Defining cellular population dynamics at single-cell resolution during prostate cancer progression.

Advanced prostate malignancies are a leading cause of cancer-related deaths in men, in large part due to our incomplete understanding of cellular drivers of disease progression. We investigate prostate cancer cell dynamics at single-cell resolution from disease onset to the development of androgen independence in an in vivo murine model. We observe an expansion of a castration-resistant intermediate luminal cell type that correlates with treatment resistance and poor prognosis in human patients.

Selective Translation of Cell Fate Regulators Mediates Tolerance to Broad Oncogenic Stress.

Human skin tolerates a surprisingly high burden of oncogenic lesions. Although adult epidermis can suppress the expansion of individual mutant clones, the mechanisms behind tolerance to oncogene activation across broader regions of tissue are unclear. Here, we uncover a dynamic translational mechanism that coordinates oncogenic HRAS-induced hyperproliferation with loss of progenitor self-renewal to restrain aberrant growth and tumorigenesis.

The androgen receptor regulates a druggable translational regulon in advanced prostate cancer.

The androgen receptor (AR) is a driver of cellular differentiation and prostate cancer development. An extensive body of work has linked these normal and aberrant cellular processes to mRNA transcription; however, the extent to which AR regulates posttranscriptional gene regulation remains unknown. Here, we demonstrate that AR uses the translation machinery to shape the cellular proteome.

Prenatal diagnosis of ectopia cordis in a twin fetus.

We report images of the 7th case worldwide of a twin fetus with a complete isolated ectopia cordis in a dichorionic diamniotic twin gestation. There is no consanguinity, family history of abnormalities, IVF, or first trimester medication. The diagnosis of this isolated anomaly was done at 23 weeks in one fetus, while the other had normal morphology; the pregnancy was complicated by preterm labor and a cesarean delivery followed at 34 weeks.

Glucocerebrosidase Deficiency in Drosophila Results in α-Synuclein-Independent Protein Aggregation and Neurodegeneration.

Mutations in the glucosidase, beta, acid (GBA1) gene cause Gaucher's disease, and are the most common genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) excluding variants of low penetrance. Because α-synuclein-containing neuronal aggregates are a defining feature of PD and DLB, it is widely believed that mutations in GBA1 act by enhancing α-synuclein toxicity. To explore this hypothesis, we deleted the Drosophila GBA1 homolog, dGBA1b, and compared the phenotypes of dGBA1b mutants in the presence and absence of α-synuclein expression.