Pathway analysis shows association between FGFBP1 and hypertension
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Nelson, Christopher , Barnes, Timothy , Denniff, Matthew , Kaiser, Michael , Debiec, Radoslaw , Christofidou, Paraskevi , Rafelt, Suzanne , Van Harst, Pim Der , Wang, William , Maric, Christine , Zukowska-Szczechowska, Ewa , Samani, Nilesh
- Date: 2011
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 22, no. 5 (2011), p. 947-955
- Full Text: false
- Reviewed:
- Description: Variants in the gene encoding fibroblast growth factor 1 (FGF1) co-segregate with familial susceptibility to hypertension, and glomerular upregulation of FGF1 associates with hypertension. To investigate whether variants in other members of the FGF signaling pathway may also associate with hypertension, we genotyped 629 subjects from 207 Polish families with hypertension for 79 single nucleotide polymorphisms in eight genes of this network. Family-based analysis showed that parents transmitted the major allele of the rs16892645 polymorphism in the gene encoding FGF binding protein 1 (FGFBP1) to hypertensive offspring more frequently than expected by chance (P = 0.005). An independent cohort of 807 unrelated Polish subjects validated this association. Furthermore, compared with normotensive subjects, hypertensive subjects had approximately 1.5- and 1.4-fold higher expression of renal FGFBP1 mRNA and protein (P = 0.04 and P = 0.001), respectively. By immunohistochemistry, hypertensionrelated upregulation of FGFBP1 was most apparent in the glomerulus and juxtaglomerular space. Taken together, these data suggest that FGFBP1 associates with hypertension and that systematic analysis of signaling pathways can identify previously undescribed genetic associations. Copyright © 2011 by the American Society of Nephrology.
Evaluation of the role of galectins in parasite immunity
- Authors: Preston, Sarah , Dunphy, Jillian , Beddoe, Travis , Meeusen, Els , Young, Anna
- Date: 2014
- Type: Text , Book chapter
- Relation: Galectins: Methods and Protocols (Methods in Molecular Biology series) Chapter 25 p. 371-395
- Full Text: false
- Reviewed:
- Description: Galectin-11 and galectin-14 are ruminant galectins involved in parasitic infections. Although their roles in parasite immunity are still being elucidated, its appears that their functions are parasite specific. In gastrointestinal infections with the nematode Haemonchus contortus, both galectin-11 and galectin-14 appear to be protective. However, in a chronic infection of liver fluke, Fasciola hepatica, these galectins may aid parasite survival. This chapter discusses the methods designed to study parasitic infections in sheep, which have provided us with insight into the functions of galectin-11 and galectin-14 during host–parasite interactions. These methods include parasite cultivation and infection, galectin staining of host and parasite tissue, surface staining of parasites with recombinant galectins and in vitro assays to monitor the effect of galectins on larval development. © Springer Science+Business Media New York 2015.
Evaluation of the role of galectins in parasite immunity
- Authors: Swan, Jaclyn , Sakthivel, Dhanasekaran , Beddoe, Travis , Stear, Michael , Piedrafita, David , Preston, Sarah
- Date: 2022
- Type: Text , Book chapter
- Relation: Galectins: Methods in Molecular Biology Chapter 7 p. 475-515
- Full Text: false
- Reviewed:
- Description: Galectin-11 (LGALS-11) and galectin-14 (LGALS-14) are ruminant specific galectins, first reported in sheep. Although their roles in parasite immunity are still being elucidated, it appears that they influence protection against parasites. In gastrointestinal infections with the nematode Haemonchus contortus, both galectin-11 and galectin-14 appear to be protective. However, in a chronic infection of liver fluke, Fasciola hepatica, these galectins may aid parasite survival. To unravel the structural, functional, and ligand profile of galectin-11 and galectin-14, recombinant production of these proteins is vital. Here we present the recombinant production of soluble galectin-11 and galectin-14 from domestic sheep for in vitro and structural biology studies. These methods include parasite cultivation and infection, galectin staining of host and parasite tissue, surface staining of parasites with recombinant galectins, pull-down assays to identify endogenous galectin binding proteins, and in vitro assays to monitor the effect of galectins on parasite development. © 2022, Springer Science+Business Media, LLC, part of Springer Nature.
Automated segmentation of mouse OCT volumes (ASiMOV): Validation & clinical study of a light damage model
- Authors: Antony, Bhavna , Kim, Byung-Jin , Lang, Andrew , Carass, Aaron , Prince, Jerry , Zack, Donald
- Date: 2017
- Type: Text , Journal article
- Relation: PLoS One Vol. 12, no. 8 (2017), p. e0181059-e0181059
- Full Text:
- Reviewed:
- Description: The use of spectral-domain optical coherence tomography (SD-OCT) is becoming commonplace for the in vivo longitudinal study of murine models of ophthalmic disease. Longitudinal studies, however, generate large quantities of data, the manual analysis of which is very challenging due to the time-consuming nature of generating delineations. Thus, it is of importance that automated algorithms be developed to facilitate accurate and timely analysis of these large datasets. Furthermore, as the models target a variety of diseases, the associated structural changes can also be extremely disparate. For instance, in the light damage (LD) model, which is frequently used to study photoreceptor degeneration, the outer retina appears dramatically different from the normal retina. To address these concerns, we have developed a flexible graph-based algorithm for the automated segmentation of mouse OCT volumes (ASiMOV). This approach incorporates a machine-learning component that can be easily trained for different disease models. To validate ASiMOV, the automated results were compared to manual delineations obtained from three raters on healthy and BALB/cJ mice post LD. It was also used to study a longitudinal LD model, where five control and five LD mice were imaged at four timepoints post LD. The total retinal thickness and the outer retina (comprising the outer nuclear layer, and inner and outer segments of the photoreceptors) were unchanged the day after the LD, but subsequently thinned significantly (p < 0.01). The retinal nerve fiber-ganglion cell complex and the inner plexiform layers, however, remained unchanged for the duration of the study.