Month: March 2021

An Eye for Wine: Alcohol May Prevent Cataracts

Two people clinking wine glasses together. Photo by Jep Gambardella from Pexels

A study from the UK has shown that people who drink up to 14 units of alcohol a week have a reduced risk of developing cataracts, with red wine having an even more pronounced effect.

Drinking less than 14 units of alcohol (or about six pints of beer, or six glasses of wine) is in line with the British Chief Medical Officer’s low risk drinking guidelines.

Cataracts are a major cause of impaired eyesight and blindness, mainly in older people. Cataract removal is simple, and is the most common surgery carried out by the UK’s National Health Service. The NHS considers drinking to be a risk factor for cataracts.

Researchers from Moorfields eye hospital in London and University College London’s institute of ophthalmology studied the medical and lifestyle history of nearly half a million participants in either the UK Biobank or Epic-Norfolk longitudinal health studies.

The results showed that people who drank within the 14 units a week guideline were less likely to have cataract surgery. Wine drinkers were even less likely to have it, compared to those who consumed beer or spirits. In the Epic-Norfolk study, drinking wine at least five times a week meant a 23% reduced chance of cataract removal than non-drinkers, while those in the UK Biobank study were 14% less likely.

“Cataract development may be due to gradual damage from oxidative stress during ageing. The fact that our findings were particularly evident in wine drinkers may suggest a protective role of polyphenol antioxidants, which are especially abundant in red wine,” said first author Dr Sharon Chua.

Research leader Dr Anthony Khawaja added: “We observed a dose-response with our findings – in other words, there was evidence for reducing chance of requiring future cataract surgery with progressively higher alcohol intake, but only up to moderate levels within current guidelines.”

The authors emphasised that there was still not a causal link between alcohol consumption and reduced cataract surgeries despite the association.

Dr Sadie Boniface, research head at the Institute of Alcohol Studies thinktank, cast doubt on the findings. She said that longitudinal studies such as UK Biobank may not accurately represent health across the nation because many volunteers were often in good health.

“Comparing the health of moderate drinkers with that of non-drinkers also carries problems. Non-drinkers are a diverse group, including people who have stopped drinking because of health problems. This means moderate drinking can artificially look like it carries health benefits, because the moderate drinkers are compared to people on average in poor health,” said Dr Boniface.

“The bigger effect seen among wine drinkers may be because of other characteristics of this group to do with their cataract risk which weren’t accounted for. If the amount of alcohol or number of units somebody drinks was having a direct effect, you’d expect this to be similar regardless of drink type.”

Source: The Guardian

Osteoporosis Rates are Increasing in US Women

Osteoporosis is present in Almost one in five American women aged 50 and older, according to data from the National Health and Nutrition Examination Survey (NHANES), and the osteoporosis rates are increasing.

Neda Sarafrazi, PhD, of the National Center for Health Statistics (NCHS) in Hyattsville, Maryland, and colleagues reported the findings in an NCHS Data Brief.

Osteoporosis is defined as bone mineral density (BMD) value at least 2.5 standard deviations below young-adult average at the femoral neck or lumbar spine was present, and was measured in NHANES with dual x-ray absorption dosimetry.

In cross-sectional survey data from 2017-2018, 19.6% of women 50 and older had osteoporosis at the femoral neck, lumbar spine, or both. In men, the age-adjusted prevalence was only 4.4% of men 50 and older.

All in all, osteoporosis was present in 12.6% of all American adults 50 and older, which was defined as a bone mineral density (BMD) value at least 2.5 standard deviations below the average for young adults at the femoral neck or lumbar spine.

Osteoporosis, as to be expected, was far more common among older adults, affecting 17.7% of all men and women 65 and older, versus 8.4% of those ages 50-64. In women ages 65 and older, the prevalence was 27% and at ages 50-64 was 13.1%. In men, prevalence values were 5.7% in those 65 and older and 3.3% for those 50-64.

