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Common approaches to analyze DNA from a community of microbes, called a microbiome, can yield erroneous results, in large part due to the incomplete databases used to identify microbial DNA sequences. A team led by Aiese Cigliano of Sequentia Biotech SL, and Clemente Fernandez Arias and Federica Bertocchini of the Centro de Investigaciones Biologicas Margarita Salas, report these findings in a paper published February 8 in the open-access journal PLOS ONE.
Microbiomes have been the focus of intense research efforts in recent decades. These studies range from attempts to understand conditions such as obesity and autism by examining the human gut, to finding microbes that degrade toxic compounds or produce biofuels by studying environmental communities. The most commonly used methods for studying microbial communities rely on comparing the DNA obtained from a biological sample to sequences in genome databanks. Therefore, researchers can only identify DNA sequences that are already in the databases — a fact that may severely compromise the reliability of microbiome data in unexpected ways.
To test the consistency of current methods of microbiome analysis, researchers used computer simulations to create virtual microbiome communities that imitate real-world bacterial populations. They used standard techniques to analyze the virtual communities and compared the results with the original composition. The experiment showed that results from DNA analyses can bear little resemblance to the actual composition of the community, and that a large number of the species “detected” by the analysis are not actually present in the community.
For the first time, the study demonstrates significant flaws in the techniques currently used to identify microbial communities. The researchers conclude that there is a need for increased efforts to collect genome information from microbes and to make that information available in public databases to improve the accuracy of microbiome analysis. In the meantime, the results of microbiome studies should be interpreted with caution, especially in cases where the available genomic information from those environments is still scarce.
The authors add: “This study reveals intrinsic constraints in metagenomic analysis stemming from current database limitations and how genomic information is used. To enhance the reliability of metagenomic data, a research effort is necessary to improve both database contents and analysis methods. Meanwhile, metagenomic data should be approached with great care.”

The risk factors linked to cognitive decline in older adults explain a surprisingly modest amount about the large variation in mental abilities between older people, according to a new national study.
Researchers found that the factors most commonly associated with cognitive functioning — including socioeconomic status, education and race — explained only 38% of the variation in functioning among Americans at age 54.
Health behaviors such as avoiding obesity and smoking and participating in vigorous exercise had only very small effects on functioning by the time people reached their mid-50s.
In addition, the factors studied explained only 5.6% of the variation in how quickly cognitive functioning declined in people between age 54 and 85.
“There’s still a lot we don’t know about why cognitive functioning varies so much between older adults,” said Hui Zheng, lead author of the study and professor of sociology at The Ohio State University.
“More research is urgently needed to discover the main causes of how quickly cognitive functioning declines and how we can slow down its progression.”
Zheng conducted the study with Kathleen Cagney, professor of sociology at the University of Michigan, and Yoonyoung Choi, a graduate student at Ohio State. Their study was published today (Feb 8, 2023) in the journal PLOS ONE.

Data came from 7,068 participants in the 1996-2016 Health and Retirement Study. Participants were born between 1931 and 1941. Researchers measured their cognitive functioning at age 54 and how it declined until they were 85.
The study provides a more robust analysis than prior studies because it used a large, nationally representative sample and followed participants for decades, using a broad range of possible predictors of cognitive functioning, Zheng said.
The most important predictor of cognitive functioning at age 54 was education, which explained about 25% of the difference between people, results showed. That was followed by race, household wealth and income, parental education, occupation and depression.
The contributions of chronic diseases, health behaviors, gender, marital status and religion were rather small — less than 5%.
The researchers found that the variation in cognitive functioning at age 54 was three times as much as the variation in how quickly the participants declined over the next 30 years.

“We found that the rate of cognitive decline was much more similar between participants than the baseline of cognitive functioning we found at age 54,” Zheng said.
Overall, all the factors examined in this study only explained 5.6% of variation in the decline of cognitive functioning with age.
“From an intervention perspective, that suggests it is much more important to try to improve functioning at the baseline than trying to slow down the rate of decline.”
Zheng said one particularly interesting finding was that the number of years of education was not associated with the rate of decline in functioning after the age of 54, but having a college degree did have a small protective effect, which explained 1.7% of the variation in the decline with age.
The value of a college degree supports the “cognitive reserve” hypothesis that, in some people, their brains have the ability to find alternative ways to solve problems and cope with challenges when they have some type of damage to the brain.
“College may provide an especially rich environment for cognitive development that may help people develop this cognitive reserve,” Zheng said.
One explanation for declines in cognitive functioning that this study could not account for is a genetic factor — the APOE4 gene. That gene has been found to increase the risk of developing dementia, including Alzheimer’s disease.
But other studies show that dementia, including Alzheimer’s disease, accounts for only 41% of cognitive decline among the elderly.
“Cognitive decline is pervasive in older adults, even those without dementia, which is why it is important to study other predictors of cognitive functioning and decline,” Zheng said.
“But still, our study raises more questions than it answers. We have a long way to go to understand the trajectories of cognitive functioning in older adults.”

