Treatment breakthrough for viruses

Scientists from RMIT University in Melbourne have discovered that a 1.5 billion-year-old cell biological process found in plants, fungi and mammals, promotes virus pathogenicity in mice and is a potential target for viral strain independent treatments which could alleviate some of the most devastating viruses worldwide. The researchers identified a protein, NOX2 oxidase, that is activated by a range of viruses that enter cells via the endocytic pathway, including influenza, rhinovirus, dengue and HIV. Once activated, NOX2 oxidase suppresses the body’s key antiviral reaction and its ability to fight and clear the viral infection, which, in mice, results in a stronger or more virulent disease. The study, published in Nature Communications, also investigated a new prototype drug to treat these debilitating viral diseases. The researchers found that the NOX2 oxidase protein activated by the viruses is located in cell compartments called endosomes. They synthesized a molecule targeted at delivering a NOX2 oxidase inhibitor directly to endosomes, so as to disrupt the viral signaling platform. In mice, the customised drug was found to be very effective at suppressing disease caused by influenza infection. “Current treatment strategies are limited as they specifically target circulating viruses and have either unknown or very little effect against new viruses that enter the human population. We have identified a protein of the immune system that contributes to the disease caused by flu viruses irrespective of their strain. We also developed a novel drug delivery system to target this protein, which drastically alleviated the burden of viral disease,” said senior author Dr Stavros Selemidis.

No link between antidepressants in pregnancy and intellectually disabled children

A US study published by JAMA Psychiatry reports that there is no evidence of an association between intellectual disability in children and mothers who took antidepressant medication during pregnancy when other mitigating factors, such as parental age and underlying psychiatric disorder, were considered. The researchers used Swedish national registers to conduct a population-based study of children born from 2006 through 2007 and followed up from birth until a diagnosis of intellectual disability, death, or the end of the follow-up period in 2014. The authors estimated the relative risk of intellectual disability in children exposed, or not exposed, to antidepressants during pregnancy and the analyses were adjusted for other potential mitigating factors. Of the 179 007 children included, the number of children diagnosed with intellectual disability (defined by an IQ below 70 with deficits that impair everyday functioning) during the follow-up period was 873 (0.5%). Intellectual disability was diagnosed in 37 (0.9%) children exposed to antidepressants and in 819 (0.5%) who were not exposed to antidepressants, according to the results. A higher estimate of relative risk that was observed by the researchers before accounting for parental factors was reduced to a statistically insignificant estimated relative risk when those factors were considered, the results show. The study notes limitations and acknowledges the outcome was rare. “After adjustment for confounding factors, however, the current study did not find evidence of an association between ID [intellectual disability] and maternal antidepressant medication use during pregnancy. Instead, the association may be attributable to mechanisms integral to other factors, such as parental age and underlying psychiatric disorder,” the study concludes.

Storing data in living cells using CRISPR

US scientists have taken images and a short movie from Eadweard Muybridge’s Human and animal locomotion and encoded them into the DNA of bacteria using the CRISPR (clustered regularly interspaced short palindromic repeats) system. This achievement, reported in Nature, expands on previous demonstrations that DNA provides a promising medium for storing digital data within living cells. Recent work has indicated that information could be transferred into living cells using the CRISPR system, which uses two proteins to insert genetic code into the DNA of target cells. Seth Shipman and colleagues from Harvard Medical School demonstrated this ability by using the CRISPR system to encode images and a short GIF file (five frames of the mare ‘Annie G’ galloping from Human and Animal Locomotion at 36×26 pixels) in Escherichia coli. They used nucleotides, the building blocks of DNA, to produce a code that related to the individual pixels of each image. For the GIF, sequences were delivered frame-by-frame over time to living bacteria, where they were inserted into the genome in the order in which they were delivered. Once inserted into the genome of E.coli, the data could then be retrieved by sequencing the DNA, and the images reconstructed by reading the pixel nucleotide code, which was achieved with about 90% accuracy. In addition to establishing that the CRISPR system may enable the recording of practical amounts of data in living cells, the study also reveals new insights into the functioning of the CRISPR system. For example, the authors determined which sequences are best for transferring data into the genome, which could also guide other applications of the CRISPR system.

Tall, obese men at greatest risk of aggressive prostate cancer

Men who are tall and obese are at increased risk of high grade prostate cancer and prostate cancer death, according to a study published in BMC Medicine. Researchers from the University of Oxford in the UK found that while height was not associated with overall prostate cancer risk, risk of high grade disease and death from prostate cancer increased by 21% and 17% respectively with every additional 10cm of height. Higher body mass index was also found to be associated with increased risk of high grade tumours, as well as increased risk of death from prostate cancer. Waist circumference, which is seen as a more accurate measure of obesity than body mass index in older adults, was associated with an 18% greater risk of death from prostate cancer and a 13% greater risk of high grade cancer with every 10cm increase in waist circumference. The study is among the first to differentiate between high grade and advanced stage tumours while investigating the links between height and obesity and prostate cancer. Most previous research did not group tumours into subtypes according to how far the tumour had spread (stage) and how abnormal tumour cells were when compared to normal cells (grade). Instead, stage and grade were grouped together in combined categories of aggressive or non-aggressive tumours. The researchers used data from the European Prospective Investigation into Cancer and Nutrition, a prospective European cohort of 141 896 men, collected in eight countries – Denmark, Italy, the Netherlands, Spain, Sweden, the UK, Germany and Greece. The data included 7024 incident prostate cancers, 726 high grade and 1388 advanced stage prostate cancers, and 934 prostate cancer deaths. Dr Perez-Cornago, the lead author, said: “Our data illustrate the complex association of adiposity and prostate cancer, which varies by disease aggressiveness. These results emphasize the importance of studying risks for prostate cancer separately by stage and grade of tumour. They may also inform strategies for prevention, but we need to do further work to understand why the differences in risk exist.”

 

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