Sarafrazi’s team found that osteoporosis had become slightly more prevalent over the years. In 2007-2008, 9.4% of Americans 50 and older had osteoporosis. While rates remained steady throughout for men, a big uptick of 5 percentage points was seen for women.

“Monitoring the prevalence of osteoporosis and low bone mass may inform public health programs that focus on reducing or preventing osteoporosis and its consequences,” suggested Sarafrazi’s group. “Healthy People 2020 has a goal of 5.3% or less for the prevalence of osteoporosis at the femur neck for adults aged 50 and over.”

“In the United States, the prevalence of osteoporosis among adults aged 50 and over at the femur neck only was 6.3% and has not met the 2020 goal,” they stressed.

The data also revealed high rates of low bone mass, a precursor of osteoporosis, defined as BMD of 1 to 2.5 standard deviations below the average for young adults.

Among all adults ages 50 and older, 43.1% had low bone mass at the femoral neck, lumbar spine, or both. Among women, prevalence was 51.5% and among men 33.5% .

The overall rate reached 47.5% in those 65 and older. However, older age seemed to be less of a factor for women, with almost no difference between the 50-64 and 65-plus age groups.

However, the prevalence rates of low bone mass in both sexes held steady during the decade between 2007-2008 and 2017-2018.  

Source: MedPage Today

Journal information: Sarafrazi N, et al “Osteoporosis or low bone mass in older adults: United States, 2017–2018” NCHS Data Brief 2021; No 405.

New X-Ray Tool to Spy into Virus’ Cellular Subversion

A new X-Ray tool called the Compact Cell-Imaging Device (CoCID) will seek to answer the questions of how viruses penetrate cells, and disrupt and subvert cellular processes to produce more virus copies.

In order to advance research into viral diseases, the aim of the project is to develop a particularly suitable cell-imaging method – which has so far been of limited access to researchers – for extensive application in medical research.

A particularly high-performance method of cell-imaging is soft X-ray microscopy (SXM), explained Dr Venera Weinhardt from the Centre for Organismal Studies of Heidelberg University. A physicist specialising in innovative X-ray procedures, she is head of the Molecular Virology division at the Department of Infectious Diseases of Heidelberg University Hospital. “SXM makes use of the special properties of the soft X-ray spectrum in order to look into the interior of a single intact cell and generate three-dimensional images of its whole internal structure. That also reveals the changes induced by viral infections,” explained Dr Weinhardt. 
Thus, soft X-ray microscopy is distinct from methods like electron microscopy, which can visualise individual parts of a cell but not the whole interior.

Professor Ralf Bartenschlager, a Molecular Virologist at the Ruprecht-Karls-Universität Heidelberg commented, “As a virologist working on how SARS-CoV-2 interacts with and alters its host cell, we will greatly benefit from the development of a soft X-ray microscope that allows us to gain unprecedented insights into this intimate interaction. We have previously used several imaging technologies to address the question of host cell reprogramming by viruses, but each technique has its limitations.”

Since the illumination required for this type of microscopy comes from huge particle accelerators called synchrotrons, currently SXM can only be performed at five research stations in the entire world. The main feature of CoCID therefore lies in further developing a miniaturised soft X-ray approach which has been patented by SiriusXT, a spin-out company from University College Dublin. The breakthrough technology will reduce the size of the X-ray source from a football-field sized synchrotron, instead using a laser-produced plasma (LPP) device that can fit on a bench.

“The SXM microscope developed by SiriusXT performs just as well but is many times smaller, less expensive, and still very fast.” said Dr Weinhardt.

Heidelberg researchers are particularly interested in the potential of the new technology in researching SARS-CoV-2. Prof Bartenschlager’s working group is mainly concerned with how the virus reprograms its host cells. He said that SXM images created under the leadership of Dr Weinhardt at Lawrence Berkeley National Laboratory in California are already promising in this respect.

Three-dimensional images of cells infected with SARS-CoV-2 were generated thanks to a cooperation agreement with the European Molecular Biology Laboratory (EMBL) in Heidelberg.

