The brain – silicone’s new frontier? 

Investigators at the University of Bath have designed neuronal chips that were able to respond to electrical stimuli in much the same way that real neurons do. The brain is one of the least regeneration-prone organs in the body, and neurodegeneration is well on its way to becoming a public health crisis. There have been multiple attempts to use stem cells to regenerate lost brain cells, for example in Parkinson’s disease (PD). So far, however, the results have not translated into routine clinical practice. The authors wrote that their approach “offers a route for repairing diseased biocircuits and emulating their function with biomedical implants that can adapt to biofeedback.” Their work appeared in the Dec. 3, 2019, issue of Nature Communications

Once a month contraceptive 

Orally active drugs that could be taken at long intervals would improve adherence to many drugs over medicines that need to be taken daily or multiple times a day. Researchers at the Massachusetts Institute of Technology and Brigham and Women’s Hospital have developed an oral delivery system that could be used to deliver contraceptives once every four weeks, or once per menstrual cycle. In a large animal model, the hormones contained in the pill were released in the stomach over a period of three weeks, mimicking the monthly birth control cycle of three weeks of hormones followed by one week off of medication. The authors noted that their approach has several features necessary to “overcome the economic and cultural barriers in low-income countries… [including] (i) opportunity for self-administration, (ii) drug administration by the oral route, (iii) circumvention of the need for clinical procedures for dosage form removal, and (iv) maintenance of privacy. Hence, our technology stands to benefit a large patient population that prefers oral medication or is in regions of the world where self-medication is the only means to chronic therapy.” Their work appeared in the Dec. 4, 2019, issue of Science Translational Medicine.  

Enterovirus contributes to islet autoimmunity 

The Environmental Determinants of Diabetes in the Young (TEDDY) study group, led by researchers from the University of South Florida, has demonstrated that prolonged enterovirus infections increased the risk of islet autoimmunity in children who were genetically at high risk of developing islet autoimmunity and type I diabetes (T1D), though repeated short-term infections did not. Previous studies have hinted at a connection between viral infection and autoimmunity to pancreatic islet cells, which precedes T1D. However, such associations have been hard to pin down, given the diversity and transient nature of viral infections. In their experiments, the team took repeated stool samples from children at increased T1D risk, and used them to analyze their viromes over time and link those viromes to islet autoimmunity and T1D. They showed that “prolonged enterovirus B rather than independent, short-duration enterovirus B infections may be involved in the development of islet autoimmunity, but not T1D, in some young children. Furthermore, we found that fewer early-life human mastadenovirus C infections, as well as CXADR rs6517774, independently correlated with islet autoimmunity.” Their work appeared in the Dec. 2, 2019, online issue of Nature Medicine.  

Acetyl CoA and metabolic health 

Researchers at Duke University have gained new insights into the links between overnutrition and mitochondrial health. The team tested the theory that overnutrition damages mitochondria because it leads to high cellular levels of the metabolite Acetyl CoA, which increases protein acetylation. However, the authors showed that mitochondrial function was essentially normal in a double knockout mouse model designed to have high levels of acetylated proteins. They hypothesized that the functionally important consequence of high acetylation levels was a change in redox potential that affected the redox state of the enzyme co-factor nicotine adenine dinucleotide (NAD), and the activity of enzymes that use that co-factor. The team reported its findings in the Dec. 5, 2019, issue of Cell Metabolism

Improbability research yields path to HIV vaccine 

For an effective HIV vaccine, the immune system will need to produce antibodies that are broadly neutralizing against multiple HIV strains. Some infected individuals do ultimately produce such broadly neutralizing antibodies (bnAbs), but the maturation of such antibodies is a multistep process involving rare maturation steps. Scientists at Duke University and Harvard University have identified a process that could reliably coax the immune system to produce bnAbs. “Our results show that the immune system, when provided with an affinity gradient between two clonally related antibodies, can be manipulated to generate HIV-1 bnAb improbable mutations,” the authors wrote. Furthermore, “although HIV-1 was the focus of this study, this strategy of selection of specific antibody nucleotides by immunogen design can be applied to B cell lineages targeting other pathogens where guided affinity maturation is needed for a protective antibody response.” They reported their results in the Dec. 6, 2019, issue of Science.  

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