Chemistry-Performance Relationships of Polymer Gel-Electrolytes for Mg-S and Li-S Batteries: Influence of Network Cation Solvation Capacity on Polymer-Polysulfide Interactions.

Metal-sulfur batteries are a promising next-generation energy storage technology, offering high theoretical energy densities with low cost and good sustainability. An active area of research is the development of electrolytes that address unwanted migration of sulfur and intermediate species known as polysulfides during operation of metal-sulfur batteries, a phenomenon that leads to low energy efficiency and short life-spans. A particular class of electrolytes, gel polymer electrolytes, are especially attractive for their ability to repel polysulfides on the basis of structure, electrostatics, and other polymer properties. Herein, within the context of magnesium- and lithium-sulfur batteries, we investigate the impact of gel polymer electrolyte cation solvation capacity, a property related to network dielectric constant and chemistry, on sulfur/polysulfide-polymer interactions, an understudied property-performance relationship. Polymers with lower cation solvation capacity are found to permanently absorb less polysulfide active material, which increases sulfur utilization for Li-S batteries and significantly increases charge efficiency and life-span for Li-S and Mg-S batteries.

Navigating the "COVID hangover" in physiology courses.

Undergraduate educators and students must navigate lingering aftereffects of the COVID pandemic on education in the 2021-2022 academic year even as COVID continues to impact delivery of undergraduate science education. This article describes ongoing difficulties for undergraduate science, technology, engineering, and mathematics (STEM) students and educators and suggests strategies and easy-to-use resources that may help educators navigate the "COVID hangover" and ongoing COVID-related disruptions.

The Development of Core Concepts for Neuroscience Higher Education: From Beginning to Summer Virtual Meeting Satellite Session.

Neuroscience curricula vary widely across higher education institutions due to the lack of an accrediting body or a set of unified educational concepts or outcomes. Each institution has developed a unique set of fundamental knowledge, topical subdisciplines, and core competencies to be delivered in a neuroscience program. Core concepts would provide neuroscience departments and programs with a generally agreed upon set of overarching principles that organize knowledge and can be applied to all sub-disciplines of the field, providing a useful framework from which to approach neuroscience education. We set out to develop a consensus set of neuroscience core concepts to aid in higher education curricular development and assessment. Suggestions for neuroscience core concepts were solicited from neuroscience faculty in a nationwide survey and analyzed using an inductive, independent coding model to identify eight core concepts based upon survey responses. Accompanying explanatory paragraphs for each core concept were developed through an iterative process. We presented the resulting core concepts to 134 neuroscience educators at a satellite session of the Faculty for Undergraduate Neuroscience 2020 Summer Virtual Meeting (SVM). Individuals and groups of faculty provided feedback regarding the accuracy, comprehensiveness, and clarity of each concept and explanatory paragraph, as well as the structure of the document as a whole. We continue to refine the core concepts based upon this feedback and will distribute the final document in a subsequent publication. Following publication of the finalized list of core concepts, we will develop tools to help educators incorporate the core concepts into their curricula.

Uterine kisspeptin receptor critically regulates epithelial estrogen receptor α transcriptional activity at the time of embryo implantation in a mouse model.

Embryo implantation failure is a major cause of infertility in women of reproductive age and a better understanding of uterine factors that regulate implantation is required for developing effective treatments for female infertility. This study investigated the role of the uterine kisspeptin receptor (KISS1R) in the molecular regulation of implantation in a mouse model. To conduct this study, a conditional uterine knockout (KO) of Kiss1r was created using the Pgr-Cre (progesterone receptor-CRE recombinase) driver. Reproductive profiling revealed that while KO females exhibited normal ovarian function and mated successfully to stud males, they exhibited significantly fewer implantation sites, reduced litter size and increased neonatal mortality demonstrating that uterine KISS1R is required for embryo implantation and a healthy pregnancy. Strikingly, in the uterus of Kiss1r KO mice on day 4 (D4) of pregnancy, the day of embryo implantation, KO females exhibited aberrantly elevated epithelial ERα (estrogen receptor α) transcriptional activity. This led to the temporal misexpression of several epithelial genes [Cftr (Cystic fibrosis transmembrane conductance regulator), Aqp5 (aquaporin 5), Aqp8 (aquaporin 8) and Cldn7 (claudin 7)] that mediate luminal fluid secretion and luminal opening. As a result, on D4 of pregnancy, the lumen remained open disrupting the final acquisition of endometrial receptivity and likely accounting for the reduction in implantation events. Our data clearly show that uterine KISS1R negatively regulates ERα signaling at the time of implantation, in part by inhibiting ERα overexpression and preventing detrimentally high ERα activity. To date, there are no reports on the regulation of ERα by KISS1R; therefore, this study has uncovered an important and powerful regulator of uterine ERα during early pregnancy.

