It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Washington, D.C. (October 4, 2022) – Belgian investigators have improved the flavor of contemporary beer by identifying and engineering a gene that is responsible for much of the flavor of beer and some other alcoholic drinks. The research appears in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.
For centuries, beer was brewed in open, horizontal vats. But in the 1970s, the industry switched to using large, closed vessels, which are much easier to fill, empty, and clean, enabling brewing of larger volumes and reducing costs. However, these modern methods produced inferior quality beer, due to insufficient flavor production.
During fermentation, yeast converts 50 percent of the sugar in the mash to ethanol, and the other 50 percent to carbon dioxide. The problem: the carbon dioxide pressurizes these closed vessels, dampening flavor.
Johan Thevelein, Ph.D., an emeritus professor of Molecular Cell Biology at Katholieke Universiteit, and his team had pioneered technology for identifying genes responsible for commercially important traits in yeast. They applied this technology to identify the gene(s) responsible for flavor in beer, by screening large numbers of yeast strains to evaluate which did the best job of preserving flavor under pressure. They focused on a gene for a banana-like flavor “because it is one of the most important flavors present in beer, as well as in other alcoholic drinks,” said Thevelein, who is also founder of NovelYeast, which collaborates with other companies in industrial biotechnology.
“To our surprise, we identified a single mutation in the MDS3 gene, which codes for a regulator apparently involved in production of isoamyl acetate, the source of the banana-like flavor that was responsible for most of the pressure tolerance in this specific yeast strain,” said Thevelein.
Thevelein and coworkers then used CRISPR/Cas9, a revolutionary gene editing technology, to engineer this mutation in other brewing strains, which similarly improved their tolerance of carbon dioxide pressure, enabling full flavor. “That demonstrated the scientific relevance of our findings, and their commercial potential,” said Thevelein.
“The mutation is the first insight into understanding the mechanism by which high carbon dioxide pressure may compromise beer flavor production,” said Thevelein, who noted that the MDS3 protein is likely a component of an important regulatory pathway that may play a role in carbon dioxide inhibition of banana flavor production, adding, “how it does that is not clear.”
The technology has also been successful in identifying genetic elements important for rose flavor production by yeast in alcoholic drinks, as well as other commercially important traits, such as glycerol production and thermotolerance.
Thanks to new technologies and cheaper sequencing, researchers are now able to dig deep into the microbes that supply fermentation for so many wonderful foods and drinks. Revisit ASM's mSystems Editors in Conversation podcast episode to learn more.
### The American Society for Microbiology is one of the largest single life science societies, composed of more than 30,000 scientists and health professionals. ASM's mission is to promote and advance the microbial sciences.
ASM advances the microbial sciences through conferences, publications, certifications, educational opportunities and advocacy efforts. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences
Polygenic Analysis of Tolerance to Carbon Dioxide Inhibition of Isoamyl Acetate “Banana” Flavor Production in Yeast Reveals MDS3 as Major Causative Gene
Great Salt Lake on path to hyper-salinity, mirroring Iranian lake, new research shows
S.J. & JESSIE E. QUINNEY COLLEGE OF NATURAL RESOURCES, UTAH STATE UNIVERSITY
IMAGE: THE GREAT SALT LAKE IS GETTING SALTIER, CREATING A SERIOUS THREAT TO THE ECOSYSTEMS AND THE ECONOMIES THAT DEPEND ON IT. NEW RESEARCH FROM WAYNE WURTSBAUGH EXAMINES THE TRAJECTORY THE TWO HALVES OF THE LAKE MIGHT TAKE ON A PATH TO HYPER-SALINITY.view more
CREDIT: USGS
Starved for freshwater, the Great Salt Lake is getting saltier. The lake is losing sources of freshwater input to agriculture, urban growth and drought, and the drawdown is causing salt concentrations to spike beyond even the tolerance of brine shrimp and brine flies, according to Wayne Wurtsbaugh from Watershed Sciences in the Quinney College of Natural Resources.