Published14 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, ReutersBy Nadine YousifBBC News, TorontoThe Canadian government has pledged nearly C$200bn ($149bn; £124bn) in funding over 10 years to aid the country’s ailing healthcare system. The funding was pitched as a generational fix for the system in an announcement on Tuesday.For months, Canada’s hospitals have grappled with a lack of staff and lengthy wait times for care. A few reports have since emerged of patients dying while awaiting treatment.Canada’s healthcare system is funded by the taxpayer to offer free, universal access to necessary hospital and doctor visits for all citizens and permanent residents.It is paid for using a mix of federal and provincial money, but administered at the local level. Around 25% of funding is from the federal government through the Canada Health Transfer. Prime Minister Justin Trudeau made the funding pitch to Canada’s provincial premiers, who have repeatedly pushed Mr Trudeau to increase federal spending on healthcare. Mr Trudeau, however, had said he would not increase funding without strings attached. Following a meeting with the premiers on Tuesday, Mr Trudeau said that his government is “taking action today so Canadians can continue to have trust in our public system.””This is a big country, built on big progressive ideas,” he said. “Few are more central to who we are as Canadians than the promise of universal, publicly funded healthcare.”His proposal includes a total of $196.1bn to be spent on healthcare over the course of a decade – $46.2bn of which is new money on top of what has already been budgeted. The total amounts to around a 61% increase in the Canada Health Transfer to provinces over the next 10 years.It is less than what Canada’s premiers wanted – they had asked Mr Trudeau for an annual top-up of $28bn. Manitoba’s premier, Heather Stefanson, said she was “disappointed” with the amount. Ontario’s premier, Doug Ford, called it a “starting point”. The premiers said they are now assessing the proposal. Mr Trudeau said the money his government has put up is a “major investment in healthcare”, but he added that money alone will not fix the country’s faltering system. He said he will also negotiate separate agreements with each province to address unique regional issues. The government has also asked provinces for better healthcare data so they can assess the system’s performance better. Canada: Why ERs are struggling to stay open nationwidePremiers demand to meet Trudeau over health crisisHealthcare has often been a point of pride in Canada, but, like many other countries, its system has grappled with mounting pressure since the Covid-19 pandemic, with growing wait times to access care.In Nova Scotia, a 67-year-old woman reportedly died after giving up on a seven-hour wait to see a doctor at a local hospital’s emergency department. Patients have also been affected by a growing backlog for surgeries and diagnostic procedures. Canada spends over 10% of its GDP on healthcare, about the same as the UK, compared with more than 16% for the US, according to World Bank data.Its healthcare system ranks higher than the US, but lower than the UK and others in some international comparisons. More on this storyWhy Canada’s ERs are struggling to stay open2 September 2022Parents stressed over flu season pain med shortage17 November 2022Canada seeks to delay euthanasia for mentally ill6 days ago

