Summer Colloquium in Theoretical Biology

Theoretical cell biology including self-reproductive systems - conference

Multidisciplinary research in theoretical biology Annual report, Jan. - Dec. 31, 1967

Biochemistry, biophysics, cell physiology, and central nervous system researc

First and second variation formulae for the sub-Riemannian area in three-dimensional pseudo-hermitian manifolds

We calculate the first and the second variation formula for the sub-Riemannian area in three dimensional pseudo-hermitian manifolds. We consider general variations that can move the singular set of a C^2 surface and non-singular variation for C_H^2 surfaces. These formulas enable us to construct a stability operator for non-singular C^2 surfaces and another one for C2 (eventually singular) surfaces. Then we can obtain a necessary condition for the stability of a non-singular surface in a pseudo-hermitian 3-manifold in term of the pseudo-hermitian torsion and the Webster scalar curvature. Finally we classify complete stable surfaces in the roto-traslation group RT .Comment: 36 pages. Misprints corrected. Statement of Proposition 9.8 slightly changed and Remark 9.9 adde

Basic properties of nonsmooth Hormander's vector fields and Poincare's inequality

We consider a family of vector fields defined in some bounded domain of R^p, and we assume that they satisfy Hormander's rank condition of some step r, and that their coefficients have r-1 continuous derivatives. We extend to this nonsmooth context some results which are well-known for smooth Hormander's vector fields, namely: some basic properties of the distance induced by the vector fields, the doubling condition, Chow's connectivity theorem, and, under the stronger assumption that the coefficients belong to C^{r-1,1}, Poincare's inequality. By known results, these facts also imply a Sobolev embedding. All these tools allow to draw some consequences about second order differential operators modeled on these nonsmooth Hormander's vector fields.Comment: 60 pages, LaTeX; Section 6 added and Section 7 (6 in the previous version) changed. Some references adde

Local behavior of p-harmonic Green's functions in metric spaces

We describe the behavior of p-harmonic Green's functions near a singularity in metric measure spaces equipped with a doubling measure and supporting a Poincar\'e inequality

Autômatos celulares unidimensionais caóticos com borda fixa aplicados à modelagem de um sistema criptográfico para imagens digitais

O principal objetivo da criptografia de dados é possibilitar que duas entidades se comuniquem ao longo de um canal inseguro, de tal forma que nenhum oponente consiga decifrar a mensagem que é enviada. Muitos métodos de criptografia clássica já foram investigados para minimizar este problema. Uma nova abordagem para este tema são os Autômatos Celulares (ACs), que estão sendo estudados por sua capacidade de processar grandes volumes de dados em paralelo. Nesse trabalho é investigado um novo modelo de autômato celular para criptografia de imagens, que tem como característica o uso do cálculo de pré-imagens. Resultados mostraram que o modelo tem grande potencial para a realização de cifragem de grandes volumes de dados

The ion channel CALHM6 controls bacterial infection-induced cellular cross-talk at the immunological synapse

Membrane ion channels of the calcium homeostasis modulator (CALHM) family promote cell–cell crosstalk at neuronal synapses via ATP release, where ATP acts as a neurotransmitter. CALHM6, the only CALHM highly expressed in immune cells, has been linked to the induction of natural killer (NK) cell anti-tumour activity. However, its mechanism of action and broader functions in the immune system remain unclear. Here, we generated Calhm6−/− mice and report that CALHM6 is important for the regulation of the early innate control of Listeria monocytogenes infection in vivo. We find that CALHM6 is upregulated in macrophages by pathogen-derived signals and that it relocates from the intracellular compartment to the macrophage-NK cell synapse, facilitating ATP release and controlling the kinetics of NK cell activation. Anti-inflammatory cytokines terminate CALHM6 expression. CALHM6 forms an ion channel when expressed in the plasma membrane of Xenopus oocytes, where channel opening is controlled by a conserved acidic residue, E119. In mammalian cells, CALHM6 is localised to intracellular compartments. Our results contribute to the understanding of neurotransmitter-like signal exchange between immune cells that fine-tunes the timing of innate immune responses

Light-Enhanced Cytotoxicity of Doxorubicin by Photoactivation

The combination of photodynamic therapy with chemotherapy (photochemotherapy, PCT) can lead to additive or synergistic antitumor effects. Usually, two different molecules, a photosensitizer (PS) and a chemotherapeutic drug are used in PCT. Doxorubicin is one of the most successful chemotherapy drugs. Despite its high efficacy, two factors limit its clinical use: severe side effects and the development of chemoresistance. Doxorubicin is a chromophore, able to absorb light in the visible range, making it a potential PS. Here, we exploited the intrinsic photosensitizing properties of doxorubicin to enhance its anticancer activity in leukemia, breast, and epidermoid carcinoma cells, upon irradiation. Light can selectively trigger the local generation of reactive oxygen species (ROS), following photophysical pathways. Doxorubicin showed a concentration-dependent ability to generate peroxides and singlet oxygen upon irradiation. The underlying mechanisms leading to the increase in its cytotoxic activity were intracellular ROS generation and the induction of necrotic cell death. The nuclear localization of doxorubicin represents an added value for its use as a PS. The use of doxorubicin in PCT, simultaneously acting as a chemotherapeutic agent and a PS, may allow (i) an increase in the anticancer effects of the drug, and (ii) a decrease in its dose, and thus, its dose-related adverse effects

Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele.

IL-7 is a key factor in T cell immunity and common variants at IL7R, encoding its receptor, are associated with autoimmune disease susceptibility. IL7R mRNA is induced in stimulated monocytes, yet a function for IL7R in monocyte biology remains unexplored. Here we characterize genetic regulation of IL7R at the protein level in healthy individuals, and find that monocyte surface and soluble IL7R (sIL7R) are markedly induced by lipopolysaccharide. In monocytes, both surface IL7R and sIL7R expression strongly associate with allelic carriage of rs6897932, a disease-associated IL7R polymorphism. Monocytes produce more sIL7R than CD4 + T cells, and the amount is additionally correlated with the expression of DDX39A, encoding a splicing factor. Synovial fluid-derived monocytes from patients with spondyloarthritis are enriched for IL7R+ cells with a unique transcriptional profile that overlaps with IL-7-induced gene sets. Our data thus suggest a previously unappreciated function for monocytes in IL-7 biology and IL7R-associated diseases