Uterine aquaporin expression is dynamically regulated by estradiol and progesterone and ovarian stimulation disrupts embryo implantation without affecting luminal closure.

The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4. Additionally, P4 inhibits E2 induction of Aqp3 and Aqp4 expression while E2 inhibits Aqp1 and Aqp11 expression. Aqp9, however, is constitutively expressed. Ovarian stimulation disrupts Aqp3, Aqp5 and Aqp8 expression on D4 and AQP1, AQP3 and AQP5 spatial expression on both D1 and D4, strikingly so in the myometrium. Interestingly, while ovarian stimulation has no overt effect on luminal closure and uterine receptivity, it reduces implantation events, likely through a disruption in myometrial activity and embryo development. The wider implication of this study is that ovarian stimulation, which results in supraphysiological levels of E2 and P4 and changes (depending on the degree of stimulation) in the E2:P4 ratio, triggers abnormal expression of uterine AQP during pregnancy, and this is associated with implantation failure. These findings lead us to recognize that abnormal expression would also occur under any pathological state (such as endometriosis) that is associated with changes in the normal E2:P4 ratio. Thus, infertility among these patients might in part be linked to abnormal uterine AQP expression.

Uterine Gαq/11 signaling, in a progesterone-dependent manner, critically regulates the acquisition of uterine receptivity in the female mouse.

A nonreceptive uterus is a major cause of embryo implantation failure. This study examined the importance of the Gαq/11-coupled class of GPCRs as regulators of uterine receptivity. Mice were created lacking uterine Gαq and Gα11; as a result, signaling by all uterine Gαq/11-coupled receptors was disrupted. Reproductive profiling of the knockout females revealed that on d 4 of pregnancy, despite adequate serum progesterone (P4) levels and normal P4 receptor (PR) expression, there was no evidence of PR signaling. This resulted in the down-regulation of heart and neural crest derivatives expressed 2, Kruppel-like factor 15, and cyclin G1 and the subsequent persistent proliferation of the luminal epithelium. Aquaporin (Aqp) 11 was also potently down-regulated, whereas Aqp5/AQP5 expression persisted, resulting in the inhibition of luminal closure. Hypertrophy of the myometrial longitudinal muscle was also dramatically diminished, likely contributing to the observed implantation failure. Further analyses revealed that a major mechanism via which uterine Gαq/11 signaling induces PR signaling is through the transcriptional up-regulation of leucine-rich repeat-containing GPCR 4 (Lgr4). LGR4 was previously identified as a trigger of PR activation and signaling. Overall, this study establishes that Gαq/11 signaling, in a P4-dependent manner, critically regulates the acquisition of uterine receptivity in the female mouse, and disruption of such signaling results in P4 resistance.-de Oliveira, V., Schaefer, J., Calder, M., Lydon, J. P., DeMayo, F. J., Bhattacharya, M., Radovick, S., Babwah, A. V. Uterine Gαq/11 signaling, in a progesterone-dependent manner, critically regulates the acquisition of uterine receptivity in the female mouse.

"Understanding Checkpoints" Followed by Self-Evaluation to Assess Students' Scientific Literacy and Mastery of Content and Techniques.

An Understanding Checkpoint (UC) presents students with previously-unseen figures from published scientific studies accompanied by questions about the study methods, results, and implications. The UCs incorporate content, concepts, and techniques previously discussed in class, although the figures and study from which they are taken are new to students. They are in-class, open-note, time-limited assessments that simultaneously assess course learning goals related to: neurobiology principles and content; process of scientific investigation, including neurobiological research tools and data interpretation; and reading and analyzing primary research literature. After students submit their work, they are provided the full publication and are asked to grade their own work, providing rationale for their evaluation. The self-evaluative portion of the assignment incentivizes students to identify and remediate ongoing weaknesses. It also provides spaced retrieval practice to enhance learning. The final grade for the UC incorporates the student's original answers and the accuracy of the self-assessment rationale. Student and instructor feedback indicates that the self - evaluative requirement develops a deeper understanding of the course material and enhances metacognitive effort, in addition to providing an opportunity to improve the UC grade. This strategy was originally presented as a teaching demonstration at the 2017 Faculty for Undergraduate Neuroscience Workshop.