“Through working with these images we have a pretty good idea of what factors play a role with imaging in connection with the virus-infected cells and we can pass these findings on to the CoCID consortium. As soon as the soft X-ray prototype from Dublin is up and running we will also deliver samples of infected cells, enable a direct comparison with available images and provide support in interpreting data,” said Prof Bartenschlager.

According to the Heidelberg researchers, a soft X-ray microscopy available for daily use should have distinct advantages over current techniques, such as being much faster. Prof Bartenschlager said: “We can’t afford long waits or a time-intensive method when it comes to novel viruses such as SARS-CoV-2, which we learn something new about and which changes on a daily basis.”

Source: News-Medical.Net

Duo of Existing Drugs Punishes Ravenous Cancer Cells

Preclinical research from VCU Massey Cancer Center published recently in the Proceedings of the National Academy of Sciences shows that the combination of two existing drugs can kill aggressive neuroblastoma cancer cells by exploiting their metabolic ‘hunger’.

A cancer of the nervous system, neuroblastomas are one of the deadliest childhood cancers, and if the MYCN gene is overexpressed, the prognosis is even worse. Although paediatric blood cancers are more treatable thanks to medical advancements, it has been much harder to treat neuroblastomas mostly due to the difficulty of targeting MYCN.

“MYCN is a transcription factor, and it’s very difficult to drug transcription factors,” said study senior author Anthony Faber, PhD, co-leader of the Developmental Therapeutics research programme and Natalie N and John R.Congdon, Sr. Endowed Chair of Cancer Research at VCU Massey Cancer Center and associate professor in the Philips Institute for Oral Health Research at the VCU School of Dentistry. “So, the next best thing is to target what MYCN does in the cell. One thing it does is to crank up metabolic activity – what it’s doing to keep the cell alive – and we can work that against itself.”

Since these ravenous cells burn cellular energy stores as quickly as they can be replenished Prof Faber’s team looked for a method to kick their metabolism over the edge without harming normal cells.

Screening 20 metabolic drug combinations in cancer cells originating from nearly 1000 different patients, the researchers found that neuroblastoma with high MYCN expression was particularly sensitive to a cocktail containing two drugs: phenformin and AZD3965..

Phenformin was developed in 1957 to treat diabetes. It blocks complex I on the surface of mitochondria, the organelle where energy production occurs.

Although phenformin was taken off the US market in the 1970s after a number of deaths, it’s still in use elsewhere in the world and is finding new application in the US as a cancer drug. Right now, phenformin is being tested in phase I clinical trial for melanoma.

Meanwhile, AZD3965 is a much newer type of drug under phase I clinical investigation. It works by blocking MCT1 rectors on the surface of cells, in this case as a cancer treatment. MCT1 receptors ferry lactate, another energy source, out of the cell. Blocking MCT1 causes lactate to accumulate, causing the cell to stop using it to make energy.

Simultaneously targeting energy production with the two different pathways used by the drugs should result in disruption of the cellular power supply, stressing and finally killing the cells.

This idea was put to the test by using mice seeded with MYCN-amplified neuroblastoma patient cells. Greater tumour reduction was seen from the cocktail than either drug given alone, with the cocktail being well tolerated.

“The data we got with AZD3965 in combination with phenformin might get people to reconsider phenformin,” said study lead author Krista Dalton, MEng, PhD Student, Virginia Commonwealth University Philips Institute for Oral Health Research. “In combination, where we can use lower doses, phenformin might have better tolerability than it previously did on its own.”

Source: News-Medical.Net

Journal information: Dalton, K. M., et al. (2021) Catastrophic ATP loss underlies a metabolic combination therapy tailored for MYCN-amplified neuroblastoma. Proceedings of the National Academy of Sciences.

As Lockdowns Ease, Masks and Social Distancing are Still Needed

A new model suggests that as lockdowns ease, other control measures such as mask use must be enhanced in order to prevent additional COVID outbreaks.

