentially inhale.

If that's not cringeworthy enough, after running additional computer simulations, they've concluded that flushing urinals does likewise. In Physics of Fluids, from AIP Publishing, the group shares its work simulating and tracking virus-laden particle movements when urinals are flushed.

The researchers' work clearly shows public restrooms can be dangerous places for potentially becoming infected from a virus, especially during the COVID-19 pandemic. Other work has shown that both feces- and urine-based virus transmission is possible.

"To do this, we used a method of computational fluid dynamics to model the particle movement that occurs with the act of flushing," said Xiangdong Liu. "The specific models are the volume of fluids model and discrete phase model."

Flushing a urinal, much like flushing a toilet, involves an interaction between gas and liquid interfaces. The result of the flushing causes a large spread of aerosol particles to be released from the urinal, which the researchers simulated and tracked.

What the simulations revealed is disturbing. The trajectory of the tiny particles ejected by flushing a urinal "manifests an external spread type, with more than 57% of the particles traveling away from the urinal," said Liu.

But that's not all. When men use urinals within a public restroom, these tiny particles can reach their thigh within 5.5 seconds when compared to the toilet flush, which takes 35 seconds to reach slightly higher. Particles from urinals, however, "show a more violent climbing tendency," Liu said. "The climbing speed is much faster than toilet flushing."

Urinals are used more frequently within densely populated areas, and the researchers point out that particles will travel faster and farther, which poses a serious public health challenge.

This work underscores how important it is to wear a mask within public places but especially restrooms.

"From our work, it can be inferred that urinal flushing indeed promotes the spread of bacteria and viruses," says Liu. "Wearing a mask should be mandatory within public restrooms during the pandemic, and anti-diffusion improvements are urgently needed to prevent the spread of COVID-19."

HOUSTON - (Aug. 18, 2020) - Bioengineers and surgeons from Rice University and Baylor College of Medicine (BCM) have shown that shielding stem cells with a novel biomaterial improves the cells' ability to heal heart injuries caused by heart attacks.

In a study using rodents, a team led by Rice's Omid Veiseh and Baylor's Ravi Ghanta showed it could make capsules of wound-healing mesenchymal stem cells (MSCs) and implant them next to wounded hearts using minimally invasive techniques. Within four weeks, heart healing was 2.5 times greater in animals treated with shielded stem cells than those treated with nonshielded stem cells, the researchers found.

The study is available online in the Royal Society of Chemistry journal Biomaterials Science.

Someone has a heart attack every 40 seconds in the United States. In each case, an artery that supplies blood to the heart becomes blocked and heart muscle tissue dies due to lack of blood. Hearts damaged by heart attacks pump less efficiently, and scar tissue from heart attack wounds can further reduce heart function.

"What we're trying to do is produce enough wound-healing chemicals called reparative factors at these sites so that damaged tissue is repaired and restored, as healthy tissue, and dead tissue scars don't form," said Veiseh, an assistant professor of bioengineering and CPRIT Scholar in Cancer Research at Rice.

Ghanta, associate professor of surgery at Baylor, a cardiothoracic surgeon at Harris Health's Ben Taub Hospital and co-lead author of the study, said prior studies have shown that MSCs, a type of adult stem cell produced in blood marrow, can promote tissue repair after a heart attack. But in clinical trials of MSCs, "cell viability has been a consistent challenge," Ghanta said.

"Many of the cells die after transplantation," he said. "Initially, researchers had hoped that stem cells would become heart cells, but that has not appeared to be the case. Rather, the cells release healing factors that enable repair and reduce the extent of the injury. By utilizing this shielded therapy approach, we aimed to improve this benefit by keeping them alive longer and in greater numbers."

A few MSC lines have been approved for human use, but Veiseh said transplant rejection has contributed to their lack of viability in trials.

"They're allogenic, meaning that they're not from the same recipient," he said. "The immune system perceives them as foreign. And so very rapidly, the immune system starts chewing at them and clearing them out."

