A kinetic model for bacterial transfection: the lambda DNA system.

A kinetic model describing the binding and uptake of free lambda phage DNA by the bacterium Escherichia coli is presented. The model is based on the assumption that adsorbed ‘helper’ phage particles serve as functional sites to which the lambda DNA specifically binds. When applied to experimental data, the model describes the reaction between cells and DNA as a rapid binding of DNA to helper phage attachment sites, followed by a slow, irreversible incorporation of bound DNA into the cells. Features of the model include a time-dependent exponential decay of functional sites required for DNA uptake and a minimum time for irreversibly bound DNA to enter the cell. We suggest that this model may be useful in studying processes involved in the active transport of DNA across a permeability barrier.     

Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age,Geography, and Lifestyle

1. Download high-res image (282KB)
2. Download full-size image

     

Motor-cargo interactions: the key to transport specificity

Eukaryotic cells organize their cytoplasm by moving different organelles and macromolecular complexes along microtubules and actin filaments. These movements are powered by numerous motor proteins that must recognize their respective cargoes in order to function. Recently, several proteins that interact with motors have been identified by yeast two-hybrid and biochemical analyses, and their roles in transport are now being elucidated. In several cases, analysis of the binding partners helped to identify new transport pathways, new types of cargo, and transport regulated at the level of motor-cargo binding. We discuss here how different motors of the kinesin, dynein and myosin families recognize their cargo and how motor-cargo interactions are regulated.     

Intérêt de la TEP/TDM au FDG dans l’investigation étiologique des syndromes paranéoplasiques

Paraneoplastic syndromes (PNS) represent a rare and heterogeneous group of entities whose clinical symptoms may sometimes antedate the diagnosis of the causative tumor. In the context, the identification of the underlying tumor becomes very important for the patient's functional and sometimes vital prognosis, by allowing an earliest treatment of the tumor. ¹⁸FDG PET/CT has become indispensable in the diagnosis and follow-up of numerous cancers but its role in etiological investigation of isolated paraneoplastic syndromes for the research of an occult tumor is not defined yet. Nevertheless, requests of PET/CT in this indication are frequent in nuclear medicine departments, with an uncertain diagnostic yield. We have listed retrospectively 64 patients, sent to nuclear medicine department of Nancy university hospital between 2004 and 2010 for the research of an occult tumor because of a clinically suspected paraneoplastic syndrome, in order to estimate its diagnostic contribution in this indication. According to our results, ¹⁸FDG PET-CT would be interesting by its negative predictive value concerning the tumoral risk, in keeping with its known sensitivity PET-CT may also present an interest for the diagnosis and the characterization of non-tumoral conditions generating symptoms initially wrongly suspected to be paraneoplastic.     

A coarse-grained model for force-induced protein deformation and kinetics

Force-induced changes in protein conformation are thought to be responsible for certain cellular responses to mechanical force. Changes in conformation subsequently initiate a biochemical response by alterations in, for example, binding affinity to another protein or enzymatic activity. Here, a model of protein extension under external forcing is created inspired by Kramers' theory for reaction rate kinetics in liquids. The protein is assumed to have two distinct conformational states: a relaxed state, C(1), preferred in the absence of external force, and an extended state, C(2), favored under force application. In the context of mechanotransduction, the extended state is a conformation from which the protein can initiate signaling. Appearance and persistence of C(2) are assumed to lead to transduction of the mechanical signal into a chemical one. The protein energy landscape is represented by two harmonic wells of stiffness kappa(1) and kappa(2), whose minima correspond to conformations C(1) and C(2). First passage time t(f) from C(1) to C(2) is determined from the Fokker-Plank equation employing several different approaches found in the literature. These various approaches exhibit significant differences in behavior as force increases. Although the level of applied force and the energy difference between states largely determine equilibrium, the dominant influence on t(f) is the height of the transition state. Distortions in the energy landscape due to force can also have a significant influence, however, exhibiting a weaker force dependence than exponential as previously reported, approaching a nearly constant value at a level of force that depends on the ratio kappa(1)/kappa(2). Two model systems are used to demonstrate the utility of this approach: a short alpha-helix undergoing a transition between two well-defined states and a simple molecular motor.