The mathematical model, developed by scientists at the Universities of Cambridge and Liverpool, provides general insights about how COVID will spread under different potential control scenarios.

They considered ‘non spatial’ control measures involving facemasks, handwashing and metre-scale social distancing can all limit the number of virus particles being spread between people. The other, ‘spatial’ control measures included lockdown and travel restrictions, which reduce how far virus particles can spread. Different combinations of COVID control measures showed that non-spatial control needs to be ramped up as lockdown is lifted.

“More effective use of control measures like facemasks and handwashing would help us to stop the pandemic faster, or to get better results in halting transmission through the vaccination programme. This also means we could avoid another potential lockdown,” said Dr. Yevhen Suprunenko, a Research Associate in the University of Cambridge’s Department of Plant Sciences and first author of the paper. The authors stress that their predictions rely on such non-spatial control measures being implemented effectively.

Their model took into account the socio-economic impact of the measures. The costs of spatial measures of lockdown increased over time, while costs for non-spatial measures decreased due to falling prices and greater availability of items such as masks, and usage becoming a habit.

“Measures such as lockdowns that limit how far potentially infected people move can have a stronger impact on controlling the spread of disease, but methods that reduce the risk of transmission whenever people mix provide an inexpensive way to supplement them,” explained co-author Dr Stephen Cornell at the University of Liverpool.

The model was derived from identifying control strategies for plant diseases threatening staple crops. Instead of the usual computer simulation model, mathematical approach allowed the authors to identify insights on how to control newly emerging infectious diseases of plants and animals.

“Our new model will help us study how different infectious diseases can spread and become endemic. This will enable us to find better control strategies, and stop future epidemics faster and more efficiently,” said co-author Professor Chris Gilligan in the University of Cambridge’s Department of Plant Sciences.

Source: Medical Xpress

Journal information: Analytical approximation for invasion and endemic thresholds, and the optimal control of epidemics in spatially explicit individual-based models, Journal of the Royal Society Interface,rsif.royalsocietypublishing.or … .1098/rsif.2020.0966

Sunlight Vulnerability of SARS-CoV-2 not Just from UV-B

A team of researchers have found that the sunlight vulnerability of SARS-CoV-2 cannot be explained by the effect of UV-B rays alone.

Most of the COVID management concepts remain as true as in the first days of the pandemic, such as handwashing with soap and social distancing, though some have changed such as the notion of the virus mainly transmitted through droplets whereas evidence showed it can linger suspended in aerosol.

The researchers, from UC Santa Barbara, Oregon State University, University of Manchester and ETH Zurich. examined the well-known vulnerability of SARS-CoV-2 to sunlight. They concluded that exposure to UV-B radiation doesn’t completely account for its inactivation by sunlight.

The idea that an additional mechanism might be in play came when the team compared data from a July 2020 study that reported rapid sunlight inactivation of SARS-CoV-2 in a lab setting, with a theory of coronavirus inactivation by solar radiation that was published just a month earlier.

“The theory assumes that inactivation works by having UV-B hit the RNA of the virus, damaging it,” said lead author Paolo Luzzatto-Fegiz, UC Santa Barbara mechanical engineering professor. “Judging from the discrepancies between the experimental results and the predictions of the theoretical model, however, the research team felt that RNA inactivation by UV-B “might not be the whole story.”

Experimentation showed 10-20 minutes to reach virus inactivation—much faster than the theory’s predictions. Viruses in simulated saliva were inactivated over eight times faster when irradiated by UV-B lamps than would have been predicted by the theory, while those cultured in a complete growth medium before exposure to UV-B were inactivated over three times faster. In order to match theory, SARS-CoV-2 would then have greater UV-B sensitivity than any currently known virus.

“The theory predicts that inactivation should happen an order of magnitude slower,” Prof Luzzatto-Fegiz said.