Deciphering the ecological and economic consequences of this change is complex and unprecedented, and experts are closely observing another stressed saline lake for clues on what to expect next—Lake Urmia in Iran. This “sister lake” offers obvious, and troubling, parallels to the fate of the Great Salt Lake, according to new research from Wurtsbaugh and Somayeh Sima from Tarbiat Modares University in Tehran.
The history of both lakes has moved along similar trajectories, though at different paces. As less freshwater moves through connected rivers and streams into these lakes, natural salts become more and more concentrated in the water. Native brine flies and brine shrimp tolerate salt, but when saline levels reach certain extreme concentrations—at times reaching saturation—even animals and plants specially adapted to saline environments can struggle. This means as well that millions of migratory birds that depend on these food sources will also struggle, starve, or leave.
Over the decades, expanding urban populations in northern Utah have claimed more freshwater for crops, lawns and faucets, putting gradually intensifying stress on the ecosystem. Now a 20-year drought is pushing salinity levels further towards untenable levels, Wurtbaugh said.
At the Great Salt Lake a causeway divides the lake in distinct halves. With no freshwater inputs, the northern arm of the lake (Gunnison Bay) has become the saltiest with levels at saturation. A transfer of salt into the north arm has allowed the south arm (Gilbert Bay) to stay at a concentration range that allows brine shrimp and brine flies to tolerate the salinity. But salinities in the south are now also increasing to levels stressful for even those hardy species.
The Great Salt Lake and Lake Urmia in Iran were once remarkably similar in size, depth, salinity and geographic setting. High rates of urban growth there also fueled demand for irrigated agriculture and human uses, putting extreme stress on the ecosystem. Compared to the Great Salt Lake, the fate of Lake Urmia is on fast-forward.
Over just 20 years, diversions caused Urmia’s salinity to jump from 190 grams of salt per liter of water to over 350 grams, said Sima. (For comparison, ocean water has a salinity of around 35 grams per liter.) The decline in Lake Urmia’s ecosystem has been precipitous and easy to recognize. It has lost nearly all of its brine shrimp. How long brine shrimp can endure in increasingly salty water in the Great Salt Lake is a question researchers are eager to understand, especially for the south arm where salt concentrations are high, but still sustaining some shrimp.
Gilbert Bay in the north arm of Great Salt Lake has reached an astounding 330 grams per liter (27% salt), and brine shrimp there are nearly absent, halting harvest there by the $70 million brine shrimp industry, said Wurtsbaugh. Now, shrimp harvest in the south arm is also being threatened by increasing salinities. Brine shrimp prefer salt levels at a comfortable 75-160 grams per liter. Brine fly larvae can tolerate higher saline concentrations, but even this uber-hardy species start to feel the pinch when things are so over-the-top.
“Brine fly larvae get smaller at these higher salt levels, signaling ecological stress,” said Wurtsbaugh. “A combined collapse of these two organisms could have catastrophic ecological consequences for migratory bird populations and for the economics of the lake.”
Managers still have some capacity to regulate flow of salt from the north to the south arms of the lake using an underwater berm at a break in the causeway. This flow is used to manage competing needs of mineral extraction companies on the lake and the brine shrimp harvesting industry. But if water development and climate change trigger further losses in water levels, even that option will become limited, Wurtsbaugh said.
Lake Urmia has already lost most of its ecological and cultural function—but the Great Salt Lake has not yet crossed that precipice, say the authors. The ongoing crises at Great Salt Lake and Lake Urmia are not unique—around the globe, other saline lakes are facing a similar crisis and are entirely desiccated or quickly losing water, said Wurtsbaugh. But communities are noticing, which gives him hope. Making any progress will require considerable sacrifice from the water users if the lakes are to be sustained, said Wurtsbaugh.
Contrasting Management and Fates of Two Sister Lakes: Great Salt Lake (USA) and Lake Urmia (Iran)
Study links omega-3s to improved brain structure, cognition at midlife
Holy mackerel! Could eating salmon, cod, tuna, herring or sardines keep our brains healthy and our thinking agile in middle age? New research makes this connection.
UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO
SAN ANTONIO(Oct. 5, 2022) — Eating cold-water fish and other sources of omega-3 fatty acids may preserve brain health and enhance cognition in middle age, new evidence indicates.
Having at least some omega-3s in red blood cells was associated with better brain structure and cognitive function among healthy study volunteers in their 40s and 50s, according to research published online Oct. 5 in Neurology®, the medical journal of the American Academy of Neurology. Faculty of The University of Texas Health Science Center at San Antonio (UT Health San Antonio) and other investigators of the Framingham Heart Study conducted the analysis.
“Studies have looked at this association in older populations. The new contribution here is that, even at younger ages, if you have a diet that includes some omega-3 fatty acids, you are already protecting your brain for most of the indicators of brain aging that we see at middle age,” said Claudia Satizabal, PhD, assistant professor of population health sciences with the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio. Satizabal is the lead author of the study.
Volunteers’ average age was 46. The team looked at the relation of red blood cell omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging. Researchers also studied the effect of omega-3 red blood cell concentrations in volunteers who carried APOE4, a genetic variation linked to higher risk of Alzheimer’s disease.
The study of 2,183 dementia- and stroke-free participants found that:
Higher omega-3 index was associated with larger hippocampal volumes. The hippocampus, a structure in the brain, plays a major role in learning and memory.
Consuming more omega-3s was associated with better abstract reasoning, or the ability to understand complex concepts using logical thinking.
APOE4 carriers with a higher omega-3 index had less small-vessel disease. The APOE4 gene is associated with cardiovascular disease and vascular dementia.
Researchers used a technique called gas chromatography to measure docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations from red blood cells. The omega-3 index was calculated as DHA plus EPA.
“Omega-3 fatty acids such as EPA and DHA are key micronutrients that enhance and protect the brain,” said study coauthor Debora Melo van Lent, PhD, postdoctoral research fellow at the Biggs Institute. “Our study is one of the first to observe this effect in a younger population. More studies in this age group are needed.”
The team divided participants into those who had very little omega-3 red blood cell concentration and those who had at least a little and more. “We saw the worst outcomes in the people who had the lowest consumption of omega-3s,” Satizabal said. “So, that is something interesting. Although the more omega-3 the more benefits for the brain, you just need to eat some to see benefits.”
Researchers don’t know how DHA and EPA protect the brain. One theory is that, because those fatty acids are needed in the membrane of neurons, when they are replaced with other types of fatty acids, that’s when neurons (nerve cells) become unstable. Another explanation may have to deal with the anti-inflammatory properties of DHA and EPA. “It’s complex. We don’t understand everything yet, but we show that, somehow, if you increase your consumption of omega-3s even by a little bit, you are protecting your brain,” Satizabal said.
It's encouraging that DHA and EPA also protected APOE4 carriers’ brain health. “It’s genetics, so you can’t change it,” Melo van Lent said, referring to the vulnerability of this risk group. “So, if there is a modifiable risk factor that can outweigh genetic predisposition, that’s a big gain.”
Association of Red Blood Cell Omega-3 Fatty Acids with MRI Markers and Cognitive Function in Midlife – The Framingham Heart Study
Claudia L. Satizabal, PhD; Jayandra J. Himali, PhD; Alexa S. Beiser, PhD; Vasan S. Ramachandran, MD; Debora Melo van Lent, PhD; Dibya Himali, MS; Hugo J. Aparicio, MD, MPH; Pauline Maillard, PhD; Charles DeCarli, MD; William S. Harris, PhD; and Sudha Seshadri, MD.
First published: Oct. 5, 2022, Neurology
The University of Texas Health Science Center at San Antonio (UT Health San Antonio), a primary driver for San Antonio’s $42.4 billion health care and biosciences sector, is the largest research university in South Texas with an annual research portfolio of $350 million. Driving substantial economic impact with its five professional schools, a diverse workforce of more than 7,000, an annual operating budget of more than $1 billion and a clinical practice that provides more than 2 million patient visits each year, UT Health San Antonio plans to add more than 1,500 higher-wage jobs over the next five years to serve San Antonio, Bexar County and South Texas. To learn about the many ways “We make lives better®,” visit http://uthscsa.edu.
The Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases is dedicated to providing comprehensive dementia care while advancing treatment through clinical trials and research. The Biggs Institute is a National Institute on Aging (NIA)-designated Alzheimer’s Disease Research Center (ADRC). In addition to patient care and research, the Biggs Institute partners with the School of Nursing at UT Health San Antonio to offer the Caring for the Caregiver program.
JOURNAL
Neurology
METHOD OF RESEARCH
Observational study
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Study links omega-3s to improved brain structure, cognition at midlife
ARTICLE PUBLICATION DATE
5-Oct-2022
Can eating omega-3 fatty acids in midlife help your brain?
MINNEAPOLIS – An exploratory study suggests that people who eat more foods with omega-3 fatty acids in midlife may have better thinking skills and even better brain structure than people who eat few foods with the fatty acids. The study is published in the October 5, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology. Omega-3 fatty acids are found in fish such as salmon, sardines, lake trout and albacore tuna. They are also found in foods fortified with the fatty acids or supplements.
“Improving our diet is one way to promote our brain health,” said study author Claudia L. Satizabal, PhD, of the University of Texas Health Science Center at San Antonio. “If people could improve their cognitive resilience and potentially ward off dementia with some simple changes to their diet, that could have a large impact on public health. Even better, our study suggests that even modest consumption of omega-3 may be enough to preserve brain function. This is in line with the current American Heart Association dietary guidelines to consume at least two servings of fish per week to improve cardiovascular health.”
The cross-sectional study involved 2,183 people with an average age of 46 who did not have dementia or stroke. Their levels of omega-3 fatty acids were measured. They took tests of their thinking skills. They had scans to measure brain volumes.
The people in the low group had an average of 3.4% of their total fatty acids as omega-3 fatty acids compared to an average of 5.2% for people in the high group. An optimal level is 8% or higher. Levels between 4% and 8% are considered intermediate. Levels below 4% are considered low.
Researchers adjusted for factors that could affect results. They also applied a mathematical process to normalize the data. They observed that people who ate higher levels of omega-3 fatty acids not only had higher average scores on a test of abstract reasoning, they also had larger average volumes in the hippocampus area of their brains, which plays an important role in memory.
“These results need to be confirmed with additional research, but it’s exciting that omega-3 levels could play a role in improving cognitive resilience, even in middle-aged people,” Satizabal said.
She noted that the study was a snapshot in time, and participants were not followed over time, so the results do not prove that eating omega-3 fatty acids will preserve brain function. It only shows an association.
While the study included a small proportion of people of many races/ethnicities, Satizabal said that the majority of the sample were non-Hispanic white adults, which may limit the ability to apply the results to other groups.
The study was supported by the National Heart, Lung, and Blood Institute, National Institute on Aging and National Institute of Neurological Disorders and Stroke.
Learn more about brain health at BrainandLife.org, home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life® on Facebook, Twitter and Instagram.
When posting to social media channels about this research, we encourage you to use the hashtags #Neurology and #AANscience.
The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with over 38,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.
Being absent while awake: how mind blanking helps us understand ongoing thinking
Study conducted by ULiège GIGA CRC In vivo Imanging researchers shows that "Mind blanking" (MB) is a distinct mental state linked to a recurrent brain profile of globally positive connectivity during ongoing mentation
Researchers from the GIGA CRC In vivo Imaging at the University of Liège (Belgium), the EPF Lausanne and the University of Geneva publish a study that shows that the phenomenology of "mind blanking" challenges the belief that the human mind is always thinking. The study is published in the journal Proceedings of the National Academy of Sciences.