Electrochemical Properties and Speciation in Mg(HMDS)2-Based Electrolytes for Magnesium Batteries as a Function of Ethereal Solvent Type and Temperature.

Magnesium batteries are a promising alternative to lithium-ion batteries due to the widespread abundance of magnesium and its high specific volumetric energy capacity. Ethereal solvents such as tetrahydrofuran (THF) are commonly used for magnesium-ion electrolytes due to their chemical compatibility with magnesium metal, but the volatile nature of THF is a concern for practical application. Herein, we investigate magnesium bis(hexamethyldisilazide) plus aluminum chloride (Mg(HMDS)2-AlCl3) electrolytes in THF, diglyme, and tetraglyme at varying temperature. We find that, despite the higher thermal stability of the glyme-based electrolytes, THF-based electrolytes have better reversibility at room temperature. Deposition/stripping efficiency is found to be a strong function of temperature. Diglyme-based Mg(HMDS)2-AlCl3 electrolytes are found to not exchange as quickly as THF and tetraglyme, stabilizing AlCl2+ and facilitating undesired aluminum deposition. Raman spectroscopy, 27Al NMR, and mass spectrometry are used to identify solution speciation.

Comparison of Nanoscale Focused Ion Beam and Electrochemical Lithiation in ß-Sn Microspheres.

The development of Li focused ion beams (Li-FIB) enables controlled Li ion insertion into materials with nanoscale resolution. We take the first step toward establishing the relevance of the Li-FIB for studies of ion dynamics in electrochemically active materials by comparing FIB lithiation with conventional electrochemical lithiation of isolated ß-Sn microspheres. Samples are characterized by cross-sectioning with Ga FIB and imaging via electron microscopy. The Li-FIB and electrochemical lithiated Sn exhibit similarities that suggest that the Li-FIB can be a powerful tool for exploring dynamical Li ion-material interactions at the nanoscale in a range of battery materials.

The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course.

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis on student competencies such as scientific process, scientific communication, and societal relevance while teaching foundational neurobiological content such as brain anatomy, cellular neurophysiology, and activity modulation. Student feedback indicates that the BRAIN Initiative is an engaging and instructional context for this course. Course module organization, suitable BRAIN Initiative commentary literature, sample primary literature, and important assignments are presented.

Early detection of maternal deaths in Senegal through household-based death notification integrating verbal and social autopsy: a community-level case study.

BACKGROUND: Reliable detection of maternal deaths is an essential prerequisite for successful diagnosis of barriers to care and formulation of relevant targeted interventions. In a community-level case study, the use of household-level surveillance in Senegal unveiled an apparent increase in maternal deaths, which triggered a rapid-cycle collaborative response to implement a multipronged set of quick-win and sustained interventions intended to improve quality care. METHODS: Part of a multi-country effort, the Millennium Villages Project is implementing a routine community-level information system in Senegal, able to detect maternal deaths in real-time and uncover clinical and social factors contributing to mortality. Within this geographically demarcated area of approximately 32 000 inhabitants, with a well-structured health system with patient referral services, deaths were registered and notified by community health workers, followed by timely verbal and social autopsies. Using the Pathway to Survival conceptual framework, case analysis and mortality reviews were conducted for evaluation and quality improvement purposes. RESULTS: The estimated maternal mortality rates rose from 67/100000 births in 2009 (1 death), to 202/100000 births in 2010 (3 deaths) and 392/100000 births (5 deaths) in 2011. Although absolute numbers of maternal deaths remained too small for robust statistical analysis, following verbal autopsy analyses in 2011, it became evident that an unexpectedly high proportion of maternal deaths were occurring at the referral hospital, mostly post-Caesarian section. Inadequate case management of post-partum haemorrhage at the referral hospital was the most frequently identified probable cause of death. A joint task team systematically identified several layers of inefficiencies, with a potential negative impact on a larger catchment area than the study community. CONCLUSIONS: In this study, routine community-based surveillance identified inefficiencies at a tertiary level of care. Community-level surveillance systems that include pregnancy, birth and death tracking through household visits by community health workers , combined with verbal and social autopsy can identify barriers within the continuum of maternal care. Use of mHealth data collection tools sensitive enough to detect small changes in community-level mortality trends in real-time, can facilitate rapid-cycle quality improvement interventions, particularly when associated with social accountability structures of mortality reviews.

