Top 3 Biorxiv Papers Today in Pathology


1.997 Mikeys
#1. Platelet Thrombus Formation in eHUS is Prevented by Anti-MBL2
Rafail Kushak, Daniel Boyle, Ivy Rosales, Julie Ingelfinger, Gregory Stahl, Masayuki Ozaki, Robert Colvin, Eric Grabowski
Epidemic Hemolytic Uremic Syndrome (eHUS) caused by Shiga toxin-producing bacteria is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury that cause acute renal failure in up to 65% of affected patients. We hypothesized that the mannose-binding lectin (MBL) pathway of complement activation plays an important role in human eHUS, as we previously demonstrated that injection of Shiga Toxin-2 (Stx-2) led to fibrin deposition in mouse glomeruli that was blocked by co-injection of the anti-MBL-2 antibody 3F8. However, the markers of platelet thrombosis in affected mouse glomeruli were not delineated. To investigate the effect of 3F8 on markers of platelet thrombosis, we used kidney sections from our mouse model (MBL-2+/+ Mbl-A/C-/-; MBL2 KI mouse). Mice in the control group received PBS, while mice in a second group received Stx-2, and those in a third group received 3F8 and Stx-2. Using double immunofluorescence (IF) followed by digital image analysis, kidney sections were stained for...
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1.989 Mikeys
#2. Developing a primary Paralichthys olivaceus gill epithelial cells as an in vitro model for propagation of VHSV show a corresponding increase in cell viability with increase in protein concentration in growth media
Sori Han, Jimin Hong, Jong-pyo Seo, Hetron Mweemba Munang'andu, In-kyu Yeo, Sung-Hyun Kim
Background: Viral Hemorrhagic Septicemia Virus (VHSV) is a rhabdovirus that causes high mortalities linked to high economic losses in aquaculture. It has been grouped in four genotypes of which some do not easily propagate on continuous cell lines. As an alternative, the objectives of this study was to develop a primary gill epithelial cell (GEC) model from olive flounder (Paralichthys olivaceus) as an in vitro model for the propagation of VHSV. Results: Our findings show that the primary GECs developed herein are highly permissive to replication of the JF-09 genotype IVa strain leading to high cytopathic effect observed within 96 hours post virus inoculation. Our findings also show that the viability GECs produced herein corresponded with increase in the concentration fetal bovine serum in growth medium. We envision that GECs produced herein will heighten our understanding of immune mechanisms associated with virus entry on gill mucosal surfaces in flounder.
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1.988 Mikeys
#3. Prolonged podocyte depletion in larval zebrafish resembles mammalian focal and segmental glomerulosclerosis
Kerrin Ursula Ingeborg Hansen, Florian Siegerist, Sophie Daniel, Maximilian Schindler, Antje Blumenthal, Weibin Zhou, Karlhans Endlich, Nicole Endlich
Although focal and segmental glomerulosclerosis (FSGS) has been in the scientific focus for many years, it is still a massive burden for patients with no causal therapeutic option. In FSGS, podocytes are injured, parietal epithelial cells (PECs) are activated and engage in the formation of cellular lesions leading to progressive glomerular scarring. Herein we show that podocyte-depleted zebrafish larvae develop acute proteinuria, severe foot process effacement and activate PECs which create cellular lesions and deposit extracellular matrix on the glomerular tuft. We therefore propose that this model shows features of human FSGS and show its applicability for a high-throughput drug screening assay.
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