SERPINs shelter the endowed migrants in a hostile land

Since metastatic lesions of solid tumors are the major cause of mortality in cancer patients, understanding the molecular mechanisms of metastasis is of paramount importance. Although extensive knowledge has been accumulated regarding the early steps in metastasis—starting with the departure of cancer cells from their primary sites, to their transit through the hematogenous and/or lymphatic systems, and ending with their entrance into the parenchyma of distant organs—it is difficult if not impossible to translate such knowledge into medicine due to the challenge of identifying patients with only primary tumors but otherwise pristine organs. In other words, autopsy studies indicate that a large proportion of patients already harbor dormant, undetectable micrometastases at the time of cancer diagnosis (Hensel et al, 2013 ). Accordingly, stopping tumor cell dissemination is too late for these patients. Therefore, understanding the survival and outgrowth of micrometastases may hold greater promise to combat metastatic disease.     

Bayesian nonparametric inference for panel count data with an informative observation process

In this paper, the panel count data analysis for recurrent events is considered. Such analysis is useful for studying tumor or infection recurrences in both clinical trial and observational studies. A bivariate Gaussian Cox process model is proposed to jointly model the observation process and the recurrent event process. Bayesian nonparametric inference is proposed for simultaneously estimating regression parameters, bivariate frailty effects, and baseline intensity functions. Inference is done through Markov chain Monte Carlo, with fully developed computational techniques. Predictive inference is also discussed under the Bayesian setting. The proposed method is shown to be efficient via simulation studies. A clinical trial dataset on skin cancer patients is analyzed to illustrate the proposed approach.     

The use of a drug resistance cartridge for in vitro insertion and deletion mutagenesis of a cosmid clone

A drug-resistant cartridge was employed in the construction of families of insertion mutants of a cosmid clone. The cartridge contains a cml gene and has identical restriction enzyme sites, EcoRI, BamHI, SalI, and PstI, on both ends. The families of mutants were made by ligation of the cartridge to the cosmid, which was linearized or partially digested, followed by in vitro packaging and transduction. From these families we selected cosmid derivatives which either have a unique BamHI site at a predetermined site in the cosmid or have deletions covering different portions of the original clone. The extent of a large gene cluster cloned into the original cosmid was identified by confirming the gene function in some of the deletion mutants. The possibility for further and various uses of this cartridge is discussed.     

Removal of the RecA C-terminus results in a conformational change in the RecA-DNA filament

The Escherichia coli RecA protein catalyzes homologous recombination of DNA molecules, and the active form of the protein is a helical polymer that it forms around DNA. Previous image analysis of electron micrographs has revealed the RecA protein to be organized into two domains or lobes within the RecA-DNA filament. We have now been able to show that a small modification of the RecA protein by proteolysis results in a significant shift in the internal mass in the RecA filament. We have cleaved approximately 18 residues from the C-terminus of the RecA protein, producing a roughly 36K MW RecA core protein that binds DNA and polymerizes normally. A three-dimensional reconstruction of this complex has been computed, and has been compared with a previous reconstruction of the intact protein. The main difference is consistent with a 15 A outward movement of the lobe that was at an inner radius in the wild-type protein. These observations yield additional evidence about the conformational flexibility of the RecA filament, and will aid in understanding the structural mechanics and dynamics of the RecA filament.