Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar ...macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion.
Formation Conditions of Chondrules and Chondrites Alexander, C.M. O'D; Grossman, J.N; Ebel, D.S ...
Science (American Association for the Advancement of Science),
06/2008, Letnik:
320, Številka:
5883
Journal Article
Recenzirano
Chondrules, which are roughly millimeter-sized silicate-rich spherules, dominate the most primitive meteorites, the chondrites. They formed as molten droplets and, judging from their abundances in ...chondrites, are the products of one of the most energetic processes that operated in the early inner solar system. The conditions and mechanism of chondrule formation remain poorly understood. Here we show that the abundance of the volatile element sodium remained relatively constant during chondrule formation. Prevention of the evaporation of sodium requires that chondrules formed in regions with much higher solid densities than predicted by known nebular concentration mechanisms. These regions would probably have been self-gravitating. Our model explains many other chemical characteristics of chondrules and also implies that chondrule and planetesimal formation were linked.
Irritable Bowel Syndrome Ford, Alexander C; Lacy, Brian E; Talley, Nicholas J
The New England journal of medicine,
06/2017, Letnik:
376, Številka:
26
Journal Article
Recenzirano
IBS affects 7 to 16% of the U.S. population, with subtypes characterized by diarrhea, constipation, or both. Patients may have a response to dietary modification, and an effective doctor–patient ...relationship may increase symptom control.
The irritable bowel syndrome (IBS) is a chronic and sometimes disabling functional bowel disorder.
1
,
2
Traditionally, this functional diagnostic label has been applied when no obvious structural or biochemical abnormalities are found, but emerging evidence suggests that distinct pathophysiological disturbances may account for the symptoms and that IBS is unlikely to be one disease or merely a psychiatric (somatosensory) disorder.
2
The Rome IV criteria,
1
derived from a consensus process by a multinational group of experts in functional gastrointestinal disorders, constitute the current standard for diagnosing IBS. According to these criteria, IBS is diagnosed on the basis of recurrent abdominal pain . . .
Background
The regulation and function of IgE in healthy individuals and in antigen‐naïve animals is not well understood. IL‐33 administration increases serum IgE in mice with unknown mechanism. We ...tested the hypothesis that IL‐33 provides an antigen‐independent stimulus for IgE production and mast cell degranulation.
Methods
IL‐33 was administered to naïve wild‐type (WT), nude and ST2−/−, IL‐4−/−, IL4Rα−/− and T‐or B‐cell‐specific IL‐4Rα−/− mice. IgEand cytokines were quantified by ELISA. T‐ and B‐lymphocyte numbers and CD40L expression were determined by flow cytometry. Anaphylaxis was measured by temperature, mast cell degranulation and histamine release.
Results
IL‐33 enhanced IgE production in naïve WT, T‐IL‐4Rα−/− but not in ST2−/−, IL‐4−/−, IL‐4Rα−/− or B‐cell‐specific IL‐4Rα−/− mice, demonstrating IL‐33 specificity and IL‐4 dependency. Moreover, IL‐4 was required for IL‐33‐induced B‐cell proliferation and T‐cell CD40L expression, which promotes IgE production. IL‐33‐induced IL‐4 production was mainly from innate cells including mast cells and eosinophils. IL‐33 increased mast cell surface IgE and triggered degranulation and systemic anaphylaxis in allergen‐naïve WT but not in IL‐4Rα−/− mice.
Conclusion
IL‐33 amplifies IgE synthesis and triggers anaphylaxis in naïve mice via IL‐4, independent of allergen. IL‐33 may play an important role in nonatopic allergy and idiopathic anaphylaxis.
