Retroviral RNase H: Structure, mechanism, and inhibition.

All retroviruses encode the enzyme, reverse transcriptase (RT), which is involved in the conversion of the single-stranded viral RNA genome into double-stranded DNA. RT is a multifunctional enzyme and exhibits DNA polymerase and ribonuclease H (RNH) activities, both of which are essential to the reverse-transcription process. Despite the successful development of polymerase-targeting antiviral drugs over the last three decades, no bona fide inhibitor against the RNH activity of HIV-1 RT has progressed to clinical evaluation.

Large Multidomain Protein NMR: HIV-1 Reverse Transcriptase Precursor in Solution.

NMR studies of large proteins, over 100 kDa, in solution are technically challenging and, therefore, of considerable interest in the biophysics field. The challenge arises because the molecular tumbling of a protein in solution considerably slows as molecular mass increases, reducing the ability to detect resonances. In fact, the typical H-C or H-N correlation spectrum of a large protein, using a C- or N-uniformly labeled protein, shows severe line-broadening and signal overlap.

Defining the correctness of a diagnosis: differential judgments and expert knowledge.

Approaches that use a simulated patient case to study and assess diagnostic reasoning usually use the correct diagnosis of the case as a measure of success and as an anchor for other measures. Commonly, the correctness of a diagnosis is determined by the judgment of one or more experts. In this study, the consistency of experts' judgments of the correctness of a diagnosis, and the structure of knowledge supporting their judgments, were explored using a card sorting task.

Back to the basic sciences: an innovative approach to teaching senior medical students how best to integrate basic science and clinical medicine.

Abraham Flexner persuaded the medical establishment of his time that teaching the sciences, from basic to clinical, should be a critical component of the medical student curriculum, thus giving rise to the "preclinical curriculum." However, students' retention of basic science material after the preclinical years is generally poor. The authors believe that revisiting the basic sciences in the fourth year can enhance understanding of clinical medicine and further students' understanding of how the two fields integrate.

Developmental downregulation of P2X3 receptors in motoneurons of the compact formation of the nucleus ambiguus.

Motoneurons of the compact division of the nucleus ambiguus (cNA) are the final output neurons of the swallowing pattern generator. Thus, their normal function is critical to neonatal survival. To explore the role of purinergic signaling in modulating the excitability of these motoneurons during development, immunohistochemical and whole-cell recording techniques were used to characterize expression patterns of ionotropic P2X receptors and the effects of ATP on cNA motoneurons.

Cranial sensory neuron development in the absence of brain-derived neurotrophic factor in BDNF/Bax double null mice.

To investigate the role of brain-derived neurotrophic factor (BDNF) in differentiation of cranial sensory neurons in vivo, we analyzed development of nodose (NG), petrosal (PG), and vestibular (VG) ganglion cells in genetically engineered mice carrying null mutations in the genes encoding BDNF and the proapoptotic Bcl-2 homolog Bax. In bax(-/-) mutants, ganglion cell numbers were increased significantly compared to wild-type animals, indicating that naturally occurring cell death in these ganglia is regulated by Bax signaling. Analysis of bdnf(-/-)bax(-/-) mutants revealed that, although the Bax null mutation completely rescued cell loss in the absence of BDNF, it did not rescue the lethality of the BDNF null phenotype.

Expression of Phox2 transcription factors and induction of the dopaminergic phenotype in primary sensory neurons.

Cell-type-specific transcription factors may regulate phenotypic diversity by conferring selective responsiveness to relatively nonspecific environmental cues. To test this hypothesis, we examined whether the homeodomain transcription factors Phox2a/2b play a role in activity-dependent expression of the dopaminergic phenotype using petrosal ganglion (PG) sensory neurons as a model. The timing of Phox2a/2b expression is precisely correlated with the ability of PG neurons to express the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), in response to depolarizing stimuli.