Publisher Health

The better we understand cellular processes such as RNA regulation, the better molecular therapies can be developed. Until now, it has been especially difficult to track the regulation of non-coding RNA, which is RNA that is not further converted into proteins. A research team from Helmholtz Munich and the Technical University of Munich (TUM) has now developed a minimally invasive reporter system that enables highly sensitive monitoring of RNA production of both coding and non-coding RNA.
For cellular processes, our genetic DNA information is transcribed into RNA, which then undergoes further processing before it either serves as a blueprint for proteins or performs a cellular function itself. Which types of RNA are produced and in which quantities reveals a lot about the condition of our cells. In case of an infection, for example, cells produce increased amounts of RNA molecules that code for proteins involved in the immune response.
When DNA molecules are translated into proteins via RNA, researchers can track the process with existing reporter systems. However, not all human genes encode proteins. The majority of human genes is non-coding, including genes for long non-coding RNAs (lncRNA). These are RNA molecules with more than 200 building blocks that do not act as blueprints for proteins. Instead, they control important processes in cells. Initial research shows that lncRNA is involved in such processes as regulating RNA production, the organization of structures in the cell nucleus or in switching certain enzymes on and off.
Despite their importance for cellular processes, it has been difficult to investigate lncRNAs with existing methods. So far, this was only partially possible, for example in fixed cells at specific time points, because classical reporter systems based on the translation into proteins cannot be used.
INSPECT permits the monitoring of non-coding RNA
A solution has now been found in the form of a new reporter system: INSPECT. A team working with Gil Westmeyer, Professor of Neurobiological Engineering at TUM and the Director of the Institute for Synthetic Biomedicine at Helmholtz Munich, has now published the newly developed reporter system in the journal Nature Cell Biology.
“Unlike previous methods, INSPECT encodes sequences for reporter proteins in modified introns. These are sequences in the pre-mature RNA molecule that are removed naturally and eliminated by the cell during processing. INSPECT stabilizes the introns such that, rather than being degraded after removal, they are transported to the cellular cytoplasm where they are translated into reporter proteins,” explains first author Dong-Jiunn Jeffery Truong. The researchers can then use conventional methods to detect reporter protein signals such as fluorescence.
INSPECT modifies neither the completed RNA nor the proteins
The new molecular biology tool thus not only solves the problem of tracking the generation of non-coding RNA, but also offers advantages for studying coding RNA. Current reporter systems often run the risk of damaging the RNA or proteins under investigation, for example, because they must be fused directly to the RNA being studied in order to be co-translated into proteins. Rather than modifying the completed RNA or the proteins, INSPECT modifies the introns.
The team has demonstrated the function of INSPECT using various examples of coding and non-coding RNA. They tracked the production of RNA for interleukin 2, a protein that is produced in larger quantities in response to infections. They have also achieved highly sensitive monitoring of the production of two lncRNAs and tracked changes in regulation during the investigation period.
“INSPECT adds an important molecular biology tool to the biomedical toolbox. It makes it easier to study the role of certain non-coding RNA molecules in cell development and to explore how their regulation can be modulated, for example, to prevent them from turning into cancer cells,” says Prof. Westmeyer. “In combination with the minimally invasive reporter system EXSISERS, which we previously developed to study protein isoforms, it may be possible in the future to study an entire genetic regulation process from RNA processing to the production of specific protein variants in living cells.”
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Materials provided by Helmholtz Munich. Note: Content may be edited for style and length.

