Molecular evolution of the leptin exon 3 in some species of the family Canidae

The structure of the leptin gene seems to be well conserved. The polymorphism of this gene in four species belonging to the Canidae family (the dog (Canis familiaris) – 16 different breeds, the Chinese racoon dog (Nyctereutes procyonoides procyonoides), the red fox (Vulpes vulpes) and the arctic fox (Alopex lagopus)) were studied with the use of single strand conformation polymorphism (SSCP), restriction fragment length polymorphism (RFLP) and DNA sequencing techniques. For exon 2, all species presented the same SSCP pattern, while in exon 3 some differences were found. DNA sequencing of exon 3 revealed the presence of six nucleotide substitutions, differentiating the studied species. Three of them cause amino acid substitutions as well. For all dog breeds studied, SSCP patterns were identical

Molecular signature of response and potential pathways related to resistance to the HSP90 inhibitor, 17AAG, in breast cancer

<p>Abstract</p> <p>Background</p> <p>HSP90 may be a favorable target for investigational therapy in breast cancer. In fact, the HSP90 inhibitor, 17AAG, currently has entered in phase II clinical trials as an anticancer agent in breast and other tumors. Since HSP90 inhibition leads to global depletion of oncogenic proteins involved in multiple pathways we applied global analysis using gene array technology to study new genes and pathways involved in the drug response in breast cancer.</p> <p>Methods</p> <p>Gene expression profiling using Whole Human Genome Agilent array technology was applied to a total of six sensitive and two resistant breast cancer cell lines pre-treatment and treated with the 17AAG for 24 and 48 hours.</p> <p>Results</p> <p>We have identified a common molecular signature of response to 17AAG composed of 35 genes which include novel pharmacodynamic markers of this drug. In addition, different patterns of HSP90 client transcriptional changes after 17AAG were identified associated to the sensitive cell lines, which could be useful to evaluate drug effectiveness. Finally, we have found differentially expressed pathways associated to resistance to 17AAG. We observed significant activation of NF-κB and MAPK pathways in resistant cells upon treatment, indicating that these pathways could be potentially targeted to overcome resistance.</p> <p>Conclusions</p> <p>Our study shows that global mRNA expression analysis is a useful strategy to examine molecular effects of drugs, which allowed us the discovery of new biomarkers of 17AAG activity and provided more insights into the complex mechanism of 17AAG resistance.</p

Lithium recovery from geothermal brine – an investigation into the desorption of lithium ions using manganese oxide adsorbents

Spinel type lithium manganese oxides (LMOs) are promising adsorption materials for selective recovery of lithium from salty brines. In this work a lithium-ion sieve material, H$_{1.6}$Mn$_{1.6}$O$_{4}$, derived from Li$_{1.6}$Mn$_{1.6}$O$_{4}$4, a spinel type LMO, was successfully prepared via hydrothermal synthesis. This lithium-ion sieve, H$_{1.6}$Mn$_{1.6}$O$_{4}$, was then used in laboratory tests to adsorb Li+ from a generic LiCl solution and geothermal brine from Bruchsal geothermal power plant. Desorption experiments were performed with the following desorption solutions: ammonium peroxydisulfate ((NH$_{4}$)$_{2}$S$_{2}$O$_{8}$), sodium peroxydisulfate (Na$_{2}$S$_{2}$O$_{8}$), acetic acid (CH$_{3}$COOH), sulfuric acid (H$_{2}$SO$_{4}$), carbonic acid (H$_{2}$CO$_{3}$), ascorbic (C$_{6}$H$_{8}$O$_{6}$) and hydrochloric acid (HCl). The results showed that C$_{6}$H$_{8}$O$_{6}$ led to adsorbent destruction and only small amount of lithium was desorbed with H$_{2}$CO$_{3}$. CH$_{3}$COOH and (NH$_{4}$)$_{2}$S$_{2}$O$_{8}$ showed the best desorption performance with high lithium recovery and low Mn dissolution. The kinetic experiments indicate that more than 90% of equilibrium was reached after 4 hours. A decline in the adsorption/desorption capacity was measured for all desorption agents after eight cycles in the long-term experiments. These long-term tests revealed that higher lithium recovery in desorption with HCl and CH$_{3}$COOH was achieved compared to (NH$_{4}$)$_{2}$S$_{2}$O$_{8}$. On the other hand, the use of CH$_{3}$COOH and (NH$_{4}$)$_{2}$S$_{2}$O$_{8}$ seems to be advantageous to HCl because of lower Mn dissolution. According to the XRD results, the spinel structure of the treated adsorbents was preserved, but a weakening of the peak intensity was observed. Analyzing the adsorbent composition after eight cycles, an accumulation of competing ions was observed. This was especially remarkable when acetic acid was used

Expression of tissue inhibitors of metalloproteinase 1 (TIMP-1) in gastric cancer tissue.