Suppression of lithium dendrite growth using cross-linked polyethylene/poly(ethylene oxide) electrolytes: a new approach for practical lithium-metal polymer batteries.

Solid polymer electrolyte (SPE) membranes are a critical component of high specific energy rechargeable Li-metal polymer (LMP) batteries. SPEs exhibit low volatility and thus increase the safety of Li-based batteries compared to current state-of-the-art Li-ion batteries that use flammable small-molecule electrolytes. However, most SPEs exhibit low ionic conductivity at room temperature, and often allow the growth of lithium dendrites that short-circuit the batteries. Both of these deficiencies are significant barriers to the commercialization of LMP batteries. Herein we report a cross-linked polyethylene/poly(ethylene oxide) SPE with both high ionic conductivity (>1.0 × 10(-4) S/cm at 25 °C) and excellent resistance to dendrite growth. It has been proposed that SPEs with shear moduli of the same order of magnitude as lithium could be used to suppress dendrite growth, leading to increased lifetime and safety for LMP batteries. In contrast to the theoretical predictions, the low-modulus (G' ≈ 1.0 × 10(5) Pa at 90 °C) cross-linked SPEs reported herein exhibit remarkable dendrite growth resistance. These results suggest that a high-modulus SPE is not a requirement for the control of dendrite proliferation.

Community-Derived Core Concepts for Neuroscience Higher Education.

Core concepts provide a framework for organizing facts and understanding in neuroscience higher education curricula. Core concepts are overarching principles that identify patterns in neuroscience processes and phenomena and can be used as a foundational scaffold for neuroscience knowledge. The need for community-derived core concepts is pressing, because both the pace of research and number of neuroscience programs are rapidly expanding. While general biology and many subdisciplines within biology have identified core concepts, neuroscience has yet to establish a community-derived set of core concepts for neuroscience higher education. We used an empirical approach involving more than 100 neuroscience educators to identify a list of core concepts. The process of identifying neuroscience core concepts was modeled after the process used to develop physiology core concepts and involved a nationwide survey and a working session of 103 neuroscience educators. The iterative process identified eight core concepts and accompanying explanatory paragraphs. The eight core concepts are abbreviated as communication modalities, emergence, evolution, gene-environment interactions, information processing, nervous system functions, plasticity, and structure-function. Here, we describe the pedagogical research process used to establish core concepts for the neuroscience field and provide examples on how the core concepts can be embedded in neuroscience education.

Magnesium Polymer Electrolytes Based on the Polycarbonate Poly(2-butyl-2-ethyltrimethylene-carbonate).

Magnesium electrolytes based on a polycarbonate with either magnesium tetrakis(hexafluoroisopropyloxy) borate (Mg(B(HFIP)4)2) or magnesium bis(trifluoromethanesulfonyl)imide (Mg(TFSI)2) for magnesium batteries were prepared and characterized. The side-chain-containing polycarbonate, poly(2-butyl-2-ethyltrimethylene carbonate) (P(BEC)), was synthesized by ring opening polymerization (ROP) of 5-ethyl-5-butylpropane oxirane ether carbonate (BEC) and mixed with Mg(B(HFIP)4)2 or Mg(TFSI)2 to form low- and high-salt-concentration polymer electrolytes (PEs). The PEs were characterized by impedance spectroscopy, differential scanning calorimetry (DSC), rheology, linear sweep voltammetry, cyclic voltammetry, and Raman spectroscopy. A transition from classical salt-in-polymer electrolytes to polymer-in-salt electrolytes was indicated by a significant change in glass transition temperature as well as storage and loss moduli. Ionic conductivity measurements indicated the formation of polymer-in-salt electrolytes for the PEs with 40 mol % Mg(B(HFIP)4)2 (HFIP40). In contrast, the 40 mol % Mg(TFSI)2 PEs showed mainly the classical behavior. HFIP40 was further found to have an oxidative stability window greater than 6 V vs Mg/Mg2+, but showed no reversible stripping-plating behavior in an Mg||SS cell.

Closed Bipolar Electrode-Enabled Electrochromic Sensing of Multiple Metabolites in Whole Blood.