A recent study by the University of Eastern Finland and Kuopio University Hospital shows that carnitine intake in the first postnatal weeks promotes better growth and larger brain size at term equivalent age in very preterm infants. Carnitine intake from breast milk in particular seems to be associated with better growth. The findings were published in Nutrients.
Carnitine is a compound similar to amino acids, and its primary function in the body is to transport long-chain fatty acids to the cell powerhouse mitochondria for energy production. In addition, earlier studies have suggested that carnitine may also be involved in nervous system development. Carnitine is both obtained from nutrition and produced by the body. In preterm infants, the main sources of carnitine are breast milk and infant formulae containing carnitine.
Very preterm infants have an increased risk for developing carnitine deficiency
“Very preterm infants born before 32 weeks of gestation are at risk of developing carnitine deficiency due to limited tissue stores, immature endogenous synthesis, and insufficient intake from nutrition. Due to rapid growth, they also have an increased need for carnitine,” says Postdoctoral Researcher Suvi Manninen of the University of Eastern Finland.
The associations of carnitine intake and serum carnitine levels with the growth and brain size of preterm infants have not been studied in a longitudinal setting before. In this new study, the researchers measured the carnitine levels of preterm infants at three time points and calculated the intake of nutrients, including carnitine, over the first five postnatal weeks. The researchers examined the associations of serum carnitine levels and nutrition with the growth of weight, length and head circumference, as well as brain diameters determined by magnetic resonance imaging.
The intake of carnitine, and free carnitine and short-chain acylcarnitine concentrations in serum, were associated with the growth of preterm infants and with cerebellar size in particular. In addition to these associations, dietary carnitine was found to correlate with free carnitine and short-chain acylcarnitine concentrations in serum, suggesting that these carnitine levels can be considered markers of carnitine intake.
Is carnitine supplementation necessary?
“Both breast milk and infant formulae contain varying amounts of carnitine. Parenteral nutrition, i.e., nutrient preparations given intravenously, on the other hand, usually do not contain carnitine,” says Adjunct Professor, Neonatologist Ulla Sankilampi from Kuopio University Hospital.
It is possible to give carnitine parenterally, but evidence on the benefits of carnitine supplementation remains contradictory and it is not generally recommended in the current parenteral nutrition guidelines for preterm infants.
“Further research is still needed on whether carnitine supplementation is necessary during prolonged parenteral nutrition and, on the other hand, whether breast milk should be enriched with carnitine in some situations in the dietary treatment of preterm infants.”
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Materials provided by University of Eastern Finland. Note: Content may be edited for style and length.

It’s not uncommon for people to lose their sense of taste and smell due to a Covid-19 infection. In others, the disease has had an even stronger impact on the nervous system, with effects ranging from lasting concentration problems to strokes. Now, researchers led by Professor Gregor Hutter from the Department of Biomedicine at the University of Basel and University Hospital of Basel have reported new insights into the development of “neuro-Covid” in the journal Nature Communications.
Specifically, the team investigated how different severities of neuro-COVID can be detected and predicted by analyzing the cerebrospinal fluid and blood plasma of affected individuals. Their findings also offer some indications of how to prevent neurological damage due to Covid-19.
The study included 40 Covid-19 patients with differing degrees of neurological symptoms. In order to identify typical changes associated with neuro-Covid, the team of researchers compared these individuals’ cerebrospinal fluid and blood plasma with samples from a control group. They also measured the brain structures of test subjects and surveyed participants 13 months after their illness in order to identify any lasting symptoms.
Holes in the blood-brain barrier
Particularly in the group with the most serious neurological symptoms, the researchers identified a link with an excessive immune response. On the one hand, affected individuals showed indications of impairment of the blood-brain barrier, which the study’s authors speculate was probably triggered by a “cytokine storm” — a massive release of pro-inflammatory factors in response to the virus.
On the other hand, the researchers also found antibodies that targeted parts of the body’s own cells — in other words, signs of an autoimmune reaction — as a result of the excessive immune response. “We suspect that these antibodies cross the porous blood-brain barrier into the brain, where they cause damage,” explains Hutter. They also identified excessive activation of the immune cells specifically responsible for the brain — the microglia.
Blood test as a long-term objective
In a further step, Hutter and his team investigated whether the severity of neurological symptoms is also perceptible in brain structures. Indeed, they found that people with serious neuro-Covid symptoms had a lower brain volume than healthy participants at specific locations in the brain and particularly at the olfactory cortex — that is, the area of the brain responsible for smell.
“We were able to link the signature of certain molecules in the blood and cerebrospinal fluid to an overwhelming immune response in the brain and reduced brain volume in certain areas, as well as neurological symptoms,” says Hutter, adding that it is now important to examine these biomarkers in a greater number of participants. The aim would be to develop a blood test that can already predict serious cases, including neuro-Covid and long Covid, at the start of an infection.
Targets for preventing consequential damage
These same biomarkers point to potential targets for drugs aimed at preventing consequential damage due to a Covid-19 infection. One of the biomarkers identified in blood, the factor MCP-3, plays a key role in the excessive immune response, and Hutter believes there is the potential to inhibit this factor medicinally.
“In our study, we show how coronavirus can affect the brain,” he says. “The virus triggers such a strong inflammatory response in the body that it spills over to the central nervous system. This can disrupt the cellular integrity of the brain.” Accordingly, Hutter says that the primary objective must be to identify and halt the excessive immune response at an early stage.
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Materials provided by University of Basel. Original written by Angelika Jacobs. Note: Content may be edited for style and length.

