Transcriptional enhancers integrate positional and temporal information to regulate the complex expression of developmentally controlled genes. Current models suggest that enhancers act as computational devices, receiving multiple inputs from activators and repressors and resolving them into a single positive or a negative signal that is transmitted to the basal transcriptional machinery. We show that a simple, compact enhancer is capable of representing both repressed and activated states at the same time and in the same nucleus. This finding suggests that closely apposed factor binding sites, situated within compact cis-elements, can be independently interpreted by the transcriptional machinery, possibly through successive enhancer-promoter interactions. These results provide clear evidence that the computational functions usually ascribed to the enhancer itself are actually shared with the basal machinery. In contrast to the autonomous computer model of enhancer function, an information-display or 'billboard' model of enhancer activity may better describe many developmentally regulated transcriptional enhancers.
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http://dx.doi.org/10.1242/dev.00890 | DOI Listing |
Adv Sci (Weinh)
January 2025
Department of Laboratory Medicine, School of Chemical Science and Engineering, Shanghai Tenth People's Hospital of Tongji University, Tongji University, Shanghai, 200092, P. R. China.
The healing of bacterial biofilm-infected wounds is a complex process, and the construction of emerging therapeutic modalities that regulate the microenvironment to magnify therapeutic effects and reduce biotoxicity is still highly challenging. Herein, an engineered microneedle (MN) patch is reported to mediate the efficient delivery of black phosphorus nanosheets (BP NSs) and copper peroxide nanodots (CP NDs) for dual nanodynamic sterilization and methicillin-resistant staphylococcus aureus (MRSA)-infected wound healing. Results demonstrate that the system can eliminate biofilm, reduce cytotoxicity, promote angiogenesis and tissue regeneration by the multiple advantages of chemodynamic therapy (CDT), enhanced photodynamic therapy (PDT), and improved degradation process from BP NSs to phosphate for promoting cell proliferation.
View Article and Find Full Text PDFCancer Res
January 2025
First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Sunitinib is a first-line targeted therapy for patients with renal cell carcinoma (RCC), but resistance represents a significant obstacle to the treatment of advanced and metastatic RCC. Metabolic reprogramming is a characteristic of RCC, and changes in metabolic processes might contribute to resistance to sunitinib. Here, we identified MTHFD2, a mitochondrial enzyme involved in one-carbon metabolism, as a critical mediator of sunitinib resistance in RCC.
View Article and Find Full Text PDFCancer Res
January 2025
Oregon Health & Science University, Portland, OR, United States.
Senescence is a non-proliferative, survival state that cancer cells can enter to escape therapy. In addition to soluble factors, senescence cells secrete extracellular vesicles (EVs), which are important mediators of intercellular communication. To explore the role of senescent cell-derived EVs (senEVs) in inflammatory responses to senescence, we developed an engraftment-based senescence model in wild-type mice and genetically blocked senEV release in vivo, without significantly affecting soluble mediators.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Orthopedic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, 200003, P. R. China.
Nucleus pulposus cell (NPC) senescence contributes to intervertebral disc degeneration (IVDD). However, the underlying molecular mechanisms are not fully understood. In this study, it is demonstrated that angiotensin-converting enzyme 2 (ACE2) counteracted the aging of NPCs and IVDD at the cellular and physiological levels.
View Article and Find Full Text PDFPLOS Glob Public Health
January 2025
Department of Global Health, University of Washington, Seattle, Washington, United States of America.
Integrating and sustaining evidence-based interventions (EBIs) in routine care is crucial to improving HIV treatment outcomes among youth living with HIV (YLH). However, EBIs are often not sustained post clinical trial. An Adolescent Transition Package (ATP) delivered by health care workers (HCWs) and tested in Kenya in 2021 significantly improved YLH readiness to transition to independent care.
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