Establishment and maintenance of proper gene expression is a requirement for normal growth and development. The DREAM complex in functions as a transcriptional repressor of germline genes in somatic cells. At 26°, DREAM complex mutants show increased misexpression of germline genes in somatic cells and High Temperature Arrest (HTA) of worms at the first larval stage. To identify transcription factors required for the ectopic expression of germline genes in DREAM complex mutants, we conducted an RNA interference screen against 123 transcription factors capable of binding DREAM target promoter loci for suppression of the HTA phenotype in mutants. We found that knock-down of 15 embryonically expressed transcription factors suppress the HTA phenotype in mutants. Five of the transcription factors found in the initial screen have associations with Wnt signaling pathways. In a subsequent RNAi suppression screen of Wnt signaling factors we found that knock-down of the non-canonical Wnt/PCP pathway factors , and in a mutant background resulted in strong suppression of the HTA phenotype. Animals mutant for both and showed almost complete suppression of the HTA phenotype, misexpression, and fertility defects associated with single mutants at 26°. We propose a model whereby a set of embryonically expressed transcription factors, and the Wnt/PCP pathway, act opportunistically to activate DREAM complex target genes in somatic cells of DREAM complex mutants at 26°.
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http://dx.doi.org/10.1534/g3.119.400850 | DOI Listing |
Trends Mol Med
December 2024
Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address:
Genetic and epigenetic defects of the p53 system have previously been associated with resistance to CDK4/6 inhibitors in women with HR breast cancer. Recent data from Kudo et al. demonstrate that CDK2-targeting agents may offer an effective strategy to circumvent such resistance by enforcing cellular senescence downstream of RBL2 dephosphorylation.
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December 2024
National Centre for Asbestos Related Diseases, Institute for Respiratory Health, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia; The Kids Research Institute, University of Western Australia, Nedlands WA 6009, Australia. Electronic address:
Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time course RNA sequencing (RNA-seq) of peripheral blood mononuclear cells with pre-treatment tumor transcriptome data from the single-arm, phase 2 DREAM trial (N = 54).
View Article and Find Full Text PDFFront Artif Intell
December 2024
Laboratorio di Biostatistica e Bioinformatica, Fisica Sanitaria, I.R.C.C.S. Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Objectives: Endometrial carcinosarcoma is a rare, aggressive high-grade endometrial cancer, accounting for about 5% of all uterine cancers and 15% of deaths from uterine cancers. The treatment can be complex, and the prognosis is poor. Its increasing incidence underscores the urgent requirement for personalized approaches in managing such challenging diseases.
View Article and Find Full Text PDFBMC Med Educ
December 2024
School of Nursing and Midwifery, Queen's University Belfast, Belfast, UK.
Background: Delirium is a complex neuropsychiatric syndrome characterised by an acute state of confusion, with a substantial impact on medical inpatients. Despite its growing recognition as a global healthcare concern, delirium remains underdiagnosed, partly due to a lack of awareness among healthcare professionals. The aim of this study was to explore how healthcare professional students experience caring for individuals experiencing delirium, the influence of their current pre-registration healthcare education, and importance of interprofessional teamwork in their role.
View Article and Find Full Text PDFACS Appl Mater Interfaces
December 2024
Interdisciplinary Center for Quantum Information, State Key Laboratory of Modern Optical Instrumentation, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China.
Invisibility─the remarkable ability to render objects imperceptible─has long been a persistent dream of humankind. However, traditional cloaking materials are typically rigid and inflexible, limiting their adaptability to various shapes and requirements. Even when flexibility is achieved, uncontrollable scattering in complex electromagnetic environments continues to pose significant challenges in the design of flexible cloaks.
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