Protein-adaptive differential scanning fluorimetry using conformationally responsive dyes.

Differential scanning fluorimetry (DSF) is a technique that reports protein thermal stability via the selective recognition of unfolded states by fluorogenic dyes. However, DSF applications remain limited by protein incompatibilities with existing DSF dyes. Here we overcome this obstacle with the development of a protein-adaptive DSF platform (paDSF) that combines a dye library 'Aurora' with a streamlined procedure to identify protein-dye pairs on demand.

Conformationally responsive dyes enable protein-adaptive differential scanning fluorimetry.

Flexible methods alter the course of biological discoveries. Differential Scanning Fluorimetry (DSF) is a particularly versatile technique which reports protein thermal unfolding via fluorogenic dye. However, applications of DSF are limited by widespread protein incompatibilities with the available DSF dyes.

Activation function 1 of progesterone receptor is required for progesterone antagonism of oestrogen action in the uterus.

Background: Progesterone receptor (PGR) is a master regulator of uterine function through antagonistic and synergistic interplays with oestrogen receptors. PGR action is primarily mediated by activation functions AF1 and AF2, but their physiological significance is unknown.

Results: We report the first study of AF1 function in mice.

High Levels of Progesterone Receptor B in MCF-7 Cells Enable Radical Anti-Tumoral and Anti-Estrogenic Effect of Progestin.

The widely reported conflicting effects of progestin on breast cancer suggest that the progesterone receptor (PR) has dual functions depending on the cellular context. Cell models that enable PR to fully express anti-tumoral properties are valuable for the understanding of molecular determinant(s) of the anti-tumoral property. This study evaluated whether the expression of high levels of PR in MCF-7 cells enabled a strong anti-tumoral response to progestin.

Activation function 1 of progesterone receptor is required for mammary development and regulation of RANKL during pregnancy.

Progesterone receptor (PGR) is a member of the nuclear receptor superfamily of transcription factors. It is critical for mammary stem cells expansion, mammary ductal branching and alveologenesis. The transcriptional activity of PGR is mainly mediated by activation functions AF1 and AF2.

Impact of an Ultrasound Demonstration on Vascular Surgery Interest in Preclinical Medical Students.

Background: One strategy to address the impending shortage of vascular surgeons is to augment interest in the trainee pipeline. Endovascular procedures are unique to vascular surgery (VS) and endovascular simulations have proven effective at generating VS interest in the past. Like endovascular techniques, the use of ultrasound (US) testing in VS is unique among medical specialties.

Prioritizing a Research Agenda of Transitional Care Interventions for Childhood-Onset Disabilities.

Transitional care interventions have the potential to optimize continuity of care, improve health outcomes and enhance quality of life for adolescents and young adults living with chronic childhood-onset disabilities, including neurodevelopmental disorders, as they transition to adult health and social care services. The paucity of research in this area poses challenges in identifying and implementing interventions for research, evaluation and implementation. The purpose of this project was to advance this research agenda by identifying the transitional care interventions from the scientific literature and prioritize interventions for study.

Transitional Care Interventions for Youth With Disabilities: A Systematic Review.

Context: Transition from the pediatric to the adult health care system is a complex process that should include medical, psychosocial, educational, recreational, and vocational considerations.

Objective: In this systematic review, we aim to synthesize the evidence on transitional care interventions (TCIs) to improve the quality of life (QoL) for adolescents and young adults with childhood-onset disabilities, including neurodevelopmental disorders.

Data Sources: Four electronic databases (Medline, Embase, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature) were searched.

Delineation of critical amino acids in activation function 1 of progesterone receptor for recruitment of transcription coregulators.

The activation functions AF1 and AF2 of nuclear receptors mediate the recruitment of coregulators in gene regulation. AF1 is mapped to the highly variable and intrinsically unstructured N terminal domain and AF2 lies in the conserved ligand binding domain. The unstructured nature of AF1 offers structural plasticity and hence functional versatility in gene regulation.

Small-molecule-based regulation of RNA-delivered circuits in mammalian cells.

Synthetic mRNA is an attractive vehicle for gene therapies because of its transient nature and improved safety profile over DNA. However, unlike DNA, broadly applicable methods to control expression from mRNA are lacking. Here we describe a platform for small-molecule-based regulation of expression from modified RNA (modRNA) and self-replicating RNA (replicon) delivered to mammalian cells.

Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution.

Epidemiological studies have indicated increased risk for breast cancer within 10 years of childbirth. Acute inflammation during mammary involution has been suggested to promote this parity-associated breast cancer. We report here that estrogen exacerbates mammary inflammation during involution.

Protein arginine methyltransferase 6 enhances ligand-dependent and -independent activity of estrogen receptor α via distinct mechanisms.

Recent studies reported that protein arginine methyltransferase 6 (PRMT6) enhances estrogen-induced activity of estrogen receptor α (ERα) and dysfunction of PRMT6 is associated with overall better survival for ERα-positive breast cancer patients. However, it is unclear how PRMT6 promotes ERα activity. Here we report that PRMT6 specifically interacts with ERα at its ligand-binding domain.

Lysine methylation of progesterone receptor at activation function 1 regulates both ligand-independent activity and ligand sensitivity of the receptor.

Progesterone receptor (PR) exists in two isoforms, PRA and PRB, and both contain activation functions AF-1 and AF-2. It is believed that AF-1 is primarily responsible for the ligand-independent activity, whereas AF-2 mediates ligand-dependent PR activation. Although more than a dozen post-translational modifications of PR have been reported, no post-translational modification on AF-1 or AF-2 has been reported.