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Research Round-up

Posted by on Wednesday, February 28, 2018 in Around the Medical Center, Winter 2018 .

Radiation and pulmonary fibrosis

Radiation-induced pulmonary fibrosis — tissue scarring that can permanently impair lung function — limits the delivery of therapeutic radiation doses to non-small cell lung cancer.

Michael Freeman, PhD, and colleagues are exploring the cell types and factors that contribute to the radiation-induced fibrotic response.

The investigators previously showed that loss of the transcription factor Nrf2 increases susceptibility to pulmonary fibrosis. They now show that thoracic (chest) radiation of mice causes a loss of alveolar type 2 cells and that this loss is enhanced in mice lacking Nrf2.

The researchers found that a specific stem/progenitor cell population was inhibited following radiation in mice missing Nrf2, and that alveolar type 2 cells in these mice were more likely to change into myofibroblasts — a cell type implicated in fibrosis.

The findings, reported in the November 2017 Free Radical Biology and Medicine, demonstrate that Nrf2 participates in stem cell mobilization and helps maintain the alveolar type 2 cell reparative process in injured lungs.


A lipid’s role in cell division 

Proper cell division is a basic process critical to cell survival. A ring composed of actin filaments and myosin motor proteins pinches the cell apart, producing two daughter cells with equal amounts of cellular components.

Reporting in the Journal of Cell Biology, Kathleen Gould, PhD, Louise B. McGavock Chair, and colleagues characterized how this powerful contractile ring remains anchored to the plasma membrane allowing symmetric division.

Decreased amounts of the lipid family of phosphoinositides (PIPs) in the plasma membrane have been shown to cause cytokinesis defects. Despite this, how lipid levels could affect contractile ring function was unknown. PIP levels are regulated by a known set of proteins including Efr3 in Schizosaccharomyces pombe. When efr3 was knocked out in S. pombe, PIP levels were reduced in the plasma membrane. Interestingly, the cytokinetic ring slid away from the cell center, leading to asymmetrical division.

The work suggests that contractile ring anchoring may be dependent on a plasma membrane localized complex regulating PIP levels.


Amoxicillin alone better choice for pediatric pneumonia: study

A combination of two antibiotics is often prescribed to treat community-acquired pneumonia in children, but a JAMA Pediatrics study is now showing that using just one of the two has the same benefit to patients in most cases.

Vanderbilt researchers report that amoxicillin alone, rather than combined with azithromycin, is just as effective and a better choice as it relates to efforts to curb antibiotic resistance.

One of the most commonly used antibiotics in pediatrics, azithromycin was prescribed to 12.2 million outpatients in 2013 and accounted for almost 20 percent of all antibiotic prescriptions for children in the U. S. ambulatory setting, according to an editorial accompanying the study.

“Combination therapy with azithromycin is unnecessary in most cases of pediatric pneumonia, both because the bacteria targeted by azithromycin are less common than other causes of pneumonia, including viruses, and the effectiveness of azithromycin has not been clearly demonstrated in prior studies,” said lead author Derek Williams, MD, MPH, assistant professor of Pediatrics.