Researchers from Charité — Universitätsmedizin Berlin, the Max Planck Institute for Molecular Genetics (MPIMG), and the University Hospital Schleswig-Holstein (UKSH) have investigated in detail how BPTA syndrome, an extremely rare hereditary condition, arises. A change in the charge of a protein disrupts cellular self-organization, resulting in a developmental disorder. The team also identified hundreds of comparable genetic changes associated with various conditions, such as brain development disorders and predisposition to cancer. This mechanism, which has now been described in the journal Nature*, could be the cause of numerous unexplained diseases and health conditions.
Thousands of genetic changes are associated with various diseases, disorders, and conditions. But how, exactly, these mutations produce disease is seldom clear. This is because the changes relate to sections of proteins with a disordered three-dimensional structure and a function inside the cell about which little is known so far. “It’s hard to study what these kinds of protein segments are responsible for doing because in many cases, they have to interact with other molecules before producing their effects,” says Dr. Martin Mensah of the Institute of Medical and Human Genetics at Charité. He is one of the study’s two first authors and a fellow in the Digital Clinician Scientist Program, which Charité operates with the Berlin Institute of Health (BIH) at Charité. “Taking BPTA syndrome as an example, we have now described in detail how changes in disordered areas of proteins can cause a genetic disease.” This means the research team has discovered a new mechanism that causes hereditary diseases- and, according to the study, one that is surprisingly not all that rare after all.
BPTA stands for “brachyphalangy, polydactyly and tibial aplasia/hypoplasia.” Patients have severe malformations affecting the extremities, face, nervous system and bones, and other organs. There are fewer than ten documented cases worldwide, making this disease extremely rare. To identify the cause of this syndrome, the researchers decoded the genetic information of five of the affected patients and discovered a change in the HMGB1 protein in all of them. Due to what is known as a frameshift mutation, the final one-third of the protein’s structure has a positive charge rather than the usual negative one.
The nucleolus solidifies
The change in the charge means that HMGB1 resembles proteins that tend to cluster in the nucleolus, a small area in the nucleus of the cell where parts of the cell’s protein factories are assembled. This role makes the nucleolus crucial to a cell’s viability. As the research team showed based on experiments on isolated proteins and cell cultures, the mutated HMGB1 protein, which now has a positively charged end section, is improperly drawn toward the nucleolus. And because the extension of the protein has also grown stiffer, the HMGB1 protein also clumps together. “Under a microscope, we were able to see that this causes the nucleolus to lose its own liquid-like properties and become increasingly rigid,” explains Dr. Henri Niskanen, a researcher at MPIMG and the study’s other first author.
This solidification of the nucleolus adversely affects the cells’ vital functioning. More cells with the mutated protein than without the mutation died in the culture. Prof. Dr. Malte Spielmann, Director of the Institute of Human Genetics at UKSH and one of the study’s three lead authors, offers his conclusion: “We showed how mutations in disordered sections of proteins can cause a disease. When there is a change in the charge, the protein wrongly accumulates in the nucleolus, adversely affecting its vital functioning. This leads to a disorder in the organism’s development.”
New explanations for existing diseases
Following their initial findings, the researchers searched databases containing the DNA sequences of thousands of people, looking for similar cases. They were able to identify more than 600 mutations in 66 proteins that gave the final part of the protein both a positive charge and stiffer properties. Of those mutations, 101 had previously been associated with various diseases, including neurodevelopmental disorders and increased susceptibility to cancer. For 13 selected proteins, the team studied the cell culture to see whether the mutations gave them a particular affinity for the nucleolus. That was the case for 12 of them. About half of the proteins tested impaired the functioning of the nucleolus, so they were similar to the disease mechanism found for BPTA syndrome.
“The mechanism that causes this disease, which we discovered in BPTA syndrome, could be implicated in many other diseases and conditions as well,” says Prof. Dr. Denise Horn, lead author of the study who works at the Institute of Medical and Human Genetics at Charité. “So we’ve opened a door that could help to explain many other diseases. The real work starts now.”
The newly identified mechanism could also lead to new therapeutic approaches, at least for some diseases. “Tumors are attributable to genetic changes in the affected cells,” explains Dr. Denes Hnisz, the head of a research group at MPIMG and the study’s third lead author. “This means we may be able to prevent cancer from developing in the future by intervening in the cell’s self-organization, which is mediated by disordered sections of proteins.”

Endocrine-disrupting chemicals (EDCs) in plastics may contribute to diabetes risk in women, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
Phthalates are chemicals widely used in plastics such as personal care products, children’s toys, and food and beverage packaging. Phthalate exposure is associated with reduced fertility, diabetes and other endocrine disorders.
“Our research found phthalates may contribute to a higher incidence of diabetes in women, especially White women, over a six-year period,” said Sung Kyun Park, Sc.D., M.P.H., of the University of Michigan School of Public Health in Ann Arbor, Mich. “People are exposed to phthalates daily increasing their risk of several metabolic diseases. It’s important that we address EDCs now as they are harmful to human health.”
The researchers studied 1,308 women from the Study of Women’s Health Across the Nation-(SWAN) over six years to see if phthalates contributed to incident diabetes in this population. About 5% of the women developed diabetes over six years. These women had concentrations of phthalates in their urine similar to middle-aged women in the U.S. in the early 2000s, when the urine samples were collected. White women exposed to high levels of some phthalates had a 30-63% higher chance of developing diabetes, while the harmful chemicals were not linked to diabetes in Black or Asian women.
The other authors of this study are Mia Q. Peng, Carrie A. Karvonen-Gutierrez and Bhramar Mukherjee of the University of Michigan School of Public Health; and William H. Herman of the University of Michigan School of Public Health and the University of Michigan Medical School in Ann Arbor, Mich.
The study received funding from the National Institutes of Health, the SWAN Repository, the National Center for Research Resources and the National Center for Advancing Translational Sciences.
“Our research is a step in the right direction towards better understanding phthalates’ effect on metabolic diseases, but further investigation is needed,” Park said.