There might be another mechanism involved besides UV-B effects on RNA; such as the synergistic effect of the less energetic UV-A rays.

“People think of UV-A as not having much of an effect, but it might be interacting with some of the molecules in the medium,” he said. Such reactive intermediate molecules could be hastening virus inactivation, a concept known in wastewater treatment and other environmental science fields.

“So, scientists don’t yet know what’s going on,” Luzzatto-Fegiz said. “Our analysis points to the need for additional experiments to separately test the effects of specific light wavelengths and medium composition.”

These findings could help develop ways to control the virus with widely available UV-A and UV-B sources. Sources which emit UV-C, which is otherwise blocked by the atmosphere, has proven effective in certain settings such as air filtration but its high energy limits applications and raises safety concerns.

“UV-C is great for hospitals,” said co-author Julie McMurry. “But in other environments—for instance kitchens or subways—UV-C would interact with the particulates to produce harmful ozone.”

Co-author and UCSB mechanical engineering professor Yangying Zhu added that UV-A’s possible effectiveness meant that inexpensive UV-A LEDs many times brighter than UV-A in normal sunlight could be used. UV-A could be used more for air filtration for example, but the specifics of each setting warrant consideration, said co-author Fernando Temprano-Coleto.

Source: Medical Xpress

Journal information: Paolo Luzzatto-Fegiz et al. UVB Radiation Alone May Not Explain Sunlight Inactivation of SARS-CoV-2, The Journal of Infectious Diseases (2021). DOI: 10.1093/infdis/jiab070

Study Shows That Viral Infections Affect Immune System like Ageing

A study from the Buck Institute and Stanford University suggests that chronic viral infections leave an impact on the human immune system, similar to those seen during ageing.

Using systems immunology and artificial intelligence, researchers profiled and compared immune responses in a cohort of aging individuals, people with HIV on long-term antiretroviral therapy, and people infected with hepatitis C (HCV) before and after the virus was treated with sofosbuvir, a drug with a 97% cure rate. Shared immune system alterations include T cell memory inflation, upregulation of intracellular signaling pathways of inflammation, and diminished sensitivity to cytokines in lymphocytes and myeloid cells.

“Chronic inflammation stemming from immune system dysfunction is associated with many of the diseases of ageing,” said senior author David Furman, PhD, Buck Institute associate professor. “Whether chronic viral infection contributes to age-associated immune dysfunction is still an open question, but studies of this type provide a way to start getting answers. At this point it’s clear that both ageing and chronic viral infections leave profound and indelible marks on immunity.”

The body is normally able to clean out acute viral infections, such as the common cold. But some viruses besides just HIV and HCV can remain alive, setting up ‘host-parasite housekeeping’ in the body, without people’s awareness. Dr Furman said that, depending on geographic location, 70 to 90% of the population is infected with cytomegalovirus. In healthy people, this is harmless and problematic only for pregnant women or those with compromised immune systems. Various herpes viruses can also lead to chronic infections.

“Each of us has our own virome; it’s the collection of the viral infections you have during your lifespan,” Furman said. “You probably have been infected by 12 or 15, or even more viruses that you never knew you had. Fortunately technology now exists that allows us to profile these infections in the human population; it is helping us move these types of inquiries forward.” Dr He said this study is the first to fully incorporate the concept of systems immunology, holistically analysing the immune system with the same technological platforms across different cohorts of patients.

The study demonstrated that in patients with HIV, immune system dysregulations were evident despite having been on antiretrovirals for over ten years. However, clearing the HCV virus partially restored cellular sensitivity to interferon-a, which inhibits viral replication. “This plasticity means there is room for intervention in both chronic viral infections and in ageing,” said Dr Furman. “It’s just a matter of identifying and understanding the molecular pathways and networks involved.” The study also identified changes in STAT1, the primary transcription factor activated by interferons. STAT1 plays a major role in normal immune responses, particularly to viral, mycobacterial and fungal pathogens.

