Boysenraun0390

The ecological niche can be thought of as a volume in multidimensional space, where each dimension describes an abiotic condition or biotic resource required by a species. The shape, size, and evolution of this volume strongly determine interactions among species and influence their current and potential geographical distributions, but the geometry of niches is poorly understood. Here, we analyse temperature response functions and host plant ranges for hundreds of potentially destructive plant-associated fungi and oomycetes. We demonstrate that niche specialization is uncorrelated on abiotic (i.e. temperature response) and biotic (i.e. host range) axes, that host interactions restrict fundamental niche breadth to form the realized niche, and that both abiotic and biotic niches show limited phylogenetic constraint. The ecological terms 'generalist' and 'specialist' therefore do not apply to these microbes, as specialization evolves independently on different niche axes. This adaptability makes plant pathogens a formidable threat to agriculture and forestry.Acute myeloid leukemia (AML) is an immune-susceptible malignancy, as demonstrated by its responsiveness to allogeneic stem cell transplantation (alloSCT). However, by employing inhibitory signaling pathways, including PD-1/PD-L1, leukemia cells suppress T cell-mediated immune attack. Notably, impressive clinical efficacy has been obtained with PD-1/PD-L1 blocking antibodies in cancer patients. Yet, these systemic treatments are often accompanied by severe toxicity, especially after alloSCT. Here, we investigated RNA interference technology as an alternative strategy to locally interfere with PD-1/PD-L1 signaling in AML. We demonstrated efficient siRNA-mediated PD-L1 silencing in HL-60 and patients' AML cells. Caspase inhibitor clinical trial Importantly, WT1-antigen T cell receptor+ PD-1+ 2D3 cells showed increased activation toward PD-L1 silenced WT1+ AML. Moreover, PD-L1 silenced AML cells significantly enhanced the activation, degranulation, and IFN-γ production of minor histocompatibility antigen-specific CD8+ T cells. Notably, PD-L1 silencing was equally effective as PD-1 antibody blockade. Together, our study demonstrates that PD-L1 silencing may be an effective strategy to augment AML immune-susceptibility. This provides rationale for further development of targeted approaches to locally interfere with immune escape mechanisms in AML, thereby minimizing severe toxicity. In combination with alloSCT and/or adoptive T cell transfer, this strategy could be very appealing to boost graft-versus-leukemia immunity and improve outcome in AML patients.Background The anticancer potential of ibuprofen has created a broad interest to explore the clinical benefits of ibuprofen in cancer therapy. However, the current understanding of the molecular mechanisms involved in the anticancer potential of ibuprofen remains limited. Methods Cancer stemness assays to validate ibuprofen function in vitro and in vivo. Histone modification assays to check the effect of ibuprofen on histone acetylation/methylation, as well as the activity of HDAC and KDM6A/B. Inhibitors' in vivo assays to evaluate therapeutic effects of various inhibitors' combination manners. Results In our in vitro studies, we report that ibuprofen diminishes cancer cell stemness properties that include reducing the ALDH + subpopulation, side population and sphere formation in three cancer types. In our in vivo studies, we report that ibuprofen decreases tumour growth, metastasis and prolongs survival. In addition, our results showed that ibuprofen inhibits inflammation-related stemness gene expression (especially ICAM3) identified by a high-throughput siRNA platform. In regard to the underlying molecular mechanism of action, we report that ibuprofen reduces HDACs and histone demethylase (KDM6A/B) expression that mediates histone acetylation and methylation, and suppresses gene expression via a COX2-dependent way. In regard to therapeutic strategies, we report that ibuprofen combined HDAC/HDM inhibitors prevents cancer progression in vivo. Conclusions The aforementioned findings suggest a molecular model that explains how ibuprofen diminishes cancer cell stemness properties. These may provide novel targets for therapeutic strategies involving ibuprofen in the prevention of cancer progression.Background Mammography is not effective in detecting breast cancer in dense breasts. Methods A search in Medline, Cochrane, EMBASE and Google Scholar databases was conducted from January 1, 1980 to April 10, 2019 to identify women with dense breasts screened by mammography (M) and/or ultrasound (US). Meta-analysis was performed using the random-effect model. Results A total of 21 studies were included. The pooled sensitivity values of M alone and M + US in patients were 74% and 96%, while specificity of the two methods were 93% and 87%, respectively. Screening sensitivity was significantly higher in M + US than M alone (risk ratio M alone vs. M + US = 0.699, P less then 0.001), but the slight difference in specificity was statistically significant (risk ratio = 1.060, P = 0.001). Pooled diagnostic performance of follow-up US after initial negative mammography demonstrated a high pooled sensitivity (96%) and specificity (88%). The findings were supported by subgroup analysis stratified by study country, US method and timing of US. Conclusions Breast cancer screening by supplemental US among women with dense breasts shows added detection sensitivity compared with M alone. However, US slightly decreased the diagnostic specificity for breast cancer. The cost-effectiveness of supplemental US in detecting malignancy in dense breasts should be considered additionally.Pesticides commonly contaminate the aquatic environments inhabited by mosquito juveniles. However, their role in shaping the mosquito microbiota is not well understood. We hypothesized that environmentally relevant concentrations of atrazine, permethrin and malathion will mediate a shift in the mosquito gut bacterial community structure due to their toxic effect on the aquatic bacterial communities, and reduce mosquito gut bacterial diversity by enriching pesticide-degrading bacterial communities over susceptible taxa. Illumina MiSeq sequencing of the V3-V4 hypervariable regions of the 16 S rRNA gene was used to characterize the microbial communities of larval and adult stages of the two mosquito species and the water samples from microcosms treated with each of the pesticides, separately. Bacterial community composition differed by sample type (larval stage vs. adult stage) and water sampling date (day 3 vs. day 7), but not by pesticide treatment. In larval stages, bacterial OTU richness was highest in samples exposed to malathion, intermediate in permethrin, and lowest in controls.