Expression, Tissue Distribution and Function of miR-21 in Esophageal Squamous Cell Carcinoma

Objective:MiR-21 is an oncomir expressed by malignant cells and/or tumor microenvironment components. In this study we focused on understanding the effects of stromal miR-21 on esophageal malignant cells.Design:MiR-21 expression was evaluated in formalin-fixed paraffin-embedded samples from patients with esophageal squamous-cell carcinoma (SCC) by quantitative RT-PCR. MiR-21 tissue distribution was visualized with in situ hybridization. A co-culture system of normal fibroblasts and esophageal cancer cells was used to determine the effects of fibroblasts on miR-21 expression levels, and on SCC cell migration and invasion.Results:MiR-21 was overexpressed in SCCs, when compared to the adjacent non-tumor tissues (P = 0.0007), and was mainly localized in the cytoplasm of stromal cells adjacent to malignant cells. Accordingly, miR-21 expression was increased in tumors with high versus low stromal content (P = 0.04). When co-cultured with normal fibroblasts, miR-21 expression was elevated in SCC cells (KYSE-30), while its expression was restricted to fibroblasts when co-cultured with adenocarcinoma cells (OE-33 and FLO-1). MiR-21 was detected in conditioned media of cancer cell lines, illustrating the release of this miRNA into the environment. Co-culturing with normal fibroblasts or addition of fibroblast conditioned media caused a significant increase in cell migration and invasion potency of KYSE-30 cells (P<0.0001). In addition, co-culturing cancer cells with fibroblasts and expression of miR-21 induced the expression of the cancer associated fibroblast (CAF) marker S100A4.Conclusions:MiR-21 expression is mostly confined to the SCC stroma and its release from fibroblasts influences the migration and invasion capacity of SCC cells. Moreover, miR-21 may be an important factor in "activating" fibroblasts to CAFs. These findings provide new insights into the role of CAFs and the extracellular matrix in tumor microenvironment formation and in tumor cell maintenance, and suggest miR-21 may contribute to cellular crosstalk in the tumor microenvironment. © 2013 Nouraee et al

Physiological and molecular insights into drought tolerance.

Water is a major limiting factor in world agriculture. In general, most crop plants are highly sensitive to even a mild dehydration stress. There are however, a few genera of plants unique to Southern Africa, called "resurrection plants" which can tolerate extreme water loss or desiccation. We have used Xerophyta viscosa, a representative of the monocotyledonous resurrection plants to isolate genes that are associated with osmotic stress tolerance. Several genes that are differentially expressed, and that confer functional sufficiency to osmotically-stressed Escherichia coli are being studied at the molecular and biochemical levels. In this review, we use this as a basis to discuss the physiological and molecular insights into drought tolerance

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* &gt; 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

Spatially resolved star formation and inside-out quenching in the TNG50 simulation and 3D-HST observations

We compare the star-forming main sequence (SFMS) of galaxies – both integrated and resolved on 1 kpc scales – between the high-resolution TNG50 simulation of IllustrisTNG and observations from the 3D-HST slitless spectroscopic survey at z ∼ 1. Contrasting integrated star formation rates (SFRs), we find that the slope and normalization of the star-forming main sequence in TNG50 are quantitatively consistent with values derived by fitting observations from 3D-HST with the Prospector Bayesian inference framework. The previous offsets of 0.2–1 dex between observed and simulated main-sequence normalizations are resolved when using the updated masses and SFRs from Prospector. The scatter is generically smaller in TNG50 than in 3D-HST for more massive galaxies with M*&amp;gt; 1010 M⊙, by ∼10–40 per cent, after accounting for observational uncertainties. When comparing resolved star formation, we also find good agreement between TNG50 and 3D-HST: average specific star formation rate (sSFR) radial profiles of galaxies at all masses and radii below, on, and above the SFMS are similar in both normalization and shape. Most noteworthy, massive galaxies with M*&amp;gt; 1010.5 M⊙, which have fallen below the SFMS due to ongoing quenching, exhibit a clear central SFR suppression, in both TNG50 and 3D-HST. In contrast, the original Illustris simulation and a variant TNG run without black hole kinetic wind feedback, do not reproduce the central SFR profile suppression seen in data. In TNG, inside-out quenching is due to the supermassive black hole (SMBH) feedback model operating at low accretion rates

Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment

DNA samples from five members of a multiplex non-consanguineous Cameroonian family, segregating prelingual and progressive autosomal recessive non-syndromic sensorineural hearing impairment, underwent whole exome sequencing. We identified novel bi-allelic compound heterozygous pathogenic variants in CLIC5. The variants identified, i.e., the missense [NM_016929.5:c.224T&gt;C; p.(L75P)] and the splicing (NM_016929.5:c.63+1G&gt;A), were validated using Sanger sequencing in all seven available family members and co-segregated with hearing impairment (HI) in the three hearing impaired family members. The three affected individuals were compound heterozygous for both variants, and all unaffected individuals were heterozygous for one of the two variants. Both variants were absent from the genome aggregation database (gnomAD), the Single Nucleotide Polymorphism Database (dbSNP), and the UK10K and Greater Middle East (GME) databases, as well as from 122 apparently healthy controls from Cameroon. We also did not identify these pathogenic variants in 118 unrelated sporadic cases of non-syndromic hearing impairment (NSHI) from Cameroon. In silico analysis showed that the missense variant CLIC5-p.(L75P) substitutes a highly conserved amino acid residue (leucine), and is expected to alter the stability, the structure, and the function of the CLIC5 protein, while the splicing variant CLIC5-(c.63+1G&gt;A) is predicted to disrupt a consensus donor splice site and alter the splicing of the pre-mRNA. This study is the second report, worldwide, to describe CLIC5 involvement in human hearing impairment, and thus confirms CLIC5 as a novel non-syndromic hearing impairment gene that should be included in targeted diagnostic gene panels

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