Degradation of connective tissue matrices by macrophages. III. Morphological and biochemical studies on extracellular, pericellular, and intracellular events in matrix proteolysis by macrophages in culture.

We have shown that macrophages in culture degrade the glycoproteins and amorphous elastin of insoluble extracellular matrices. Ultrastructural observation of the macrophage-matrix interaction revealed that connective tissue macromolecules were solubilized from the matrix extracellularly. At least part of the matrix breakdown was localized to the immediate vicinity of the cells, as shown by morphological and biochemical studies, although the rate of degradation correlated closely with the secretion of proteinases by various inflammatory stimuli in vivo, by glucocorticoids, prostaglandin E2 or colchicine, or by phagocytosis of latex, zymosan, or cholesterol-albumin complexes in culture was reflected in altered rates of glycoprotein and elastin degradation by the macrophages. Alteration of endocytosis and lysosomal digestion by cytochalasin B, NH4Cl, and proteinase inhibitors did not decrease the overall rate of matrix solubilization, but reduced the processing of the matrix fragments to peptides. Therefore, extracellular, pericellular, and lysosomal events each contribute to degradation of extracellular matrix macromolecules by inflammatory macrophages

Neurotrophin and Wnt signaling cooperatively regulate dendritic spine formation

Dendritic spines are major sites of excitatory synaptic transmission and changes in their numbers and morphology have been associated with neurodevelopmental and neurodegenerative disorders. Brain-derived Neurotrophic Factor (BDNF) is a secreted growth factor that influences hippocampal, striatal and neocortical pyramidal neuron dendritic spine density. However, the mechanisms by which BDNF regulates dendritic spines and how BDNF interacts with other regulators of spines remain unclear. We propose that one mechanism by which BDNF promotes dendritic spine formation is through an interaction with Wnt signaling. Here, we show that Wnt signaling inhibition in cultured cortical neurons disrupts dendritic spine development, reduces dendritic arbor size and complexity, and blocks BDNF-induced dendritic spine formation and maturation. Additionally, we show that BDNF regulates expression of Wnt2, and that Wnt2 is sufficient to promote cortical dendrite growth and dendritic spine formation. Together, these data suggest that BDNF and Wnt signaling cooperatively regulate dendritic spine formation

Are Patient Self-Reported Outcome Measures Sensitive Enough to Be Used as End Points in Clinical Trials? Evidence from the United Kingdom Glaucoma Treatment Study

PURPOSE: The United Kingdom Glaucoma Treatment Study (UKGTS) demonstrated the effectiveness of an intraocular pressure-lowering drug in patients with glaucoma using visual field progression as a primary outcome. The present study tested the hypothesis that responses on patient-reported outcome measures (PROMs; secondary outcome measure) differ between patients receiving a topical prostaglandin analog (latanoprost) or placebo eye drops in UKGTS. DESIGN: Multicenter, randomized, triple-masked, placebo-controlled trial. PARTICIPANTS: Newly diagnosed glaucoma patients in the UKGTS with baseline and exit PROMs (n = 182 and n = 168 patients from the treatment and placebo groups, respectively). METHODS: In the UKGTS (trial registration number, ISRCTN96423140), patients with open-angle glaucoma were allocated to receive latanoprost (treatment) or placebo; the observation period was 24 months. Patients completed general health PROMs (European Quality of Life in 5 Dimensions [EQ-5D] and 36-item Short Form [SF-36]) and PROMs specific to glaucoma (15-item Glaucoma Quality of Life [GQL-15] and 9-item Glaucoma Activity Limitation [GAL-9]) at baseline and exit from the trial. Percentage changes between measurement on PROMs were calculated for each patient and compared between treatment arms. In addition, differences between stable patients (n = 272) and those with glaucomatous progression (n = 78), as determined by visual field change (primary outcome), were assessed. MAIN OUTCOME MEASURE: PROMs on health-related and vision-related quality of life. RESULTS: Average percentage change on PROMs was similar for patients in both arms of the trial, with no statistically significant differences between treatment and placebo groups (EQ-5D, P = 0.98; EQ-5D visual analog scale, P = 0.88; SF-36, P = 0.94, GQL-15, P = 0.66; GAL-9, P = 0.87). There were statistically significant differences between stable and progressing patients on glaucoma-specific PROMs (GQL-15, P = 0.02; GAL-9, P = 0.02), but not on general health PROMs (EQ-5D, P = 0.62; EQ-5D visual analog scale, P = 0.23; SF-36, P = 0.65). CONCLUSIONS: Average change in PROMs on health-related and vision-related quality of life was similar for the treatment and placebo groups in the UKGTS. The PROMs used may not be sensitive enough to function as primary end points in clinical trials when participants have newly diagnosed early-stage glaucoma

On what scales can GOSAT flux inversions constrain anomalies in terrestrial ecosystems?

