The Preprotein Binding Domain of SecA Displays Intrinsic Rotational Dynamics

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Type III protein translocase: HrcN is a peripheral ATPase that is activated by oligomerization

Type III protein secretion (TTS) is catalyzed by translocases that span both membranes of Gram-negative bacteria. A hydrophilic TTS component homologous to F1/V1-ATPases is ubiquitous and essential for secretion. We show that hrcN encodes the putative TTS ATPase of Pseudomonas syringae pathovar phaseolicola and that HrcN is a peripheral protein that assembles in clusters at the membrane. A decahistidinyl HrcN derivative was overexpressed in Escherichia coli and purified to homogeneity in a folded state. Hydrodynamic analysis, cross-linking, and electron microscopy revealed four distinct HrcN forms: I, 48 kDa (monomer); II, approximately 300 kDa (putative hexamer); III, 575 kDa (dodecamer); and IV, approximately 3.5 MDa. Form III is the predominant form of HrcN at the membrane, and its ATPase activity is dramatically stimulated (>700-fold) over the basal activity of Form I. We propose that TTS ATPases catalyze protein translocation as activated homo-oligomers at the plasma membrane.     

The Nobel Prize laureate - father of anaphylaxis Charles-Robert Richet (1850-1935) and his anticancerous serum

Professor of physiology Charles-Robert Richet, winner of the Nobel Prize in 1913, is best known for his work on anaphylaxis. However, with his collaborator Jules Héricourt studied the effects of antibody treatment and made the very first attempts to fight cancer with serotherapy. Being versatile, Richet contributed in neurology, psychology and was also a poet, playwrighter, pacifist and pioneer in aviation.     

A role for dendritic cells in the dissemination of mycobacterial infection

The ability of mycobacteria to disseminate from the initial site of infection has an important role in immune priming and in the seeding of disease in multiple organs. To study this phenomenon, we used flow cytometry to analyse the distribution of green fluorescent protein-labelled BCG amongst different populations of antigen-presenting cells in the lungs of mice following intranasal infection, and monitored appearance of live bacteria in the draining mediastinal lymph nodes. BCG predominantly infected alveolar macrophages (CD11c(+)/CD11b(-)) and dendritic cells (CD11c(+)/CD11b(+)) in the lungs. The bacteria that disseminated to the lymph node were found in dendritic cells. The results are consistent with a model in which mycobacterial dissemination from the lung is initiated by the migration of infected dendritic cells to the draining lymph nodes.     

Cloning, purification and characterization of a functional anthracycline glycosyltransferase

We have cloned the gene that encodes a novel glucosyl transferase (AraGT) involved in rhamnosylation of the polyketide antibiotic Aranciamycin in Streptomyces echinatus. AraGT comprises two domains characteristic of bacterial glycosyltranferases. AraGT was synthesized in E. coli as a decahistidinyl-tagged polypeptide. Purified AraGT is dimeric, displays a T(mapp) of 30 degrees C and can glycosylate the aglycone of an Aranciamycin derivative as shown by liquid chromatography and mass spectrometry. The availability of functional AraGT will allow the generation Aranciamycin-based combinatorial libraries.     

The role of heparins and nano-heparins as therapeutic tool in breast cancer

Glycosaminoglycans are integral part of the dynamic extracellular matrix (ECM) network that control crucial biochemical and biomechanical signals required for tissue morphogenesis, differentiation, homeostasis and cancer development. Breast cancer cells communicate with stromal ones to modulate ECM mainly through release of soluble effectors during cancer progression. The intracellular cross-talk between cell surface receptors and estrogen receptors is important for the regulation of breast cancer cell properties and production of ECM molecules. In turn, reorganized ECM-cell surface interface modulates signaling cascades, which regulate almost all aspects of breast cell behavior. Heparan sulfate chains present on cell surface and matrix proteoglycans are involved in regulation of breast cancer functions since they are capable of binding numerous matrix molecules, growth factors and inflammatory mediators thus modulating their signaling. In addition to its anticoagulant activity, there is accumulating evidence highlighting various anticancer activities of heparin and nano-heparin derivatives in numerous types of cancer. Importantly, heparin derivatives significantly reduce breast cancer cell proliferation and metastasis in vitro and in vivo models as well as regulates the expression profile of major ECM macromolecules, providing strong evidence for therapeutic targeting. Nano-formulations of the glycosaminoglycan heparin are possibly novel tools for targeting tumor microenvironment. In this review, the role of heparan sulfate/heparin and its nano-formulations in breast cancer biology are presented and discussed in terms of future pharmacological targeting.     

Léon Athanase Gosselin (1815–1887) et ses recherches sur les maladies du testicule

Leon Athanase Gosselin was one of the greatest French surgeons of the 19th century. He successfully directed many university surgical departments and excelled in orthopaedics, anatomy, physiology and urology. Thanks to his advanced research into testicular, scrotal and spermatic cord diseases and their effects on fertilisation and virility, Gosselin is rightly considered to have been a great andrologist before this branch of medical science had been recognised.     

Long-Lived Folding Intermediates Predominate the Targeting-Competent Secretome

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