In today’s newsletter, keeping lymph on the move, the impact of stress on different fear responses, and beware short p53 proteins. Plus, what happened when researchers investigated the reproducibility of research into immunity in Drosophila?
– Peter Rodgers, Chief Magazine Editor
p53 isoforms bind to full-length p53 proteins to form aggregates. Image Credit: Zhao, Punga and Sanyal (CC BY 4.0)
p53 proteins prevent the development of cancer by binding to certain genes and regulating various processes inside cells. Cells also contain shortened versions of p53 called isoforms, and recent research published in eLife has shown that these isoforms disrupt cells in two ways. First, they are unable to bind genes, so they cannot prevent cancer. Second, to make matters worse, they are able to bind to their longer siblings to form structures called tetramers and aggregates, which prevents the full-length version of p53 from fighting cancer.
Fear behavior can be learned – when, for example, we associate a certain sound with something harmful – or unlearned, when an innocuous sound we have not heard before invokes a fear response. Exploring the impact of stress on fear has long been a focus of research in behavioural neuroscience. Now, as this Insight article explains, researchers have discovered that a region of the brain called the paraventricular thalamus mediates the impact of stress on unlearned fear, but not on learned fear. Changes in fear responses are common in psychiatric conditions, including PTSD, and the unlearned fear response is especially difficult to target therapeutically because its origins are not fully understood.
It has been suggested that exercise might reduce pain through the release of endogenous opioids, but this idea remains controversial. To investigate further, researchers conductors experiments in which 39 healthy adults - 18 males and 21 females - cycled for ten minutes on a stationary bicycle, and were then exposed to various painful stimuli while they were inside an fMRI scanner. The researchers found that, overall, high-intensity exercise did not reduce pain compared with low-intensity exercise, although there were hints of an intensity-dependent effect for males with high fitness levels.
The lymphatic system is a network of vessels and nodes that extends from the surface of the brain to the tips of the toes. This system relies on the contraction of muscle cells to move lymph – a combination of interstitial fluid, antigens and other compounds – around the body, but it is not clear which cells act as the pacemaker that drives these contractions. Now, as outlined in this Insight article, researchers have studied four different cell types found in the wall of lymph vessels, and deduced that lymphatic muscle cells act as pacemaker cells, as well as doing the hard work of contracting to keep lymph circulating in the body.
Zebrafish are well known for their capacity to regenerate damaged tissue. Researchers have also shown that genetic elements involved in heart regeneration in zebrafish can improve heart repair in both mice and pigs. However, as these genetic elements lead to a proliferation of cells, it is vital that they are only delivered to those regions of the heart where they are needed. Now, as this Insight article explains, research published in eLife has shown that bioluminescent imaging can be used to gain a better understanding of the delivery process in a mouse model of myocardial infarction.
A project to investigate the reproducibility of research in Drosophila immunity has found that 61% of the claims made in the papers it analyzed had been verified by subsequent papers. Joseph Lemaitre and co-workers identified 1006 claims in 400 papers published between 1959 and 2011, including 285 claims that had not been checked by an independent group. Lemaitre et al. then performed experiments to check if a subset of these “unchallenged” claims could be verified, but found that most were not reproducible. Taking these results into account, Lemaitre et al. report that 7% of the claims had been challenged, 24% had not been challenged , and that partial verification or mixed results accounted for the remaining 8% of claims.
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