We report a closed bipolar electrode (CBE)-based sensing platform for the detection of diagnostic metabolites in undiluted whole human blood. The sensor is enabled by electrode chemistry based on: (1) a mixed layer of blood-compatible adsorption-resistant phosphorylcholine (PPC) and phenylbutyric acid (PBA), (2) ferrocene (Fc) redox mediators, and (3) immobilized redox-active enzymes. This scheme is designed to overcome nonspecific protein adsorption and amplify sensing currents in whole human fluids. The scheme also incorporates a diffusing mediator to increase electronic communication between the immobilized redox enzyme and the working electrode. The use of both bound and freely diffusing mediators is synergistic in producing the electrochemical response. The sensor is realized by linking the analyte cell, containing the specific electrode surface architecture, through a CBE to a reporter cell containing the electrochromic reporter, methyl viologen (MV). The colorless-to-purple color change accompanying the 1e- reduction of MV2+ is captured using a smartphone camera. Subsequent red-green-blue analysis is performed on the acquired images to determine cholesterol, glucose, and lactate concentrations in whole blood. The CBE blood metabolite sensor produces a linear color change at clinically relevant concentration ranges for all metabolites with good reproducibility (∼5% or better) and with limits of detection of 79 µM for cholesterol, 59 µM for glucose, and 86 µM for lactate. Finally, metabolite concentration measurements from the CBE blood metabolite sensor are compared with results from commercially available FDA-approved blood cholesterol, glucose, and lactate meters, with an average difference of ∼3.5% across all three metabolites in the ranges studied.

Sarcina sp. as a presumptive cause of fatal acute gastric dilation and gastric emphysema in rhesus macaques.

A 4-y-old female and 3-y-old male rhesus macaque (Macaca mulatta), both housed in the same facility, died unexpectedly within 2 wk. Postmortem examination revealed severe gastric dilation in both macaques and gastric emphysema in the female macaque. Histologically, bacteria consistent with Sarcina sp. were present in both macaques within the lungs and lumen of the trachea, esophagus, and gastrointestinal (GI) tract without associated inflammation. Additionally, in the female macaque, the bacteria were found in the gastric mucosa and associated with emphysematous spaces in the gastric wall without associated inflammation. PCR and Sanger sequencing of amplicons were subsequently performed on GI contents and non-alimentary tissues from the 2 affected monkeys and on comparative samples from unaffected rhesus monkeys in the same facility and an adjacent primate facility. The cases were compared using the 2-tailed Fisher exact test (p-value at 95% confidence). PCR identified Sarcina in GI contents of both affected and unaffected monkeys (p = 0.6084) and in non-alimentary tissues of affected monkeys only (p = 0.0083). These results suggest that the presence of Sarcina sp. in non-alimentary tissues is associated with gastric distension, gas accumulation, and unexpected death in nonhuman primates.

Sleep-disordered breathing in school-aged children with Prader-Willi syndrome.

STUDY OBJECTIVES: Studies of sleep-disordered breathing (SDB) in children with Prader-Willi syndrome (PWS) have focused on early childhood and growth hormone (GH)-naïve children, but little is known about older children, including those on long-term GH therapy. This study aimed to describe the nature and prevalence of SDB in school-aged children with PWS in the growth hormone era. METHODS: This retrospective single-center chart review included children aged 6-18 years with PWS who had overnight polysomnography not involving respiratory support over 5 years (2012-2017). The main outcome measures were the presence of obstructive sleep apnea, central sleep apnea, or hypoventilation defined by an elevated transcutaneous partial pressure of carbon dioxide (TcPCO2) as per standard pediatric criteria. RESULTS: Seventeen children (8 males; median age 11.6 years, range 6.6-16.1 years) were included. Fifteen demonstrated SDB of different types: central sleep apnea (18%), obstructive sleep apnea (24%), both obstructive and central sleep apnea (29%), or hypoventilation without obstructive or central sleep apnea (18%). Twelve (71%) children had evidence of hypoventilation. Those with hypoventilation had a higher central apnea-hypopnea index but no difference in the obstructive apnea-hypopnea index, age, sex, growth parameters, or the presence of scoliosis or sleep-related symptoms compared with those without hypoventilation. CONCLUSIONS: Sleep-related hypoventilation is common in school-aged children with PWS. The presence of central sleep apnea, including the quantification of central hypopneas, but not obstructive sleep apnea or clinical factors, predicted the presence of hypoventilation. Long-term polysomnography surveillance in children with PWS should include identification of central hypopneas and measurement of continuous pCO2. CITATION: Schaefer J, Davey MJ, Nixon GM. Sleep-disordered breathing in school-aged children with Prader-Willi syndrome. J Clin Sleep Med. 2022;18(4):1055-1061.

Electrochemical Immunosensing of Interleukin-6 in Human Cerebrospinal Fluid and Human Serum as an Early Biomarker for Traumatic Brain Injury.