Degradation of extracellular matrix (ECM) is an essential step of invasion and metastasis of gastric cancer. The proteolysis of basement membranes depends on the balance between activities of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The aim of the study was to assess the expression of TIMP-1 in gastric cancer (GC) and interstitial inflammatory infiltrate cells within GC tissue in relation to clinico-pathological features of tumor and to estimate the prognostic significance of TIMP-1 expression for patients' survival. The presence of TIMP-1 in 54 cases of gastric cancer samples was investigated by immunohistochemistry. The expression of TIMP-1 in cancer and interstitial inflammatory infiltrate cells was evaluated in semi-quantitative scale. The immunoreactivity of TIMP-1 in cancer and inflammatory cells was positive in 100% of cases and varied from weak to intense reaction. The intensity of TIMP-1 expression increased with more advanced tumor stages and in patients who died of cancer during 2-year observation. TIMP-1 expression in interstitial inflammatory infiltrate cells was the independent prognostic factor for patients' survival. The results suggest the role of TIMP-1 in gastric tumorigenesis, although this issue requires further investigtions

Electrochemical Performance of Carbon-Rich Silicon Carbonitride Ceramic as Support for Sulfur Cathode in Lithium Sulfur Battery

As a promising matrix material for anchoring sulfur in the cathode for lithium-sulfur (Li-S) batteries, porous conducting supports have gained much attention. In this work, sulfur-containing C-rich SiCN composites are processed from silicon carbonitride (SiCN) ceramics, synthesized at temperatures from 800 to 1100 °C. To embed sulfur in the porous SiCN matrix, an easy and scalable procedure, denoted as melting-diffusion method, is applied. Accordingly, sulfur is infiltrated under solvothermal conditions at 155 °C into pores of carbon-rich silicon carbonitride (C-rich SiCN). The impact of the initial porosity and microstructure of the SiCN ceramics on the electrochemical performance of the synthesized SiCN-sulfur (SiCN-S) composites is analysed and discussed. A combination of the mesoporous character of SiCN and presence of a disordered free carbon phase makes the electrochemical performance of the SiCN matrix obtained at 900 °C superior to that of SiCN synthesized at lower and higher temperatures. A capacity value of more than 195 mAh/g over 50 cycles at a high sulfur content of 66 wt.% is achieved

IL-12 DNA Displays efficient adjuvant effects improving immunogenicity of Ag85A in DNA prime/MVA boost immunizations

Mycobacterium tuberculosis (Mtb) infection is one of the leading causes of death worldwide. The Modified Vaccinia Ankara (MVA) vaccine vector expressing the mycobacterial antigen 85A (MVA85A) was demonstrated to be safe, although it did not improve BCG efficacy, denoting the need to search for improved tuberculosis vaccines. In this work, we investigated the effect of IL-12 DNA -as an adjuvant- on an Ag85A DNA prime/MVA85A boost vaccination regimen. We evaluated the immune response profile elicited in mice and the protection conferred against intratracheal Mtb H37Rv challenge. We observed that the immunization scheme including DNA-A85A+DNA-IL-12/MVA85A induced a strong IFN-γ production to Ag85A in vitro, with a significant expansion of IFN-γ+CD4+ and IFN-γ+CD8+ anti-Ag85A lymphocytes. Furthermore, we also detected a significant increase in the proportion of specific CD8+CD107+ T cells against Ag85A. Additionally, inclusion of IL-12 DNA in the DNA-A85A/MVA85A vaccine scheme induced a marked augment in anti-Ag85A IgG levels. Interestingly, after 30 days of infection with Mtb H37Rv, DNA-A85A+DNA-IL-12/MVA85A vaccinated mice displayed a significant reduction in lung bacterial burden. Together, our findings suggest that IL-12 DNA might be useful as a molecular adjuvant in an Ag85A DNA/MVA prime-boost vaccine against Mtb infection.Instituto de BiotecnologíaFil: Morelli, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Del Medico Zajac, Maria Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina.Fil: Pellegrini, Joaquín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Tateosian, Nancy Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Calamante, Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina.Fil: Gherardi, Maria Magdalena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina.Fil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Pellegrini, Joaquín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Pellegrini, Joaquín Miguel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica; Argentina.Fil: Pellegrini, Joaquín Miguel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Morelli, María Paula. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica; Argentina.Fil: Morelli, María Paula. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Del Medico Zajac, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Amiano, Nicolás Oscar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica; Argentina.Fil: Amiano, Nicolás Oscar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Tateosian, Nancy Liliana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica; Argentina.Fil: Tateosian, Nancy Liliana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Calamante, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gherardi, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García, Verónica Edith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica; Argentina.Fil: García, Verónica Edith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin

Electrochemical Li Storage Properties of Carbon-Rich B–C–N Ceramics

Amorphous BCN ceramics were synthesized via a thermal conversion procedure of piperazine–borane and pyridine–borane. The synthesized BC₂N and BC₄N ceramics contained, in their final amorphous structure, 45 and 65 wt % of carbon, respectively. Elemental analysis revealed 45 and 65 wt % of carbon for BC₂N and BC₄N, respectively. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) confirmed the amorphous nature of studied compounds. Lateral cluster size of carbon crystallites of 7.43 and 10.3 nm for BC₂N and BC₄N, respectively, was calculated from Raman spectroscopy data. This signified a higher order of the carbon phase present in BC₄N. The electrochemical investigation of the low carbon BC₂N composition as anodes for Li-ion batteries revealed initial capacities of 667 and 235 mAh·g⁻¹ for lithium insertion/extraction, respectively. The material with higher carbon content, BC₄N, disclosed better reversible lithium storage properties. Initial capacities of 1030 and 737 mAh·g⁻¹ for lithium insertion and extraction were recovered for carbon-rich BC₄N composition. Extended cycling with high currents up to 2 C/2 D revealed the cycling stability of BC4N electrodes. Cycling for more than 75 cycles at constant current rates showed a stable electrochemical behavior of BC₄N anodes with capacities as high as 500 mAh·g⁻¹