Veiseh has spent years developing encapsulation technologies that are specifically designed not to activate the body's immune system. He co-founded Sigilon Therapeutics, a Cambridge, Massachusetts-based biotech company that is developing encapsulated cell therapeutics for chronic diseases. Trials of Sigilon's treatment for hemophilia A are expected to enter the clinic later this year.

"The immune system doesn't recognize our hydrogels as foreign, and doesn't initiate a reaction against the hydrogel," Veiseh said. "So we can load MSCs within these hydrogels, and the MSCs live well in the hydrogels. They also secrete the same reparative factors that they normally do, and because the hydrogels are porous, the wound-healing factors just diffuse out."

In previous studies, Veiseh and colleagues have shown that similar capsules can keep insulin-producing islet cells alive and thriving in rodents for more than six months. In the heart study, study co-lead author Samira Aghlara-Fotovat, a Rice bioengineering graduate student in Veiseh's lab, created 1.5-millimeter capsules that each contained about 30,000 MSCs. Several of the capsules were placed alongside wounded sections of heart muscle in animals that had experienced a heart attack. The study compared rates of heart healing in animals treated with shielded and unshielded stem cells, as well as an untreated control group.

"We can deliver the capsules through a catheter port system, and that's how we imagine they would be administered in a human patient," Veiseh said. "You could insert a catheter to the area outside of the heart and inject through the catheter using minimally invasive, image-guided techniques."

Veiseh said capsules in the study were held in place by the pericardium, a membrane that sheaths the heart. Tests at two weeks showed that MSCs were alive and thriving inside the implanted spheres.

More than 800,000 Americans have hearts attacks each year, and Ghanta is hopeful that encapsulated MSCs can one day be used to treat some of them.

"With further development, this combination of biomaterials and stem cells could be useful in delivering reparative therapy to heart attack patients," he said.

Veiseh said the pathway to regulatory approval could be streamlined as well.

"Clinical grade, allogenic MSCs are commercially available and are actively being used in patients for a range of applications," he said.

Veiseh credited Aghlara-Fotovat with doing much of the work on the project.

"She basically executed the vision," he said. "She developed the hydrogel formulation, the concept of how to package the MSCs within the hydrogel, and she did all the in vitro validation work to show that MSCs remained viable in the capsules."

Aghlara-Fotovat is co-mentored by Ghanta and worked in his lab at Baylor alongside research assistant Aarthi Pugazenthi, including assisting in rodent surgeries and experiments.

"What attracted me to the project was the unmet clinical need in (heart attack) recovery," Aghlara-Fotovat said. "Using hydrogels to deliver therapeutics was an exciting approach that aimed to overcome many challenges in the field of drug delivery. I also saw a clear path to translation into the clinic, which is the ultimate goal of my Ph.D."

"I think one of the things that attracts students to my lab in particular is the opportunity to do translational work," Veiseh said. "We work closely with physicians like Dr. Ghanta to address relevant problems to human health."

EVANSTON, Ill. --- Even for infants just beginning to speak their first words, the way an object is named guides infants' encoding, representation and memory for that object, according to new Northwestern University research.

Encoding objects in memory and recalling them later is fundamental to human cognition and emerges in infancy.

Evidence from a new recognition memory task reveals that as they encode objects, infants are sensitive to a principled link between naming and object representation by 12 months.

During training, all infants viewed four distinct objects from the same object category, each introduced in conjunction with either the same novel noun (Consistent Name condition), a distinct novel noun for each object (Distinct Names condition), or the same sine-wave tone sequence (Consistent Tone condition).

Researchers then tested whether infants remembered which objects they had just seen during training. To do so, infants viewed each training object again, this time presented in silence along with a new object from the same object category. Infants' memory for the individual objects was sensitive to how they had been named. Infants in the Consistent Name condition showed poor recognition memory at test, suggesting that consistently applied names focused them primarily on commonalities among the named objects at the expense of distinctions among them. In contrast, infants in the Distinct Names condition recognized three of the four objects, suggesting that applying distinct names enhanced infants' encoding of the distinctions among the individual objects. Infants in the control Consistent Tone condition recognized only the object they had most recently seen.

