112 research outputs found
Schwaller, Robert C.: GĂ©neros de Gente in Early Colonial Mexico: Defining Racial Difference, Norman, University of Oklahoma Press, 2016.
A systems biology approach to dissection of the effects of small bicyclic peptidomimetics on a panel of Saccharomyces cerevisiae mutants
In recent years, an approach called âchemical geneticsâ has been adopted in drug research to discover and validate new targets and to identify and optimize leads by high throughput screening. In this work, we tested the ability of a library of small peptidomimetics to induce phenotypic effects with functional implications on a panel of strains of the budding yeast Saccharomyces cerevisiae, both wild type and mutants, for respiratory function and multidrug resistance. Further elucidation of the function of these peptidomimetics was assessed by testing the effects of the compound with the most prominent inhibitory activity, 089, on gene expression using DNA microarrays. Pathway analysis showed the involvement of such a molecule in inducing oxidative damage through alterations in mitochondrial functions. Transcriptional experiments were confirmed by increased levels of ROS and activation of mitochondrial membrane potential. Our results demonstrate the influence of a functional HAP1 gene in the performance of S. cerevisiae as a model system
Chemical genetics approach to identify new small molecule modulators of cell growth by phenotypic screening of Saccharomyces cerevisiae strains with a library of morpholine-derived compounds
Synthesis of 5,6,6-[2H3]finasteride and quantitative determination of finasteride in human plasma at picogram level by an isotope-dilution mass spectrometric method.
3-Aza-6,8-dioxabicyclo[3.2.1]octanes as new enantiopure heteroatom-rich tropane-like ligands of human dopamine transporter.
Isotopic dilution GC-MS measurement of 4-Hydroxyandrostendione in postmenopausal breast cancer
Human osteoarthritic chondrocytes exposed to extremely low-frequency electromagnetic fields (ELF) and therapeutic application of musically modulated electromagnetic fields (TAMMEF) systems: a comparative study.
Osteoarthritis (OA) is the most common joint disease, characterized by matrix
degradation and changes in chondrocyte morphology and metabolism. Literature
reported that electromagnetic fields (EMFs) can produce benefits in OA patients,
even if EMFs mechanism of action is debated. Human osteoarthritic chondrocytes
isolated from femoral heads were cultured in vitro in bidimensional (2-D) flasks
and in three-dimensional (3-D) alginate beads to mimic closely cartilage
environment in vivo. Cells were exposed 30 min/day for 2 weeks to extremely
low-frequency electromagnetic field (ELF) with fixed frequency (100 Hz) and to
therapeutic application of musically modulated electromagnetic field (TAMMEF)
with variable frequencies, intensities, and waveforms. Cell viability was
measured at days 7 and 14, while healthy-cell density, heavily vacuolized (hv)
cell density, and cluster density were measured by light microscopy only for 3-D
cultures after treatments. Cell morphology was observed for 2-D and 3-D cultures
by transmission electron microscopy (TEM). Chondrocyte exposure to TAMMEF
enhances cell viability at days 7 and 14 compared to ELF. Light microscopy
analysis showed that TAMMEF enhances healthy-cell density, reduces hv-cell
density and clustering, compared to ELF. Furthermore, TEM analysis showed
different morphology for 2-D (fibroblast-like) and 3-D (rounded shape) cultures,
confirming light microscopy results. In conclusion, EMFs are effective and safe
for OA chondrocytes. TAMMEF can positively interfere with OA chondrocytes
representing an innovative non-pharmacological approach to treat OA
Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine
Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base
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