Inhibition of pluripotency networks by the Rb tumor suppressor restricts reprogramming and tumorigenesis

Mutations in the retinoblastoma tumor suppressor gene Rb are involved in many forms of human cancer. In this study, we investigated the early consequences of inactivating Rb in the context of cellular reprogramming. We found that Rb inactivation promotes the reprogramming of differentiated cells to a pluripotent state. Unexpectedly, this effect is cell cycle independent, and instead reflects direct binding of Rb to pluripotency genes, including Sox2 and Oct4, which leads to a repressed chromatin state. More broadly, this regulation of pluripotency networks and Sox2 in particular is critical for the initiation of tumors upon loss of Rb in mice. These studies therefore identify Rb as a global transcriptional repressor of pluripotency networks, providing a molecular basis for previous reports about its involvement in cell fate pliability, and implicate misregulation of pluripotency factors such as Sox2 in tumorigenesis related to loss of Rb function

Inhibition of pluripotency networks by the Rb tumor suppressor restricts reprogramming and tumorigenesis

Mutations in the retinoblastoma tumor suppressor gene Rb are involved in many forms of human cancer. In this study, we investigated the early consequences of inactivating Rb in the context of cellular reprogramming. We found that Rb inactivation promotes the reprogramming of differentiated cells to a pluripotent state. Unexpectedly, this effect is cell cycle independent, and instead reflects direct binding of Rb to pluripotency genes, including Sox2 and Oct4, which leads to a repressed chromatin state. More broadly, this regulation of pluripotency networks and Sox2 in particular is critical for the initiation of tumors upon loss of Rb in mice. These studies therefore identify Rb as a global transcriptional repressor of pluripotency networks, providing a molecular basis for previous reports about its involvement in cell fate pliability, and implicate misregulation of pluripotency factors such as Sox2 in tumorigenesis related to loss of Rb function

Effectiveness of the head CT choice decision aid in parents of children with minor head trauma: study protocol for a multicenter randomized trial

Background: Blunt head trauma is a common cause of death and disability in children worldwide. Cranial computed tomography (CT), the reference standard for the diagnosis of traumatic brain injury (TBI), exposes children to ionizing radiation which has been linked to the development of brain tumors, leukemia, and other cancers. We describe the methods used to develop and test the effectiveness of a decision aid to facilitate shared decision-making with parents regarding whether to obtain a head CT scan or to further observe their child at home. Methods/Design: This is a protocol for a multicenter clinician-level parallel randomized trial to compare an intervention group receiving a decision aid, ‘Head CT Choice’, to a control group receiving usual care. The trial will be conducted at five diverse emergency departments (EDs) in Minnesota and California. Clinicians will be randomized to decision aid or usual care. Parents visiting the ED with children who are less than 18-years-old, have experienced blunt head trauma within 24 hours, and have one or two risk factors for clinically-important TBI (ciTBI) from the Pediatric Emergency Care Applied Research Network head injury clinical prediction rules will be eligible for enrollment. We will measure the effect of Head CT Choice on: (1) parent knowledge regarding their child’s risk of ciTBI, the available diagnostic options, and the risks of radiation exposure associated with a cranial CT scan (primary outcome); (2) parent engagement in the decision-making process; (3) the degree of conflict parents experience related to feeling uninformed; (4) patient and clinician satisfaction with the decision made; (5) the rate of ciTBI at seven days; (6) the proportion of patients in whom a cranial CT scan is obtained; and (7) seven-day healthcare utilization. To capture these outcomes, we will administer parent and clinician surveys immediately after each clinical encounter, obtain video recordings of parent-clinician discussions, administer parent healthcare utilization diaries, analyze hospital billing records, review the electronic medical record, and conduct telephone follow-up. Discussion: This multicenter trial will robustly assess the effectiveness of a decision aid on patient-centered outcomes, safety, and healthcare utilization in parents of children with minor head trauma in five diverse EDs. Trial registration: ClinicalTrials.gov registration number: NCT02063087. Registration date February 13, 2014

Study 3: Emotionality Judgments of Happiness Sequences

The goal of Study 3 was to replicate the effect of target gender on judgments of emotionality from Study 2 using expressions of happiness

Study 4: Memory and Emotionality Judgments of Anger Sequences

The goal of Study 4 was to replicate the Study 2 findings and explore a potential mechanism by which target gender affects judgments of emotionality. The study included two blocks; the first block was the same emotionality judgment task with angry faces used in Study 2 (except with 25 trials instead of 50), and the second was a memory task to test if people preferentially remember women’s (compared to men’s) emotionally intense anger expressions

Study 1: Stereotype Survey

The goal of Study 1 was to ascertain if the stereotype that women are more emotional than men persists and if gender-emotion stereotypes vary for different discrete emotions

Supplementary Study: Emotionality Judgments of Sadness Sequences

We conducted two additional studies with the same design as Studies 2 and 3 but with sadness expressions and found no effect of face gender on emotionality judgments. These studies are not included in the main paper but are reported in the Supplementary Materials