"We show that the way an object is named, either as a member of a category, for example, "This is a dog" or as a unique individual, for example, "This is Fido," is instrumental in 12-month-old infants' encoding of and memory for that object," said Alexander S. LaTourrette, co-author of the study. "When the same name is applied consistently to a set of objects, infants encode primarily their commonalties. In contrast, when a unique name is applied to each object, infants encode each object's unique features."

Sandra Waxman, co-author of the study and the Lewis W. Menk professor of psychology in the Weinberg College of Arts and Sciences, said this provides the first demonstration that for infants as young as 12 months of age, whether and how an object is named has rapid and conceptually precise consequences on infants' representation of that object.

"Moreover, the precision of infants' responses reveal that naming objects, even a single naming episode, can have a lasting impact on how infants encode that object, represent it in memory and remember it later," said Waxman, a faculty fellow with the University's Institute for Policy Research.

The researchers said this work sheds new light on the powerful and well-documented advantage of naming on infant object categorization, leaving little doubt that naming a set of distinct individual objects with the same noun invites infants to form an object category.

"Here, we show that hearing the same name for objects invites infants to focus on the commonalities among the objects, but at the expense of remembering the features that are unique to each individual," LaTourrette said.

Waxman said the new evidence opens new avenues for future investigations.

"First, because the current experiment focused exclusively on novel nouns, it remains an open question how familiar nouns, for example, 'Fido' or 'dog,' influence infants' object representations," she said.

"Addressing this question should also shed light on current debates concerning the link between language and cognition in adults. Second, it will be important to specify the effects of naming on infants' object representations throughout the first year of life. We know that naming supports the establishment of object categories consistently throughout the first year, beginning as early as 3 months of age. What remains unknown is whether naming confers its benefits via the same mechanisms throughout this period."

"Naming guides how 12-month-old infants encode and remember objects" published Aug. 17 in the Proceedings of the National Academy of Sciences (PNAS).

Scientists across the globe often use mouse models in the study of human conditions to advance the pursuit of medicines and treatments. Now, Johns Hopkins Medicine researchers and their collaborators have created and characterized a new mouse replica of Down syndrome, long considered one of the most challenging disorders to simulate in laboratory animals.

A report of their research appeared June 29, 2020, in the journal eLife Sciences.

The new model may help researchers better understand how people with Down syndrome learn and develop, and eventually, lead to new therapies for potentially deadly complications of the condition, such as heart disease and thyroid problems.

Down syndrome, caused by trisomy 21, occurs when a person is born with an extra partial or entire copy of the 21st chromosome. Typically associated with distinct facial features and developmental delays, people with Down syndrome also experience difficulties with learning and memory, as well as higher rates of thyroid disease, blood and immune disorders and heart disease. Treating these conditions in people with Down syndrome is complicated by their genetics.

"There are more than 500 genes on chromosome 21 that can be overexpressed," says Roger Reeves, Ph.D., professor of physiology at the Johns Hopkins University School of Medicine. "So, in comparison to many other genetic conditions, Down syndrome is vastly more complex."

Further complicating the development of successful treatments is the lack of an accurate animal model to study the biology of Down syndrome and test potential therapies for conditions associated with it.

Reeves and his team endeavored to improve research efforts by creating a more precise replica of the condition in mice. They did this by inserting a human copy of chromosome 21 into mice using the rodent's own cellular structures that organize DNA. This enables the mouse cells to reliably copy and sort the extra human chromosome into new cells as they divide. It also lets the mice pass the additional genetic material on to their offspring.

This means that these mice, named TcMAC21 by the researchers, can be used relatively easily and at low cost in long-term experiments.

The resulting TcMAC21 mice have many characteristics indicative of Down syndrome in humans, including a distinct facial structure, a greater prevalence for congenital heart defects, a smaller-than-usual cerebellum and learning difficulties.

