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PNAS Papers on Mosquito MicroRNAs, Acute Kidney Injury, Trichothiodystrophy

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted this week.

University of California, Riverside, researchers explore microRNA regulatory mechanisms involved in reproduction in Aedes aegypti mosquitoes, which can transmit viruses behind dengue fever, yellow fever, and other serious diseases. The team used an RNA interference screen and small RNA sequencing to search for miRNAs showing expression shifts in response ecdysone receptor (EcR)-mediated 20-hydroxyecdysone (20E) signaling — an ovarian pathway that responds to blood meals in female mosquitoes — before digging into other mechanisms involved in this regulation with a series of follow-up experiments. The authors found that after a blood meal EcR appears to bump up levels of egg development-related miRNAs called miR-275 and miR-305 in a mosquito fat body structure that functionally resembles the liver in vertebrates, for example, while keeping levels of the miRNAs low prior to blood feeding. "Our study gives valuable clues for miRNA utilization to control mosquito populations and, thus, mosquito-borne diseases," they say.

A University of Southern California team considers proximal tubule cell (PTC) responses to acute kidney injury using a mouse model of such injuries, which sometimes progresses to chronic kidney conditions. Using genetically labeled PTCs, single-nucleus RNA-seq, and other approaches, the investigators tracked transcriptomic features one week or one month after ischemia-reperfusion kidney injury, identifying expression markers that appeared to coincide with a late injury cell type showing failed PTC repair and related proinflammatory features. From these and other analyses of PTC expression dynamics over time and space, the authors suggest that even moderate acute kidney injury "is associated with lasting injury, which spreads from the [cortico-medullary boundary] to cortical regions" in the mouse kidney model, hinting that a subset of PTCs with failed repair after acute injury "are likely triggers for chronic disease progression."

Investigators in Italy and France present findings from a transcriptomic comparison of two rare skin conditions that both stem from mutations in the ERCC2 or ERCC3/XPB genes but show different relationships to skin cancer risk. While cancer-prone xeroderma pigmentosum (XP) has been linked to higher-than-usual cancer risk, they note, cancer-free photosensitive trichothiodystrophy (PS-TTD) is marked by ultraviolet light-related DNA lesions and other symptoms without a related rise in skin cancer. Based on RNA-seq on primary fibroblast cells from unaffected individuals or individuals with TTD or XP, the team narrowed in on expression shifts specific to TTD cases, including particularly low levels of the prostaglandin I2 synthase (PTGIS) enzyme. "Besides supporting the hypothesis that transcriptional defects make a major contribution to the TTD phenotype while DNA repair defects represent the major abnormality in XP, these findings demonstrate a specific transcription deregulation that results in reduced synthesis and secretion of PTGIS amounts in TTD patients," they write, noting that the results may provide clues to finding and treating TTD.

The Scan

Interfering With Invasive Mussels

The Chicago Tribune reports that researchers are studying whether RNA interference- or CRISPR-based approaches can combat invasive freshwater mussels.

Participation Analysis

A new study finds that women tend to participate less at scientific meetings but that some changes can lead to increased involvement, the Guardian reports.

Right Whales' Decline

A research study plans to use genetic analysis to gain insight into population decline among North American right whales, according to CBC.

Science Papers Tie Rare Mutations to Short Stature, Immunodeficiency; Present Single-Cell Transcriptomics Map

In Science this week: pair of mutations in one gene uncovered in brothers with short stature and immunodeficiency, and more.