Tranrutledge4161

Microbial production of antibiotics is common, but our understanding of their roles in the environment is limited. In this study, we explore long-standing observations that microbes increase the production of redox-active antibiotics under phosphorus limitation. The availability of phosphorus, a nutrient required by all life on Earth and essential for agriculture, can be controlled by adsorption to and release from iron minerals by means of redox cycling. Using phenazine antibiotic production by pseudomonads as a case study, we show that phenazines are regulated by phosphorus, solubilize phosphorus through reductive dissolution of iron oxides in the lab and field, and increase phosphorus-limited microbial growth. Phenazines are just one of many examples of phosphorus-regulated antibiotics. Our work suggests a widespread but previously unappreciated role for redox-active antibiotics in phosphorus acquisition and cycling.Structural hierarchy can enhance the mechanical behavior of materials and systems. This is exemplified by the fracture toughness of nacre or enamel in nature and by human-made architected microscale network structures. Nanoscale structuring promises further strengthening, yet macroscopic bodies built this way contain an immense number of struts, calling for scalable preparation schemes. In this work, we demonstrated macroscopic hierarchical network nanomaterials made by the self-organization processes of dealloying. Their hierarchical architecture affords enhanced strength and stiffness at a given solid fraction, and it enables reduced solid fractions by dealloying. Scaling laws for the mechanics and atomistic simulation support the observations. Because they expose the systematic benefits of hierarchical structuring in nanoscale network structures, our materials may serve as prototypes for future lightweight structural materials.In vivo models that recapitulate human erythropoiesis with persistence of circulating red blood cells (RBCs) have remained elusive. We report an immunodeficient murine model in which combined human liver and cytokine humanization confer enhanced human erythropoiesis and RBC survival in the circulation. We deleted the fumarylacetoacetate hydrolase (Fah) gene in MISTRG mice expressing several human cytokines in place of their murine counterparts. Liver humanization by intrasplenic injection of human hepatocytes (huHep) eliminated murine complement C3 and reduced murine Kupffer cell density. Engraftment of human sickle cell disease (SCD)-derived hematopoietic stem cells in huHepMISTRGFah-/- mice resulted in vaso-occlusion that replicated acute SCD pathology. Combined liver-cytokine-humanized mice will facilitate the study of diseases afflicting RBCs, including bone marrow failure, hemoglobinopathies, and malaria, and also preclinical testing of therapies.Past research argues for an internal multidecadal (40- to 60-year) oscillation distinct from climate noise. Recent studies have claimed that this so-termed Atlantic Multidecadal Oscillation is instead a manifestation of competing time-varying effects of anthropogenic greenhouse gases and sulfate aerosols. That conclusion is bolstered by the absence of robust multidecadal climate oscillations in control simulations of current-generation models. Paleoclimate data, however, do demonstrate multidecadal oscillatory behavior during the preindustrial era. By comparing control and forced "Last Millennium" simulations, we show that these apparent multidecadal oscillations are an artifact of pulses of volcanic activity during the preindustrial era that project markedly onto the multidecadal (50- to 70-year) frequency band. We conclude that there is no compelling evidence for internal multidecadal oscillations in the climate system.Spread of contagious pathogens critically depends on the number and types of contacts between infectious and susceptible hosts. Changes in social behavior by susceptible, exposed, or sick individuals thus have far-reaching downstream consequences for infectious disease spread. Although "social distancing" is now an all too familiar strategy for managing COVID-19, nonhuman animals also exhibit pathogen-induced changes in social interactions. Here, we synthesize the effects of infectious pathogens on social interactions in animals (including humans), review what is known about underlying mechanisms, and consider implications for evolution and epidemiology.The mechanisms that underly the adaptation of enzyme activities and stabilities to temperature are fundamental to our understanding of molecular evolution and how enzymes work. Selleck OTSSP167 Here, we investigate the molecular and evolutionary mechanisms of enzyme temperature adaption, combining deep mechanistic studies with comprehensive sequence analyses of thousands of enzymes. We show that temperature adaptation in ketosteroid isomerase (KSI) arises primarily from one residue change with limited, local epistasis, and we establish the underlying physical mechanisms. This residue change occurs in diverse KSI backgrounds, suggesting parallel adaptation to temperature. We identify residues associated with organismal growth temperature across 1005 diverse bacterial enzyme families, suggesting widespread parallel adaptation to temperature. We assess the residue properties, molecular interactions, and interaction networks that appear to underly temperature adaptation.Our study showed that increases in seasonal productivity drive earlier autumn senescence of temperate trees. Norby argues that this finding is contradicted by observations from free-air CO2 enrichment (FACE) experiments, where elevated CO2 has been found to delay senescence in some cases. We provide a detailed answer showing that the results from FACE studies are in agreement with our conclusions.Zani et al (Research Articles, 27 November 2020, p. 1066) propose that enhancement of deciduous tree photosynthesis in a CO2-enriched atmosphere will advance autumn leaf senescence. This premise is not supported by consistent observations from free-air CO2 enrichment (FACE) experiments. In most FACE experiments, leaf senescence or abscission was not altered or was delayed in trees exposed to elevated CO2.Most multicellular organisms have a major body cavity that harbors immune cells. In primordial species such as purple sea urchins, these cells perform phagocytic functions but are also crucial in repairing injuries. In mammals, the peritoneal cavity contains large numbers of resident GATA6+ macrophages, which may function similarly. However, it is unclear how cavity macrophages suspended in the fluid phase (peritoneal fluid) identify and migrate toward injuries. In this study, we used intravital microscopy to show that cavity macrophages in fluid rapidly form thrombus-like structures in response to injury by means of primordial scavenger receptor cysteine-rich domains. Aggregates of cavity macrophages physically sealed injuries and promoted rapid repair of focal lesions. In iatrogenic surgical situations, these cavity macrophages formed extensive aggregates that promoted the growth of intra-abdominal scar tissue known as peritoneal adhesions.Biomolecular assemblies govern the physiology of cells. Their function often depends on the changes in molecular arrangements of constituents, both in the positions and orientations. While recent advancements of fluorescence microscopy including super-resolution microscopy have enabled us to determine the positions of fluorophores with unprecedented accuracy, monitoring the orientation of fluorescently labeled molecules within living cells in real time is challenging. Fluorescence polarization microscopy (FPM) reports the orientation of emission dipoles and is therefore a promising solution. For imaging with FPM, target proteins need labeling with fluorescent probes in a sterically constrained manner, but because of difficulties in the rational three-dimensional design of protein connection, a universal method for constrained tagging with fluorophore was not available. Here, we report POLArIS, a genetically encoded and versatile probe for molecular orientation imaging. Instead of using a direct tagging approach, we used a recombinant binder connected to a fluorescent protein in a sterically constrained manner that can target specific biomolecules of interest by combining with phage display screening. As an initial test case, we developed POLArISact, which specifically binds to F-actin in living cells. We confirmed that the orientation of F-actin can be monitored by observing cells expressing POLArISact with FPM. In living starfish early embryos expressing POLArISact, we found actin filaments radially extending from centrosomes in association with microtubule asters during mitosis. By taking advantage of the genetically encoded nature, POLArIS can be used in a variety of living specimens, including whole bodies of developing embryos and animals, and also be expressed in a cell type/tissue specific manner.