That is actually the case. Both animals have proteins in their bodies that enables them to light up.
Researchers from the University of Copenhagen now invented a way to use these fluorescent proteins to gain new knowledge about brain diseases like depression, Alzheimer’s, and strokes.
“We developed a new method to visualize the blood flow in the brain in experimental mice for months,” says professor at the Center for Translational Neuromedicine at the University of Copenhagen, Hajime Hirase. He is one of the researchers behind the new method.
Before the newly developed method, the researchers used chemical dyes instead. That dye only made it possible to observe the blood flow in the brain for a few hours at a time.
Marie Curie fellow Antonis Asiminas who also worked on the method adds that the method brings brand new possibilities to track disease progression over time.

As growing numbers of adolescents who identify as transgender are prescribed drugs to block puberty, the treatment is becoming a source of confusion and controversy.We spent months scouring the scientific evidence, interviewing doctors around the world and speaking to patients and families.Here’s a closer look at what we found. →

A decades-long effort to lower the stillbirth rate in the United States has stalled, as has progress in closing a persistent gap in excess stillbirths experienced by Black women compared with White women, according to a Rutgers-led study.
“Over the last 40 years, we have reduced certain risk factors for stillbirth, such as smoking and alcohol use before and during pregnancy, but these gains have been countered by substantial increases in other risk factors, like obesity and structural racism,” said Cande Ananth, chief of Epidemiology and Biostatistics in the Department of Obstetrics, Gynecology and Reproductive Sciences at the Rutgers Robert Wood Johnson Medical School and lead author of the study published in The Lancet Regional Health — Americas.
“Our findings illustrate that past progress has now been offset by these newly identified risks,” Ananth said.
To determine how cultural and environmental factors impact stillbirths among Black and White women in the U.S., Ananth and a team of Rutgers obstetricians examined changes in stillbirth rates between 1980 and 2020.
Using data compiled by the National Center for Health Statistics of the Centers for Disease Control and Prevention and covering all 50 states and the District of Columbia, the researchers measured how maternal age, year of death (indicative of changes in prenatal and intrapartum care and other factors) and maternal birth cohorts (indicative of social and environmental elements, such as socioeconomic status, education, nutrition and substance use at the time of the women’s birth) shaped stillbirth trends.
More than 157 million live births and nearly 711,000 stillbirths delivered at 24 or more weeks over the last four decades in the U.S. were included in the study.

Cambridge researchers have highlighted how lack of access to a computer was linked to poorer mental health among young people and adolescents during COVID-19 lockdowns.
The team found that the end of 2020 was the time when young people faced the most difficulties and that the mental health of those young people without access to a computer tended to deteriorate to a greater extent than that of their peers who did have access.
The COVID-19 pandemic had a significant effect on young people’s mental health, with evidence of rising levels of anxiety, depression, and psychological distress. Adolescence is a period when people are particularly vulnerable to developing mental health disorders, which can have long-lasting consequences into adulthood. In the UK, the mental health of children and adolescents was already deteriorating before the pandemic, but the proportion of people in this age group likely to be experiencing a mental health disorder increased from 11% in 2017 to 16% in July 2020.
The pandemic led to the closure of schools and an increase in online schooling, the impacts of which were not felt equally. Those adolescents without access to a computer faced the greatest disruption: in one study 30% of school students from middle-class homes reported taking part in live or recorded school lessons daily, while only 16% of students from working-class homes reported doing so.
In addition to school closures, lockdown often meant that young people could not meet their friends in person. During these periods, online and digital forms of interaction with peers, such as through video games and social media, are likely to have helped reduce the impact of these social disruptions.
Tom Metherell, who at the time of the study was an undergraduate student at Fitzwilliam College, University of Cambridge, said: “Access to computers meant that many young people were still able to ‘attend’ school virtually, carry on with their education to an extent and keep up with friends. But anyone who didn’t have access to a computer would have been at a significant disadvantage, which would only risk increasing their sense of isolation.”
To examine in detail the impact of digital exclusion on the mental health of young people, Metherell and colleagues examined data from 1,387 10-15-year-olds collected as part of Understanding Society, a large UK-wide longitudinal survey. They focused on access to computers rather than smartphones, as schoolwork is largely possible only on a computer while at this age most social interactions occur in person at school.

Six-year-old Cohen survives off the machines in his home and his mum’s energy bills could rise to more than £3,000 a year.Cohen has DiGeorge syndrome and 15q11.2 genetic deletions which means he can’t walk, talk or digest food properly. Lauren, Cohen’s mum said: “The cost of living crisis, for most people, it’s ‘Oh we just won’t go on holiday this year’ but for us it’s our son’s life.”Video by Gem O’Reilly