Quantitative profiling of adaptation to cyclin E overproduction.

Cyclin E/CDK2 drives cell cycle progression from G1 to S phase. Despite the toxicity of cyclin E overproduction in mammalian cells, the cyclin E gene is overexpressed in some cancers. To further understand how cells can tolerate high cyclin E, we characterized non-transformed epithelial cells subjected to chronic cyclin E overproduction.

Intrinsic checkpoint deficiency during cell cycle re-entry from quiescence.

To maintain tissue homeostasis, cells transition between cell cycle quiescence and proliferation. An essential G1 process is minichromosome maintenance complex (MCM) loading at DNA replication origins to prepare for S phase, known as origin licensing. A p53-dependent origin licensing checkpoint normally ensures sufficient MCM loading before S phase entry.

Measuring psychological flexibility in medical students and residents: a psychometric analysis.

Purpose: Psychological flexibility involves mindful awareness of our thoughts and feelings without allowing them to prohibit acting consistently with our values and may have important implications for patient-centered clinical care. Although psychological flexibility appears quite relevant to the training and development of health care providers, prior research has not evaluated measures of psychological flexibility in medical learners. Therefore, we investigated the validity of our learners' responses to three measures related to psychological flexibility.

Strategic, value-based delivery in global health care: innovations at Harvard University and Brigham and Women's Hospital.

Investments in global health have more than doubled over the past decade, generating a cadre of new institutions. To date, most of the funded research in global health has focused on discovery, and, more recently, on the development of new tools, which has tightened the implementation bottleneck. This article introduces the concept of global health delivery and the need to catalog and analyze current implementation efforts to bridge gaps in delivery.

Regulation of alternative splicing: more than just the ABCs.

Alternative pre-mRNA splicing, the differential inclusion or exclusion of portions of a nascent transcript into the final protein-coding mRNA, is widely recognized to be a ubiquitous mechanism for controlling protein expression. Thus, understanding the molecular basis of alternative splicing is essential for deciphering post-transcriptional control of the genome. Pre-mRNA splicing in general is catalyzed by a large dynamic macromolecular machine known as the spliceosome.

An exonic splicing silencer represses spliceosome assembly after ATP-dependent exon recognition.

Precursor messenger RNA splicing is catalyzed by the spliceosome, a macromolecular complex that assembles in a stepwise process. The spliceosome's dynamic nature suggests the potential for regulation at numerous points along the assembly pathway; however, thus far, naturally occurring regulation of splicing has only been found to influence a small subset of spliceosomal intermediates. Here we report that the exonic splicing silencer (ESS1) that represses splicing of PTPRC (encoding CD45) exon 4 does not function by the typical mechanism of inhibiting binding of U1 or U2 small nuclear ribonucleoproteins (snRNPs) to the splice sites.

Increasing the usability of cognitive processing therapy for survivors of child sexual abuse.

There is an ongoing need for empirically based treatments for child sexual abuse (CSA) that are time-efficient and cost-effective. This article describes a modification of cognitive processing therapy for child sexual abuse (CPT-SA) that increases the therapy's usability by reducing the number of individual therapy sessions required. The modifications are based on the developing literature on stage-based approaches to the treatment of CSA and incorporate dialectical behavior therapy skills training into the treatment protocol.

HnRNP L represses exon splicing via a regulated exonic splicing silencer.

Skipping of mammalian exons during pre-mRNA splicing is commonly mediated by the activity of exonic splicing silencers (ESSs). We have recently identified a regulated ESS within variable exon 4 of the CD45 gene, named ESS1, that is necessary and sufficient for partial exon repression in resting T cells and has additional silencing activity upon T-cell activation. In this study, we identify three heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind specifically to ESS1.

The moderating role of parental warmth on the effects of exposure to family violence.

Previous research has shown parental warmth to have mixed effects on individuals in violent families. While positively associated with psychological health in some victims, parental warmth has also been positively associated with measures of psychological distress in other victims. The current study examined two models (the "buffering" and "inconsistency" theories) to clarify the effects of parental warmth.