We generally consider that our mind is full of thoughts when we are awake. Like a river stream always running, similarly we entertain our own dynamic mental stream: a thought can lead to another, relevant to what we do or not, ebbing between our inner life and the outer environment. How can the brain sustain such a thought-related mode constantly, though? A study just published in the Proceedings of the National Academy of Sciencesindicates that it actually cannot, and that our brains also need to “go offline” for some moments, which we can experience as blanks in the mind.
Researchers from the University of Liège and EPF Lausanne & University of Geneva re-analyzed a previously collected dataset where healthy participants were reporting their mental state as this was before hearing an auditory probe (beep) while resting in the MRI scanner. The choices were among perceptions of the environment, stimulus-dependent thoughts, stimulus-independent thoughts, and mental absences. Functional images were being collected during this experience-sampling method. The researchers found that mind blanking episodes were reported quite rarely compared to the other states, and that they were re-appearing also scarcely across time. Using machine learning, the researchers further found that our brains during mind-blanking episodes organized in a way where all brain regions were communicating with each other at the same time. This ultra-connected brain pattern was further characterized by high amplitude of the fMRI global signal, which is a proxy of low cortical arousal. In other words, when reporting mind blanking our brains seem to be in a mode similar to that of deep sleep, only that we are awake.
“Mind blanking is a relatively new mental state within the study of spontaneous cognition. It opens exciting avenues about the underlying biological mechanisms that happen during waking life. It might be that the boundaries of sleep and wakefulness might not be that discrete as they appear to be after all”, says the principal investigator Dr. Demertzi Athena, FNRS researcher at GIGA ULiège. “The continuously and rapidly changing brain activity requires robust analysis methods to confirm the specific signature of mind blanking”, continues Dr. Van De Ville Dimitri.
The researchers claim that the rigid neurofunctional profile of mind blanking could account for the inability to report mental content due to the brain’s inability to differentiate signals in an informative way. While waiting for the underlying mechanisms to be illuminated, this work suggests that instantaneous non-reportable mental events can happen during wakefulness, setting mind blanks as a prominent mental state during ongoing experience.
Scientific reference
Mortaheb, S., Van Calster, L., Raimondo, F., Klados, M. A., Boulakis, P. A., Georgoula, K., Majerus, S., Van De Ville, D., & Demertzi, A. (2022). Mind blanking is a distinct mental state linked to a recurrent brain profile of globally positive connectivity during ongoing mentation.Proceedings of the National Academy of Sciences, 119(41), e2200511119.
A small study has found that cats may change their behaviour when they hear their owner’s voice talking in a tone directed to them, the cats, but not when hearing the voice of a stranger or their owner’s voice directed at another person. The study of 16 cats is published in the journal Animal Cognition and adds to evidence that cats may form strong bonds with their owner.
Human tone is known to vary depending on who the speech is directed to, such as when talking to infants and dogs. The tone of human speech has been shown in previous studies to change when directed at cats, but less is known about how cats react to this.
The authors investigated three conditions, with the first condition changing the voice of the speaker from a stranger’s voice to the cat’s owner. The second and third conditions changed the tone used (cat-directed or adult-directed) for the cat’s owner or a stranger’s voice, respectively. The authors recorded and rated the behaviour intensity of cats reacting to the audio, checking for behaviours such as resting, ear moving, pupil dilation, and tail moving, amongst others.
In the first condition, 10 out of the 16 cats showed a decrease in behaviour intensity as they heard three audio clips of a stranger’s voice calling them by their name. However, when hearing their owner’s voice their behaviour intensity significantly increased again. The cats displayed behaviours such as turning their ears to the speakers, increased movement around the room, and pupil dilation when hearing their owners’ voice. The authors suggest that the sudden rebound in behaviour indicates that cats could discriminate their owner’s voice from that of a stranger.
In the second condition, 10 cats (8 of which were the same from the first condition) decreased their behaviour as they heard audio from their owner in an adult-directed tone but significantly increased their behaviour when hearing the cat-directed tone from their owner. The change in behaviour intensity was not found in the third condition when a stranger was speaking in an adult-directed and cat-directed tone.