Opioid overdose and abuse have reached epidemic rates in the United States. Medical prescriptions are a large source of opioid misuse. Our quality improvement initiative aimed to reduce opioid exposure from the pediatric emergency department (ED). Objective was to reduce opioid doses prescribed weekly from our ED by 50% within 4 months.

Three categories of interventions were implemented in Plan-Do-Study-Act cycles guidelines and education, electronic medical record optimization, and provider-specific feedback. Primary measures were opioid doses prescribed weekly from the ED and opioid doses per 100 ED visits. Process measures were opioid prescriptions, opioid doses per prescription, and opioid prescriptions for unspecified abdominal pain, headache, and viral upper respiratory infection. Balancing measures were phone calls and return visits for poor pain control in patients prescribed opioids and reports of poor pain control in call backs to orthopedic reduction patients. We used statistical process control to examine changes in measures over time.

Opioid doses decreased from 153 to 14 per week and from 8 to 0.7 doses per 100 ED visits in 10 months, sustained for 9 months. Opioid prescriptions, opioid doses per prescription, and prescriptions for unspecified abdominal pain, headache, and viral upper respiratory infection decreased. Phone calls and return visits in patients prescribed opioids did not increase. There were 2 reports of poor pain control among 152 orthopedic reduction patients called back.

We decreased opioid doses prescribed weekly from the pediatric ED by 91% while minimizing return visits and reports of poor pain control.

We decreased opioid doses prescribed weekly from the pediatric ED by 91% while minimizing return visits and reports of poor pain control.

Pediatric ethics consultations are important but understudied, with little known about consultations' contextual attributes, which may influence how ethically problematic situations are perceived and addressed.

We analyzed data regarding 245 pediatric clinical ethics consultations performed between 2013 and 2018 at a large children's hospital. Prespecified data elements included 17 core problematic issues that initiate consultations, 9 ethical considerations identified by the consultation service, and 7 relational, emotional, and pragmatic contextual attributes of the consultation. The main process measure was the cumulative consultation process, ranging from one-on-one discussions with the requestor, to meeting with the clinical team, separate meetings with the patient or family and the clinical team, or combined meeting with the patient or family and the clinical team.

The most-prevalent core problematic issues were intensity or limitation of treatment (38.8%) and treatment adherence and refusal (31%).