We present the final Sloan Digital Sky Survey IV (SDSS-IV) quasar catalog from Data Release 16 of the extended Baryon Oscillation Spectroscopic Survey (eBOSS). This catalog comprises the largest ...selection of spectroscopically confirmed quasars to date. The full catalog includes two subcatalogs (the current versions are DR16Q_v4 and DR16Q_Superset_v3 at https://data.sdss.org/sas/dr16/eboss/qso/DR16Q/): a "superset" of all SDSS-IV/eBOSS objects targeted as quasars containing 1,440,615 observations and a quasar-only catalog containing 750,414 quasars, including 225,082 new quasars appearing in an SDSS data release for the first time, as well as known quasars from SDSS-I/II/III. We present automated identification and redshift information for these quasars alongside data from visual inspections for 320,161 spectra. The quasar-only catalog is estimated to be 99.8% complete with 0.3%-1.3% contamination. Automated and visual inspection redshifts are supplemented by redshifts derived via principal component analysis and emission lines. We include emission-line redshifts for H , Hβ, Mg ii, C iii, C iv, and Ly . Identification and key characteristics generated by automated algorithms are presented for 99,856 broad absorption-line quasars and 35,686 damped Lyman alpha quasars. In addition to SDSS photometric data, we also present multiwavelength data for quasars from the Galaxy Evolution Explorer, UKIDSS, the Wide-field Infrared Survey Explorer, FIRST, ROSAT/2RXS, XMM-Newton, and Gaia. Calibrated digital optical spectra for these quasars can be obtained from the SDSS Science Archive Server.
Summary
Background
Estimation of the prevalence of oesophageal narrowing and its clinical relevance in patients with oesophageal eosinophilia is probably underestimated by endoscopy.
Aims
To ...determine the sensitivity and specificity of oesophagogastroduodenoscopy (EGD) for oesophageal narrowing when compared to a structured oesophagram.
Methods
We conducted a retrospective chart review at Mayo Clinic, Rochester of adult patients with eosinophilic oesophageal infiltration of >15 eosinophils/hpf with symptomatic dysphagia, who underwent a structured barium oesophagram. The sensitivity and specificity of EGD were evaluated against the gold standard of oesophagram. Demographic and multiple clinical factors were evaluated as potential predictors of oesophageal narrowing.
Results
Of the 58 patients identified, 34 (58.6%) had a narrowed oesophageal diameter (<21 mm). EGD had poor sensitivity (14.7%, 95% CI 5.0–31.1%) for detection of a narrowed oesophagus and only modest specificity (79.2%, 95% CI 57.8–92.9%). Even at a cut‐off diameter of EDmax ≤ 15 mm, EGD had a sensitivity of only 25.0% (95% CI 5.5–57.2%) for narrowed oesophagus. A history of >5 food impaction episodes, endoscopic rings, and female sex were the best predictors of oesophageal narrowing. 86% (6/7) patients with persistent dysphagia despite remission of histological eosinophilia responded to oesophageal dilation all of whom had radiological oesophageal narrowing and 71% of whom had no perceived oesophageal narrowing at EGD.
Conclusions
Symptomatic oesophageal narrowing identified by barium oesophagography is common and under‐recognised at endoscopy in patients with oesophageal eosinophilia.
Outputs from new state‐of‐the‐art climate models under the Coupled Model Inter‐comparison Project phase 6 (CMIP6) promise improvement and enhancement of climate change projections information for ...Australia. Here we focus on three key aspects of CMIP6: what is new in these models, how the available CMIP6 models evaluate compared to CMIP5, and their projections of the future Australian climate compared to CMIP5 focussing on the highest emissions scenario. The CMIP6 ensemble has several new features of relevance to policymakers and others, for example, the integrated matrix of socioeconomic and concentration pathways. The CMIP6 models show incremental improvements in the simulation of the climate in the Australian region, including a reduced equatorial Pacific cold tongue bias, slightly improved rainfall teleconnections with large‐scale climate drivers, improved representation of atmosphere and ocean extreme heat events, as well as dynamic sea level. However, important regional biases remain, evident in the excessive rainfall over the Maritime Continent and rainfall pattern biases in the nearby tropical convergence zones. Projections of Australian temperature and rainfall from the available CMIP6 ensemble broadly agree with those from CMIP5, except for a group of CMIP6 models with higher climate sensitivity and greater warming and increase in some extremes after 2050. CMIP6 rainfall projections are similar to CMIP5, but the ensemble examined has a narrower range of rainfall change in austral summer in Northern Australia and austral winter in Southern Australia. Overall, future national projections are likely to be similar to previous versions but perhaps with some areas of improved confidence and clarity.
Key Points
CMIP6 shows incremental improvement of the simulation of Australian climate compared to CMIP5
CMIP6 climate projections are similar to CMIP5 except for a group of higher sensitivity models with warmer projected change
Penicillin-binding protein 4 (PBP4), a nonessential, low-molecular-weight penicillin-binding protein of
, has been implicated in low-level resistance to β-lactam antibiotics, although the mechanism ...is unknown. Mutations in PBP4 and its promoter were identified in a laboratory-generated mutant strain, CRB, which expresses high-level resistance to β-lactams, including resistance to the new-generation cephalosporins active against methicillin-resistant strains of
These mutations did not appreciably alter the β-lactam antibiotic binding affinity of purified recombinant mutant PBP4 compared to that of wild-type PBP4. Compared to the susceptible parent strain, COLnex, the CRB strain produces a highly cross-linked cell wall peptidoglycan, indicative of increased transpeptidase activity. The
promoter mutation of CRB was associated with greatly increased amounts of PBP4 in membranes compared to those in the COLnex parent. Replacement of the native promoter of COLnex with the mutant promoter of CRB resulted in increased amounts of PBP4 in membranes and a highly cross-linked cell wall. PBP4 can be repurposed to provide essential transpeptidase activity
and confer high-level resistance to β-lactam antibiotics, such as ceftobiprole and ceftaroline.
Purpose To assess the agreement and repeatability of horizontal visible iris diameter (HVID) or white-to-white (WTW) measurements between four imaging modalities; combination slit scanning ...elevation/Placido tomography, infrared biometry, dual rotating scheimpflug camera/Placido tomography, and swept source anterior segment optical coherence tomography (AS-OCT). Methods A prospective study of 35 right eyes of healthy volunteers were evaluated using the Orbscan IIz, IOL Master 700, Galilei G2, and DRI Triton OCT devices. The inter-device agreement and repeatability of HVID/WTW measurements for each device were analysed. Results Mean HVID/WTW values obtained by the Orbscan IIz, IOL Master 700, Galilei G2 and DRI Triton OCT were 11.77 ± 0.40 mm, 12.40 ± 0.43 mm, 12.25 ± 0.42 mm, and 12.42 ± 0.47 mm, respectively. All pairwise comparisons revealed statistically significant differences in mean HVID/WTW measurements (p = <0.01) except for the IOL Master 700-DRI OCT Triton pair (p = 0.56). Mean differences showed that the DRI Triton OCT produced the highest HVID/WTW values, followed by the IOL Master 700, Galilei G2 and Orbscan IIz, respectively. The limits of agreement were large on all device pairs. There was high repeatability for all devices (ICC greater than or equal to 0.980). The highest repeatability was seen in the Galilei G2 (ICC = 0.995) and lowest in the Orbscan IIz (ICC = 0.980). Conclusions The four devices exhibit high repeatability, but should not be used interchangeably for HVID/WTW measurements in clinical practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cultivated bacteria such as actinomycetes are a highly useful source of biomedically important natural products. However, such 'talented' producers represent only a minute fraction of the entire, ...mostly uncultivated, prokaryotic diversity. The uncultured majority is generally perceived as a large, untapped resource of new drug candidates, but so far it is unknown whether taxa containing talented bacteria indeed exist. Here we report the single-cell- and metagenomics-based discovery of such producers. Two phylotypes of the candidate genus 'Entotheonella' with genomes of greater than 9 megabases and multiple, distinct biosynthetic gene clusters co-inhabit the chemically and microbially rich marine sponge Theonella swinhoei. Almost all bioactive polyketides and peptides known from this animal were attributed to a single phylotype. 'Entotheonella' spp. are widely distributed in sponges and belong to an environmental taxon proposed here as candidate phylum 'Tectomicrobia'. The pronounced bioactivities and chemical uniqueness of 'Entotheonella' compounds provide significant opportunities for ecological studies and drug discovery.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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