Alien Registration- Lepus, Joseph (Millinocket, Penobscot County)

https://digitalmaine.com/alien_docs/8049/thumbnail.jp

Alien Registration- Lepus, Elizabeth (Millinocket, Penobscot County)

https://digitalmaine.com/alien_docs/8048/thumbnail.jp

An Implantable Vascularized Protein Gel Construct That Supports Human Fetal Hepatoblast Survival and Infection by Hepatitis C Virus in Mice

Widely accessible small animal models suitable for the study of hepatitis C virus (HCV) in vivo are lacking, primarily because rodent hepatocytes cannot be productively infected and because human hepatocytes are not easily engrafted in immunodeficient mice.We report here on a novel approach for human hepatocyte engraftment that involves subcutaneous implantation of primary human fetal hepatoblasts (HFH) within a vascularized rat collagen type I/human fibronectin (rCI/hFN) gel containing Bcl-2-transduced human umbilical vein endothelial cells (Bcl-2-HUVEC) in severe combined immunodeficient X beige (SCID/bg) mice. Maturing hepatic epithelial cells in HFH/Bcl-2-HUVEC co-implants displayed endocytotic activity at the basolateral surface, canalicular microvilli and apical tight junctions between adjacent cells assessed by transmission electron microscopy. Some primary HFH, but not Huh-7.5 hepatoma cells, appeared to differentiate towards a cholangiocyte lineage within the gels, based on histological appearance and cytokeratin 7 (CK7) mRNA and protein expression. Levels of human albumin and hepatic nuclear factor 4alpha (HNF4alpha) mRNA expression in gel implants and plasma human albumin levels in mice engrafted with HFH and Bcl-2-HUVEC were somewhat enhanced by including murine liver-like basement membrane (mLBM) components and/or hepatocyte growth factor (HGF)-HUVEC within the gel matrix. Following ex vivo viral adsorption, both HFH/Bcl-2-HUVEC and Huh-7.5/Bcl-2-HUVEC co-implants sustained HCV Jc1 infection for at least 2 weeks in vivo, based on qRT-PCR and immunoelectron microscopic (IEM) analyses of gel tissue.The system described here thus provides the basis for a simple and robust small animal model of HFH engraftment that is applicable to the study of HCV infections in vivo

Alien Registration- Lepus, Elizabeth (Millinocket, Penobscot County)

https://digitalmaine.com/alien_docs/8048/thumbnail.jp

[Halle (Saale), Universitäts- und Landesbibliothek Sachsen-Anhalt, Morbio 2 (176)]

Zucalla Lepus aus Domodossola, Notar und procurator caneuarius des Odemarus Busio, Bischof von Novara, belehnt im Namen des Bischofs den Bonusfans de Strimido aus Domodossola und den Martinus, Sohn des verstorbenen Homodeus Nouolius aus Bognanco, mit dem vollen Recht am Zehnt, das der Bischof in Domodossola besessen hat, für eine jährliche Abgabe.Handschrift DE-3, GND 2024680-8, Signatur: Morbio 2 (176)Die Illustrationen sind: NotarszeichenÜberlieferungsart: originalBeschreibstoff: PergamentErhaltungszustand: gutDas Indiktionsjahr könnte auch eine Datierung auf 1242 nahelegen.HandschriftUrkund

Alien Registration- Lepus, Joseph (Millinocket, Penobscot County)

https://digitalmaine.com/alien_docs/8049/thumbnail.jp

Complement component C1q limits osteoarthritis pathology by regulating macrophage activation

Abstract Osteoarthritis (OA), the most common form of arthritis in the world, is characterized by articular cartilage breakdown in synovial joints. There is evidence of low-grade inflammatory responses in OA, but their contribution to OA pathogenesis is unclear. Studies have demonstrated that dysregulated complement activity is involved in OA pathogenesis. The complement component, C1q, is known to regulate inflammation via mechanisms involving apoptotic cell clearance and macrophage activation. Thus, we hypothesized that C1q is a key negative regulator of inflammatory mechanisms in OA. Using a combination of NanoString-based mRNA quantification and Luminex-based analyses for cytokine profiling, we found that differentiation of human monocyte-derived macrophages in C1q-depleted serum followed by stimulation with cartilage debris resulted in enhanced pro-inflammatory (e.g., IL1β) and reduced anti-inflammatory (e.g,. IL10) cytokine expression and secretion compared to cells grown in normal human serum. To definitively establish a regulatory role for C1q in OA, we used a well-established destabilization of the medial meniscus (DMM) model of knee OA in genetically-deficient mice. We found that knees of C1q-deficient mice subjected to DMM developed worse OA pathologies including exacerbated cartilage damage, osteophyte formation and synovitis relative to C1q-sufficient mice. Our data suggest that C1q deficiency exacerbates inflammation and cartilage damage through mechanisms involving dysregulated macrophage activation. Understanding the precise mechanisms underlying C1q-mediated regulation of inflammation may lead to the identification of novel targets for the treatment of inflammatory diseases including OA.</jats:p