Mechanical Instabilities of Biological Tubes

We study theoretically the shapes of biological tubes affected by various pathologies. When epithelial cells grow at an uncontrolled rate, the negative tension produced by their division provokes a buckling instability. Several shapes are investigated : varicose, enlarged, sinusoidal or sausage-like, all of which are found in pathologies of tracheal, renal tubes or arteries. The final shape depends crucially on the mechanical parameters of the tissues : Young modulus, wall-to-lumen ratio, homeostatic pressure. We argue that since tissues must be in quasistatic mechanical equilibrium, abnormal shapes convey information as to what causes the pathology. We calculate a phase diagram of tubular instabilities which could be a helpful guide for investigating the underlying genetic regulation

Tilt-induced clustering of cell adhesion proteins

Cell adhesion proteins are transmembrane proteins that bind cells to their environment. These proteins typically cluster into disk-shaped or linear structures. Here we show that such clustering patterns spontaneously emerge when the protein sense the membrane deformation gradient, for example by reaching a lower-energy conformation when the membrane is tilted relative to the underlying binding substrate. Increasing the strength of the membrane gradient-sensing mechanism first yields isolated disk-shaped clusters and then long linear structures. Our theory is coherent with experimental estimates, suggesting that a tilt-induced clustering mechanism is relevant in the context of cell adhesion proteins.Comment: 6 pages, 3 figures, with SI (ancillary files

Mechanochemical action of the dynamin protein

Dynamin is a ubiquitous GTPase that tubulates lipid bilayers and is implicated in many membrane severing processes in eukaryotic cells. Setting the grounds for a better understanding of this biological function, we develop a generalized hydrodynamics description of the conformational change of large dynamin-membrane tubes taking into account GTP consumption as a free energy source. On observable time scales, dissipation is dominated by an effective dynamin/membrane friction and the deformation field of the tube has a simple diffusive behavior, which could be tested experimentally. A more involved, semi-microscopic model yields complete predictions for the dynamics of the tube and possibly accounts for contradictory experimental results concerning its change of conformation as well as for plectonemic supercoiling.Comment: 17 pages, 4 figures; typos corrected, reference adde

Homeostatic competition drives tumor growth and metastasis nucleation

We propose a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show that competition between surface and bulk effects leads to the existence of a critical size that must be overcome by metastases to reach macroscopic sizes. This property can qualitatively explain the observed size distributions of metastases, while size-independent growth rates cannot account for clinical and experimental data. In addition, it potentially explains the observed preferential growth of metastases on tissue surfaces and membranes such as the pleural and peritoneal layers, suggests a mechanism underlying the seed and soil hypothesis introduced by Stephen Paget in 1889 and yields realistic values for metastatic inefficiency. We propose a number of key experiments to test these concepts. The homeostatic pressure as introduced in this work could constitute a quantitative, experimentally accessible measure for the metastatic potential of early malignant growths.Comment: 13 pages, 11 figures, to be published in the HFSP Journa

Genetic structure of drone congregation areas of Africanized honeybees in southern Brazil

As yet, certain aspects of the Africanization process are not well understood, for example, the reproductive behavior of African and European honeybees and how the first Africanized swarms were formed and spread. Drone congregation areas (DCAs) are the ideal place to study honeybee reproduction under natural conditions since hundreds of drones from various colonies gather together in the same geographical area for mating. In the present study, we assessed the genetic structure of seven drone congregations and four commercial European-derived and Africanized apiaries in southern Brazil, employing seven microsatellite loci for this purpose. We also estimated the number of mother-colonies that drones of a specific DCA originated from. Pairwise comparison failed to reveal any population sub-structuring among the DCAs, thus indicating low mutual genetic differentiation. We also observed high genetic similarity between colonies of commercial apiaries and DCAs, besides a slight contribution from a European-derived apiary to a DCA formed nearby. Africanized DCAs seem to have a somewhat different genetic structure when compared to the European

Real-Time Online Monitoring of the Ion Range by Means of Prompt Secondary Radiations

International audiencePrompt secondary radiations such as gamma rays and protons can be used for ion-range monitoring during ion therapy either on an energy-slice basis or on a pencil-beam basis. We present a review of the ongoing activities in terms of detector developments, imaging, experimental and theoretical physics issues concerning the correlation between the physical dose and hadronic processe

Year in review in Intensive Care Medicine 2011: III. ARDS and ECMO, weaning, mechanical ventilation, noninvasive ventilation, pediatrics and miscellanea

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Damaged DNA Binding Protein 2 Plays a Role in Breast Cancer Cell Growth

The Damaged DNA binding protein 2 (DDB2), is involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation. Loss of DDB2 function may be related to tumor susceptibility. However, hypothesis of this study was that DDB2 could play a role in breast cancer cell growth, resulting in its well known interaction with the proliferative marker E2F1 in breast neoplasia. DDB2 gene was overexpressed in estrogen receptor (ER)-positive (MCF-7 and T47D), but not in ER-negative breast cancer (MDA-MB231 and SKBR3) or normal mammary epithelial cell lines. In addition, DDB2 expression was significantly (3.0-fold) higher in ER-positive than in ER-negative tumor samples (P = 0.0208) from 16 patients with breast carcinoma. Knockdown of DDB2 by small interfering RNA in MCF-7 cells caused a decrease in cancer cell growth and colony formation. Inversely, introduction of the DDB2 gene into MDA-MB231 cells stimulated growth and colony formation. Cell cycle distribution and 5 Bromodeoxyuridine incorporation by flow cytometry analysis showed that the growth-inhibiting effect of DDB2 knockdown was the consequence of a delayed G1/S transition and a slowed progression through the S phase of MCF-7 cells. These results were supported by a strong decrease in the expression of S phase markers (Proliferating Cell Nuclear Antigen, cyclin E and dihydrofolate reductase). These findings demonstrate for the first time that DDB2 can play a role as oncogene and may become a promising candidate as a predictive marker in breast cancer