Electrical Conductance of Molecular Wires

Molecular wires (MW) are the fundamental building blocks for molecular electronic devices. They consist of a molecular unit connected to two continuum reservoirs of electrons (usually metallic leads). We rely on Landauer theory as the basis for studying the conductance properties of MW systems. This relates the lead to lead current to the transmission probability for an electron to scatter through the molecule. Two different methods have been developed for the study of this scattering. One is based on a solution of the Lippmann-Schwinger equation and the other solves for the {\bf t} matrix using Schroedinger's equation. We use our methodology to study two problems of current interest. The first MW system consists of 1,4 benzene-dithiolate (BDT) bonded to two gold nanocontacts. Our calculations show that the conductance is sensitive to the chemical bonding between the molecule and the leads. The second system we study highlights the interesting phenomenon of antiresonances in MW. We derive an analytic formula predicting at what energies antiresonances should occur in the transmission spectra of MW. A numerical calculation for a MW consisting of filter molecules attached to an active molecule shows the existence of an antiresonance at the energy predicted by our formula.Comment: 14 pages, 5 figure

Role of PPARs in Trypanosoma cruzi Infection: Implications for Chagas Disease Therapy

Chagas disease, which is caused by Trypanosoma cruzi (T. cruzi), remains a substantial public health concern and an important cause of morbidity and mortality in Latin America. T. cruzi infection causes an intense inflammatory response in diverse tissues by triggering local expression of inflammatory mediators, which results in the upregulation of the levels of cytokines and chemokines, and important cardiac alterations in the host, being one of the most characteristic damages of Chagas disease. Therefore, controlling the inflammatory reaction becomes critical for the control of the proliferation of the parasite and of the evolution of Chagas disease. The nuclear receptors known as peroxisome proliferator-activated receptors (PPARs) have emerged as key regulators of lipid metabolism and inflammation. The precise role of PPAR ligands in T. cruzi infection or in Chagas disease is poorly understood. This review summarizes our knowledge about T. cruzi infection as well as about the activation of PPARs and the potential role of their ligands in the resolution of inflammation, with the aim to address a new pharmacological approach to improve the host health

IL-10 Inhibits the NF-kB and ERK/MAPK-Mediated Production of Pro-Inflammatory Mediators by UpRegulation of SOCS-3 in Trypanosoma cruzi-Infected Cardiomyocytes

Trypanosoma cruzi (T. cruzi) infection produces an intense inflammatory response which is critical for the control of the evolution of Chagas´ disease. Interleukin (IL)-10 is one of the most important anti-inflammatory cytokines identified as modulator of the inflammatory reaction. This work shows that exogenous addition of IL-10 inhibited ERK1/2 and NF-κB activation and reduced inducible nitric oxide synthase (NOS2), metalloprotease (MMP) -9 and MMP-2 expression and activities, as well as tumour necrosis factor (TNF)-α and interleukin (IL)-6 expression, in T. cruzi-infected cardiomyocytes. We found that T. cruzi and IL-10 promote STAT3 phosphorylation and up-regulate the expression of suppressor of cytokine signalling (SOCS)-3 thereby preventing NF-κB nuclear translocation and ERK1/2 phosphorylation. Specific knockdown of SOCS-3 by small interfering RNA (siRNA) impeded the IL-10-mediated inhibition of NF-κB and ERK1/2 activation. As a result, the levels of studied pro-inflammatory mediators were restored in infected cardiomyocytes. Our study reports the first evidence that T. cruzi up- regulates SOCS-3 expression and highlights the relevance of IL-10 in the modulation of pro-inflammatory response of cardiomyocytes in Chagas´ disease.Fil: Hovsepian, Eugenia. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones En Microbiologia y Parasitologia Medica;Fil: Penas, Federico Nicolás. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones En Microbiologia y Parasitologia Medica;Fil: Siffo, Sofía. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones En Microbiologia y Parasitologia Medica;Fil: Mirkin Gerardo A.. INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA;Fil: Goren, Nora Beatriz. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones En Microbiologia y Parasitologia Medica

Coupling Transcriptional State to Large-Scale Repeat Expansions in Yeast

SummaryExpansions of simple DNA repeats cause numerous hereditary disorders in humans. Replication, repair, and transcription are implicated in the expansion process, but their relative contributions are yet to be distinguished. To separate the roles of replication and transcription in the expansion of Friedreich’s ataxia (GAA)n repeats, we designed two yeast genetic systems that utilize a galactose-inducible GAL1 promoter but contain these repeats in either the transcribed or nontranscribed region of a selectable cassette. We found that large-scale repeat expansions can occur in the lack of transcription. Induction of transcription strongly elevated the rate of expansions in both systems, indicating that active transcriptional state rather than transcription through the repeat per se affects this process. Furthermore, replication defects increased the rate of repeat expansions irrespective of transcriptional state. We present a model in which transcriptional state, linked to the nucleosomal density of a region, acts as a modulator of large-scale repeat expansions

Treatment with a new peroxisome proliferator-activated receptor gamma agonist, pyridinecarboxylic acid derivative, increases angiogenesis and reduces inflammatory mediators in the heart of Trypanosoma cruzi-infected mice

Trypanosoma cruzi infection induces an intense inflammatory response in diverse host tissues. The immune response and the microvascular abnormalities associated with infection are crucial aspects in the generation of heart damage in Chagas disease. Upon parasite uptake, macrophages, which are involved in the clearance of infection, increase inflammatory mediators, leading to parasite killing. The exacerbation of the inflammatory response may lead to tissue damage. Peroxisome proliferator-activated receptor gamma (PPAR\u3b3) is a ligand-dependent nuclear transcription factor that exerts important anti-inflammatory effects and is involved in improving endothelial functions and proangiogenic capacities. In this study, we evaluated the intermolecular interaction between PPAR\u3b3 and a new synthetic PPAR\u3b3 ligand, HP24, using virtual docking. Also, we showed that early treatment with HP24, decreases the expression of NOS2, a pro-inflammatory mediator, and stimulates proangiogenic mediators (vascular endothelial growth factor A, CD31, and Arginase I) both in macrophages and in the heart of T. cruzi-infected mice. Moreover, HP24 reduces the inflammatory response, cardiac fibrosis and the levels of inflammatory cytokines (TNF-\u3b1, interleukin 6) released by macrophages of T. cruzi-infected mice. We consider that PPAR\u3b3 agonists might be useful as coadjuvants of the antiparasitic treatment of Chagas disease, to delay, reverse, or preclude the onset of heart damage

Attachment of Motile Bacterial Cells to Prealigned Holed Microarrays

Construction of biomotors is an exciting area of scientific research that holds great promise for the development of new technologies with broad potential applications in areas such as the energy industry and medicine. Herein, we demonstrate the fabrication of prealigned microarrays of motile Escherichia coli bacterial cells on SiOx substrates. To prepare these arrays, holed surfaces with a gold layer on the bottom of the holes were utilized. The attachment of bacteria to the holes was achieved via nonspecific interactions using poly-l-lysine hydrobromide (PLL). Our data suggest that a single motile bacterial cell can be selectively attached to an individual hole on a surface and bacterial cell binding can be controlled by altering the pH, with the greatest occupancy occurring at pH 7.8. Cells attached to hole arrays remained motile for at least 4 h. These data indicate that holed surface structures provide a promising footprint for the attachment of motile bacterial cells to form high-density site-specific functional bacterial microarrays

Brief clinical report: prune belly syndrome in an anencephalic male

We describe a postmature anencephalic infant with atrophy of the abdominal musculature (prune belly syndrome). Other associations of these conditions are noted