Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

Background: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear.

Methods: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States.

Copy number alterations identify a smoking-associated expression signature predictive of poor outcome in head and neck squamous cell carcinoma.

Cigarette smoking is a risk factor for the development of head and neck squamous cell carcinoma (HNSCC), partially due to tobacco-induced large-scale chromosomal copy-number alterations (CNAs). Identifying CNAs caused by smoking is essential in determining how gene expression from such regions impact tumor progression and patient outcome. We utilized The Cancer Genome Atlas (TCGA) whole genome sequencing data for HNSCC to directly identify amplified or deleted genes correlating with smoking pack-year based on linear modeling.

Early Neurologic Recovery, Practice Pattern Variation, and the Risk of Endotracheal Intubation Following Established Status Epilepticus.

Objective: To quantify the association between early neurologic recovery, practice pattern variation, and endotracheal intubation during established status epilepticus, we performed a secondary analysis within the cohort of patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT).

Methods: We evaluated factors associated with the endpoint of endotracheal intubation occurring within 120 minutes of ESETT study drug initiation. We defined a blocked, stepwise multivariate regression, examining 4 phases during status epilepticus management: (1) baseline characteristics, (2) acute treatment, (3) 20-minute neurologic recovery, and (4) 60-minute recovery, including seizure cessation and improving responsiveness.

Student and faculty perceptions: appropriate consequences of lapses in academic integrity in health sciences education.

Background: A breadth of evidence supports that academic dishonesty is prevalent among higher education students, including students in health sciences educational programs. Research suggest individuals who engage in academic dishonesty may continue to exhibit unethical behaviors in professional practice. Thus, it is imperative to appropriately address lapses in academic dishonesty among health sciences students to ensure the future safety of patients.

Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map.

Defining the functional relationships between proteins is critical for understanding virtually all aspects of cell biology. Large-scale identification of protein complexes has provided one important step towards this goal; however, even knowledge of the stoichiometry, affinity and lifetime of every protein-protein interaction would not reveal the functional relationships between and within such complexes. Genetic interactions can provide functional information that is largely invisible to protein-protein interaction data sets.

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.

Identification of protein-protein interactions often provides insight into protein function, and many cellular processes are performed by stable protein complexes. We used tandem affinity purification to process 4,562 different tagged proteins of the yeast Saccharomyces cerevisiae. Each preparation was analysed by both matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography tandem mass spectrometry to increase coverage and accuracy.

Role for PSF in mediating transcriptional activator-dependent stimulation of pre-mRNA processing in vivo.

In a recent study, we provided evidence that strong promoter-bound transcriptional activators result in higher levels of splicing and 3'-end cleavage of nascent pre-mRNA than do weak promoter-bound activators and that this effect of strong activators requires the carboxyl-terminal domain (CTD) of RNA polymerase II (pol II). In the present study, we have investigated the mechanism of activator- and CTD-mediated stimulation of pre-mRNA processing. Affinity chromatography experiments reveal that two factors previously implicated in the coupling of transcription and pre-mRNA processing, PSF and p54(nrb)/NonO, preferentially bind a strong rather than a weak activation domain.

Interaction between BRCA2 and replication protein A is compromised by a cancer-predisposing mutation in BRCA2.

Mutations in the BRCA1 and BRCA2 genes predispose women to familial, early-onset breast cancer. Both the BRCA1 and BRCA2 proteins appear to function in the homologous recombination pathway of DNA double-strand break repair. Both BRCA1 and BRCA2 have also been implicated in transcription by RNA polymerase II, for both proteins have domains which, when tethered adjacent to a promoter, can activate transcription.

Splicing and transcription-associated proteins PSF and p54nrb/nonO bind to the RNA polymerase II CTD.

The carboxyl-terminal domain (CTD) of the largest subunit of eukaryotic RNA polymerase II (pol II) plays an important role in promoting steps of pre-mRNA processing. To identify proteins in human cells that bind to the CTD and that could mediate its functions in pre-mRNA processing, we used the mouse CTD expressed in bacterial cells in affinity chromatography experiments. Two proteins present in HeLa cell extract, the splicing and transcription-associated factors, PSF and p54nrb/NonO, bound specifically and could be purified to virtual homogeneity by chromatography on immobilized CTD matrices.