Since the identification of mutations in MECP2 in girls and women with apparent Rett syndrome, numerous efforts have been made to develop phenotype-genotype correlations. These studies have produced conflicting results in part related to use of different clinical severity scales, different diagnostic criteria, and different stratification by age and mutation group as well as the possible effects of unbalanced X-chromosome inactivation. The present study applied a revised ordinal scoring system that allowed for correction for patient ages. We analyzed 85 patients with mutation in MECP2. Sixty-five (76%) had one of eight common mutations. Patients with missense mutations had lower total severity scores and better language performance than those with nonsense mutations. No difference was noted between severity scores for mutations in the methyl-binding domain (MBD) and the transcriptional repression domain (TRD). However, patients with missense mutations in TRD had the best overall scores and better preservation of head growth and language skills. Analysis of specific mutation groups demonstrated a striking difference for patients with the R306C mutation including better overall score, later regression, and better language with less motoric impairment. Indeed, these patients as a group accounted for the differences in overall scores between the missense and nonsense groups. Thus, the impact of specific mutations coupled with possible variation in X-chromosome inactivation must be considered carefully in the derivation of phenotype-genotype correlations. These results emphasize the limitations of such analyses in larger mutation groups, either by type or position.
Androgen receptor (AR) mediates transcriptional activation of diverse target genes through interactions with various coactivators that may alter its function and help mediate the switch between prostate cell proliferation and differentiation. We recently identified p44/MEP50 as an AR coactivator and further showed that it is expressed primarily in the nucleus and cytoplasm of benign prostate epithelial and prostate cancer cells, respectively. We also showed that haploinsufficiency in p44 ؉/؊ mice causes prostate epithelial cell proliferation. To establish direct cause-andeffect relationships, we have used p44 fusion proteins that are selectively expressed in the nucleus or cytoplasm of prostate cancer cells (LNCaP), along with RNAi analyses, to examine effects of p44 both in vitro and in vivo (in tumor xenografts). We show that preferential expression of p44 in the nucleus inhibits proliferation of LNCaP cells in an AR-dependent manner, whereas preferential expression of p44 in the cytoplasm enhances cell proliferation. These effects appear to be mediated, at least in part, through the regulation of distinct cell-cycle regulatory genes that include p21 (up-regulated by nuclear p44) and cyclin D2 and CDK6 (up-regulated by cytoplasmic p44). Importantly, we also demonstrate that altered p44 expression is associated with androgen-independent prostate cancer. Our results indicate that nuclear p44 and cytoplasmic p44 have distinct and opposing functions in the regulation of prostate cancer cell proliferation. Mep50 ͉ prostate cancer growth H ormone refractory or androgen-independent prostate cancer remains the primary cause of cancer-related death. Androgens and androgen receptors (ARs) play crucial roles in prostate cancer oncogenesis and progression, including progression into androgenindependent cancer (1-3). AR, a member of the steroid hormone receptor family (4), is a transcription factor with an important role in the regulation of normal prostate growth and differentiation. On the one hand, AR can increase prostate cell proliferation; on the other hand, AR can also inhibit proliferation of prostate cells (5, 6). The mechanism underlying the AR-mediated switch between proliferation and growth suppression remains to be elucidated. In association with its coactivators, AR binds to androgen-responsive elements and activates transcription of AR target genes (4). AR coactivators affect the transcriptional activity of AR by altering its association with either the general transcriptional machinery (7) or chromatin-modifying complexes such as those with histone acetylation or methylation activity (8, 9).Increasing numbers of AR coactivators have been described recently. We and others have observed diverse expression patterns of some cofactors involved in human prostate cancer. Increased expression of some cofactors (ARA24, PIAS1, cyclinD1, SRC1, FHL2, and Par4) and decreased expression of others (ARA70 and ART-27) are found in prostate cancer tissue when compared with adjacent benign tissue (10-15). Thus alterations in ...
A data visualization style guide does for graphs what the Chicago Manual of Style does for English grammar: it defines the components of a graph and their proper, consistent use. At the Urban Institute, a nonprofit research institution based in Washington, DC, our data visualization style guide defines these styles for our research and communications staff. In the process of revising and expanding the style guide, we are taking a more diverse, equitable, and inclusive (DEI) perspective to our research, data, and visualizations. To date, our approach has been to create a set of recommendations and issues to consider, rather than a set of rules that researchers must follow. In this paper, we discuss eight techniques that data visualization producers should consider when creating visuals with this DEI approach. As with our existing style guide, we consider this a first step in our thought process of creating graphs and producing content through a DEI lens.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.