Rhabdovirus Matrix Protein Structures Reveal a Novel Mode of Self-Association

The matrix (M) proteins of rhabdoviruses are multifunctional proteins essential for virus maturation and budding that also regulate the expression of viral and host proteins. We have solved the structures of M from the vesicular stomatitis virus serotype New Jersey (genus: Vesiculovirus) and from Lagos bat virus (genus: Lyssavirus), revealing that both share a common fold despite sharing no identifiable sequence homology. Strikingly, in both structures a stretch of residues from the otherwise-disordered N terminus of a crystallographically adjacent molecule is observed binding to a hydrophobic cavity on the surface of the protein, thereby forming non-covalent linear polymers of M in the crystals. While the overall topology of the interaction is conserved between the two structures, the molecular details of the interactions are completely different. The observed interactions provide a compelling model for the flexible self-assembly of the matrix protein during virion morphogenesis and may also modulate interactions with host proteins

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality in the world, with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) comprising the two major cell types. Although these cell types can be distinguished readily at the histological level, knowledge of their underlying molecular differences is very limited. In this study, we compared 14 SCLC cell lines against 27 NSCLC cell lines using an integrated array comparative genomic hybridisation and gene expression profiling approach to identify subtype-specific disruptions. Using stringent criteria, we have identified 159 of the genes that are responsible for the different biology of these cell types. Sorting of these genes by their biological functions revealed the differential disruption of key components involved in cell cycle pathways. Our novel comparative combined genome and transcriptome analysis not only identified differentially altered genes, but also revealed that certain shared pathways are preferentially disrupted at different steps in these cell types. Small cell lung cancer exhibited increased expression of MRP5, activation of Wnt pathway inhibitors, and upregulation of p38 MAPK activating genes, while NSCLC showed downregulation of CDKN2A, and upregulation of MAPK9 and EGFR. This information suggests that cell cycle upregulation in SCLC and NSCLC occurs through drastically different mechanisms, highlighting the need for differential molecular target selection in the treatment of these cancers

Work Activities of Clinician-Educators

In order to make meaningful scholarly contributions, clinician-educators need protected time. Forty-one clinician-educators at the University of Washington recorded their work activities in 30-minute intervals for 2 weeks. The average work week was 58.7 hours (SD = 13.8). The time devoted to scholarship, 7.6 hours (13%), was significantly less than the 20% designated for scholarship in the clinician-educator job description (p < .001); 42% of scholarly work occurred outside the regular work week. At a time when many schools rely on clinician-educators to sustain their clinical and teaching missions, schools should ensure that faculty have adequate time and resources to meet scholarly expectations for promotion

A Survival Guide for Generalist Physicians in Academic Fellowships

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75240/1/j.1525-1497.1999.12138.x.pd

Indicators of Early Research Productivity Among Primary Care Fellows

OBJECTIVE: Little is known about the impact of fellowship training in primary care on subsequent research productivity. Our goal was to identify characteristics of research fellows and their training associated with subsequent publications and research funding. DESIGN: Mail survey in 1998. SETTING AND PARTICIPANTS: 1988–1997 graduates of 25 National Research Service Award primary care research fellowships in the United States. OUTCOME MEASURES: 1) Publishing 1 or more papers per year since the beginning of fellowship, or 2) serving as principal investigator (PI) on a federal or non-federal grant. RESULTS: One hundred forty-six of two hundred fifteen program graduates (68%) completed the survey. The median age was 38 years, and 51% were male. Thirty-two percent had published 1 or more papers per year, and 44% were PIs. Male gender (odds ratio [OR], 3.6; 95% confidence interval [95% CI], 1.4 to 9.2), self-reported allocation of 40% or more of fellowship time to research (OR, 4.4; 95% CI, 1.8 to 11.2), and having an influential mentor during fellowship (OR, 5.0; 95% CI, 1.5 to 17.2) were independently associated with publishing 1 or more papers per year. Fellows with funding as a PI were also more likely to have an influential mentor (OR, 3.0; 95% CI, 1.3 to 7.2). CONCLUSION: Primary care fellows who had influential mentors were more productive in research early after fellowship. Awareness of the indicators of early research success can inform the policies of agencies that fund research training and the curricula of training programs themselves