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Divergent regulating inflammatory cytokines through mTORC1 throughout THP-1-derived macrophages as well as colon epithelial Caco-2 tissues.
AIMS Classic Hodgkin lymphoma (cHL) is a common malignancy of the pediatric age. Although clinical-radiological features are routinely used for disease risk stratification, the role of tumor histology has yet to be defined. This study aimed to characterize the clinical-pathological features of a large cohort of pediatric cHL specifically investigating the relevance of tumor histology for the prognostic stratification of patients. Inflammation related antagonist METHODS AND RESULTS The study considered 96 clinically annotated cases of pediatric cHL treated according to the AIEOP-LH2004 protocol. The following histological parameters were considered (i) cHL variant; (ii) grade of nodular sclerosis (NS); (iii) staining for Bcl2 and p53, and expression of B-cell (BCA) and T-cell antigens (TCA) by Hodgkin/Reed-Sternberg cells. The study population consisted of 51 males and 45 females (median age 13.6 years) with five-year overall and progression-free survival of 94% and 81%, respectively. Most cases featured NS morphology (96%) with a prevalence of NS1 over NS2 grades. Two NS2 variants were recognized (sarcomatous/syncytial and fibrohistiocytic). A consistent subset of cases disclosed positivity for BCA (34%), TCA (26%), p53 (13%), and Bcl2 (19%). Clinical-pathological correlations showed a more aggressive clinical course for NS2 over NS1 cases. The NS2 fibrohistiocytic variant was associated with the worst outcome. No other histological features correlated with prognosis. CONCLUSIONS Pediatric cHL is a clinically and histologically heterogeneous neoplasm. The majority of cases disclose NS morphology and aberrant phenotypes are frequently encountered. In the pediatric population, NS grading and NS2 subtyping bear significant prognostic impact. © 2020 Wiley Periodicals, Inc.Congenital heart defects (CHDs) are caused by a disruption in heart morphogenesis, which is dependent, in part, on a network of transcription factors (TFs) that regulate myocardial development. Heterozygous sequence variants in the basic helix-loop-helix TF gene heart and neural crest derivatives expressed 2 (HAND2) have been reported among some patients with CHDs; however, HAND2 has not yet been established as a Mendelian disease gene. We report a 31-month-old male with unicommissural unicuspid aortic valve, moderate aortic stenosis, and mild pulmonic stenosis. Chromosome analysis revealed a normal 46,XY karyotype, and a CHD sequencing panel was negative for pathogenic variants in NKX2.5, GATA4, TBX5, and CHD7. However, chromosomal microarray (CMA) testing identified a heterozygous 546.0-kb deletion on chromosome 4q34.1 (174364195_174910239[GRCh37/hg19]) that included exons 1 and 2 of SCRG1, HAND2, and HAND2-AS1. Familial CMA testing determined that the deletion was paternally inherited, which supported a likely pathogenic classification as the proband's father had previously undergone surgery for Tetralogy of Fallot. The family history was also notable for a paternal uncle who had previously died from complications related to an unknown heart defect. Taken together, this first report of a HAND2 and HAND2-AS1 deletion in a family with CHDs strongly supports haploinsufficiency of HAND2 as an autosomal dominant cause of CHD. © 2020 Wiley Periodicals, Inc.AIM Comparisons between the resting full-cycle ratio (RFR), a new physiological resting index, and fractional flow reserve (FFR) in terms of prognostic value are limited. We aimed to identify the prognostic value of concordance between RFR and FFR and to determine the stability of measured RFR. METHODS AND RESULTS We measured FFR and RFR in 161 coronary arteries of 119 patients and classified the data using known cutoffs for FFR (≤0.80) and RFR (≤0.89) into groups; high FFR and high RFR (high FFR/low RFR) group, high FFR and low RFR (high FFR/low RFR) group, low FFR and high RFR (low FFR/high RFR) group, and low FFR and low RFR (low FFR/low RFR) group. The concordance rates in these groups were 42.2% (68/161), 4.4% (7/161), 14.3% (23/161), and 39.1% (63/161), respectively. The concordance between FFR and RFR was 81.4%. The prevalence of females was significantly higher, values for hemoglobin values were significantly lower, and average E/E' (an index of left ventricular (LV) diastolic function by echocardiography) was significantly higher in high FFR/low RFR group than in low FFR/high RFR group (p = .008, .050, and .028, respectively). CONCLUSIONS The RFR and FFR values consistently agreed. Female, anemia, and LV diastolic dysfunction may be related to the difference of discordance between high FFR/low RFR and low FFR/high RFR. © 2020 Wiley Periodicals, Inc.N-glycosylation is defined as a key quality attribute for the majority of complex biological therapeutics. Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases. Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging. Among many other influential factors, the level of productivity can steer N-glycosylation towards less mature N-glycan structures. Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load. Here, this system was applied to evaluate engineering strategies for enhanced N-glycan processing. The tool proves to indeed be valuable for a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity. The gene editing approaches tested include overexpression of key Golgi-resident glycosyltransferases, partially coupled with multiple gene deletions. Changes in galactosylation, sialylation, and branching potential as well as N-acetyllactosamine formation were evaluated. © 2020 The Authors. Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers.Bioaerosols are an important component of the total atmospheric aerosol load, with implications for human health, climate feedbacks and the distribution and dispersal of microbial taxa. Bioaerosols are sourced from marine, freshwater and terrestrial surfaces, with different mechanisms potentially responsible for releasing biological particles from these substrates. Little is known about the production of freshwater and terrestrial bioaerosols in polar regions. We used portable collection devices to test for the presence of picocyanobacterial aerosols above freshwater and soil substrates in the southwestern Greenland tundra and the McMurdo Dry Valleys of Antarctica. We show that picocyanobacterial cells are present in the near-surface air at concentrations ranging from 2,431 to 28,355 cells m-3 of air, with no significant differences among substrates or between polar regions. Our concentrations are lower than those measured using the same methods in temperate ecosystems. We suggest that aerosolization is an important process linking terrestrial and aquatic ecosystems in these polar environments, and that future work is needed to explore aerosolization mechanisms and taxon-specific aerosolization rates.
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