SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Annual review of physical chemistry

ix, 416 p.; 23 cm

Arabidopsis NPH1: a flavoprotein with the properties of a photoreceptor for phototropism.

The NPH1 gene of Arabidopsis thaliana encodes a 120-kilodalton serine-threonine protein kinase hypothesized to function as a photoreceptor for phototropism. When expressed in insect cells, the NPH1 protein is phosphorylated in response to blue light irradiation. The biochemical and photochemical properties of the photosensitive protein reflect those of the native protein in microsomal membranes. Recombinant NPH1 noncovalently binds flavin mononucleotide, a likely chromophore for light-dependent autophosphorylation. The fluorescence excitation spectrum of the recombinant protein is similar to the action spectrum for phototropism, consistent with the conclusion that NPH1 is an autophosphorylating flavoprotein photoreceptor mediating phototropic responses in higher plants

Dietary iron does not impact the quality of life of patients with quiescent ulcerative colitis: an observational study

Background: In animal models, excess luminal iron exacerbates colonic inflammation and cancer development. Moreover, in inflammatory bowel disease (IBD) patients with mild to moderate disease activity dietary fortificant iron intake is inversely related to quality of life. Here we sought to determine whether dietary iron intakes were also related to quality of life in IBD patients in remission. Methods. Forty eight patients with ulcerative colitis (UC), 42 of which had quiescent disease during this observational study, and 53 healthy control subjects completed quality of life questionnaires and 7-day food diaries. For comparative analysis, 34/group were matched and the linear relationship between dietary iron intakes (total, haem, non-haem or fortificant) and EuroQol quality of life measures was investigated. For UC patients the linear relationship between dietary iron intakes and the scores from the disease specific inflammatory bowel disease questionnaire (IBDQ) was also considered. Results: The intake of dietary iron, and its various sub-fractions, were not associated with quality of life (EuroQol) in patients with quiescent disease or in healthy control subjects. The picture was similar for the 42 quiescent UC patients when disease-specific IBDQ was used. However, the 6 patients who relapsed during the study again showed an inverse association between IBDQ and dietary iron intake (p = 0.03). Conclusions: Our data suggest that dietary iron does not impact on quality of life in quiescent UC patients but support that, once the disease is triggered, luminal iron may be a permissive factor for exacerbation of disease activity resulting in lower quality of life. © 2013 Tolkien et al.; licensee BioMed Central Ltd

Effects of anthocyanidins on myogenic differentiation and antioxidant defense in primary myogenic cells isolated from rainbow trout (Oncorhynchus mykiss)

There is increasing interest in using plant-derived extracts to promote growth and health in finfish species in recent years. Elucidating the effects of plant secondary metabolites on skeletal muscle growth signaling will contribute to an improved understanding of the effects of feeding carnivorous fish diets supplemented with plant extracts on fish somatic growth. Dietary intake of anthocyanins, a type of flavonoid widely distributed in plants, has long been associated with beneficial effects in both human and animal health; however, their effects in finfish are largely unknown. We conducted an experiment to test the effect of three doses (treatments A, B and C; 1. ×, 2.5. × and 10. ×, respectively) of a mixture of three types of anthocyanidins (peonidin, cyanidin and pelargonidin chloride) on the expression of several genes in primary myogenic cells isolated from the skeletal muscle of rainbow trout (Oncorhynchus mykiss) after 24. h of treatment. The genes of interest analyzed are involved in myogenic programing (pax7, myoD and myogenin), Notch signaling (her6 and hey2) and antioxidant enzymes (sod1, cat and gpx1). Significantly greater expression of pax7 in cells under treatment B compared with the untreated cells was detected. Although no differences in expression of myogenic regulatory factors, myoD and myogenin between test groups or the control were detected, a trend toward significantly lower expression in all groups tested compared with the control group was observed. Moreover, significantly higher expression levels of her6 and hey2 in cells under treatments A and B compared with untreated cells were detected. Although no significant differences in the expression of cat and sod1, significantly greater expression in gpx1 in all treated groups compared with the control group was detected. Collectively, we demonstrated that anthocyanidins enhance the expression of gpx1 in primary myogenic cells, thereby contributing to skeletal muscle tissue defense against oxidative stress in finfish species. Further, anthocyanidins appear to delay myogenic differentiation in primary myogenic cells by up-regulating the expression of pax7 while decreasing myogenic regulatory factors in a Notch signaling-dependent interaction. Whether this effect results a reduced growth performance and/or an increase in feed conversion ratio in fish fed diets supplemented with plant extracts rich in anthocyanins or anthocyanidins needs further study, and the need to better define the potential effects of different polyphenol classes in myogenic differentiation on primary myogenic cells from carnivorous fish is warranted. Statement of relevance: The study contributes to increase our understanding regarding the effect of plant-derived secondary metabolites such as anthocyanidins on myogenic program and antioxidant enzyme defense in differentiating myogenic cells from carnivorous fish. We have demonstrated that anthocyanidins may delay the progress of the myogenic differentiation process and promote antioxidant defense expression in myogenic cells. © 2015 Elsevier B.V

Establishment of a cell line from a hepatocellular carcinoma from a patient with hemochromatosis

We describe the establishment and characterization of a novel hepatoma cell line. This cell line, designated RBHF-1, was established from a hepatocellular carcinoma of a 67-yr-old man with a history of genetic hemochromatosis. At this writing, the cells have been maintained in RPMI- 1640 tissue-culture medium and fetal calf serum without any additional supplements for 30 mo. The cells form colonies on soft agar and are not tumorigenic in nude mice. The cell line is polymorphic and displays characteristics of mature hepatocytes by synthesizing albumin, α- macroglobulin, fibronectin and α-fetoprotein. Cytogenetic analysis shows multiple chromosomal aberrations, with a consistent deletion in the long arm and deletions or rearrangements in the short arm of chromosome 1. There is no evidence for hepatitis B or hepatitis C virus infection of the cell line. The cells contain no detectable intracellular iron after staining with Perls' stain. Unlike other hepatoma cell lines, there is no detectable binding of epidermal growth factor to RBHF-1 cells. This is the first cell line to be established from a patient with hemochromatosis, and it provides a potentially important model for the study of hepatocyte transformation in association with iron overload