The researchers caution that no single animal model can perfectly replicate a human condition. However, they believe that the TcMAC21 mouse model developed in this study is a good starting point to create new and better strategies for helping people with Down syndrome.

"Our goal is to improve the health of people with Down syndrome to give them the best chance at achieving their full potential," says Reeves.

People who experience threats to their existence -- including economic and political instability -- are more likely to experience miracles, according to a Baylor University study.

While many sociologists have studied the effects of religious experiences, what causes a person to have miraculous experiences has received little attention, said Baylor University sociologist Ed Eschler, Ph.D.

His study -- "In the Valley of the Shadow of Death: Insecurity and Miraculous Experiences" -- is published in the Review of Religious Research.

Eschler investigated the prevalence of miracles in Latin America using data from a 2013 Pew Research Center survey of religious beliefs and experiences. Data were analyzed from 15,400 respondents from 16 countries.

For the study, he defined a miracle as any experience in which a person believes an event or outcome was influenced by supernatural agents.

"It's tempting to think of miracles on a biblical scale: Moses parting the Red Sea and Jesus restoring sight to the blind," Eschler said. "However, unless I've been reading the wrong newspapers, this thinking excludes the lived experiences of most people.

"There's a societal assumption that wealthy and educated people favor scientific, more "rational" explanations for these events," he said. "However, there is rising evidence that it has more to do with the security that being rich and educated brings: people who experience fewer existential threats do not rely on religious explanations of events."

Eschler chose Latin America for his research because "people assume miracles are a rare occurrence in developed nations despite the fact most people have had some sort of supernatural experience.

"Latin America is less developed, so researchers are willing to ask about these 'fringe beliefs' -- although again, these beliefs actually aren't that fringe in the U.S. either."

Eschler's first major finding was that 57% of respondents believed they had experienced a miracle of some kind.

Second, he found that education had no relationship with experiencing miracles.

His third finding was the income does not influence the likelihood of experiencing a miracle, although "absolute poverty" -- not being able to afford food, clothing or medicine -- does.

"Respondents with no formal education were just as likely to experience a miracle as those with a college degree," Eschler said. "The people who live in Latin America are just as intelligent as anywhere else, but there is not the same education infrastructure. In the United States, more than 90% of people have a high school education, compared to around 40% in Latin America. This lets us study if miracles are for the uneducated in a population where the majority has an elementary school education or less."

Additionally, despite an economic downturn at the end of the Cold War, Latin America has made incredible developmental gains in the past 30 years. That allowed him to test whether a country's human and economic development matter more than an individual's education and class.

The findings go against the idea that societies become less religious as science and rationality replace religion, but they support the theory that people become more religious when their existence is threatened and less religious when their life is stable.

Eschler found that most likely to experience a miracle is an older, Black, Pentecostal Protestant woman with strongly held traditional social and religious beliefs who is uncertain about her financial future -- including having difficulty paying for health care, clothing or food. The opposite is true for a young, white/mestizo Catholic with fewer traditional social and religious beliefs and who is financially secure. But every group has members who have experienced miracles.

"The richest and most well educated are still more likely to experience miracles if their life becomes uncertain or is threatened," Eschler said.

Historically, because basically everyone believed in the supernatural, miracles were more common," he said. But as the world has become more secular, "we are aware that it all could just be random chance, even if we believe in the divine."

What has not changed is that attributions to the divine are a way to bring order into a world where people feel they do not have control.

"In my study, I looked at individual economic hardship, but other studies compare countries impacted by warfare or terrorist extremism to those where there has been relative peace," he said. "We may be more likely to turn to doctors or the government instead of magic and miracles, but there are uncertainties in modern life which some still address with the supernatural.

"What strikes me about this project is that it helps me understand some of the craziness going on in our world today, particularly the recent explosion of conspiracy theories. The people pushing these things are likely doing it because it helps them deal with uncertainty. For them, a world controlled by a villainous conspiracy is better than a world controlled by nobody."