As for COVID, Dr Furman said that we are in the midst of an ongoing “living” experiment. Future studies are needed to determine whether the functional imprinting of the immune system is hardwired to only involve the chronic nature of specific infections, or whether short but vigorous ones such as COVID also leave a lasting mark on the immune system. “Has the immune system of those infected with the coronavirus taken a big hit? That’s a theory, but we don’t know what will happen,” says Furman, who is collaborating with Stanford University and the University of California, San Francisco on projects involving COVID-19 and immunity.

Source: Medical Xpress

Journal information: Cesar J. Lopez Angel et al., “Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination,” PNAS (2021).

Mystery Brain Disease Baffles Canadian Doctors

Doctors in Canada are struggling to explain a spate of cases involving memory loss, hallucinations and muscle atrophy.

For more than a year public health officials in New Brunswick province have been tracking a “cluster” of 43 cases of suspected neurological disease with no known cause.

A leaked memo from the province’s public health agency asking physicians to be on the lookout for symptoms similar to Creutzfeldt-Jakob disease (CJD), a rare, fatal and largely sporadic disease caused by prion proteins. Symptoms such as memory loss, vision problems and abnormal jerking movements were similar enough to trigger an alert with Canada’s CJD surveillance network. However, it was confirmed that this disease was not CJD.

“We don’t have evidence to suggest it’s a prion disease,” said Dr Alier Marrero, the neurologist leading New Brunswick’s investigation.
Patients initially reported unexplained pains, spasms and behavioural changes, easily misdiagnosed as anxiety or depression.

However, over 18 to 36 months they began to develop cognitive decline, muscle wasting, drooling and teeth chattering. Some also began experiencing frightening hallucinations, including the sensation of crawling insects on their skin.  

Each time a possible case arises, a battery of tests is administered to determine if they match the cluster. Cases have risen from only one in 2015 to 24 in 2020, and so far five people are believed to have died from the illness.

“We have not seen over the last 20-plus years a cluster of diagnosis-resistant neurological disease like this one,” said Michael Coulthart, head of Canada’s CJD surveillance network.

The majority of cases are linked a sparsely populated region of the province, with the overall number of cases in the cluster remaining low. However, New Brunswick has a population of fewer than 800 000 people.

Dr Marrero and his team have consulted experts in neurology, environmental health, field epidemiology, zoonotics and toxicology to better understand the possible cause of the mysterious illness.

A growing team of researchers are trying to pin down a common cause or perhaps environmental effect.

“We don’t know what is causing it,” said Dr Marrero. “At this time we only have more patients appearing to have this syndrome.”

Valerie Sim, a researcher of neurodegenerative diseases at the University of Alberta cautioned against jumping to conclusions. “I don’t really know if we even have a defined syndrome. There just isn’t enough information yet,” she said.

She observed that key markers for degenerative neurological illnesses had not been identified, with the cluster’s wide range of symptoms being “atypical” for most brain diseases. Conversely, the scope of symptoms could be explained by certain cancers, dementia or even misdiagnoses.

Frustratingly, when the ailment is unclear a number of tools can be deployed, “and then the patient somehow recovers. You come away never knowing what they actually had,” said Sim.

“We see odd neurological syndromes from time to time. Sometimes we figure them out. Sometimes we don’t.”

Source: The Guardian

Study Reveals Additional Pathway From Brain to Cardiovascular System

Researchers at  University of Tsukuba in Japan have uncovered a previously unknown pathway from the brain to the cardiovascular system.

Though the cardiovascular system has a degree of autonomy to allow their independent functioning from the brain, the brain still has some control over it in order to respond to life-threatening situations. This control is exerted through the sympathetic and parasympathetic systems of the autonomic nervous system.

“From an evolutionary standpoint, the brain has had an incredibly important function in protecting the individual from predators,” says the lead author of the study Professor Tadachika Koganezawa. “But even in the absence of predators, our bodies react to stressful situations. In this study, we wanted to determine how the brain regulated the cardiovascular system via the autonomic nervous system.”

