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This Week in PLoS: Jun 27, 2011

In PLoS Genetics this week, a team led my MIT researchers has found a latent pro-survival function for the mir-290-295 cluster, the dominant miRNA cluster in mouse embryonic stem cells. By examining a target list generated from bioinformatic prediction, as well as expression data following miRNA loss, the team found that apoptotic regulators were strongly enriched. Consistent with this observation, the researchers write, mouse embryonic stem cells lacking miRNAs were more likely to initiate apoptosis following exposure to gamma irradiation or doxorubicin. "In contrast to the basal regulatory roles previously identified, the pro-survival phenotype shown here may be most relevant to stressful gestations, where pro-oxidant metabolic states induce DNA damage," the authors write. "Similarly, this cluster may mediate chemotherapeutic resistance in a neoplastic context, making it a useful clinical target."

Also in PLoS Genetics this week, researchers in Japan write that the novel and conserved protein macoilin is required for diverse neuronal functions in C. elegans. Organisms with mutated maco-1 showed abnormal behaviors, such as defective locomotion, thermotaxis, and chemotaxis, the researchers write. But expression of human macoilin in the C. elegans nervous system "weakly rescued the abnormal thermotactic phenotype of the maco-1 mutants," they write, suggesting that macoilin is functionally conserved across species. "Studies on localization of MACO-1 showed that C. elegans and human macoilins are localized mainly to the rough endoplasmic reticulum," the team adds. "Our results suggest that macoilin is required for various neural events, such as the regulation of neuronal activity."

In PLoS Biology this week, US researchers present findings from a study of the metabolic regulation of mycobacterial growth and antibiotic sensitivity. In their paper, the researchers demonstrate that diverse growth-limiting stresses trigger a common signal transduction pathway in M. tuberculosis that leads to the induction of triglyceride synthesis — a pathway which plays a causal role in reducing growth and antibiotic efficacy. "Mutants in which this metabolic switch is disrupted are unable to arrest their growth in response to stress and remain sensitive to antibiotics during infection," the authors write. "Thus, this regulatory pathway contributes to antibiotic tolerance in vivo."

And in PLoS One this week, researchers in the Netherlands show that HSPB1, HSPB6, HSPB7 and HSPB8 protect against RhoA GTPase-induced remodeling in tachypaced atrial myocytes. The team had previously demonstrated that the small heat shock protein HSPB1 could be used in preventing tachycardia remodeling in in vitro and in vivo models for atrial fibrillation. In this paper, the team found that in addition to HSPB1, overexpression of HSPB6, HSPB7 and HSPB8 protected against tachypacing-induced CaT reduction. "Moreover, tachypacing induced RhoA GTPase activity and caused F-actin stress fiber formation. The ROCK inhibitor Y27632 significantly prevented tachypacing-induced F-actin formation and CaT reductions, showing that RhoA activation is required for remodeling," the authors write. "Overexpression of HSPB1, as well as HSPB6, HSPB7 and HSPB8 independently protect against tachycardia remodeling by attenuation of the RhoA GTPase pathway at different levels. The cardioprotective role for multiple HSPB members indicate a possible therapeutic benefit of compounds able to boost the expression of single or multiple members of the HSPB family."

The Scan

Another Resignation

According to the Wall Street Journal, a third advisory panel member has resigned following the US Food and Drug Administration's approval of an Alzheimer's disease drug.

Novavax Finds Its Vaccine Effective

Reuters reports Novavax's SARS-CoV-2 vaccine is more than 90 percent effective in preventing COVID-19.

Can't Be Used

The US Food and Drug Administration says millions of vaccine doses made at an embattled manufacturing facility cannot be used, the New York Times reports.

PLOS Papers on Frozen Shoulder GWAS, Epstein-Barr Effects on Immune Cell Epigenetics, More

In PLOS this week: genome-wide association study of frozen shoulder, epigenetic patterns of Epstein-Barr-infected B lymphocyte cells, and more.