Lecithin : cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings

LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.Peer reviewe

Lecithin:cholesterol acyltransferase:symposium on 50 years of biomedical research from its discovery to latest findings

LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.</p

A novel single amino acid deletion impairs fibronectin function and causes familial glomerulopathy with fibronectin deposits: case report of a family

Abstract Background Glomerulopathy with fibronectin deposits is an autosomal dominant disease associated with proteinuria, hematuria, hypertension and renal function decline. Forty percent of the cases are caused by mutations in FN1, the gene that encodes fibronectin. Case presentation This report describes two cases of Glomerulopathy with fibronectin deposits, involving a 47-year-old father and a 14-year-old son. The renal biopsies showed glomeruli with endocapillary hypercellularity and large amounts of mesangial and subendothelial eosinophilic deposits. Immunohistochemistry for fibronectin was markedly positive. Whole exome sequencing identified a novel FN1 mutation that leads to an amino-acid deletion in both patients (Ile1988del), a variant that required primary amino-acid sequence analysis for assessment of pathogenicity. Our primary sequence analyses revealed that Ile1988 is very highly conserved among relative sequences and is positioned in a C-terminal FN3 domain containing heparin- and fibulin-1-binding sites. This mutation was predicted as deleterious and molecular mechanics simulations support that it can change the tertiary structure and affect the complex folding and its molecular functionality. Conclusion The current report not only documents the occurrence of two GFND cases in an affected family and deeply characterizes its anatomopathological features but also identifies a novel pathogenic mutation in FN1, analyzes its structural and functional implications, and supports its pathogenicity.https://deepblue.lib.umich.edu/bitstream/2027.42/152212/1/12882_2019_Article_1507.pd

Sensitivity of the Cherenkov Telescope Array for probing cosmology and fundamental physics with gamma-ray propagation

The Cherenkov Telescope Array (CTA), the new-generation ground-based observatory for γ astronomy, provides unique capabilities to address significant open questions in astrophysics, cosmology, and fundamental physics. We study some of the salient areas of γ cosmology that can be explored as part of the Key Science Projects of CTA, through simulated observations of active galactic nuclei (AGN) and of their relativistic jets. Observations of AGN with CTA will enable a measurement of γ absorption on the extragalactic background light with a statistical uncertainty below 15% up to a redshift z=2 and to constrain or detect γ halos up to intergalactic-magnetic-field strengths of at least 0.3 pG . Extragalactic observations with CTA also show promising potential to probe physics beyond the Standard Model. The best limits on Lorentz invariance violation from γ astronomy will be improved by a factor of at least two to three. CTA will also probe the parameter space in which axion-like particles could constitute a significant fraction, if not all, of dark matter. We conclude on the synergies between CTA and other upcoming facilities that will foster the growth of γ cosmology.</p

Early or delayed bronchoscopy in patients admitted to the emergency department for mild-to-moderate hemoptysis?

BACKGROUND: The correct timing for bronchoscopy in massive hemoptysis is well established, whereas in mild-to-moderate hemoptysis there still is uncertainty. The aim of our study was to evaluate if performing a fibrobronchoscopy (FBS) within 48 hours after the onset of mild-to-moderate hemoptysis was related to a higher possibility to identify the site and the cause of bleeding, compared to a delayed one. METHODS: We conducted a retrospective study over one-year period from March 2015, in which consecutive patients admitted to the emergency department underwent FBS for spontaneous mild-to-moderate hemoptysis in our medium-size teaching hospital. RESULTS: We included 69 patients. Definitive diagnosis was achieved in 52 cases (75%) combining clinical, imaging and endoscopic data (neoplastic diseases 22%, infections 20%, alveolar hemorrhage 13%). FBS was performed within 48 hours of symptoms onset in 41 patients (59%). The site of bleeding was identified in 28 cases (41%), 64% of which underwent FBS within 48 hours. Endoscopic diagnosis was reached in 45 patients (65%), 60% of which underwent FBS within 48 hours. No statistical association with localization (P=0.62) or diagnosis (P=1.00) was found with early FBS. Despite a high prevalence in our cohort of patients treated with anticoagulant or antiplatelet drugs (39%), we found no statistical association with bronchoscopy localization (P=0.12) and diagnosis (P=0.21). CONCLUSIONS: In conclusion, in case of mild to moderate hemoptysis, an early bronchoscopy in the emergency department setting does not seem to improve the possibility to find neither the cause nor the localization of the bleeding source