Dynamic context-dependent regulation of auxin feedback signaling in synthetic gene circuits.

Phytohormone auxin plays a key role in regulating plant organogenesis. However, understanding the complex feedback signaling network that involves at least 29 proteins in Arabidopsis in the dynamic context remains a significant challenge. To address this, we transplanted an auxin-responsive feedback circuit responsible for plant organogenesis into yeast. By generating dynamic microfluidic conditions controlling gene expression, protein degradation, and binding affinity of auxin response factors to DNA, we illuminate feedback signal processing principles in hormone-driven gene expression. In particular, we recorded the regulatory mode shift between stimuli counting and rapid signal integration that is context-dependent. Overall, our study offers mechanistic insights into dynamic auxin response interplay trackable by synthetic gene circuits, thereby offering instructions for engineering plant architecture.

Macroscopic control of cell electrophysiology through ion channel expression.

Cells convert electrical signals into chemical outputs to facilitate the active transport of information across larger distances. This electrical-to-chemical conversion requires a tightly regulated expression of ion channels. Alterations of ion channel expression provide landmarks of numerous pathological diseases, such as cardiac arrhythmia, epilepsy, or cancer. Although the activity of ion channels can be locally regulated by external light or chemical stimulus, it remains challenging to coordinate the expression of ion channels on extended spatial-temporal scales. Here, we engineered yeast Saccharomyces cerevisiae to read and convert chemical concentrations into a dynamic potassium channel expression. A synthetic dual-feedback circuit controls the expression of engineered potassium channels through phytohormones auxin and salicylate to produce a macroscopically coordinated pulses of the plasma membrane potential. Our study provides a compact experimental model to control electrical activity through gene expression in eukaryotic cell populations setting grounds for various cellular engineering, synthetic biology, and potential therapeutic applications.

Sedación administrada por médicos generales para procedimientos endoscópicos de baja complejidad: experiencia en una unidad de endoscopia de una clínica de alta complejidad en Cali / Sedation Administered by General Practitioners for Low Complexity Endoscopic Procedures: Experience in an Endoscopy Unit of a Tertiary Referral Hospital in Cali

Resumen Objetivos: en Colombia se ha venido implementando la sedación por médicos no anestesiólogos para procedimientos endoscópicos fuera del quirófano. Se describió la experiencia en la unidad de gastroenterología de una clínica de alto nivel de atención en Cali, Colombia. Materiales y métodos: estudio observacional, de tipo cohorte analítica para describir la frecuencia y el tipo de eventos adversos asociados a los procedimientos de sedación por médicos generales, y evaluar los factores asociados a su ocurrencia en pacientes que acudieron a la unidad de endoscopia de la Fundación Valle del Lili para la realización de estudios endoscópicos bajo sedación intravenosa que, por ser de bajo riesgo, fue aplicada por un médico no anestesiólogo entre noviembre de 2018 y junio de 2019. Se realizó análisis descriptivo, se calcularon mediana y rango intercuartílico para las variables numéricas, y frecuencias para las variables cualitativas. Resultados: se incluyeron 1506 participantes, 59,4 % ASA I y 40,6 % ASA II. En promedio, la dosis inicial de propofol fue de 60 mg y la dosis total, de 140 mg. Se registraron eventos adversos no serios en 46 pacientes (3,05 %) y el más común fue la desaturación transitoria (80,4 %). Ningún paciente presentó eventos adversos serios. El puntaje inicial promedio de la escala de Aldrete fue 8, mientras que al alta el puntaje promedio fue de 10. Conclusiones: la sedación para procedimientos endoscópicos dada por médicos no anestesiólogos es segura, siempre y cuando sea realizado por personal entrenado que realice una adecuada valoración de los antecedentes (cardiovasculares, gastrointestinales y neurológicos) y factores de riesgo del paciente dentro del marco de los lineamientos institucionales vigentes.

Abstract Objectives: in Colombia, sedation by non-anesthesiologists for endoscopic procedures outside the operating room has been implemented. A description of an experience in the gastroenterology unit of a tertiary referral hospital in Cali, Colombia, was conducted. Materials and methods: an analytical cohort observational study to describe the frequency and type of adverse events associated with sedation procedures performed by general practitioners and evaluate the factors related to their occurrence in patients who attended the endoscopy unit of Fundación Valle del Lili for endoscopic studies under intravenous sedation. Between November 2018 and June 2019, non-anesthesiologist physicians performed this procedure due to the minimal risk implied. A descriptive analysis was completed, and the median and interquartile range were calculated for numerical variables and frequencies for qualitative variables. Results: There were 1506 participants, 59.4% ASA I and 40.6% ASA II in this study. On average, the starting dose of propofol was 60 mg, and the total dose was 140 mg. Forty-six patients (3.05%) reported non-severe adverse events; the most common occurrence was transient desaturation (80.4%). No patients experienced severe adverse events. The average initial Aldrete scale score was 8, while at discharge, the average score was 10. Conclusions: sedation for endoscopic procedures performed by non-anesthesiologists is safe provided that it is performed by trained personnel conducting a correct assessment of the patient's (cardiovascular, gastrointestinal, and neurological) history and risk factors within the framework of the current institutional guidelines.

Synchronization of gene expression across eukaryotic communities through chemical rhythms.

The synchronization is a recurring phenomenon in neuroscience, ecology, human sciences, and biology. However, controlling synchronization in complex eukaryotic consortia on extended spatial-temporal scales remains a major challenge. Here, to address this issue we construct a minimal synthetic system that directly converts chemical signals into a coherent gene expression synchronized among eukaryotic communities through rate-dependent hysteresis. Guided by chemical rhythms, isolated colonies of yeast Saccharomyces cerevisiae oscillate in near-perfect synchrony despite the absence of intercellular coupling or intrinsic oscillations. Increased speed of chemical rhythms and incorporation of feedback in the system architecture can tune synchronization and precision of the cell responses in a growing cell collectives. This synchronization mechanism remain robust under stress in the two-strain consortia composed of toxin-sensitive and toxin-producing strains. The sensitive cells can maintain the spatial-temporal synchronization for extended periods under the rhythmic toxin dosages produced by killer cells. Our study provides a simple molecular framework for generating global coordination of eukaryotic gene expression through dynamic environment.