This is the final version. Available on open access from European Geosciences Union via the DOI in this recordData availability. CarbonTracker CT2016 results were provided by NOAA ESRL, Boulder, Colorado, USA, from the website at https://www.esrl.noaa.gov/gmd/ccgg/carbontracker/ (National Oceanic and Atmospheric Administration (NOAA) Earth System Laboratory (ESRL), 2019a). CASA GFED 4.1 and CASA CMS NEE fluxes were also downloaded from the CT2016 website. The GOSAT L4 product and VISIT NEE were downloaded from the GOSAT Data Archive Service (https://data2.gosat.nies.go.jp; NIES, 2019). The Dai Global Palmer Drought Severity Index was downloaded from the Research Data Archive at the National Center for Atmospheric Research, Computational and Information Systems Laboratory (https://doi.org/10.5065/D6QF8R93; Dai, 2017). NASA GOME-2 SIF products were obtained from the Aura Validation Data Center (https://avdc.gsfc.nasa.gov/; Aura Validation Data Center, 2019). FLUXCOM products were obtained from the data portal of the Max Planck Institute for Biochemistry (https://www.bgc-jena.mpg.de/geodb/projects/Home.php.; Max Plank Institue for Biogeochemistry, 2019). MERRA-2 products were downloaded from MDISC (https://gmao.gsfc.nasa.gov/reanalysis/MERRA-2/; Global Modeling and Assimilation Office, 2019), managed by the NASA Goddard Earth Sciences (GES) Data and Information Services Center (DISC). The GEOS-Chem forward and adjoint models are freely available to the public. Instructions for downloading and running the models can be found at http://wiki.seas.harvard.edu/geos-chem (Atmospheric Chemistry Modeling Group at Harvard University , 2019). ACOS GOSAT lite files were obtained from the CO2 Virtual Science Data Environment (https://co2.jpl.nasa.gov/; Jet Propulsion Laboratory, California Institute of Technology, 2019). The SST anomalies were downloaded from the National Oceanic and Atmospheric Administration (NOAA) Earth System Research Laboratory (ESRL) website (https://www.esrl.noaa.gov; National Oceanic and Atmospheric Administration (NOAA) Earth System Laboratory (ESRL), 2019b).Interannual variations in temperature and precipitation impact the carbon balance of terrestrial ecosystems, leaving an imprint in atmospheric CO2. Quantifying the impact of climate anomalies on the net ecosystem exchange (NEE) of terrestrial ecosystems can provide a constraint to evaluate terrestrial biosphere models against and may provide an emergent constraint on the response of terrestrial ecosystems to climate change. We investigate the spatial scales over which interannual variability in NEE can be constrained using atmospheric CO2 observations from the Greenhouse Gases Observing Satellite (GOSAT). NEE anomalies are calculated by performing a series of inversion analyses using the GEOS-Chem adjoint model to assimilate GOSAT observations. Monthly NEE anomalies are compared to "proxies", variables that are associated with anomalies in the terrestrial carbon cycle, and to upscaled NEE estimates from FLUXCOM. Statistically significant correlations (P<0.05) are obtained between posterior NEE anomalies and anomalies in soil temperature and FLUXCOM NEE on continental and larger scales in the tropics, as well as in the northern extratropics on subcontinental scales during the summer (R2≥0.49), suggesting that GOSAT measurements provide a constraint on NEE interannual variability (IAV) on these spatial scales. Furthermore, we show that GOSAT flux inversions are generally better correlated with the environmental proxies and FLUXCOM NEE than NEE anomalies produced by a set of terrestrial biosphere models (TBMs), suggesting that GOSAT flux inversions could be used to evaluate TBM NEE fluxes.Environment and Climate Change CanadaNatural Sciences and Engineering Research Council of CanadaCanadian Space Agenc

High Conservatism in the Composition of Scent Gland Secretions in Cyphophthalmid Harvestmen: Evidence from Pettalidae

The scent gland secretion of Austropurcellia forsteri was analyzed by gas chromatography–mass spectrometry, providing the first description of the secretion chemistry in the cyphophthalmid family Pettalidae. The secretion contained a total of 21 compounds: About 60% of the whole secretion consisted of a series of saturated, mono-unsaturated and doubly unsaturated methylketones, from C11 to C15, with a cluster of saturated and mono-unsaturated C13-methylketones dominating. A second fraction included several naphthoquinones such as 1,4-naphthoquinone (ca. 20% of secretion), 6-methyl-1,4-naphthoquinone (ca. 17%), and minor amounts of chloronaphthoquinones (ca. 2%). When compared with scent gland compositions of other representatives of cyphophthalmids (e.g. from families Sironidae and Stylocellidae), a highly conservative chemistry of cyphophthalmid secretions is apparent, based on a restricted number of methylketones and naphthoquinones

Research priorities for improving infant and young child feeding in humanitarian emergencies

Background There are many challenges during emergencies to ensure that optimal infant and young child feeding is protected, promoted and supported, but there is a dearth of evidence on strategies and programmes to improve Infant and Young Child Feeding in Emergencies (IYCF-E) and a need to determine research priorities. Methods Based on interviews with key informants who are experts in the subject, we developed a list of 48 research questions on IYCF-E. A framework, following the Child Health and Nutrition Research Initiative method to set priorities in child health research, was developed to rank the research questions. Four criteria were applied to create a ranking based on answerability, operational relevance, disease burden reduction and prevention, and originality. Using an on-line survey, prioritisation of research questions was done by 27 people from 14 NGOs, universities and research institutions, and UN organisations. Results The top-ten research questions identified focused on the following: • Use of cash-transfer to buy breast-milk substitutes; • Effectiveness of complementary feeding strategies; • Long-term effect of IYCF-E interventions; • Design of IYCF-E programmes in a context where breastfeeding rates are low and breast milk substitutes use is high; • Design of effective re-lactation interventions; • Provision of psychological support to young children’s care-takers; • Determination of number of beneficiaries and coverage of IYCF-E programmes; • Pros and cons of distributing ready-to-use infant formula compared with distributing powdered infant formula plus kit for safer use of BMS, when use of infant formula is necessary; • Assessment of the impact of specific IYCF-E programmes on nutritional status, morbidity and mortality; • Linking and mainstreaming IYCF-E interventions with other sectors such as health, WASH, food security and child protection. Conclusion The questions found by this study could form the basis of future research on IYCF-E and could be integrated into the agenda of relevant stakeholders. Results of studies based on these questions will be fundamental to fill the evidence gap in IYCF-E, improve IYCF-E programming and ultimately contribute to the reduction in morbidity and mortality among infants and young children in humanitarian emergencies