A simulation facility for testing Space Station assembly procedures

NASA plans to construct the Space Station Freedom (SSF) in one of the most hazardous environments known to mankind - space. It is of the utmost importance that the procedures to assemble and operate the SSF in orbit are both safe and effective. This paper describes a facility designed to test the integration of the telerobotic systems and to test assembly procedures using a real-world robotic arm grappling space hardware in a simulated microgravity environment

A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15

Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Pro-inflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed regeneration-promoting program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6C(high), infiltrating inflammatory Ly6C(high), and reparative Ly6C(low) macrophages, isolated from injured muscle, identified the TGF-β superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and on muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARγ. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (growth factor-expressing macrophages [GFEMs])

A Unique Role for the Host ESCRT Proteins in Replication of Tomato bushy stunt virus

Plus-stranded RNA viruses replicate in infected cells by assembling viral replicase complexes consisting of viral- and host-coded proteins. Previous genome-wide screens with Tomato bushy stunt tombusvirus (TBSV) in a yeast model host revealed the involvement of seven ESCRT (endosomal sorting complexes required for transport) proteins in viral replication. In this paper, we show that the expression of dominant negative Vps23p, Vps24p, Snf7p, and Vps4p ESCRT factors inhibited virus replication in the plant host, suggesting that tombusviruses co-opt selected ESCRT proteins for the assembly of the viral replicase complex. We also show that TBSV p33 replication protein interacts with Vps23p ESCRT-I and Bro1p accessory ESCRT factors. The interaction with p33 leads to the recruitment of Vps23p to the peroxisomes, the sites of TBSV replication. The viral replicase showed reduced activity and the minus-stranded viral RNA in the replicase became more accessible to ribonuclease when derived from vps23Δ or vps24Δ yeast, suggesting that the protection of the viral RNA is compromised within the replicase complex assembled in the absence of ESCRT proteins. The recruitment of ESCRT proteins is needed for the precise assembly of the replicase complex, which might help the virus evade recognition by the host defense surveillance system and/or prevent viral RNA destruction by the gene silencing machinery

Atomic and vibrational origins of mechanical toughness in bioactive cement during setting

Bioactive glass ionomer cements (GICs) have been in widespread use for ~40 years in dentistry and medicine. However, these composites fall short of the toughness needed for permanent implants. Significant impediment to improvement has been the requisite use of conventional destructive mechanical testing, which is necessarily retrospective. Here we show quantitatively, through the novel use of calorimetry, terahertz (THz) spectroscopy and neutron scattering, how GIC’s developing fracture toughness during setting is related to interfacial THz dynamics, changing atomic cohesion and fluctuating interfacial configurations. Contrary to convention, we find setting is non-monotonic, characterized by abrupt features not previously detected, including a glass–polymer coupling point, an early setting point, where decreasing toughness unexpectedly recovers, followed by stress-induced weakening of interfaces. Subsequently, toughness declines asymptotically to long-term fracture test values. We expect the insight afforded by these in situ non-destructive techniques will assist in raising understanding of the setting mechanisms and associated dynamics of cementitious materials

Successful conservation of global waterbird populations depends on effective governance

Understanding global patterns of biodiversity change is crucial for conservation research, policies and practices. However, the lack of systematically collected data at a global level has limited our understanding of biodiversity changes and their local-scale drivers in most ecosystems. We address this challenge by focusing on wetlands, which are among the most biodiverse and productive environments providing essential ecosystem services, but are also amongst the most seriously threatened ecosystems. Using birds as an indicator taxon of wetland biodiversity, we model time-series abundance data for 461 waterbird species at 25,769 survey sites across the globe. We show that countries’ effective governance is the strongest predictor of waterbird abundance changes as well as benefits of conservation efforts. Waterbirds are declining especially where governance is, on average, less effective, such as Western/Central Asia, sub-Saharan Africa and South America. Higher protected area coverage facilitates waterbird increases, but only in countries with more effective governance. Our findings highlight that sociopolitical instability can lead to biodiversity loss and also undermine the benefit of existing conservation efforts, such as the expansion of protected area coverage. Data deficiency in areas with less effective governance could cause an underestimation of the extent of biodiversity crisis. Alternative language abstracts are in Supplementary Information

Design of 280 GHz feedhorn-coupled TES arrays for the balloon-borne polarimeter SPIDER

