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Assembly of the hair bundle, the sensory organelle of the inner ear, depends on differential growth of actin-based stereocilia. Separate rows of stereocilia, labeled 1 through 3 from tallest to shortest, lengthen or shorten during discrete time intervals during development. We used lattice structured illumination microscopy and surface rendering to measure dimensions of stereocilia from mouse apical inner hair cells during early postnatal development; these measurements revealed a sharp transition at postnatal day 8 between stage III (row 1 and 2 widening; row 2 shortening) and stage IV (final row 1 lengthening and widening). Tip proteins that determine row 1 lengthening did not accumulate simultaneously during stages III and IV; while the actin-bundling protein EPS8 peaked at the end of stage III, GNAI3 peaked several days later—in early stage IV—and GPSM2 peaked near the end of stage IV. To establish the contributions of key macromolecular assemblies to bundle structure, we examined mouse mutants that eliminated tip links ( Cdh23 v2J or Pcdh15 av3J ), transduction channels ( Tmie KO ), or the row 1 tip complex ( Myo15a sh2 ). Cdh23 v2J/v2J and Pcdh15 av3J/av3J bundles had adjacent stereocilia in the same row that were not matched in length, revealing that a major role of these cadherins is to synchronize lengths of side-by-side stereocilia. Use of the tip-link mutants also allowed us to distinguish the role of transduction from effects of transduction proteins themselves. While levels of GNAI3 and GPSM2, which stimulate stereocilia elongation, were greatly attenuated at the tips of Tmie KO/KO row 1 stereocilia, they accumulated normally in Cdh23 v2J/v2J and Pcdh15 av3J/av3J stereocilia. These results reinforced the suggestion that the transduction proteins themselves facilitate localization of proteins in the row 1 complex. By contrast, EPS8 concentrates at tips of all Tmie KO/KO , Cdh23 v2J/v2J , and Pcdh15 av3J/av3J stereocilia, correlating with the less polarized distribution of stereocilia lengths in these bundles. These latter results indicated that in wild-type hair cells, the transduction complex prevents accumulation of EPS8 at the tips of shorter stereocilia, causing them to shrink (rows 2 and 3) or disappear (row 4 and microvilli). Reduced rhodamine-actin labeling at row 2 stereocilia tips of tip-link and transduction mutants suggests that transduction’s role is to destabilize actin filaments there. These results suggest that regulation of stereocilia length occurs through EPS8 and that CDH23 and PCDH15 regulate stereocilia lengthening beyond their role in gating mechanotransduction channels.

The use of unmanned aerial vehicles or \"drones\" has expanded in the last decade, as their technology has become more sophisticated, and costs have decreased. They are now used routinely in farming, environmental surveillance, public safety, commercial product delivery, recreation, and other applications. Health-related applications are only recently becoming more widely explored and accepted. The use of drone technology in emergency medicine is especially promising given the need for a rapid response to enhance patient outcomes. The purpose of this paper is to describe some of the main current and expanding applications of drone technology in emergency medicine and to describe challenges and future opportunities. Current applications being studied include delivery of defibrillators in response to out-of-hospital cardiac arrest, blood and blood products in response to trauma, and rescue medications. Drones are also being studied and actively used in emergency response to search and rescue operations as well as disaster and mass casualty events. Current challenges to expanding their use in emergency medicine and emergency medical system (EMS) include regulation, safety, flying conditions, concerns about privacy, consent, and confidentiality, and details surrounding the development, operation, and maintenance of a medical drone network. Future research is needed to better understand end user perceptions and acceptance. Continued technical advances are needed to increase payload capacities, increase flying distances, and integrate drone networks into existing 9-1-1 and EMS systems. Drones are a promising technology for improving patient survival, outcomes, and quality of life, particularly for those in areas that are remote or that lack funds or infrastructure. Their cost savings compared with ground transportation alone, speed, and convenience make them particularly applicable in the field of emergency medicine. Research to date suggests that use of drones in emergency medicine is feasible, will be accepted by the public, is cost-effective, and has broad application.

The mammalian cerebral cortex arises from precursor cells that reside in a proliferative region surrounding the lateral ventricles of the developing brain. Recent work has shown that precursor cells in the subventricular zone (SVZ) provide a major contribution to prenatal cortical neurogenesis, and that the SVZ is significantly thicker in gyrencephalic mammals such as primates than it is in lissencephalic mammals including rodents. Identifying characteristics that are shared by or that distinguish cortical precursor cells across mammalian species will shed light on factors that regulate cortical neurogenesis and may point toward mechanisms that underlie the evolutionary expansion of the neocortex in gyrencephalic mammals. We immunostained sections of the developing cerebral cortex from lissencephalic rats, and from gyrencephalic ferrets and macaques to compare the distribution of precursor cell types in each species. We also performed time-lapse imaging of precursor cells in the developing rat neocortex. We show that the distribution of Pax6+ and Tbr2+ precursor cells is similar in lissencephalic rat and gyrencephalic ferret, and different in the gyrencephalic cortex of macaque. We show that mitotic Pax6+ translocating radial glial cells (tRG) are present in the cerebral cortex of each species during and after neurogenesis, demonstrating that the function of Pax6+ tRG cells is not restricted to neurogenesis. Furthermore, we show that Olig2 expression distinguishes two distinct subtypes of Pax6+ tRG cells. Finally we present a novel method for discriminating the inner and outer SVZ across mammalian species and show that the key cytoarchitectural features and cell types that define the outer SVZ in developing primates are present in the developing rat neocortex. Our data demonstrate that the developing rat cerebral cortex possesses an outer subventricular zone during late stages of cortical neurogenesis and that the developing rodent cortex shares important features with that of primates.

How does one genome give rise to multiple, often markedly different, phenotypes in response to an environmental cue? This phenomenon, known as phenotypic plasticity, is common amongst plants and animals, but arguably the most striking examples are seen in insects. Well-known insect examples include seasonal morphs of butterfly wing patterns, sexual and asexual reproduction in aphids, and queen and worker castes of eusocial insects. Ultimately, we need to understand how phenotypic plasticity works at a mechanistic level; how do environmental signals alter gene expression, and how are changes in gene expression translated into novel morphology, physiology and behaviour? Understanding how plasticity works is of major interest in evolutionary-developmental biology and may have implications for understanding how insects respond to global change. It has been proposed that epigenetic mechanisms, specifically DNA methylation, are the key link between environmental cues and changes in gene expression. Here, we review the available evidence on the function of DNA methylation of insects, the possible role(s) for DNA methylation in phenotypic plasticity and also highlight key outstanding questions in this field as well as new experimental approaches to address these questions.

Hair cell bundles consist of stereocilia arranged in rows of increasing heights, connected by tip links that transmit sound-induced forces to shorter stereocilia tips. Auditory mechanotransduction channel complexes, composed of proteins TMC1/2, TMIE, CIB2, and LHFPL5, are located at the tips of shorter stereocilia. While most components can interact with the tip link in vitro, their ability to maintain the channel complexes at the tip link in vivo is uncertain. Using mouse models, we show that an additional component, LOXHD1, is essential for keeping TMC1-pore forming subunits at the tip link but is dispensable for TMC2. Using SUB-immunogold-SEM, we showed that TMC1 localizes near the tip link but mislocalizes without LOXHD1. LOXHD1 selectively interacts with TMC1, CIB2, LHFPL5, and tip-link protein PCDH15. Our results demonstrate that TMC1-driven mature auditory channels require LOXHD1 to stay connected to the tip link and remain functional, while TMC2-driven developmental channels do not. The Grillet lab identified an additional component of the auditory mechanotransduction Machinery, the protein LOXHD1, which is indispensable to keep the ion channel subunit TMC1 next to the tip-link, where the force induced-by sound is transmitted.

In many ways, clergy and religious leaders are an ignored, yet high-risk population. A clergy member unable to cope with challenges in his or her own life may be ineffective at helping church members to cope with their stress. In the present study, we developed and tested an operational model of clergy holistic health, including occupational demands, and personal and job-related resources. Data were collected from clergy (N = 418) and analyzed using correlational and regression-based techniques. Results from the present study provide support for the demands-control-support model (Johnson and Hall in Am J Public Health 78(10):1336–1342, 1988). Specifically, our findings suggest that clergy mental health may be improved by (a) an increase in the work-related social support needed to take advantage of job control followed by (b) an increase in job control. Furthermore, the present findings expand on previous research by identifying spiritual well-being as an important outcome that may be impacted by job-related demands. The present findings also underscore the value of contextualized or occupation-specific measures, given the stronger correlations that were observed between the occupation-specific measure of perceived job demands than the general measure of perceived job demands.

Many scholars have written about the role of spirituality in health care. One mechanism for incorporating spirituality into the care of patients is to integrate clinically trained chaplains into hospital care teams. We examined in a mixed-methods fashion, the effects of this type of integrated care team within a teaching hospital setting. The quality and impact of chaplain involvement were studied from patient and physician-in-training perspectives, using data from more than 200 patients and physicians in training. Findings clearly show that clinically trained chaplains can contribute meaningful expertise and real value to the quality and comprehensiveness of patient and physician experiences.