In this work, we develop a label-free electrochemical immunosensor for the detection of interleukin-6 (IL-6) in human cerebrospinal fluid (CSF) and serum for diagnostic and therapeutic monitoring. The IL-6 immunosensor is fabricated from gold interdigitated electrode arrays (IDEAs) that are modified with IL-6 antibodies for direct antigen recognition and capture. A rigorous surface analysis of the sensor architecture was conducted to ensure high structural fidelity and performance. Electrochemical characterization was conducted by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and sensing was performed using differential pulse voltammetry (DPV). The DPV peak current was used to quantify IL-6 in buffer, CSF, and serum in the range 1 pg mL-1 < [IL-6] < 1 µg mL-1. The IL-6 IDEA sensor achieved a limit of detection (LOD) of 1.63 pg mL-1 in PBS, 2.34 pg mL-1 in human CSF, and 11.83 pg mL-1 in human serum. The sensor response is linear in the concentration range 10 pg mL-1 < [IL-6] < 10 ng mL-1, and the sensor is selective for IL-6 over other common cytokines, including IL-10 and TNF-α. EIS measurements showed that the resistance to charge transfer, R CT, decreases upon IL-6 binding, an observation attributed to a structural change upon Ab-Ag binding that opens up the architecture so that the redox probe can more easily access the electrode surface. The IL-6 IDEA sensor can be used as a point-of-care diagnostic tool to deliver rapid results (∼3 min) in clinical settings for traumatic brain injury, and potentially address the unmet need for effective diagnostic and prognostic tools for other cytokine-related illnesses, such as sepsis and COVID-19 induced cytokine storms. Given the interdigitated electrode form factor, it is likely that the performance of the sensor can be further improved through redox cycling.

Phagocyte extracellular traps in children with neutrophilic airway inflammation.

Childhood lung infection is often associated with prominent neutrophilic airway inflammation and excess production of proteases such as neutrophil elastase (NE). The mechanisms responsible for this inflammation are not well understood. One potentially relevant pathway is the production of extracellular traps by neutrophils (NETs) and macrophages (METs). The aim of this study was to measure NET and MET expression in children and the effect of deoxyribonculease (DNase) 1 and α1-antitrypsin (AAT) on this process. We studied 76 children (median age of 4.0 years) with cystic fibrosis or chronic cough who underwent investigational bronchoscopy. NETs, METs and neutrophil elastase activity in bronchoalveolar lavage (BAL) samples were measured using confocal microscopy and functional assays. The effects of DNase 1 and AAT on NET/MET expression and neutrophil elastase activity were examined in vitro. Both subject groups had airway neutrophilia with prominent BAL production of NETs with neutrophil elastase co-expression; the mean %±standard error of the mean of neutrophils expressing NETs in the cystic fibrosis group was 23.3±2.8% and in the non-cystic fibrosis group was 28.4±3.9%. NET expression was higher in subjects who had detectable neutrophil elastase activity (p≤0.0074). The percentage of macrophages expressing METs in the cystic fibrosis group was 10.7±1.2% and in the non-cystic fibrosis group was 13.2±1.9%. DNase 1 decreased NET/MET expression (p<0.0001), but increased neutrophil elastase activity (p≤0.0137). The combination of AAT and DNase 1 reduced neutrophil elastase activity (p≤0.0049). We observed prominent extracellular trap formation in symptomatic children with and without cystic fibrosis. This innate inflammatory response was down-regulated by a combination of currently available therapeutics.

Role of intrinsic properties in Drosophila motoneuron recruitment during fictive crawling.

Motoneurons in most organisms conserve a division into low-threshold and high-threshold types that are responsible for generating powerful and precise movements. Drosophila 1b and 1s motoneurons may be analogous to low-threshold and high-threshold neurons, respectively, based on data obtained at the neuromuscular junction, although there is little information available on intrinsic properties or recruitment during behavior. Therefore in situ whole cell patch-clamp recordings were used to compare parameters of 1b and 1s motoneurons in Drosophila larvae. We find that resting membrane potential, voltage threshold, and delay-to-spike distinguish 1b from 1s motoneurons. The longer delay-to-spike in 1s motoneurons is a result of the shal-encoded A-type K(+) current. Functional differences between 1b and 1s motoneurons are behaviorally relevant because a higher threshold and longer delay-to-spike are observed in MNISN-1s in pairwise whole cell recordings of synaptically evoked activity during bouts of fictive locomotion.