The authors observed that the cats can distinguish when their owner is talking in a cat-directed tone compared to an adult-directed tone, but did not react any differently when a stranger changes tone.
The small sample size used in this study may not represent all cat behaviour but the authors propose that future research could investigate if their findings can be replicated in more socialised cats that are used to interacting with strangers.
The authors suggest that their findings bring a new dimension to cat-human relationships, with cat communication potentially relying on experience of the speaker’s voice. They conclude that one-to-one relationships are important for cats and humans to form strong bonds.
2. Please name the journal in any story you write. If you are writing for the web, please link to the article.
Animal Cognition is an interdisciplinary journal publishing current research from various backgrounds and disciplines (ethology, behavioral ecology, animal behaviour and learning, cognitive sciences, comparative psychology and evolutionary psychology) on all aspects of animal (and human) cognition in an evolutionary framework.
Machine learning enables an 'almost perfect' diagnosis of an elusive global killer
by Chan Zuckerberg Biohub
Credit: Pixabay/CC0 Public Domain
Sepsis, the overreaction of the immune system in response to an infection, causes an estimated 20% of deaths globally and as many as 20 to 50% of U.S. hospital deaths each year.Despite its prevalence and severity, however, the condition is difficult to diagnose and treat effectively.
The disease can cause decreased blood flow to vital organs, inflammation throughout the body, and abnormal blood clotting. Therefore, if sepsis isn't recognized and treated quickly, it can lead to shock, organ failure, and death. But it can be difficult to identify which pathogen is causing sepsis, or whether an infection is in the bloodstream or elsewhere in the body. And in many patients with symptoms that resemble sepsis, it can be challenging to determine whether they truly have an infection at all.
Now, researchers at the Chan Zuckerberg Biohub (CZ Biohub), the Chan Zuckerberg Initiative (CZI), and UC San Francisco (UCSF) have developed a new diagnostic method that applies machine learning to advanced genomics data from both microbe and host—to identify and predict sepsis cases. As reported on October 20, 2022 in Nature Microbiology, the approach is surprisingly accurate, and has the potential to far exceed current diagnostic capabilities.
"Sepsis is one of the top 10 public health issues facing humanity," said senior author Chaz Langelier, M.D., Ph.D., an associate professor of medicine in UCSF's Division of Infectious Diseases and a CZ Biohub Investigator. "One of the key challenges with sepsis is diagnosis. Existing diagnostic tests are not able to capture the dual-sided nature of the disease—the infection itself and the host's immune response to the infection."
Current sepsis diagnostics focus on detecting bacteria by growing them in culture, a process that is "essential for appropriate antibiotic therapy, which is critical for sepsis survival," according to the researchers behind the new method. But culturing these pathogens is time-consuming and doesn't always correctly identify the bacterium that is causing the infection. Similarly for viruses, PCR tests can detect that viruses are infecting a patient but don't always identify the particular virus that's causing sepsis.
"This results in clinicians being unable to identify the cause of sepsis in an estimated 30 to 50% of cases," Langelier said. "This also leads to a mismatch in terms of the antibiotic treatment and the pathogen causing the problem."
In the absence of a definitive diagnosis, doctors often prescribe a cocktail of antibiotics in an effort to stop the infection, but the overuse of antibiotics has led to increased antibiotic resistance worldwide. "As physicians, we never want to miss a case of infection," said Carolyn Calfee, M.D., M.A.S., a professor of medicine and anesthesia at UCSF and co-senior author of the new study. "But if we had a test that could help us accurately determine who doesn't have an infection, then that could help us limit antibiotic use in those cases, which would be really good for all of us."
Eliminating ambiguity
The researchers analyzed whole blood and plasma samples from more than 350 critically ill patients who had been admitted to UCSF Medical Center or the Zuckerberg San Francisco General Hospital between 2010 and 2018.