Located deep within the brain, the lateral habenula (LHb) has been known to elicit strong behavioural and cardiovascular responses to stressful events. But how it did so was still unclear. so to find out the researchers electrically stimulated the LHb in rats. This resulted in bradycardia and increased mean arterial pressure (MAP). The researchers then turned off the parasympathetic system by means of cutting the main parasympathetic nerve, the vagal nerve, or using a drug to antagonise it. 
Though this suppressed the LHb’s effect on the heart rate, the MAP was unchanged. Antagonising the sympathetic system had the opposite effect—decreasing the MAP but there was no effect on the heart rate.

To understand the mechanism by which the LHb elicits these cardiovascular responses, the researchers focused on the neurotransmitter serotonin, which plays an important role in the brain in modulating mood, cognition, and memory, among other functions.

While blocking all serotonin receptors significantly reduced the LHb’s effect on both the MAP and heart rate, the researchers found that specific subtypes of serotonin receptors were particularly involved in the process.

“These are striking results that show how the lateral habenula controls the cardiovascular system,” said study author Professor Masayuki Matsumoto , University of Tsukuba. “Our results demonstrate the mechanism of a neural circuit that plays an important role in stress-induced behavioral responses.”

Source: News-Medical.Net

Journal information: Doan, T. H., et al. (2021) Lateral Habenula Regulates Cardiovascular Autonomic Responses via the Serotonergic System in Rats. Frontiers in Neuroscience.

New Bioluminescent System Illuminates Biological Processes

Scientists at the Federal University of São Carlos (UFSCar) have developed a new bioluminescent system that can enable greatly improved imaging of biological and pathological processes in organisms.

Luciferases are enzymes that catalyse the oxidation of luciferins present in organisms such as fireflies, which results in bioluminescence in the visible light spectrum. Images of cell cultures and live animal models are made using the luciferin-luciferase system found in fireflies. For example, this can show the structure and activity of tumours, or follow the viral process in cells, helping physicians develop treatments.

“We obtained a novel luciferin-luciferase system that produces far-red light at the wavelength of 650 nanometres and emits the brightest bioluminescence ever reported in this part of the spectrum,” said principal investigator Professor Vadim Viviani, biochemist at UFSCar. “It’s a highly promising result for bioluminescence imaging of biological and pathological processes in mammalian tissues.”

“Red bioluminescence is preferred when imaging biological or pathological processes in mammalian tissues because haemoglobin, myoglobin and melanin absorb little long-wavelength light. Detection is best of all in the far red and near-infrared bands, but bioluminescent systems that naturally emit far red light don’t exist,” Prof Viviani added.

“Some genetically modified forms of luciferase and synthetic analogs of natural luciferins are produced commercially. In conjunction, they produce light at wavelengths as long as 700 nanometers, but the light produced by these artificial systems is generally much weaker and more short-lived than light from natural bioluminescent systems.”

Prof Viviani and collaborators genetically modified luciferase from the Railroad worm Phrixothrix hirtus, the only luciferase that naturally emits red light, and combined with luciferin analogues synthesised by colleagues at the University of Electro-Communications in Tokyo. The resulting luciferin-luciferase generates a much more efficient far-red bioluminescence.

“Our best combination produces far-red at 650 nanometres, three times brighter than natural luciferin and luciferase, and roughly 1000 times brighter than the same luciferase with a commercial analog,” Viviani said.

“Besides the long-wavelength and intense brightness, our combination has better thermal stability and cell membrane penetrability. Above all, it produces more lasting continuous bioluminescence, taking at least an hour to decay and significantly facilitating the real-time imaging of biological and pathological processes.”

Source: News-Medical.Net

Journal information: Viviani, R. V, et al. (2021) A Very Bright Far-Red Bioluminescence Emitting Combination Based on Engineered Railroad Worm Luciferase and 6′-Amino-Analogs for Bioimaging Purposes. International Journal of Molecular Sciences.