Effects of methoprene on extreme temperature tolerance and reproduction of Tribolium castaneum (Coleoptera: Tenebrionidae)

The juvenile hormone analogue methoprene is a reduced-risk insecticide. It disrupts insect development of immature stages preventing the emergence of adults. Several studies have shown that lower concentrations that permit the emergence of adults also have sub-lethal effects. Exposure to methoprene (Diacon II) at 3.33 ppm reduced the heat tolerance of Tribolium castaneum (Herbst) adults. However, it did not affect the heat tolerance of larvae at 0.07 ppm. Higher concentrations of methoprene were lethal to larvae without heat treatment. Methoprene (67 ppm) had no effect on the cold tolerance of adults. Furthermore, methoprene (0.03 ppm) did not alter cold tolerance of larvae. Exposure to 15°C for 2 weeks increased the cold tolerance of adults from 4 d to 7 d, and larvae 3 d to 5 d; however, methoprene concentrations had no effect on cold tolerance. Tribolium castaneum larvae exposed to methoprene (0.001 ppm) had lower fecundity as adults. Males were more affected than females in reducing the offspring when paired with untreated mates. These results show the potential of methoprene as an emerging insecticide and a viable alternative to currently used synthetic insecticides. The data on the effect of methoprene on extreme temperature tolerance of T. castaneum have been submitted to the Journal of Stored Products Research.Keywords: Methoprene, Extreme temperature tolerance, Reproduction, Larvae, Adult

Decreased expression of Yes-associated protein is associated with outcome in the luminal A breast cancer subgroup and with an impaired tamoxifen response

Background: Yes-associated protein (YAP1) is frequently reported to function as an oncogene in many types of cancer, but in breast cancer results remain controversial. We set out to clarify the role of YAP1 in breast cancer by examining gene and protein expression in subgroups of patient material and by downregulating YAP1 in vitro and studying its role in response to the widely used anti-estrogen tamoxifen. Methods: YAP1 protein intensity was scored as absent, weak, intermediate or strong in two primary breast cancer cohorts (n = 144 and n = 564) and mRNA expression of YAP1 was evaluated in a gene expression dataset (n = 1107). Recurrence-free survival was analysed using the log-rank test and Cox multivariate analysis was used to test for independence. WST-1 assay was employed to measure cell viability and a luciferase ERE (estrogen responsive element) construct was used to study the effect of tamoxifen, following downregulation of YAP1 using siRNAs. Results: In the ER+ (Estrogen Receptor a positive) subgroup of the randomised cohort, YAP1 expression was inversely correlated to histological grade and proliferation (p = 0.001 and p = 0.016, respectively) whereas in the ER-(Estrogen Receptor a negative) subgroup YAP1 expression correlated positively to proliferation (p = 0.005). Notably, low YAP1 mRNA was independently associated with decreased recurrence-free survival in the gene expression dataset, specifically for the luminal A subgroup (p less than 0.001) which includes low proliferating tumours of lower grade, usually associated with a good prognosis. This subgroup specificity led us to hypothesize that YAP1 may be important for response to endocrine therapies, such as tamoxifen, extensively used for luminal A breast cancers. In a tamoxifen randomised patient material, absent YAP1 protein expression was associated with impaired tamoxifen response which was significant upon interaction analysis (p = 0.042). YAP1 downregulation resulted in increased progesterone receptor (PgR) expression and a delayed and weaker tamoxifen in support of the clinical data. Conclusions: Decreased YAP1 expression is an independent prognostic factor for recurrence in the less aggressive luminal A breast cancer subgroup, likely due to the decreased tamoxifen sensitivity conferred by YAP1 downregulation

Correction: Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden.

[This corrects the article DOI: 10.1371/journal.pntd.0010091.]

Outbreak of severe acute respiratory infection in Southern Province, Sri Lanka in 2018: a cross-sectional study

Objectives To determine aetiology of illness among children and adults presenting during outbreak of severe respiratory illness in Southern Province, Sri Lanka, in 2018.Design Prospective, cross-sectional study.Setting 1600-bed, public, tertiary care hospital in Southern Province, Sri Lanka.Participants 410 consecutive patients, including 371 children and 39 adults, who were admitted with suspected viral pneumonia (passive surveillance) or who met case definition for acute respiratory illness (active surveillance) in May to June 2018.Results We found that cocirculation of influenza A (22.6% of cases), respiratory syncytial virus (27.8%) and adenovirus (AdV) (30.7%; type B3) was responsible for the outbreak. Mortality was noted in 4.5% of paediatric cases identified during active surveillance. Virus type and viral coinfection were not significantly associated with mortality.Conclusions This is the first report of intense cocirculation of multiple respiratory viruses as a cause of an outbreak of severe acute respiratory illness in Sri Lanka, and the first time that AdV has been documented as a cause of a respiratory outbreak in the country. Our results emphasise the need for continued vigilance in surveying for known and emerging respiratory viruses in the tropics

Effect of fluorination on the pharmacological profile of 11β isomers of fulvestrant in breast carcinoma cells

We describe the synthesis of an 11beta isomer 3 of the steroidal antiestrogen fulvestrant 2. Partial fluorination of the 11beta side chain in 3 leads to 4, which still shows strong antiproliferative activity on MCF-7 cells. However, unlike 2 and 3, compound 4 fails to down-regulate estrogen receptor alpha (ERalpha). This result suggests that ERalpha down-regulation is not a sine qua non condition for the antitumor activity of steroidal antiestrogens.SCOPUS: ar.jinfo:eu-repo/semantics/publishe