Developmental Expression Patterns of KCC2 and Functionally Associated Molecules in the Human Brain

Peer reviewe

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Evidence for differential effects of hepcidin in macrophages and intestinal epithelial cells

Background and aims: Reticulo-endothelial macrophages together with duodenal enterocytes coordinate body iron homeostasis. The aim of this study was to investigate the regulatory actions of the hormone hepcidin on ferroportin expression in these two cell types.Methods: We investigated the in vitro effects of hepcidin in well-characterised human cell culture models of macrophages (differentiated THP-1 cells) and intestinal epithelial cells (Caco-2 cells). The in vivo effects of hepcidin were also investigated in mice injected with a synthetic hepcidin peptide.Results: Exposure to hepcidin (presented either as conditioned medium from interleukin-6-stimulated HuH7 cells or as a synthetic peptide) resulted in a rapid (within 4 h) decrease in ferroportin expression in THP-1 macrophages but had no effect on ferroportin levels in Caco-2 cells. To determine whether these rapid effects of hepcidin were also evident in vivo we injected mice with a synthetic hepcidin peptide. Four hours post-injection, ferroportin levels in the macrophage-rich red pulp of the spleen were decreased significantly and the hepcidin-treated mice developed hypoferraemia. Interestingly, in the same mice there was no effect of hepcidin on duodenal ferroportin protein expression or duodenal iron transport.Conclusions: These data suggests that the rapid response to hepcidin is cell type and tissue specific. Upon its release, hepcidin initially targets macrophage iron recycling. The duodenum appears to be less sensitive to this initial rise in hepcidin levels. We believe the fact that macrophages respond more acutely to a hepcidin challenge is fully consistent with their central role in maintaining body iron homeostasis

Prescribing practices of inhaled corticosteroids for premature infants in the neonatal intensive care unit.

OBJECTIVE: Despite limited safety and efficacy data, inhaled corticosteroids (ICS) are prescribed to premature infants in the neonatal intensive care unit (NICU). We examined contemporary use and risk factors for ICS use in the NICU. STUDY DESIGN: Infants <33 weeks gestational age and <1500 gm birth weight discharged from Pediatrix Medical Group NICUs between 2010 and 2020 were included. We evaluated the association between ICS prescription and clinical characteristics using univariable and multivariable logistic regression. RESULTS: Of 74,123 infants from 308 NICUs, 9253 (12.5%) were prescribed ICS: budesonide, fluticasone, or beclomethasone. Diagnosis of bronchopulmonary dysplasia (BPD), earlier gestational age, male sex, longer mechanical ventilation, oxygen support, and systemic steroids were independent risk factors for ICS prescription. CONCLUSIONS: Use of ICS is common in many NICUs and is associated with a diagnosis of BPD and healthcare utilization. Prospective trials are needed to establish the safety, efficacy, and optimal indication in this vulnerable population

A light-gated potassium channel for sustained neuronal inhibition

Currently available inhibitory optogenetic tools provide short and transient silencing of neurons, but they cannot provide long-lasting inhibition because of the requirement for high light intensities. Here we present an optimized blue-light-sensitive synthetic potassium channel, BLINK2, which showed good expression in neurons in three species. The channel is activated by illumination with low doses of blue light, and in our experiments it remained active over (tens of) minutes in the dark after the illumination was stopped. This activation caused long periods of inhibition of neuronal firing in ex vivo recordings of mouse neurons and impaired motor neuron response in zebrafish in vivo. As a proof-of-concept application, we demonstrated that in a freely moving rat model of neuropathic pain, the activation of a small number of BLINK2 channels caused a long-lasting (>30 min) reduction in pain sensation

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4 m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5 m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 yr, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit