13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis

This work was supported by funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (Grant 677542), a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant 107613/Z/15/Z), and the Barts Charity (Grant MGU0343). This work was also funded, in part, by Medical Research Council Advance Course Masters (Grant MR/J015741/1). The authors declare no conflicts of interest

Structural Evolution in Massive Galaxies at z ∼ 2

We present 0.′′2 resolution Atacama Large Millimeter/submillimeter Array (ALMA) observations at 870 μm in a stellar mass-selected sample of 85 massive (M* > 1011 M⊙) star-forming galaxies (SFGs) at z = 1.9-2.6 in the CANDELS/3D-Hubble Space Telescope fields of UDS and GOODS-S. We measure the effective radius of the rest-frame far-infrared (FIR) emission for 62 massive SFGs. They are distributed over wide ranges of FIR size from Re,FIR = 0.4 kpc to Re,FIR = 6 kpc. The effective radius of the FIR emission is smaller by a factor of 2.3-1.0+1.9 than the effective radius of the optical emission and is smaller by a factor of 1.9-1.0+1.9 than the half-mass radius. Taking into account potential extended components, the FIR size would change only by ∼10%. By combining the spatial distributions of the FIR and optical emission, we investigate how galaxies change the effective radius of the optical emission and the stellar mass within a radius of 1 kpc, M1kpc. The compact starburst puts most of the massive SFGs on the mass-size relation for quiescent galaxies (QGs) at z ∼ 2 within 300 Myr if the current star formation activity and its spatial distribution are maintained. We also find that within 300 Myr, ∼38% of massive SFGs can reach the central mass of M1kpc = 1010.5 M ⊙, which is around the boundary between massive SFGs and QGs. These results suggest an outside-in transformation scenario in which a dense core is formed at the center of a more extended disk, likely via dissipative in-disk inflows. Synchronized observations at ALMA 870 μm and James Webb Space Telescope 3-4 μm will explicitly verify this scenario

The near-infrared imager and slitless spectrograph for the James Webb Space Telescope. II. Wide field slitless spectroscopy

We acknowledge support from the Natural Sciences and Engineering Research Council of Canada (NSERC) through a variety of its funding programs. This work is in part supported by Canadian Space Agency grant 18JWSTGTO1. C.P., S.R. and K.V. are supported by the Canadian Space Agency under a contract with NRC Herzberg Astronomy and Astrophysics. K.M. acknowledges funding by the Science and Technology Foundation of Portugal (FCT), grants No. IF/00194/2015, PTDC/FIS-AST/28731/2017, UIDB/00099/2020.We present the wide field slitless spectroscopy mode of the NIRISS instrument on the James Webb Space Telescope. This mode employs two orthogonal low-resolution (resolving power ≈150) grisms in combination with a set of six blocking filters in the wavelength range 0.8–2.3 μm to provide a spectrum of almost every source across the field-of-view. When combined with the low background, high sensitivity and high spatial resolution afforded by the telescope, this mode will enable unprecedented studies of the structure and evolution of distant galaxies. We describe the performance of the as-built hardware relevant to this mode and expected imaging and spectroscopic sensitivity. We discuss operational and calibration procedures to obtain the highest quality data. As examples of the observing mode usage, we present details of two planned Guaranteed Time Observations programs: The Canadian NIRISS Unbiased Cluster Survey and The NIRISS Survey for Young Brown Dwarfs and Rogue Planets.Publisher PDFPeer reviewe

Acute ischaemic stroke associated with SARS-CoV-2 infection in North America

BACKGROUND: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age \u3e60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p\u3c0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. CONCLUSION: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality

A kilometer-scale asteroid inside Venus's orbit

Near-Earth asteroid population models predict the existence of asteroids located inside the orbit of Venus. However, despite searches up to the end of 2019, none have been found. Here we report the discovery by the Zwicky Transient Facility of the first known asteroid located inside of Venus' orbit, 2020 AV₂, possessing an aphelion distance of 0.65 au and ∼2 km in size. While it is possible that 2020 AV₂ is the largest of its kind, we find that its discovery is surprising in the context of population models where the expected count is close to zero. If this discovery is not a statistical fluke, then 2020 AV₂ may come from a yet undiscovered source population of asteroids interior to Venus, and currently favored asteroid population models may need to be adjusted

A kilometer-scale asteroid inside Venus's orbit

Near-Earth asteroid population models predict the existence of asteroids located inside the orbit of Venus. However, despite searches up to the end of 2019, none have been found. Here we report the discovery by the Zwicky Transient Facility of the first known asteroid located inside of Venus' orbit, 2020 AV₂, possessing an aphelion distance of 0.65 au and ∼2 km in size. While it is possible that 2020 AV₂ is the largest of its kind, we find that its discovery is surprising in the context of population models where the expected count is close to zero. If this discovery is not a statistical fluke, then 2020 AV₂ may come from a yet undiscovered source population of asteroids interior to Venus, and currently favored asteroid population models may need to be adjusted

Experimental Verification of a Predicted Intronic MicroRNA in Human NGFR Gene with a Potential Pro-Apoptotic Function