But rather than relying on cultures to identify pathogens in these samples, a team led by CZ Biohub scientists Norma Neff, Ph.D., and Angela Pisco, Ph.D., instead used metagenomic next-generation sequencing (mNGS). This method identifies all the nucleic acids or genetic data present in a sample, then compares those data to reference genomes to identify the microbial organisms present. This technique allows scientists to identify genetic material from entirely different kingdoms of organisms—whether bacteria, viruses, or fungi—that are present in the same sample.
However, detecting and identifying the presence of a pathogen alone isn't enough for accurate sepsis diagnosis, so the Biohub researchers also performed transcriptional profiling—which quantifies gene expression—to capture the patient's response to infection.
Next they applied machine learning to the mNGS and transcriptional data to distinguish between sepsis and other critical illnesses and thus confirm the diagnosis. Katrina Kalantar, Ph.D., a lead computational biologist at CZI and co-first author of the study, created an integrated host-microbe model trained on data from patients in whom either sepsis or non-infectious systemic inflammatory illnesses had been established, which enabled sepsis diagnosis with very high accuracy.
"We developed the model by looking at a bunch of metagenomics data alongside results from traditional clinical tests," Kalantar explained. To start, the researchers identified changes in gene expression between patients with confirmed sepsis and non-infectious systemic inflammatory conditions that appear clinically similar, then used machine learning to identify the genes that could best predict those changes.
The researchers found that when traditional bacterial culture identified a sepsis-causing pathogen, there was usually an overabundance of genetic material from that pathogen in the corresponding plasma sample analyzed by mNGS. With that in mind, Kalantar programmed the model to identify organisms present in disproportionately high abundance compared to other microbes in the sample, and to then compare those to a reference index of well-known sepsis-causing microbes.
"In addition to that, we also noted any viruses that were detected, even if they were at lower levels, because those really shouldn't be there," Kalantar explained. "With this relatively straightforward set of rules, we were able to do pretty well."
'Almost perfect' performance
The researchers found that the mNGS method and their corresponding model worked better than expected: They were able to identify 99% of confirmed bacterial sepsis cases, 92% of confirmed viral sepsis cases, and were able to predict sepsis in 74% of clinically suspected cases that hadn't been definitively diagnosed.
"We were expecting good performance, or even great performance, but this was almost perfect," said Lucile Neyton, Ph.D., a postdoctoral researcher in the Calfee lab and co-first author of the study. "By using this approach, we get a pretty good idea of what is causing the disease, and we know with relatively high confidence if a patient has sepsis or not."
The team was also excited to discover that they could use this combined host-response and microbe detection method to diagnose sepsis using plasma samples, which are routinely collected from most patients as part of standard clinical care. "The fact that you can actually identify sepsis patients from this widely available, easy-to-collect sample type has big implications in terms of practical utility," Langelier said.
The idea for the work stemmed from previous research by Langelier, Kalantar, Calfee, UCSF researcher and CZ Biohub President Joe DeRisi, Ph.D., and their colleagues, in which they used mNGS to effectively diagnose lower respiratory tract infections in critically ill patients. Because the method worked so well, "we wanted to see if the same type of approach could work in the context of sepsis," said Kalantar.
Broader implications
The team hopes to build upon this successful diagnostic technique by developing a model that can also predict antibiotic resistance from pathogens detected with this method. "We've had some success doing that for respiratory infections, but no one has come up with a good approach for sepsis," Langelier said.
Furthermore, the researchers hope to eventually be able to predict outcomes of patients with sepsis, "such as mortality or length of stay in the hospital, which would provide key information that would allow clinicians to better care for their patients and match resources to the patients who need them the most," Langelier said.
"There's a lot of potential for novel sequencing approaches such as this to help us more precisely identify the causes of a patient's critical illness," added Calfee. "If we can do that, it's the first step towards precision medicine and understanding what's going on at an individual patient level."Consumer health: What do you know about sepsis?
