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1.
Chem Biol Interact ; 392: 110905, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38373627

Aldose reductase is a member of the 1B1 subfamily of aldo-keto reductase gene superfamily. The action of aldose reductase (AR) has been implicated in the pathogenesis of a variety of disease states, most notably complications of diabetes mellitus including neuropathy, retinopathy, nephropathy, and cataracts. To explore for mechanistic roles for AR in disease pathogenesis, we established mutant strains produced using Crispr-Cas9 to inactivate the AKR1B3 gene in C57BL6 mice. Phenotyping AR-knock out (ARKO) strains confirmed previous reports of reduced accumulation of tissue sorbitol levels. Lens epithelial cells in ARKO mice showed markedly reduced epithelial-to-mesenchymal transition following lens extraction in a surgical model of cataract and posterior capsule opacification. A previously unreported phenotype of preputial sebaceous gland swelling was observed frequently in male ARKO mice homozygous for the mutant AKR1B3 allele. This condition, which was shown to be accompanied by infiltration of proinflammatory CD3+ lymphocytes, was not observed in WT mice or mice heterozygous for the mutant allele. Despite this condition, reproductive fitness of the ARKO strain was indistinguishable from WT mice housed under identical conditions. These studies establish the utility of a new strain of AKR1B3-null mice created to support mechanistic studies of cataract and diabetic eye disease.


Capsule Opacification , Cataract , Lens, Crystalline , Animals , Male , Mice , Aldehyde Reductase/genetics , Capsule Opacification/pathology , Cataract/genetics , Cataract/pathology , Incidence , Inflammation/pathology , Lens, Crystalline/pathology , Mice, Inbred C57BL , Mice, Knockout , Sebaceous Glands
2.
Article En | MEDLINE | ID: mdl-32431769

Inclusion of multiple viewpoints increases when teams are diverse and provides value in scientific communication and discovery. To promote retention and raise the critical mass of underrepresented persons in science, all voices must be heard "at the table" to include "ways of knowing" outside the dominant institutional culture. These community-based inclusive concepts promote hearing all diverse perspectives for inclusive recognition of deeper socio-historical cultural wealth-collectively termed cultural wellness. When undergraduates and graduates in active-learning groups in class, or faculty collaborative teams on campus, start a project too quickly on task, opportunities are missed to be inclusive. While beginning a larger science project, we, student and faculty co-authors, first addressed this challenge -the need for greater inclusion of diverse perspectives-by starting a conversation. Here, we share ideas from our inclusive process. Based on social constructivist theories of co-constructing learning interpersonally, we co-mentored each other, learning from one another in community. We experientially considered how to inclusively collaborate across a demographically, geographically, and structurally heterogeneous group including multiple academic tiers from multiple ethnic backgrounds, cultural experiences, and institutions. Through an asset-based process grounded in several frameworks, we documented our introduction process of listening deeply, being mindful of identities including invisible cultural identities, recognizing each other with mutual respect, applying inclusive practices, and developing mutual trust and understanding. Building community takes time. Initial conversations can, and should, go deeper than mere introductions to build trust beyond social norms for relationships promoting cultural wellness.

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