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Biology subjects

Weiser, D.

Publications and source records attributed to Weiser, D..

3 recordsLinked to original sources

Breeding Males, But Not Females, Have Elevated Androgen Receptor Expression in the Northern House Wren (Troglodytes Aedon), a Temperate Songbird with Female Song

In many male temperate-breeding songbirds, increased plasma testosterone in the early breeding season regenerates song control nuclei that regulate song. Females of some temperate species also sing but have lower circulating testosterone concentrations. We hypothesized that upregulation of steroid receptors in females could compensate for low circulating testosterone, focusing on the northern house wren (Troglodytes aedon), a temperate-breeding songbird in which both sexes sing. We collected brain tissue from both sexes during the early breeding, late breeding, and nonbreeding season. Using quantitative PCR, we quantified mRNA expression of four genes--androgen receptor (AR), estrogen receptors (ER and ER{beta}), and aromatase (AROM)--in three song nuclei--HVC, Area X, and RA--and compared sexes. We found females had lower expression than males of AR, AROM and ER in most song nuclei, especially of AR in HVC in the breeding season. Both sexes, however, had low ER expression in Area X and RA. In males, expression differed seasonally: breeding males had higher expression of AR in RA and AROM in HVC than nonbreeding males. In both sexes, expression differed among song nuclei: in most genes, HVC had the highest expression, followed by RA, then Area X. These findings suggest singing female house wrens do not compensate for low plasma testosterone by upregulating steroid receptors beyond male levels or during early breeding, when they sing most. Conversely, increased AR expression in breeding males indicates differences in the mechanisms regulating male and female song, with testosterone playing a greater role in male birdsong.

animal behavior and cognition↗

Destabilized 3UTR ARE therapeutically degrades ERBB2 in drug-resistant ERBB2+ cancer models

Breast, lung, and colorectal cancer resistance to molecular targeted therapy is a major challenge and unfavorably impacts clinical outcomes, leading to hundreds of thousands of deaths yearly. In ERBB2+ cancers regardless of the tissue of origin, ERBB2 is the driver oncogene of resistance. We discovered that the ERBB2+ cancers are enriched with poly U sequences on their 3UTR AU rich elements which are mRNA stabilizing sequences. We developed a novel technology, in which we engineered these ERBB2 mRNA stabilizing sequences to unstable forms and specifically controlled and degraded ERBB2 transcript and protein across multiple cancer types both in the wildtype and drug resistance settings in vitro and in vivo, offering a unique novel modality to control ERBB2 and other pervasive oncogenic signals where other therapies fail. One-Sentence SummaryEngineered destabilized 3UTR ARE of ERBB2 degrades ERBB2 in many cancer types and controlled resistance. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/503914v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@139d8dborg.highwire.dtl.DTLVardef@cc1fd3org.highwire.dtl.DTLVardef@13d9086org.highwire.dtl.DTLVardef@db69bf_HPS_FORMAT_FIGEXP M_FIG A. Depiction represents multiple ERBB2 expressing cancer cells with stable 3UTR ARE and the signaling cascade known to cause chemo resistance. B. Depiction of the engineered destabilized 3UTR ARE of ERBB2 and the destabilization and degradation of the ERBB2 transcript, protein and kinases involved in mediation of drug resistance C_FIG

cancer biology↗

Donor-derived vasculature is required to support neocortical cell grafts after stroke

Neural precursor cells (NPCs) transplanted into the adult neocortex generate neurons that synaptically integrate with host neurons, supporting the possibility of achieving functional tissue repair. However, poor survival of transplanted NPCs greatly limits efficient engraftment. Here, we test the hypothesis that combining blood vessel-forming vascular cells with neuronal precursors improves engraftment. By transplanting mixed embryonic neocortical cells into adult mice with neocortical strokes, we show that transplant-derived neurons synapse with appropriate targets while donor vascular cells form vessels that fuse with the host vasculature to perfuse blood within the graft. Although all grafts became vascularized, larger grafts had greater contributions of donor-derived vessels that increased as a function of their distance from the host-graft border. Moreover, excluding vascular cells from the donor cell population strictly limited graft size. Thus, inclusion of vessel-forming vascular cells with NPCs is required for more efficient engraftment and ultimately for tissue repair.

neuroscience↗