University of Utah

About: University of Utah is a education organization based out in Salt Lake City, Utah, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 52894 authors who have published 124076 publications receiving 5265834 citations. The organization is also known as: The U & The University of Utah.

The Evolution of Mating Preferences and Major Histocompatibility Complex Genes.

Abstract: House mice prefer mates genetically dissimilar at the major histocompatibility complex (MHC). The highly polymorphic MHC genes control immunological self/nonself recognition; therefore, this mating preference may function to provide “good genes” for an individual's offspring. However, the evidence for MHC‐dependent mating preferences is controversial, and its function remains unclear. Here we provide a critical review of the studies on MHC‐dependent mating preferences in mice, sheep, and humans and the possible functions of this behavior. There are three adaptive hypotheses for MHC‐dependent mating preferences. First, MHC‐disassortative mating preferences produce MHC‐heterozygous offspring that may have enhanced immunocompetence. Although this hypothesis is not supported by tests of single parasites, MHC heterozygotes may be resistant to multiple parasites. Second, we propose that MHC‐dependent mating preferences enable hosts to provide a “moving target” against rapidly evolving parasites that e...

Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche.

Abstract: The in vitro analysis of intestinal epithelium has been hampered by a lack of suitable culture systems. Here we describe robust long-term methodology for small and large intestinal culture, incorporating an air-liquid interface and underlying stromal elements. These cultures showed prolonged intestinal epithelial expansion as sphere-like organoids with proliferation and multilineage differentiation. The Wnt growth factor family positively regulates proliferation of the intestinal epithelium in vivo. Accordingly, culture growth was inhibited by the Wnt antagonist Dickkopf-1 (Dkk1) and markedly stimulated by a fusion protein between the Wnt agonist R-spondin-1 and immunoglobulin Fc (RSpo1-Fc). Furthermore, treatment with the gamma-secretase inhibitor dibenzazepine and neurogenin-3 overexpression induced goblet cell and enteroendocrine cell differentiation, respectively, consistent with endogenous Notch signaling and lineage plasticity. Epithelial cells derived from both leucine-rich repeat-containing G protein-coupled receptor-5-positive (Lgr5(+)) and B lymphoma moloney murine leukemia virus insertion region homolog-1-positive (Bmi1(+)) lineages, representing putative intestinal stem cell (ISC) populations, were present in vitro and were expanded by treatment with RSpo1-Fc; this increased number of Lgr5(+) cells upon RSpo1-Fc treatment was subsequently confirmed in vivo. Our results indicate successful long-term intestinal culture within a microenvironment accurately recapitulating the Wnt- and Notch-dependent ISC niche.

Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers.

Abstract: Recent studies have suggested the existence of a tumor suppressor gene located at chromosome region 5q21. DNA probes from this region were used to study a panel of sporadic colorectal carcinomas. One of these probes, cosmid 5.71, detected a somatically rearranged restriction fragment in the DNA from a single tumor. Further analysis of the 5.71 cosmid revealed two regions that were highly conserved in rodent DNA. These sequences were used to identify a gene, MCC (mutated in colorectal cancer), which encodes an 829-amino acid protein with a short region of similarity to the G protein-coupled m3 muscarinic acetylcholine receptor. The rearrangement in the tumor disrupted the coding region of the MCC gene. Moreover, two colorectal tumors were found with somatically acquired point mutations in MCC that resulted in amino acid substitutions. MCC is thus a candidate for the putative colorectal tumor suppressor gene located at 5q21. Further studies will be required to determine whether the gene is mutated in other sporadic tumors or in the germ line of patients with an inherited predisposition to colonic tumorigenesis.

Brief report: specific executive function profiles in three neurodevelopmental disorders

Abstract: It has been proposed that deficient executive functions, such as flexibility, set maintenance, organization, planning, and working memory, may be primary cognitive deficits of autism (Hughes, Russell, & Robbins, 1994; Ozonoff, Pennington, & Rogers, 1991). Executive deficits may also play a part in several other developmental and neurological disorders, however (Ozonoff, 1997; Pennington & Ozonoff, 1996), including attentiondeficit hyperactivity disorder (ADHD; Chelune, Ferguson, Koon, & Dickey, 1986) and Tourette syndrome (TS; Bornstein, 1990; Gladstone el al., 1993). This finding has raised the so-called "discriminant validity question" (Pennington, 1994; Pennington & Ozonoff, 1996): That is, how can disorders differing in behavioral phenotype share the same cognitive underpinnings? One answer to this question is that specific types of executive impairment may be associated with specific neurodevelopmental disorders. Since the class of executive behaviors is large and diverse, it is important to clarify precisely which functions are impaired in each disorder. We hypothesized that when the broad domain of executive function was parsed into specific components (e.g., planning, flexibility, inhibition), different disorders would demonstrate different executive profiles. Three measures, the Wisconsin Card Sorting Task (WCST), the Tower of Hanoi (TOH), and the Stroop Color-Word Test, have traditionally been used to measure executive function deficits in neurodevelopmental disorders. The WCST (Grant & Berg, 1948; Heaton, Chelune, Talley, Kay, & Curtiss, 1993) was designed primarily to test flexibility, the TOH (Borys, Spitz, &