In animals, Hox transcription factors define regional identity in distinct anatomical domains. How Hox genes encode this specificity is a paradox, because different Hox proteins bind with high ...affinity in vitro to similar DNA sequences. Here, we demonstrate that the Hox protein Ultrabithorax (Ubx) in complex with its cofactor Extradenticle (Exd) bound specifically to clusters of very low affinity sites in enhancers of the shavenbaby gene of Drosophila. These low affinity sites conferred specificity for Ubx binding in vivo, but multiple clustered sites were required for robust expression when embryos developed in variable environments. Although most individual Ubx binding sites are not evolutionarily conserved, the overall enhancer architecture—clusters of low affinity binding sites—is maintained and required for enhancer function. Natural selection therefore works at the level of the enhancer, requiring a particular density of low affinity Ubx sites to confer both specific and robust expression.
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•shavenbaby enhancers contain multiple low affinity binding sites for Ubx-Exd•Replacing low affinity sites with high-affinity sites reduced specificity•Each Ubx-Exd binding site is required for robust enhancer function•Enhancer architecture is evolutionarily conserved, but most single sites are not
Transcriptional enhancers employ a strategy for balancing the need for specificity with the need for robustness with multiple clusters of low affinity binding sites.
Adult stem cells must continuously fine‐tune their behavior to regenerate damaged organs and avoid tumors. While several signaling pathways are well known to regulate somatic stem cells, the ...underlying mechanisms remain largely unexplored. Here, we demonstrate a cell‐intrinsic role for the OvoL family transcription factor, Shavenbaby (Svb), in balancing self‐renewal and differentiation of Drosophila intestinal stem cells. We find that svb is a downstream target of Wnt and EGFR pathways, mediating their activity for stem cell survival and proliferation. This requires post‐translational processing of Svb into a transcriptional activator, whose upregulation induces tumor‐like stem cell hyperproliferation. In contrast, the unprocessed form of Svb acts as a repressor that imposes differentiation into enterocytes, and suppresses tumors induced by altered signaling. We show that the switch between Svb repressor and activator is triggered in response to systemic steroid hormone, which is produced by ovaries. Therefore, the Svb axis allows intrinsic integration of local signaling cues and inter‐organ communication to adjust stem cell proliferation versus differentiation, suggesting a broad role of OvoL/Svb in adult and cancer stem cells.
SYNOPSIS
How somatic stem cells integrate cell‐intrinsic and extrinsic cues to fine‐tune their output remains unclear. Here, the OvoL‐family transcription factor Shavenbaby (Svb) is shown to balance Drosophila intestinal stem cell (ISCs) fate decisions in response to systemic hormones.
Svb is a direct target of EGFR and Wnt signaling in ISCs.
Svb is switched from transcriptional repressor into activator by limited proteasomal degradation.
Repressor Svb induces differentiation into enterocytes.
Activator Svb promotes survival and proliferation of stem cells.
The Svb repressor‐to‐activator switch is remotely induced by ovarian steroids.
Post‐translational processing of the transcription factor Shavenbaby defines its dichotomous function in fly midgut homeostasis.
Telepharmacy is a technology-based service that provides promoted services such as counseling, medication administration and compounding, drug therapy monitoring, and prescription review. It is ...unclear whether hospital pharmacists possess the necessary knowledge, attitudes, and willingness to practice telepharmacy. The current study sought to investigate Saudi Arabian hospital pharmacists' understanding, attitudes, and level of preparedness for telepharmacy services. A total of 411 pharmacists responded to the survey. Only 43.33% of the respondents agreed that telepharmacy is available in Saudi Arabia and 36.67% of the respondents agreed that patients in rural areas can have more medication access and information via telepharmacy. Only 29.33% of pharmacists agreed that telepharmacy improves patient medication adherence, and about 34.00% of the pharmacists agreed that telepharmacy saves patients money and time by eliminating the need for them to travel to healthcare facilities. This research found that hospital pharmacists were unsure of their level of knowledge, their attitude toward telepharmacy, and their willingness to incorporate it into their future pharmacy practices. To ensure that tomorrow's pharmacists have the skills they need to provide telepharmacy services, telepharmacy practice models must be incorporated into the educational programs that prepare them.
Telepharmacy is a practical part of telemedicine that refers to providing pharmaceutical services within the scope of the pharmacist's obligations while maintaining a temporal and spatial distance ...between patients, users of health services, and healthcare professionals. The present study was a cross-sectional study conducted among community pharmacists in Saudi Arabia between March and May 2022 to assess their knowledge, perceptions, and readiness for telepharmacy. The survey was filled out by 404 respondents. The majority of respondents were male (59.90%) and the age of more than half of them was between 30 and 39 years old (54.46%). Most participants worked in urban areas (83.66%), and 42.57% had less than five years of experience in a pharmacy. Most participants agreed that telepharmacy is available in Saudi Arabia (82.67%). Approximately 70% of pharmacists felt that telepharmacy promotes patient medication adherence, and 77.72% agreed that telepharmacy increases patient access to pharmaceuticals in rural areas. More than 72% of pharmacists said they would work on telepharmacy initiatives in rural areas for free, and 74.26% said they would work outside of usual working hours if necessary. In the future, this research could aid in adopting full-fledged telepharmacy pharmaceutical care services in Saudi Arabia. It could also help academic initiatives by allowing telepharmacy practice models to be included as a topic course in the curriculum to prepare future pharmacists to deliver telepharmacy services.
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