Rare k-decays

This article reviews the current situation in the field of rare K decays: the relevant phenomenology, the present experimental situation, and prospects for the near future. Study of rare K decays can make a significant contribution in a number of different frontier areas of research in high-energy physics. In the area of CP violation, study of such rare decays as K(L)0 --> pi0e+e-, K(L)0 --> pi0mu+mu-, K(L)0 --> pi0nunuBAR, and muon polarization in K(L)0 --> mu+mu- can provide important complementary information to what has been learned from the decay K(L)0 --> pipi. Even though experiments with sufficient accuracy to make a meaningful study of CP violation are still a few years away, significant progress has been made in this general area during the last decade. A second major area of interest in the field of rare K decays is the search for processes forbidden in the Standard Model, e.g., K(L)0 --> mue and K+ --> pi+mu+e-. Various extensions of the Standard Model predict that these processes will occur with branching fractions in the range of 10(-10) to 10(-15). Experiments of the last decade have pushed the limits into the 10(-10) to 10(-11) range, and further improvements in sensitivity of one to two orders of magnitude can be expected in the next few years. K decays allow one also to study higher-order weak-interaction processes such as K(L)0 --> mu+mu-, K(L)0 --> e+e-, K+ --> pi+nunuBAR, which are forbidden to first order in the Standard Model. Because of strong suppression, these decay modes offer potential windows on new physics; in addition, they may offer the most reliable measurement of V(td), one of the elements of the weak mixing matrix in the quark sector. The studies of the mu+mu- channel have achieved data samples of close to 1000 events; the other two modes should be observed for the first time in the next few years. Finally, as a byproduct of these studies, one has been able to look simultaneously for new light particles into which the K meson could decay. Limits obtained for various hypothetical particles are summarized.Physic

Establishment of wMel Wolbachia in Aedes aegypti mosquitoes and reduction of local dengue transmission in Cairns and surrounding locations in northern Queensland, Australia.

Background: The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and subsequently shown in laboratory studies to reduce transmission of a range of viruses including dengue, Zika, chikungunya, yellow fever, and Mayaro viruses that cause human disease. Here we report the entomological and epidemiological outcomes of staged deployment of Wolbachia across nearly all significant dengue transmission risk areas in Australia. Methods: The  wMel strain of  Wolbachia was backcrossed into the local  Aedes aegypti genotype (Cairns and Townsville backgrounds) and mosquitoes were released in the field by staff or via community assisted methods. Mosquito monitoring was undertaken and mosquitoes were screened for the presence of  Wolbachia. Dengue case notifications were used to track dengue incidence in each location before and after releases. Results: Empirical analyses of the Wolbachia mosquito releases, including data on the density, frequency and duration of Wolbachia mosquito releases, indicate that Wolbachia can be readily established in local mosquito populations, using a variety of deployment options and over short release durations (mean release period 11 weeks, range 2-22 weeks). Importantly, Wolbachia frequencies have remained stable in mosquito populations since releases for up to 8 years. Analysis of dengue case notifications data demonstrates near-elimination of local dengue transmission for the past five years in locations where Wolbachia has been established. The regression model estimate of Wolbachia intervention effect from interrupted time series analyses of case notifications data prior to and after releases, indicated a 96% reduction in dengue incidence in Wolbachia treated populations (95% confidence interval: 84 - 99%). Conclusion: Deployment of the wMel strain of Wolbachia into local Ae. aegypti populations across the Australian regional cities of Cairns and most smaller regional communities with a past history of dengue has resulted in the reduction of local dengue transmission across all deployment areas

Modulation of the tumour promoting functions of cancer associated fibroblasts by phosphodiesterase type 5 inhibition increases the efficacy of chemotherapy in human preclinical models of esophageal adenocarcinoma

Background and aims: Esophageal adenocarcinoma (EAC) is chemoresistant in the majority of cases. The tumor-promoting biology of cancer associated fibroblasts (CAF) make them a target for novel therapies. Phosphodiesterase type 5 inhibitors (PDE5i) have been shown to regulate the activated fibroblast phenotype in benign disease. We investigated the potential for CAF modulation in EAC using PDE5i to enhance the efficacy of chemotherapy. Methods: EAC fibroblasts were treated with PDE5i and phenotypic effects examined using immunoblotting, immunohistochemistry, gel contraction, transwell invasion, organotypics, single cell RNAseq and shotgun proteomics. The combination of PDE5i with standard-of-care chemotherapy (Epirubicin, 5-Fluorouracil and Cisplatin) was tested for safety and efficacy in validated near-patient model systems (3D tumor growth assays (3D-TGAs) and patient derived xenograft (PDX) mouse models). Results: PDE5i treatment reduced alpha-SMA expression in CAFs by 50% (p<0.05), associated with a significant reduction in the ability of CAFs to contract collagen-1 gels and induce cancer cell invasion, (p<0.05). RNAseq and proteomic analysis of CAF and EAC cell lines revealed PDE5i specific regulation of pathways related to fibroblast activation and tumor promotion. 3D-TGA assays confirmed the importance of stromal cells to chemoresistance in EAC, which could be attenuated by PDE5i. Chemotherapy+PDE5i in PDX-bearing mice was safe and significantly reduced PDX tumor volume (p<0.05). Conclusion: PDE5 is a candidate for clinical trials to alter the fibroblast phenotype in esophageal cancer. We demonstrate the specificity of PDE5i for fibroblasts to prevent transdifferentiation and revert the CAF phenotype. Finally, we confirm the efficacy of PDE5i in combination with chemotherapy in close-to-patient in vitro and in vivo PDX-based model systems

Field cricket genome reveals the footprint of recent, abrupt adaptation in the wild.

Evolutionary adaptation is generally thought to occur through incremental mutational steps, but large mutational leaps can occur during its early stages. These are challenging to study in nature due to the difficulty of observing new genetic variants as they arise and spread, but characterizing their genomic dynamics is important for understanding factors favoring rapid adaptation. Here, we report genomic consequences of recent, adaptive song loss in a Hawaiian population of field crickets (Teleogryllus oceanicus). A discrete genetic variant, flatwing, appeared and spread approximately 15 years ago. Flatwing erases sound-producing veins on male wings. These silent flatwing males are protected from a lethal, eavesdropping parasitoid fly. We sequenced, assembled and annotated the cricket genome, produced a linkage map, and identified a flatwing quantitative trait locus covering a large region of the X chromosome. Gene expression profiling showed that flatwing is associated with extensive genome-wide effects on embryonic gene expression. We found that flatwing male crickets express feminized chemical pheromones. This male feminizing effect, on a different sexual signaling modality, is genetically associated with the flatwing genotype. Our findings suggest that the early stages of evolutionary adaptation to extreme pressures can be accompanied by greater genomic and phenotypic disruption than previously appreciated, and highlight how abrupt adaptation might involve suites of traits that arise through pleiotropy or genomic hitchhiking

A population-based matched cohort study of early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection

Our thanks to the EAVE II Patient Advisory Group and Sands charity for their support. COPS is a sub-study of EAVE II, which is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE—The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government DG Health and Social Care and the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation. COPS has received additional funding from Tommy’s charity. S.J.S. is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). S.V.K. acknowledges funding from an NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). K.B. is funded by a Wellcome Senior Research Fellowship (220283/Z/20/Z).Peer reviewedPublisher PD