We describe 280 GHz bolometric detector arrays that instrument the balloon-borne polarimeter SPIDER. A primary science goal of SPIDER is to measure the large-scale B-mode polarization of the cosmic microwave background in search of the cosmic-inflation, gravitational-wave signature. 280 GHz channels aid this science goal by constraining the level of B-mode contamination from galactic dust emission. We present the focal plane unit design, which consists of a 16$\times$16 array of conical, corrugated feedhorns coupled to a monolithic detector array fabricated on a 150 mm diameter silicon wafer. Detector arrays are capable of polarimetric sensing via waveguide probe-coupling to a multiplexed array of transition-edge-sensor (TES) bolometers. The SPIDER receiver has three focal plane units at 280 GHz, which in total contains 765 spatial pixels and 1,530 polarization sensitive bolometers. By fabrication and measurement of single feedhorns, we demonstrate 14.7$^{\circ}$ FHWM Gaussian-shaped beams with $<$1% ellipticity in a 30% fractional bandwidth centered at 280 GHz. We present electromagnetic simulations of the detection circuit, which show 94% band-averaged, single-polarization coupling efficiency, 3% reflection and 3% radiative loss. Lastly, we demonstrate a low thermal conductance bolometer, which is well-described by a simple TES model and exhibits an electrical noise equivalent power (NEP) = 2.6 $\times$ 10$^{-17}$ W/$\sqrt{\mathrm{Hz}}$, consistent with the phonon noise prediction.Comment: Proceedings of SPIE Astronomical Telescopes + Instrumentation 201

The transcription factor EGR2 is the molecular linchpin connecting STAT6 activation to the late, stable epigenomic program of alternative macrophage polarization

Macrophages polarize into functionally distinct subtypes while responding to microenvironmental cues. The identity of proximal transcription factors (TFs) downstream from the polarization signals are known, but their activity is typically transient, failing to explain the long-term, stable epigenomic programs developed. Here, we mapped the early and late epigenomic changes of interleukin-4 (IL-4)-induced alternative macrophage polarization. We identified the TF, early growth response 2 (EGR2), bridging the early transient and late stable gene expression program of polarization. EGR2 is a direct target of IL-4-activated STAT6, having broad action indispensable for 77% of the induced gene signature of alternative polarization, including its autoregulation and a robust, downstream TF cascade involving PPARG. Mechanistically, EGR2 binding results in chromatin opening and the recruitment of chromatin remodelers and RNA polymerase II. Egr2 induction is evolutionarily conserved during alternative polarization of mouse and human macrophages. In the context of tissue resident macrophages, Egr2 expression is most prominent in the lung of a variety of species. Thus, EGR2 is an example of an essential and evolutionarily conserved broad acting factor, linking transient polarization signals to stable epigenomic and transcriptional changes in macrophages

Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

Dienoic acids and pentadienyl alcohols are coupled in a decarboxylative and dehydrative manner at ambient temperature using Pd(0) catalysis to generate 1,3,6,8-tetraenes. Contrary to related decarboxylative coupling reactions, an anion-stabilizing group is not required adjacent to the carboxyl group. Of mechanistic importance, it appears that both the diene of the acid and the diene of the alcohol are required for this reaction. To further understand this reaction, substitutions at every unique position of both cou- pling partners was examined and two potential mechanisms are presented

The loss of histone H3 lysine 9 acetylation due to dSAGA-specific dAda2b mutation influences the expression of only a small subset of genes

In Drosophila, the dADA2b-containing dSAGA complex is involved in histone H3 lysine 9 and 14 acetylation. Curiously, although the lysine 9- and 14-acetylated histone H3 levels are drastically reduced in dAda2b mutants, these animals survive until a late developmental stage. To study the molecular consequences of the loss of histone H3 lysine 9 and 14 acetylation, we compared the total messenger ribonucleic acid (mRNA) profiles of wild type and dAda2b mutant animals at two developmental stages. Global gene expression profiling indicates that the loss of dSAGA-specific H3 lysine 9 and 14 acetylation results in the expression change (up- or down-regulation) of a rather small subset of genes and does not cause a general transcription de-regulation. Among the genes up-regulated in dAda2b mutants, particularly high numbers are those which play roles in antimicrobial defense mechanisms. Results of chromatin immunoprecipitation experiments indicate that in dAda2b mutants, the lysine 9-acetylated histone H3 levels are decreased both at dSAGA up- and down-regulated genes. In contrast to that, in the promoters of dSAGA-independent ribosomal protein genes a high level of histone H3K9ac is maintained in dAda2b mutants. Our data suggest that by acetylating H3 at lysine 9, dSAGA modifies Pol II accessibility to specific promoters differently