More information: Katrina L. Kalantar et al, Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults, Nature Microbiology (2022). DOI: 10.1038/s41564-022-01237-2
MY FATHER DIED OF SEPSIS FROM AN INFECTION CAUSED AT THE HOSPITAL USING A BAD SALINE SOLUTION FOR HIS HIP JOINT
Underground microbes may have swarmed ancient Mars
This image captured by the United Arab Emirates' "Amal" ("Hope") probe shows the planet Mars on Feb. 10, 2021. Ancient Mars may have had an environment capable of harboring an underground world teeming with microscopic organisms. That's according to French scientists who published their findings Monday, Oct. 10, 2022. Credit: Mohammed bin Rashid Space Center/UAE Space Agency, via AP, File
Ancient Mars may have had an environment capable of harboring an underground world teeming with microscopic organisms, French scientists reported Monday.
But if they existed, these simple life forms would have altered the atmosphere so profoundly that they triggered a Martian Ice Age and snuffed themselves out, the researchers concluded.
The findings provide a bleak view of the ways of the cosmos. Life—even simple life like microbes—"might actually commonly cause its own demise," said the study's lead author, Boris Sauterey, now a post-doctoral researcher at Sorbonne University.
The results "are a bit gloomy, but I think they are also very stimulating.," he said in an email. "They challenge us to rethink the way a biosphere and its planet interact."
In a study in the journal Nature Astronomy, Sauterey and his team said they used climate and terrain models to evaluate the habitability of the Martian crust some 4 billion years ago when the red planet was thought to be flush with water and much more hospitable than today.
They surmised that hydrogen-gobbling, methane-producing microbes might have flourished just beneath the surface back then, with several inches (a few tens of centimeters) of dirt, more than enough to protect them against harsh incoming radiation. Anywhere free of ice on Mars could have been swarming with these organisms, according to Sauterey, just as they did on early Earth.
Early Mars' presumably moist, warm climate, however, would have been jeopardized by so much hydrogen sucked out of the thin, carbon dioxide-rich atmosphere, Sauterey said. As temperatures plunged by nearly minus 400 degrees Fahrenheit (minus 200 degrees Celsius), any organisms at or near the surface likely would have buried deeper in an attempt to survive.
This image made available by NASA shows the Jezero Crater area on the planet Mars, captured by the Mars Reconnaissance Orbiter. Ancient Mars may have had an environment capable of harboring an underground world teeming with microscopic organisms. That's according to French scientists who published their findings, Monday, Oct. 10, 2022. Credit: NASA/JPL-Caltech/USGS via AP, File
By contrast, microbes on Earth may have helped maintain temperate conditions, given the nitrogen-dominated atmosphere, the researchers said.
The SETI Institute's Kaveh Pahlevan said future models of Mars' climate need to consider the French research.
Pahlevan led a separate recent study suggesting Mars was born wet with warm oceans lasting millions of years. The atmosphere would have been dense and mostly hydrogen back then, serving as a heat-trapping greenhouse gas that eventually was transported to higher altitudes and lost to space, his team concluded.
The French study investigated the climate effects of possible microbes when Mars' atmosphere was dominated by carbon dioxide and so is not applicable to the earlier times, Pahlevan said.
"What their study makes clear, however, is that if (this) life were present on Mars" during this earlier period, "they would have had a major influence on the prevailing climate," he added in an email.
The best places to look for traces of this past life? The French researchers suggest the unexplored Hellas Planita, or plain, and Jezero Crater on the northwestern edge of Isidis Planita, where NASA's Perseverance rover currently is collecting rocks for return to Earth in a decade.
Next on Sauterey's to-do list: looking into the possibility that microbial life could still exist deep within Mars.
![Underground microbes may have swarmed ancient Mars](https://scx1.b-cdn.net/csz/news/800a/2022/underground-microbes-m.jpg "This image captured by the United Arab Emirates' "Amal" ("Hope") probe shows the planet Mars on Feb. 10, 2021. Ancient Mars may have had an environment capable of harboring an underground world teeming with microscopic organisms. That's according to French scientists who published their findings Monday, Oct. 10, 2022. Credit: Mohammed bin Rashid Space Center/UAE Space Agency, via AP, File")