Neurotrophins (NTs) are a family of secreted growth factor proteins primarily involved in the regulation of survival and appropriate development of neural cells, functioning by binding to their specific (TrkA, TtkB, and TrkC) and/or common NGFR receptor. NGFR is the common receptor of NTs, binding with low-affinity to all members of the family. Among different functions assigned to NGFR, it is also involved in apoptosis induction and tumorigenesis processes. Interestingly, some of the functions of NGFR appear to be ligand-independent, suggesting a probable involvement of non-coding RNA residing within the sequence of the gene. Here, we are reporting the existence of a conserved putative microRNA, named Hsa-mir-6165 [EBI accession#: FR873488]. Transfection of a DNA segment corresponding to the pre-mir-6165 sequence in Hela cell line caused the generation of mature exogenous mir-6165 (a ∼200,000 fold overexpression). Furthermore, using specific primers, we succeeded to detect the endogenous expression of mir-6165 in several glioma cell lines and glioma primary tumors known to express NGFR. Similar to the pro-apoptotic role of NGFR in some cell types, overexpression of pre-mir-6165 in U87 cell line resulted in an elevated rate of apoptosis. Moreover, coordinated with the increased level of mir-6165 in the transfected U87 cell line, two of its predicted target genes (Pkd1 and DAGLA) were significantly down-regulated. The latter findings suggest that some of the previously attributed functions of NGFR could be explained indirectly by co-transcription of mir-6165 in the cells

Interaction of plant growth regulators and reactive oxygen species to regulate petal senescence in wallflowers (Erysimum linifolium)

Background In many species floral senescence is coordinated by ethylene. Endogenous levels rise, and exogenous application accelerates senescence. Furthermore, floral senescence is often associated with increased reactive oxygen species, and is delayed by exogenously applied cytokinin. However, how these processes are linked remains largely unresolved. Erysimum linifolium (wallflower) provides an excellent model for understanding these interactions due to its easily staged flowers and close taxonomic relationship to Arabidopsis. This has facilitated microarray analysis of gene expression during petal senescence and provided gene markers for following the effects of treatments on different regulatory pathways. Results In detached Erysimum linifolium (wallflower) flowers ethylene production peaks in open flowers. Furthermore senescence is delayed by treatments with the ethylene signalling inhibitor silver thiosulphate, and accelerated with ethylene released by 2-chloroethylphosphonic acid. Both treatments with exogenous cytokinin, or 6-methyl purine (which is an inhibitor of cytokinin oxidase), delay petal senescence. However, treatment with cytokinin also increases ethylene biosynthesis. Despite the similar effects on senescence, transcript abundance of gene markers is affected differentially by the treatments. A significant rise in transcript abundance of WLS73 (a putative aminocyclopropanecarboxylate oxidase) was abolished by cytokinin or 6-methyl purine treatments. In contrast, WFSAG12 transcript (a senescence marker) continued to accumulate significantly, albeit at a reduced rate. Silver thiosulphate suppressed the increase in transcript abundance both of WFSAG12 and WLS73. Activity of reactive oxygen species scavenging enzymes changed during senescence. Treatments that increased cytokinin levels, or inhibited ethylene action, reduced accumulation of hydrogen peroxide. Furthermore, although auxin levels rose with senescence, treatments that delayed early senescence did not affect transcript abundance of WPS46, an auxin-induced gene. Conclusions A model for the interaction between cytokinins, ethylene, reactive oxygen species and auxin in the regulation of floral senescence in wallflowers is proposed. The combined increase in ethylene and reduction in cytokinin triggers the initiation of senescence and these two plant growth regulators directly or indirectly result in increased reactive oxygen species levels. A fall in conjugated auxin and/or the total auxin pool eventually triggers abscission

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Fatty Acid Composition of Developing Sea Buckthorn (Hippophae rhamnoides L.) Berry and the Transcriptome of the Mature Seed

Background: Sea buckthorn (Hippophae rhamnoides L.) is a hardy, fruit-producing plant known historically for its medicinal and nutraceutical properties. The most recognized product of sea buckthorn is its fruit oil, composed of seed oil that is rich in essential fatty acids, linoleic (18:2\u3c9-6) and \u3b1-linolenic (18:3\u3c9-3) acids, and pulp oil that contains high levels of monounsaturated palmitoleic acid (16:1\u3c9-7). Sea buckthorn is fast gaining popularity as a source of functional food and nutraceuticals, but currently has few genomic resources; therefore, we explored the fatty acid composition of Canadian-grown cultivars (ssp. mongolica) and the sea buckthorn seed transcriptome using the 454 GS FLX sequencing technology. Results: GC-MS profiling of fatty acids in seeds and pulp of berries indicated that the seed oil contained linoleic and \u3b1-linolenic acids at 33-36% and 30-36%, respectively, while the pulp oil contained palmitoleic acid at 32-42%. 454 sequencing of sea buckthorn cDNA collections from mature seeds yielded 500,392 sequence reads, which identified 89,141 putative unigenes represented by 37,482 contigs and 51,659 singletons. Functional annotation by Gene Ontology and computational prediction of metabolic pathways indicated that primary metabolism (protein>nucleic acid>carbohydrate>lipid) and fatty acid and lipid biosynthesis pathways were highly represented categories. Sea buckthorn sequences related to fatty acid biosynthesis genes in Arabidopsis were identified, and a subset of these was examined for transcript expression at four developing stages of the berry. Conclusion: This study provides the first comprehensive genomic resources represented by expressed sequences for sea buckthorn, and demonstrates that the seed oil of Canadian-grown sea buckthorn cultivars contains high levels of linoleic acid and \u3b1-linolenic acid in a close to 1:1 ratio, which is beneficial for human health. These data provide the foundation for further studies on sea buckthorn oil, the enzymes involved in its biosynthesis, and the genes involved in the general hardiness of sea buckthorn against environmental conditions.Peer reviewed: YesNRC publication: Ye