High mortality in aquatic predators of mosquito larvae caused by exposure to insect repellent.

In the face of mosquito-borne disease outbreaks, effective mosquito control is a primary goal for public health. Insect repellents, containing active compounds such as DEET and picaridin, are a first defence against biting insects. Owing to widespread use and incomplete sewage treatment, these compounds are frequently detected in surface waters, but their effects on aquatic taxa such as mosquito larvae or their naturally occurring aquatic predators are poorly understood. We investigated the effects of environmentally realistic concentrations of commercial products containing DEET and picaridin on survivorship of mosquito larvae, and their potential indirect effects on survival of larval salamanders, a major predator of mosquito larvae. Larval mosquitos were not affected by exposure to repellents containing DEET or picaridin. We found no larval salamander mortality in control and DEET treatments, but mortality rates in picaridin treatments ranged from 45 to 65% after 25 days of exposure. Salamander larvae exposed to repellents containing picaridin began to display tail deformities and impaired development four days after the experiment began. Our findings suggest the possibility that environmentally realistic concentrations of picaridin-containing repellents in surface waters may increase the abundance of adult mosquitos owing to decreased predation pressure.

Non-ovarian Wolbachia pipientis titer correlates with fertility rescue of a Drosophila melanogaster bag of marbles hypomorph.

Bag of marbles ( bam ) is an essential gene that regulates germline stem cell maintenance and germline stem cell daughter cell differentiation in Drosophila melanogaster . When bam is partially functional (hypomorphic), the introduction of Wolbachia pipientis rescues the mutant fertility phenotype that would otherwise result in partial sterility. Infection by different W. pipientis variants results in differential rescue of the bam hypomorph fertility phenotype. We were intrigued by the varying degrees of rescue exhibited in the bam hypomorph when exposed to different W. pipientis variants, prompting us to investigate whether this phenomenon is attributable to variations in the titers of W. pipientis variants. We found no significant difference in ovarian titer between two W. pipientis variant groups, w Mel-like (low bam hypomorph fertility rescue) and w MelCS-like variants (higher bam hypomorph fertility rescue), at bam hypomorph peak fertility. However, carcass (whole flies without the ovaries) titer between w Mel-like and w MelCS-like infected bam hypomorph differed during peak fertility rescue. A positive correlation emerged between the combined titers of ovarian and carcass infections and fertility, implying a more extensive influence that extends beyond ovarian infection alone.

Neoadjuvant Cisplatin, Gemcitabine, and Docetaxel in Sarcomatoid Bladder Cancer: Clinical Activity and Whole Transcriptome Analysis.

BACKGROUND: Sarcomatoid urothelial cancer of the bladder (SBC) is a rare, but aggressive histological subtype for which novel treatments are needed. OBJECTIVE: We evaluated the clinical activity and safety of neoadjuvant cisplatin plus gemcitabine plus docetaxel (CGD) in muscle-invasive patients with SBC and assessed SBC tumor biology by whole transcriptome RNA sequencing. METHODS: A single-institution, retrospective analysis of muscle-invasive SBC patients treated with neoadjuvant CGD with molecular analysis. Patients received cisplatin 35 mg/m2 + gemcitabine 800 mg/m2 + docetaxel 35 mg/m2 intravenously on days 1 and 8 + pegfilgrastim 6 mg subcutaneously on day 9 every 3 weeks for 4 cycles followed by cystectomy. The primary endpoint was pathologic complete response (ypCR) rate. RESULTS: Sixteen patients with SBC received neoadjuvant CGD with a ypCR rate of 38% and a < ypT2 rate of 50%. Grade 3 and 4 toxicity occurred in 80% and 40% of patients, but was manageable with 81% of patients completing > 3 CGD cycles. Whole transcriptome RNA sequencing demonstrates co-clustering of SBC with conventional urothelial tumors. SBC tumors are characterized by basal-squamous and stroma rich gene signatures with frequent increased expression of immune checkpoint (CD274 (PD-L1)), chemokine (CXCL9), and T-cell (CD8A) genes. CONCLUSIONS: SBC is a chemosensitive subtype, with ypCR rate similar to urothelial bladder cancer following CGD neoadjuvant therapy. Whole transcriptome tissue analyses demonstrate increased expression of immune checkpoint and T-cell genes with therapeutic implications.